Daniel M. Weinberger et al.

Excess Mortality Among Patients in the Veterans Affairs Health System Compared With the Overall US Population During the First Year of the COVID-19 Pandemic

JAMA, May 2023; doi:10.1001/jamanetworkopen.2023.12140


Importance  During the first year of the COVID-19 pandemic, there was a substantial increase in the rate of death in the United States. It is unclear whether those who had access to comprehensive medical care through the Department of Veterans Affairs (VA) health care system had different death rates compared with the overall US population.

Objective  To quantify and compare the increase in death rates during the first year of the COVID-19 pandemic between individuals who received comprehensive medical care through the VA health care system and those in the general US population.

Design, Setting, and Participants  This cohort study compared 10.9 million enrollees in the VA, including 6.8 million active users of VA health care (those with a visit in the last 2 years), with the general population of the US, with deaths occurring from January 1, 2014, to December 31, 2020. Statistical analysis was conducted from May 17, 2021, to March 15, 2023.

Main Outcomes and Measures  Changes in rates of death from any cause during the COVID-19 pandemic in 2020 compared with previous years. Changes in all-cause death rates by quarter were stratified by age, sex, race and ethnicity, and region, based on individual-level data. Multilevel regression models were fit in a bayesian setting. Standardized rates were used for comparison between populations.

Results  There were 10.9 million enrollees in the VA health care system and 6.8 million active users. The demographic characteristics of the VA populations were predominantly male (>85% in the VA health care system vs 49% in the general US population), older (mean [SD], 61.0 [18.2] years in the VA health care system vs 39.0 [23.1] years in the US population), and had a larger proportion of patients who were White (73% in the VA health care system vs 61% in the US population) or Black (17% in the VA health care system vs 13% in the US population). Increases in death rates were apparent across all of the adult age groups (≥25 years) in both the VA populations and the general US population. Across all of 2020, the relative increase in death rates compared with expected values was similar for VA enrollees (risk ratio [RR], 1.20 [95% CI, 1.14-1.29]), VA active users (RR, 1.19 [95% CI, 1.14-1.26]), and the general US population (RR, 1.20 [95% CI, 1.17-1.22]). Because the prepandemic standardized mortality rates were higher in the VA populations prior to the pandemic, the absolute rates of excess mortality were higher in the VA populations.

Conclusions and Relevance  In this cohort study, a comparison of excess deaths between populations suggests that active users of the VA health system had similar relative increases in mortality compared with the general US population during the first 10 months of the COVID-19 pandemic.

Heng Yao et al.

Impact of the COVID-19 lockdown on typical ambient air pollutants: Cyclical response to anthropogenic emission reduction

Cell, May 2023; doi.org/10.1016/j.heliyon.2023.e15799


Preliminary studies have confirmed that ambient air pollutant concentrations are significantly influenced by the COVID-19 lockdown measures, but little attention focus on the long term impacts of human countermeasures in cities all over the world during the period. Still, fewer have addressed their other essential properties, especially the cyclical response to concentration reduction. This paper aims to fill the gaps with combined methods of abrupt change test and wavelet analysis, research areas were made of five cities, Wuhan, Changchun, Shanghai, Shenzhen and Chengdu, in China. Abrupt changes in contaminant concentrations commonly occurred in the year prior to the outbreak. The lockdown has almost no effect on the short cycle below 30 d (days) for both pollutants, and a negligible impact on the cycle above 30 d. PM2.5 (fine particulate matter) has a stable short-cycle nature, which is greatly influenced by anthropogenic emissions. The analysis revealed that the sensitivity of PM2.5 to climate is increased along with the concentrations of PM2.5 were decreasing by the times when above the threshold (30–50 μg m−3), and which could lead to PM2.5 advancement relative to the ozone phase over a period of 60 d after the epidemic. These results suggest that the epidemic may have had an impact earlier than when it was known. And significant reductions in anthropogenic emissions have little impact on the cyclic nature of pollutants, but may alter the inter-pollutant phase differences during the study period.

Heng Yao et al

Impact of the COVID-19 lockdown on typical ambient air pollutants: Cyclical response to anthropogenic emission reduction

Cell, May 2023; doi.org/10.1016/j.heliyon.2023.e15799


Preliminary studies have confirmed that ambient air pollutant concentrations are significantly influenced by the COVID-19 lockdown measures, but little attention focus on the long term impacts of human countermeasures in cities all over the world during the period. Still, fewer have addressed their other essential properties, especially the cyclical response to concentration reduction. This paper aims to fill the gaps with combined methods of abrupt change test and wavelet analysis, research areas were made of five cities, Wuhan, Changchun, Shanghai, Shenzhen and Chengdu, in China. Abrupt changes in contaminant concentrations commonly occurred in the year prior to the outbreak. The lockdown has almost no effect on the short cycle below 30 d (days) for both pollutants, and a negligible impact on the cycle above 30 d. PM2.5 (fine particulate matter) has a stable short-cycle nature, which is greatly influenced by anthropogenic emissions. The analysis revealed that the sensitivity of PM2.5 to climate is increased along with the concentrations of PM2.5 were decreasing by the times when above the threshold (30–50 μg m−3), and which could lead to PM2.5 advancement relative to the ozone phase over a period of 60 d after the epidemic. These results suggest that the epidemic may have had an impact earlier than when it was known. And significant reductions in anthropogenic emissions have little impact on the cyclic nature of pollutants, but may alter the inter-pollutant phase differences during the study period.

Dielle J. Lundberg et al.

COVID-19 Mortality by Race and Ethnicity in US Metropolitan and Nonmetropolitan Areas, March 2020 to February 2022

JAMA, May 2023; doi:10.1001/jamanetworkopen.2023.11098


Importance Prior research has established that Hispanic and non-Hispanic Black residents in the US experienced substantially higher COVID-19 mortality rates in 2020 than non-Hispanic White residents owing to structural racism. In 2021, these disparities decreased.

Objective To assess to what extent national decreases in racial and ethnic disparities in COVID-19 mortality between the initial pandemic wave and subsequent Omicron wave reflect reductions in mortality vs other factors, such as the pandemic’s changing geography.

Design, Setting, and Participants This cross-sectional study was conducted using data from the US Centers for Disease Control and Prevention for COVID-19 deaths from March 1, 2020, through February 28, 2022, among adults aged 25 years and older residing in the US. Deaths were examined by race and ethnicity across metropolitan and nonmetropolitan areas, and the national decrease in racial and ethnic disparities between initial and Omicron waves was decomposed. Data were analyzed from June 2021 through March 2023.

Exposures Metropolitan vs nonmetropolitan areas and race and ethnicity.

Main Outcomes and Measures Age-standardized death rates.

Results There were death certificates for 977 018 US adults aged 25 years and older (mean [SD] age, 73.6 [14.6] years; 435 943 female [44.6%]; 156 948 Hispanic [16.1%], 140 513 non-Hispanic Black [14.4%], and 629 578 non-Hispanic White [64.4%]) that included a mention of COVID-19. The proportion of COVID-19 deaths among adults residing in nonmetropolitan areas increased from 5944 of 110 526 deaths (5.4%) during the initial wave to a peak of 40 360 of 172 515 deaths (23.4%) during the Delta wave; the proportion was 45 183 of 210 554 deaths (21.5%) during the Omicron wave. The national disparity in age-standardized COVID-19 death rates per 100 000 person-years for non-Hispanic Black compared with non-Hispanic White adults decreased from 339 to 45 deaths from the initial to Omicron wave, or by 293 deaths. After standardizing for age and racial and ethnic differences by metropolitan vs nonmetropolitan residence, increases in death rates among non-Hispanic White adults explained 120 deaths/100 000 person-years of the decrease (40.7%); 58 deaths/100 000 person-years in the decrease (19.6%) were explained by shifts in mortality to nonmetropolitan areas, where a disproportionate share of non-Hispanic White adults reside. The remaining 116 deaths/100 000 person-years in the decrease (39.6%) were explained by decreases in death rates in non-Hispanic Black adults.

Conclusions and Relevance This study found that most of the national decrease in racial and ethnic disparities in COVID-19 mortality between the initial and Omicron waves was explained by increased mortality among non-Hispanic White adults and changes in the geographic spread of the pandemic. These findings suggest that despite media reports of a decline in disparities, there is a continued need to prioritize racial health equity in the pandemic response.

Linda Nab et al.

Changes in COVID-19-related mortality across key demographic and clinical subgroups in England from 2020 to 2022: a retrospective cohort study using the OpenSAFELY platform

The Lancet, May 2023; doi.org/10.1016/S2468-2667(23)00079-8


COVID-19 has been shown to differently affect various demographic and clinical population subgroups. We aimed to describe trends in absolute and relative COVID-19-related mortality risks across clinical and demographic population subgroups during successive SARS-CoV-2 pandemic waves.


We did a retrospective cohort study in England using the OpenSAFELY platform with the approval of National Health Service England, covering the first five SARS-CoV-2 pandemic waves (wave one [wild-type] from March 23 to May 30, 2020; wave two [alpha (B.1.1.7)] from Sept 7, 2020, to April 24, 2021; wave three [delta (B.1.617.2)] from May 28 to Dec 14, 2021; wave four [omicron (B.1.1.529)] from Dec 15, 2021, to April 29, 2022; and wave five [omicron] from June 24 to Aug 3, 2022). In each wave, we included people aged 18–110 years who were registered with a general practice on the first day of the wave and who had at least 3 months of continuous general practice registration up to this date. We estimated crude and sex-standardised and age-standardised wave-specific COVID-19-related death rates and relative risks of COVID-19-related death in population subgroups.


There was a substantial decrease in absolute COVID-19-related death rates over time in the overall population, but demographic and clinical relative risk profiles persisted and worsened for people with lower vaccination coverage or impaired immune response. Our findings provide an evidence base to inform UK public health policy for protecting these vulnerable population subgroups.

Mark W Tenforde, Ruth Link-Gelles

Reduction in COVID-19-related mortality over time but disparities across population subgroups

The Lancet, May 2023; doi.org/10.1016/S2468-2667(23)00078-6


More than 3 years into the pandemic, the world has made major progress in understanding, preventing, and treating COVID-19, and has experienced periods of substantial individual and societal disruption. High rates of immunity from vaccination and recovery from previous infection are now observed among populations,1 which are likely to attenuate the severity of new infections due to long-lasting cellular and humoral immunity.2 Greater normalcy has returned as governments have ended pandemic restrictions or declared an end to COVID-19 as a public health emergency.3, 4 Despite this progress, SARS-CoV-2 continues to circulate and thousands of COVID-19-related deaths occur weekly worldwide,5 suggesting that there is further room for improvement.

In this issue of The Lancet Public Health, Linda Nab and colleagues6 report the findings of a retrospective cohort study in England that used the OpenSAFELY platform to examine COVID-19-related mortality in adults aged 18 years or older across five pandemic waves spanning almost 2·5 years. Each pandemic wave cohort included data from about 19 million adults with continuous general practice registration. COVID-19-related deaths were captured from death registry linkage and defined by citation of COVID-19 as an underlying or contributing cause of death. Crude and age-standardised and sex-standardised mortality rates and relative hazards of COVID-19-related deaths across demographic and clinical subgroups were assessed for each pandemic wave. Because of dynamic changes in public health measures, population immunity, clinical management, and transmissibility and severity of SARS-CoV-2 variants, the study could not disentangle precise contributions of individual factors but nevertheless provides valuable insights and a comprehensive picture of temporal changes.Nab and colleagues6 found that COVID-19-related mortality rates decreased over time, with crude rates per 1000 person-years declining from 4·48 deaths during wave one (March 23–May 30, 2020) to 0·67 deaths during wave five (June 24–Aug 3, 2022). Compared with wave one, wave two (Sept 7, 2020–April 24, 2021), corresponding with alpha (B.1.1.7) variant circulation and before most adults were vaccinated against COVID-19, showed broad decreases in mortality rates. This might reflect the effects of early public health efforts or improved clinical management, although this should be interpreted in the context of measuring incidence of COVID-19-related deaths over periods with varying lengths and rates of SARS-CoV-2 infection. During wave three (May 28–Dec 14, 2021; in which delta [B.1.617.2] was the dominant variant), the largest decreases in mortality rates were observed among groups who were prioritised for COVID-19 vaccination, especially older adults who had very high primary vaccine series coverage. This finding is consistent with data that have shown a lower risk of severe COVID-19-related outcomes among vaccinated adults, and highlights the fundamental importance of vaccination for all adults.7, 8

Despite overall reductions in COVID-19-related mortality rates over time, improvements were not realised equally across population subgroups. Notwithstanding higher vaccine coverage and relative reductions in COVID-19-related mortality over time, older adults continued to show higher COVID-19-related mortality rates than younger adults, although this study could not discern whether COVID-19 was the primary cause of death or a contributing factor, such as by exacerbating chronic health conditions. Furthermore, in settings of high vaccine coverage, adults with conditions associated with frailty or reduced vaccine response (eg, organ transplant, haematological malignancy, or advanced kidney disease) did not show the same reductions in mortality rates as those without these conditions, suggesting that focused efforts in key population subgroups remain crucial. These efforts might include differential vaccine schedules in groups who are at high risk of severe outcomes, a low threshold for testing and early initiation of effective but underused antiviral therapies (such as nirmatrelvir–ritonavir), and implementation of non-pharmaceutical measures, such as face masks indoors in some settings and improved ventilation.9 The broader community should also protect people who are at high risk of severe outcomes, such as through testing and avoiding public places when unwell. Using the Index of Multiple Deprivation, the Nab and colleagues6 additionally found that relative mortality in populations living in the most socially deprived areas was higher than in less deprived areas. This finding corresponded with lower vaccination coverage in areas with greater deprivation and might also reflect other differences in access to or utilisation of health-care services, or more crowded living conditions. These findings underscore a need for improved outreach and COVID-19 vaccination among the most vulnerable groups in society.

Major progress has been made and we are no longer seeing the dramatic mortality rates observed during earlier COVID-19 pandemic periods. However, COVID-19 continues to kill thousands of people, and specific population subgroups have a greater burden. The study by Nab and colleagues6 shows the value of strong national and integrated surveillance and vaccine registry data to record the implications of the pandemic and inform public health responses. It also provides robust data on groups in whom measures to reduce severe COVID-19-related outcomes could be more effectively focused, while continuing to minimise individual and societal impacts from COVID-19.

LangjunTang et al.

Exploration on wastewater-based epidemiology of SARS-CoV-2: Mimic relative quantification with endogenous biomarkers as internal reference

Cell, April 2023; doi.org/10.1016/j.heliyon.2023.e15705


Wastewater-based epidemiology has become a powerful surveillance tool for monitoring the pandemic of COVID-19. Although it is promising to quantitatively correlate the SARS-CoV-2 RNA concentration in wastewater with the incidence of community infection, there is still no consensus on whether the viral nucleic acid concentration in sewage should be normalized against the abundance of endogenous biomarkers and which biomarker should be used as a reference for the normalization. Here, several candidate endogenous reference biomarkers for normalization of SARS-CoV-2 signal in municipal sewage were evaluated. The human fecal indicator virus (crAssphage) is a promising candidate of endogenous reference biomarker for data normalization of both DNA and RNA viruses for its intrinsic viral nature and high and stable content in sewage. Without constructing standard curves, the relative quantification of sewage viral nucleic acid against the abundance of the reference biomarker can be used to correlate with community COVID-19 incidence, which was proved via mimic experiments by spiking pseudovirus of different concentrations in sewage samples. Dilution of pseudovirus-seeded wastewater did not affect the relative abundance of viral nucleic acid, demonstrating that relative quantification can overcome the sewage dilution effects caused by the greywater input, precipitation and/or groundwater infiltration. The process of concentration, recovery and detection of the endogenous biomarker was consistent with that of SARS-CoV-2 RNA. Thus, it is necessary to co-quantify the endogenous biomarker because it can be not only an internal reference for data normalization, but also a process control.

Simon Galmiche et al.

SARS-CoV-2 incubation period across variants of concern, individual factors, and circumstances of infection in France: a case series analysis from the ComCor study

The Lamcet, April 2023; doi.org/10.1016/S2666-5247(23)00005-8


The incubation period of SARS-CoV-2 has been estimated for the known variants of concern. However, differences in study designs and settings make comparing variants difficult. We aimed to estimate the incubation period for each variant of concern compared with the historical strain within a unique and large study to identify individual factors and circumstances associated with its duration.


SARS-CoV-2 incubation period is notably reduced in omicron cases compared with all other variants of concern, in young people, after transmission from a symptomatic index case, after transmission to a maskless secondary case, and (to a lesser extent) in men. These findings can inform future COVID-19 contact-tracing strategies and modelling.

EridiongOnyenweaku et al.

The role of nutrition knowledge in dietary adjustments during COVID-19 pandemic

Cell, march 2023; doi.org/10.1016/j.heliyon.2023.e15044


Knowledge/awareness significantly influences people's dietary choices, lifestyle, and inadvertently their health outcomes; hence it is imperative that people have correct information with regards to food and health. This study was undertaken to establish the role of nutrition knowledge on dietary choices and habits of people in Calabar, especially after the hard COVID-19 lockdown, and to ascertain if there was any positive or negative effect on the lifestyle of the people. It consisted of a cross-sectional survey in Calabar, Cross River State – Nigeria. An online questionnaire was prepared after sample size determination and its content validated. The questionnaire was designed to obtain data on the socio-economic status, participants' lifestyle, and changes in dietary intake/health before and during the COVID-19 lockdown, while the questionnaire link was in circulation for 6 weeks (April/May 2021). Descriptive statistics was used to define the proportion of responses for each question and Pearson's correlation was used to check for association between variables. Most participants were undergraduates depending on parents/sponsors. Financial decline appeared to have contributed to a post lockdown decrease in food consumption. Many (82.6%) respondents recorded high nutrition knowledge scores (NKS) and 83.1% of the respondents had high health scores. The results show that NKS influenced the kind of foods the respondents consumed frequently and there was a positive correlation between NKS consumption of fruits/vegetables. NKS had effect on their access to healthy foods and it varied significantly with respondent's total health score. No association existed between NKS and the reason for skipping meal - ‘lack of time to prepare meals’. Nutrition knowledge and proper awareness, contributed significantly in dietary choices (regardless of limited resources), thus ensuring adequate nutrition and reduced health problems (most respondents recorded high health scores) during a pandemic. This study affirms the effectiveness of adequate nutrition education and awareness in ensuring healthy dietary choices, promoting optimal health, and reducing risks of diseases.

Alexandria B Boehm et al.

Wastewater concentrations of human influenza, metapneumovirus, parainfluenza, respiratory syncytial virus, rhinovirus, and seasonal coronavirus nucleic-acids during the COVID-19 pandemic: a surveillance study

The Lancet, March 2023; doi.org/10.1016/S2666-5247(22)00386-X


Respiratory disease is a major cause of morbidity and mortality; however, surveillance for circulating respiratory viruses is passive and biased. Wastewater-based epidemiology has been used to understand SARS-CoV-2, influenza A, and respiratory syncytial virus (RSV) infection rates at a community level but has not been used to investigate other respiratory viruses. We aimed to use wastewater-based epidemiology to understand community viral respiratory infection occurrence.


Wastewater-based epidemiology can be used to obtain information on circulation of respiratory viruses at a localised, community level without the need to test many individuals because a single sample of wastewater represents the entire contributing community. Results from wastewater can be available within 24 h of sample collection, generating real time information to inform public health responses, clinical decision making, and individual behaviour modifications.

Brian E. McGarry et al.                               

Covid-19 Surveillance Testing and Resident Outcomes in Nursing Homes

NEJM, March 2023; DOI: 10.1056/NEJMoa2210063



Despite widespread adoption of surveillance testing for coronavirus disease 2019 (Covid-19) among staff members in skilled nursing facilities, evidence is limited regarding its relationship with outcomes among facility residents.


Using data obtained from 2020 to 2022, we performed a retrospective cohort study of testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among staff members in 13,424 skilled nursing facilities during three pandemic periods: before vaccine approval, before the B.1.1.529 (omicron) variant wave, and during the omicron wave. We assessed staff testing volumes during weeks without Covid-19 cases relative to other skilled nursing facilities in the same county, along with Covid-19 cases and deaths among residents during potential outbreaks (defined as the occurrence of a case after 2 weeks with no cases). We reported adjusted differences in outcomes between high-testing facilities (90th percentile of test volume) and low-testing facilities (10th percentile). The two primary outcomes were the weekly cumulative number of Covid-19 cases and related deaths among residents during potential outbreaks.


Greater surveillance testing of staff members at skilled nursing facilities was associated with clinically meaningful reductions in Covid-19 cases and deaths among residents, particularly before vaccine availability.

AbdoulieKanteh et al.

Genomic epidemiology of SARS-CoV-2 infections in The Gambia: an analysis of routinely collected surveillance data between March, 2020, and January, 2022

The Lancet, March 2023; doi.org/10.1016/S2214-109X(22)00553-8



COVID-19, caused by SARS-CoV-2, is one of the deadliest pandemics of the past 100 years. Genomic sequencing has an important role in monitoring of the evolution of the virus, including the detection of new viral variants. We aimed to describe the genomic epidemiology of SARS-CoV-2 infections in The Gambia.


More cases of SARS-CoV-2 infection were recorded in The Gambia during peaks of the pandemic that coincided with the rainy season, in line with transmission patterns for other respiratory viruses. The introduction of new lineages or variants preceded epidemic waves, highlighting the importance of implementing well structured genomic surveillance at a national level to detect and monitor emerging and circulating variants.

Van Vo et al.

Detection of the Omicron BA.1 Variant of SARS-CoV-2 in Wastewater From a Las Vegas Tourist Area

JAMA, February 2023; doi:10.1001/jamanetworkopen.2023.0550


Importance  Interpretation of wastewater surveillance data is potentially confounded in communities with mobile populations, so it is important to account for this issue when conducting wastewater-based epidemiology (WBE).

Objectives  To leverage spatial and temporal differences in wastewater whole-genome sequencing (WGS) data to quantify relative SARS-CoV-2 contributions from visitors to southern Nevada.

Design, Setting, and Participants  This cross-sectional wastewater surveillance study was performed during the COVID-19 pandemic (March 2020 to February 2022) and included weekly influent wastewater samples that were analyzed by reverse transcription–quantitative polymerase chain reaction to quantify SARS-CoV-2 RNA and WGS for identification of variants of concern. This study was conducted in the Las Vegas, Nevada, metropolitan area, which is a semi-urban area with approximately 2.3 million residents and nearly 1 million weekly visitors. Samples were collected from 7 wastewater treatment plant (WWTP) locations that collectively serve the vast majority of southern Nevada (excluding the small number of septic systems) and 1 manhole serving the southern portion of the Las Vegas Strip. With Las Vegas tourism returning to prepandemic levels in 2021, it was hypothesized that visitors were contributing a disproportionate fraction of SARS-CoV-2 RNA to the largest WWTP in southern Nevada, potentially confounding efforts to estimate COVID-19 incidence in the local community through WBE.

Main Outcomes and Measures  Relative SARS-CoV-2 load and variants from visitors vs the local population.

Conclusions and Relevance  Wastewater surveillance is a valuable complement to clinical tools and can provide time-sensitive data for decision-makers and policy makers. This study represents a novel approach for quantifying the confounding effects of mobile populations on wastewater surveillance data, thereby allowing for modification of an existing WBE framework for estimating COVID-19 incidence in southern Nevada.

Eleonora Genovese et al.

Learning from the COVID-19 pandemic response to strengthen undocumented migrant-sensitive health systems: case studies from four countries

The Lancet, February 2023; doi.org/10.1016/j.lanepe.2023.100601


Undocumented migrants are a vulnerable population group in the context of the COVID-19 pandemic due to increased risk of infection, severe morbidity, and mortality. In this Personal View, we analyze the COVID-19 pandemic responses, particularly vaccination campaigns, vis à vis undocumented migrants, and discuss lessons learned. Our empirical observations as clinicians and public health practitioners in Italy, Switzerland, France, and the United States are supplemented by a literature review, and presented through country case studies focusing on Governance, Service Delivery, and Information. We propose recommendations to capitalize on the COVID-19 pandemic response as an entry point to strengthen migrant-sensitive provisions into health system frameworks, by: providing specific guidance in health policies and plans; developing tailored implementation approaches with outreach and mobile services, with translated and socio-culturally adapted information, and engagement of migrant communities and third sector actors; and developing systematic monitoring & evaluation systems with disaggregated migrant data from National Health Service and third sector providers.

Olawoye IB et al.

Emergence and spread of two SARS-CoV-2 variants of interest in Nigeria

Nature, February 2023; doi.org/10.1038/s41467-023-36449-5


Identifying the dissemination patterns and impacts of a virus of economic or health importance during a pandemic is crucial, as it informs the public on policies for containment in order to reduce the spread of the virus. In this study, we integrated genomic and travel data to investigate the emergence and spread of the SARS-CoV-2 B.1.1.318 and B.1.525 (Eta) variants of interest in Nigeria and the wider Africa region. By integrating travel data and phylogeographic reconstructions, we find that these two variants that arose during the second wave in Nigeria emerged from within Africa, with the B.1.525 from Nigeria, and then spread to other parts of the world. Data from this study show how regional connectivity of Nigeria drove the spread of these variants of interest to surrounding countries and those connected by air-traffic. Our findings demonstrate the power of genomic analysis when combined with mobility and epidemiological data to identify the drivers of transmission, as bidirectional transmission within and between African nations are grossly underestimated as seen in our import risk index estimates.

Kogan NE et al

Leveraging Serosurveillance and Postmortem Surveillance to Quantify the Impact of Coronavirus Disease 2019 in Africa

CID, October 2022; doi.org/10.1093/cid/ciac797



The coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact on global health, the magnitude of which appears to differ intercontinentally: For example, reports suggest that 271 900 per million people have been infected in Europe versus 8800 per million people in Africa. While Africa is the second-largest continent by population, its reported COVID-19 cases comprise <3% of global cases. Although social and environmental explanations have been proposed to clarify this discrepancy, systematic underascertainment of infections may be equally responsible.


We sought to quantify magnitudes of underascertainment in COVID-19's cumulative incidence in Africa. Using serosurveillance and postmortem surveillance, we constructed multiplicative factors estimating ratios of true infections to reported cases in Africa since March 2020.


Multiplicative factors derived from serology data (subset of 12 nations) suggested a range of COVID-19 reporting rates, from 1 in 2 infections reported in Cape Verde (July 2020) to 1 in 3795 infections reported in Malawi (June 2020). A similar set of multiplicative factors for all nations derived from postmortem data points toward the same conclusion: Reported COVID-19 cases are unrepresentative of true infections, suggesting that a key reason for low case burden in many African nations is significant underdetection and underreporting.


While estimating the exact burden of COVID-19 is challenging, the multiplicative factors we present furnish incidence estimates reflecting likely-to-worst-case ranges of infection. Our results stress the need for expansive surveillance to allocate resources in areas experiencing discrepancies between reported cases, projected infections, and deaths.

AbdoulieKanteh et al.

Genomic epidemiology of SARS-CoV-2 infections in The Gambia: an analysis of routinely collected surveillance data between March, 2020, and January, 2022

The Lancet, March 2023; doi.org/10.1016/S2214-109X(22)00553-8



COVID-19, caused by SARS-CoV-2, is one of the deadliest pandemics of the past 100 years. Genomic sequencing has an important role in monitoring of the evolution of the virus, including the detection of new viral variants. We aimed to describe the genomic epidemiology of SARS-CoV-2 infections in The Gambia.


Nasopharyngeal or oropharyngeal swabs collected from people with suspected cases of COVID-19 and international travellers were tested for SARS-CoV-2 with standard RT-PCR methods. SARS-CoV-2-positive samples were sequenced according to standard library preparation and sequencing protocols. Bioinformatic analysis was done using ARTIC pipelines and Pangolin was used to assign lineages. To construct phylogenetic trees, sequences were first stratified into different COVID-19 waves (waves 1–4) and aligned. Clustering analysis was done and phylogenetic trees constructed.


Between March, 2020, and January, 2022, 11 911 confirmed cases of COVID-19 were recorded in The Gambia, and 1638 SARS-CoV-2 genomes were sequenced. Cases were broadly distributed into four waves, with more cases during the waves that coincided with the rainy season (July–October). Each wave occurred after the introduction of new viral variants or lineages, or both, generally those already established in Europe or in other African countries. Local transmission was higher during the first and third waves (ie, those that corresponded with the rainy season), in which the B.1.416 lineage and delta (AY.34.1) were dominant, respectively. The second wave was driven by the alpha and eta variants and the B.1.1.420 lineage. The fourth wave was driven by the omicron variant and was predominantly associated with the BA.1.1 lineage.


More cases of SARS-CoV-2 infection were recorded in The Gambia during peaks of the pandemic that coincided with the rainy season, in line with transmission patterns for other respiratory viruses. The introduction of new lineages or variants preceded epidemic waves, highlighting the importance of implementing well structured genomic surveillance at a national level to detect and monitor emerging and circulating variants.

COVID-19 Weekly Epidemiological Update - Edition 129 published 8 February 2023


Pan Y. et al.

Characterisation of SARS-CoV-2 variants in Beijing during 2022: an epidemiological and phylogenetic analysis

The Lancet, February 2023; doi.org/10.1016/S0140-6736(23)00129-0



Due to the national dynamic zero-COVID strategy in China, there were no persistent local transmissions of SARS-CoV-2 in Beijing before December, 2022. However, imported cases have been frequently detected over the past 3 years. With soaring growth in the number of COVID-19 cases in China recently, there are concerns that there might be an emergence of novel SARS-CoV-2 variants. Routine surveillance of viral genomes has been carried out in Beijing over the last 3 years. Spatiotemporal analyses of recent viral genome sequences compared with that of global pooled and local data are crucial for the global response to the ongoing COVID-19 pandemic.


We routinely collected respiratory samples covering both imported and local cases in Beijing for the last 3 years (of which the present study pertains to samples collected between January and December, 2022), and then randomly selected samples for analysis. Next-generation sequencing was used to generate the SARS-CoV-2 genomes. Phylogenetic and population dynamic analyses were performed using high-quality complete sequences in this study.


We obtained a total of 2994 complete SARS-CoV-2 genome sequences in this study, among which 2881 were high quality and were used for further analysis. From Nov 14 to Dec 20, we sequenced 413 new samples, including 350 local cases and 63 imported cases. All of these genomes belong to the existing 123 Pango lineages, showing there are no persistently dominant variants or novel lineages. Nevertheless, BA.5.2 and BF.7 are currently dominant in Beijing, accounting for 90% of local cases since Nov 14 (315 of 350 local cases sequenced in this study). The effective population size for both BA.5.2 and BF.7 in Beijing increased after Nov 14, 2022.


The co-circulation of BF.7 and BA.5.2 has been present in the current outbreak since Nov 14, 2022 in Beijing, and there is no evidence that novel variants emerged. Although our data were only from Beijing, the results could be considered a snapshot of China, due to the frequent population exchange and the presence of circulating strains with high transmissibility.

Wafaa M. El-Sadr et al.

Facing the New Covid-19 Reality

NEJM, February 2023; DOI: 10.1056/NEJMp2213920


We’ve come a long way. From the early, terrifying days of a rapidly spreading deadly infection to the current circumstances in which — despite a recent steep rise in transmission rates — Covid-19 has, for many people, become no more than an occasional inconvenience, involving a few days of symptoms and a short isolation period. It’s clear that for many, if not most, people, SARS-CoV-2 infection no longer carries the same risks of adverse outcomes as it did in the early months of the pandemic. These shifts have led to a widespread assumption, fueled by political and economic priorities, that the pandemic is behind us — that it’s time to let go of caution and resume prepandemic life.

The reality, however, would starkly contradict such a belief. Covid-19 currently results in about 300 to 500 deaths per day in the United States — equivalent to an annual mortality burden higher than that associated with a bad influenza season. In addition, many people continue to face severe short- or long-term Covid-19 illness, including people who lack access to vaccines or treatment and those with underlying conditions that impair their immune response to vaccines or render them especially vulnerable to Covid-associated complications. The ever-looming threat of the evolution of a new variant, one that can evade our vaccines and antivirals, remains very real. These facts support the assumption that SARS-CoV-2 will continue to play a major role in our lives for the foreseeable future. This new reality compels us to navigate a more complex social, economic, political, and clinical terrain and to take to heart the lessons learned from the Covid-19 response thus far — both the successes and the missteps.

To date, monitoring of the effects of Covid-19 has rested on several epidemiologic and clinical measures, which have shaped the recommended or mandated protective actions. Most commonly, these measures have included estimated rates of Covid-19 cases, hospitalizations, and deaths; monitoring has also been conducted of circulating SARS-CoV-2 variants and their susceptibility to available vaccines and treatments.

Yet in the current situation, some of these traditional measures have limited value. For example, the availability of rapid antigen tests that can be conducted at home — the results of which often aren’t captured by public health surveillance systems — challenges the validity of reported case numbers and transmission rates in some jurisdictions. There is therefore a need for unbiased monitoring of transmission and infection rates by means of regular testing of sentinel populations or randomly selected representative samples of the general population.1,2 Hospitalization and death rates are certainly more reliable measures than case rates, but these measures are limited by the fact that some hospitalized patients with SARS-CoV-2 infection have been admitted for other reasons and only incidentally tested positive. Furthermore, hospitalization and death are distal outcomes, so their rates have limited value for triggering early action to control the spread of infection and averting the consequences of a surge in cases. Other measures have gained prominence and now play a critical role in defining risk for infection or severe disease. Vaccine and booster coverage and availability and utilization of treatment for Covid-19 are critical variables that affect both the risk of severe illness or death from SARS-CoV-2 and health system capacity and access.

We have gained a deeper appreciation of the breadth of the pandemic’s effects, beyond its obvious health effects. These effects have included loss of employment or housing, disruption of educational systems, and increased rates of food insecurity. Many of these negative social and economic effects were unintended results of mitigation measures, including stay-at-home orders, the shutting down of public venues, and transitions to remote learning. Although these measures were appropriate at the time, their effects weren’t evenly distributed, with some communities facing disproportionate hardship, particularly historically marginalized racial and ethnic groups and communities with limited social and economic reserves. It is thus necessary to take into account the ways in which public health recommendations and policies may differentially affect various subgroups of the population. Government and nongovernmental entities need to create clear pathways for vulnerable populations to obtain access to the resources they need, including masks, vaccines, no-cost treatment, direct economic assistance, supplemental food, rent abatement, and Internet access to support virtual learning and remote access to health services.3 Such an approach requires that the federal government continue to invest in the Covid-19 response, since private-sector investment will be insufficient to meet all needs.4

One of the key challenges that the public health community faces as the pandemic evolves is the need to move away from universal recommendations, or population-wide prevention policy, toward a more differentiated or tailored approach — one that takes into account the characteristics of various communities and the pathogen. Relevant characteristics may include those that influence virus transmission or clinical outcomes, such as vaccine and booster coverage and risk factors for severe outcomes, including chronic medical conditions, racism and discrimination based on ethnicity, and lack of adequate health insurance. The implementation of tailored guidance for specific populations, however, is complicated by the legacy of glaring health disparities, the threat of stigmatization, and prevailing mistrust of authorities in some communities. Health-equity and antiracist principles and insights from the fields of health communication and behavioral science must therefore be taken into account from the start in the development and dissemination of recommendations and the implementation of programs and policies.3,5

There is much to lament in the politicization of the Covid-19 pandemic, the spread of disinformation and misinformation, the deep divisions within the U.S. population and, globally, in people’s perceptions of the pandemic and willingness to trust guidance and embrace protective measures. These divisions should inspire a reexamination of the reasons that some public health recommendations fell flat, in addition to an acknowledgment that political expedience played a role in sowing mistrust. As the pandemic evolves, as the measures of its effects become more complex, and as guidance requires greater tailoring to specific populations, effective communication becomes even more important. Providing clear guidance, including explaining the rationale for various recommendations, acknowledging the social and economic trade-offs involved in complying with them, and offering people the resources they will need to effectively manage these trade-offs, would go a long way toward enabling the adoption of those recommendations.

Most important, attention to the engagement of trusted community leaders and spokespeople is required, as is listening authentically to communities from the start. Rather than focusing solely on what is being recommended, it’s equally important for public health leaders to focus on how recommendations are communicated and disseminated. Early engagement of community representatives is critical so that various aspects of anticipated guidance can be discussed in detail, including rationales, trade-offs, and the most appropriate communication channels and formats. Engagement must not only come in the form of an emergency response, but must involve a consistent presence, which can then be leveraged and activated further during times of urgent need.

The current moment in the Covid-19 pandemic is a pivotal one. There is an urgent need to confront a future in which SARS-CoV-2 will remain with us, threatening the health and well-being of millions of people throughout the world. At the same time, it’s important to acknowledge that objectively we are in a better place with regard to the virus than we’ve ever been and that in fact many people believe the pandemic is behind us. This reality compels us to avoid using alarmist language and to offer valid and feasible solutions to bring people along to a new, nonemergency phase of the pandemic. How we craft our policies, programs, and associated messaging in this context and who delivers the messages is as important as ever.

Soo Park et al.

Unreported SARS-CoV-2 Home Testing and Test Positivity

JAMA, January 2023; doi:10.1001/jamanetworkopen.2022.52684


Timely SARS-CoV-2 testing is critical to reducing transmission. Throughout the COVID-19 pandemic, COVID-19 test sites have been required to report SARS-CoV-2 test results to local or state public health departments,1 and these data are used for detecting new surges of transmission. With increasing availability of home antigen tests, however, it is unclear how to interpret time trends in officially reported case counts and test positivity.


The COVID-19 Citizen Science Study was approved by the institutional review board at the University of California, San Francisco, and was launched in March 2020 to gather patient-reported data about the COVID-19 pandemic.2 This cohort study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies. Participants were invited by word of mouth or social media or from our recruitment partners via email, telephone, or patient portal message and then provided informed consent and baseline demographic information. Race and ethnicity were self-reported by the participants and were analyzed in this study to understand differences in unreported test frequency and test positivity. Each week, we asked participants about recent COVID-19 testing and test results. In March 2022, a question was added to distinguish tests conducted with a “Fully at-home test kit, with my own sample collection and reading of my own results” vs tests where “a healthcare provider collected my sample” or that were “sent to a clinical lab.”


In this cohort study, we found home testing to be increasingly common through spring and into summer 2022, most recently comprising more than 80% of all SARS-CoV-2 testing reported. Home test positivity appears to track closely with national data from reported tests, but these trends are starting to diverge. Home testing patterns differ by demographic subgroup, as previously shown,4 perhaps because of differential COVID-19 worry or availability and cost of test kits. Our study has limitations. Home testing may be conducted repeatedly during an illness episode, may be less common in the US population than in our engaged participants, and may sometimes be officially reported despite being conducted at home (eg, via employers), all of which could bias our estimates of test positivity and the proportion of tests that are unreported.

Bridget M. Kuehn.

US Life Expectancy in 2021 Lowest Since 1996

JAMA, January 2023; doi:10.1001/jama.2022.23562


Life expectancy in the US decreased by about a half year between 2020 and 2021, from 77 years to 76.4 years, according to final 2021 mortality data from the National Center for Health Statistics. Life expectancy in 2021 was at its lowest level since 1996. The report attributed the drop mainly to increased deaths from COVID-19 and drug overdoses.

The 0.6-year drop between 2020 and 2021 followed a 1.8-year decrease in life expectancy between 2019 and 2020. The overall death rate from 2020 to 2021 in the US increased by 5.3%, from 835.4 to 879.7 deaths per 100 000 people. Life expectancy in the US decreased for every age group starting at age 1 year or older, but there was not a statistically significant change in infant mortality during this period.

The leading causes of death in 2021 were heart disease, cancer, and COVID-19. Deaths attributed to COVID-19 increased from 2020 to 2021 by 18.8%, from 350 831 to 416 893 deaths. Influenza and pneumonia dropped out of the top 10 causes of death in 2021, likely because of pandemic-related infection prevention precautions. Chronic liver disease moved up to the 9th leading cause of death. However, the other leading causes of death in the top 10, including unintentional injuries, stroke, chronic lower respiratory diseases, Alzheimer disease, and diabetes, remained the 4th to 8th leading causes of death, respectively, and kidney disease remained the 10th leading cause of death.

Some racial, ethnic, or other demographic groups were disproportionately affected by reductions in life expectancy. The gap in life expectancy between the sexes grew between 2020 and 2021. Males experienced a 0.7-year decrease in life expectancy, from 74.2 years to 73.5 years. Females, by contrast, saw a 0.6-year decrease, from 79.9 to 79.3 years. Death rates decreased for Black and Hispanic males by about 2% between 2020 and 2021 and stayed the same for Asian males and females. American Indian or Alaska Native males and females saw about a 6% to 7% increase in death rates, Black females saw a 1.3% increase, Hispanic females saw a 2.3% increase, and White males and females saw about a 7% increase in death rates.

The COVID-19 pandemic in 2023: far from over

The Lancet, January 2023; doi.org/10.1016/S0140-6736(23)00050-8


3 years ago, on Jan 5, 2020, the Department of Zoonoses at the National Institute of Communicable Disease Control and Prevention (Chinese Center for Disease Control and Prevention) announced the isolation of a new Coronavirus responsible for a wave of respiratory illnesses. On Jan 30, WHO declared a Public Health Emergency of International Concern. Despite many efforts to learn from the pandemic during the past 3 years, and discussions on international treaties of pandemic preparedness, the global response remains inadequate and fragmented. In 2023, far from it being the end of the pandemic (as hoped by many and announced for the USA by President Biden in September last year), there is a new, dangerous phase that requires urgent attention.

On Dec 7, China seemed to react to a wave of protests against its draconian so-called dynamic zero-Covid policy by dropping most of its restrictive controls. Chinese people with mild or asymptomatic disease were able to quarantine at home, travel in public was no longer restricted by electronic health passes, and lockdowns were now highly focused and no longer required for whole municipal areas or cities and were relaxed after 5 days for new cases. Additionally, from Jan 8 onwards, people were able to travel internationally again. The sudden turnaround caused rapid infection in many millions of Chinese people in December, 2022. A struggling health system was at its limits and many older people were dying, although official figures did not capture these deaths as COVID 19-related because Chinese authorities applied a very narrow definition and stopped information on numbers of infections, hospital admissions, and intensive care admissions. Although infections might have peaked in Beijing, China and its population are entering a precarious and difficult phase for several reasons.

First, the vaccination rate, especially of older people, is insufficient. According to figures from the Chinese National Health Commission, at the end of November, 69% of those 60 years and older and only 40% of those 80 years or older had a course of two vaccinations and a booster with Chinese-licensed vaccines, although these are not specifically aimed against the prevailing omicron variants. A vaccination drive, especially aimed at older people, is underway. Additionally, several Chinese companies are working on a bivalent mRNA vaccine, but it will take some time for these more effective vaccines to be licensed.

Second, in addition to the winter season, the Lunar Chinese New Year on Jan 22 and the expected travel wave across the country to see relatives will mean spread of infections to rural areas where the health-care system is weaker, and where many older people with comorbidities and poor health live, as a recent Peking University-Lancet Commission outlines. Understandably, Chinese people want to lead normal lives again and see friends and family after such a long period of restrictions, but the health consequences could be dire.

Third, the international community, far from showing compassion, has quickly reacted by imposing or strongly encouraging travel restrictions and requirements of a pre-travel negative SARS-CoV-2 test for Chinese people. This move was regarded as unnecessary by the European Centre for Disease Prevention and Control as the variants seen in China, the omicron subvariants BA.5.2 and BF.7, are the ones that have been circulating in Europe and elsewhere in populations that now have high levels of immunity. Although precaution is understandable and variant monitoring and data sharing should be widely encouraged, singling out Chinese travellers is counterproductive and might have unintended consequences.

The more worrying omicron subvariant and one to watch closely is XBB1.5, which has rapidly spread in the USA, where it comprised 40·5% of cases at the end of December, 2022, and had a doubling time of 1 week, according to the Centers for Disease Control and Prevention. Maria Van Kerkhove, WHO's COVID-19 technical lead, called it the most transmissible yet with mutations in the protein spike that allow a closer binding to the ACE-2 receptor and facilitate immune evasion, although so far there are no signs that it causes more severe disease. However, there are some early indications that hospital admissions are increasing in the northeast of the USA, where it is most prevalent.

Rather than hoping for the end, letting our guard down, and thinking that the problem is somewhere else, everyone needs to remain alert; encourage maximum transparency in reporting cases, hospital admissions, and deaths; and accelerate collaborative surveillance of variant testing and vaccinations. The pandemic is far from over.

Riou J et al.

Direct and indirect effects of the COVID-19 pandemic on mortality in Switzerland

Nature, January 2023; doi.org/10.1038/s41467-022-35770-9


The direct and indirect impact of the COVID-19 pandemic on population-level mortality is of concern to public health but challenging to quantify. Using data for 2011–2019, we applied Bayesian models to predict the expected number of deaths in Switzerland and compared them with laboratory-confirmed COVID-19 deaths from February 2020 to April 2022 (study period). We estimated that COVID-19-related mortality was underestimated by a factor of 0.72 (95% credible interval [CrI]: 0.46–0.78). After accounting for COVID-19 deaths, the observed mortality was −4% (95% CrI: −8 to 0) lower than expected. The deficit in mortality was concentrated in age groups 40–59 (−12%, 95%CrI: −19 to −5) and 60–69 (−8%, 95%CrI: −15 to −2). Although COVID-19 control measures may have negative effects, after subtracting COVID-19 deaths, there were fewer deaths in Switzerland during the pandemic than expected, suggesting that any negative effects of control measures were offset by the positive effects. These results have important implications for the ongoing debate about the appropriateness of COVID-19 control measures.

Lasser J. et al.

Assessment of the Effectiveness of Omicron Transmission Mitigation Strategies for European Universities Using an Agent-Based Network Model

CID, May 2022, doi.org/10.1093/cid/ciac340


Returning universities to full on-campus operations while the coronavirus disease 2019 pandemic is ongoing has been a controversial discussion in many countries. The risk of large outbreaks in dense course settings is contrasted by the benefits of in-person teaching. Transmission risk depends on a range of parameters, such as vaccination coverage and efficacy, number of contacts, and adoption of nonpharmaceutical intervention measures. Owing to the generalized academic freedom in Europe, many universities are asked to autonomously decide on and implement intervention measures and regulate on-campus operations. In the context of rapidly changing vaccination coverage and parameters of the virus, universities often lack sufficient scientific insight on which to base these decisions.


Here we show that, with the Omicron variant of the severe acute respiratory syndrome coronavirus 2, even a reduction to 25% occupancy and universal mask mandates are not enough to prevent large outbreaks, given the vaccination coverage of about 85% reported for students in Austria.


Our results show that controlling the spread of the virus with available vaccines in combination with nonpharmaceutical intervention measures is not feasible in the university setting if presence of students and faculty on campus is required.

Howard Larkin

Dogs May Reliably Detect SARS-CoV-2 Infections at Mass Events

JAMA, December 2022; doi:10.1001/jama.2022.20040


Dogs trained to detect SARS-CoV-2 infection by smell correctly identified individuals with active infections at concerts with a specificity of nearly 100% and a sensitivity of 82%, researchers reported in BMJ Global Health. The results suggest that dogs may provide a fast and reliable screening option for public events at which mass screening is required.

Eight trained dogs of various breeds were presented with sweat samples from 2802 concertgoers at 4 events in Germany organized for the study. Each person underwent SARS-CoV-2 antigen and polymerase chain reaction (PCR) testing at the concert, but the investigators, dog handlers, and dogs did not know the results. Most of the human participants were vaccinated against COVID-19 but this did not affect the dogs’ ability to detect active infections.

Sweat samples collected previously from 38 patients with SARS-CoV-2 infections were randomly introduced into the test lineup, raising the total sample prevalence to 1.34% from a background rate of 0.2%. A positive finding was confirmed by a second dog sniffing the same sample. It took about 1 to 2 seconds for the dogs to smell each sample.

The dogs turned up only 2 false-positive results and 1 false-negative result. Positive identification of SARS-CoV-2 infection by 2 dogs was confirmed for another patient by a PCR test 2 days later, suggesting that dogs may be able to detect an infection before virus shedding, the authors wrote. Overall, the canine test had a positive predictive value of 70% and a negative predictive value of 99.7% assuming a prevalence rate of 0.2%.

Previous studies found that dogs can identify SARS-CoV-2 infections with high diagnostic accuracy, but the new research demonstrated it under real-world mass screening conditions, the authors wrote. Medical scent-detection dogs provide an additional opportunity to control the ongoing COVID-19 pandemic and possibly future pandemics, especially in areas or countries with limited test infrastructure or financial means, they concluded.

Cleber Vinicius Brito dos Santos et al.

Estimated COVID-19 severe cases and deaths averted in the first year of the vaccination campaign in Brazil: A retrospective observational study

Lancet, December 2022;  doi.org/10.1016/j.lana.2022.100418


A nationwide Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination campaign was initiated in Brazil in January 2021 with CoronaVac (Sinovac Biotech) and ChAdOx1 nCoV-19 (AstraZeneca) followed by BNT162b2 mRNA (Pfizer–BioNTech) and Ad26.COV2.S (Johnson & Johnson–Janssen) vaccines. Here we provide estimates of the number of severe cases and deaths due to coronavirus disease (COVID-19) averted during the first year of the mass vaccination.


The first year of the COVID-19 vaccination program in Brazil saved the lives of at least 303,129 adults. The results highlight the need for future vaccination campaigns, including those required in the current pandemic, to rapidly achieve high uptake, particularly among the elderly and residents of the least populous regions.

Bisbas G.

Race, inequalities, and burden of COVID-19 in the USA

Lancet, December 2022; doi.org/10.1016/S1473-3099(22)00862-3


In the wake of the COVID-19 pandemic, which first gripped the world in December 2019, scores of books were published criticising the handling of bureaucratic protocols, national safety, and the subsequent economic recovery. A whole sub-genre of non-fiction has emerged as scientists, academics, and cultural thinkers point fingers at how the global death toll could have been mitigated if governments acted sooner, or perhaps, with less corruption and hubris, thousands of lives could have been saved. COVID-19 was initially and lazily referred to as a ‘great equaliser’ as it was believed that anyone and everyone could contract the virus and the detrimental impact was largely the same regardless of socioeconomic background. The pandemic divide- How Covid increased inequality in America, edited by Gwendolyn Wright, Lucas Hubbard, and William Darity, proves how systematically misguided this belief was. At the time of writing, WHO reports that a staggering 1 million US citizens have died because of SARSCoV-2. With that in mind this book offers an interesting and conscientious observation on not just how such widespread mortality could have been avoided, but that those most affected by the virus and its financial fallout were predisposed to it. The book is a collection of essays interrogating how preexisting structures meant that marginalised communities in the USA became the worst affected by the virus itself and how the attendant lockdowns impacted their livelihoods and businesses. Mary Bassett, Health Commissioner at the New York State Department of Health, writes in the foreword that the ‘susceptibility to severe or fatal COVID-19 was enhanced by the already higher rates of common conditions among communities of colour, a pattern itself attributable to bad policies which keep a decent life out of reach’. Those communities of colour were unequivocally more likely to contract the virus, and to die from it. Each essay in this book interrogates the data that points to this uncomfortable truth, that health disparities in general in America ‘strongly evidence systemic racism’. The editors of this book are experts in such a field, and hold senior positions within The Samuel DuBois Cook Center on Social Equity. This Centre is a scholarly organisation that studies the causes and consequences of inequality and develops remedies for these disparities and their adverse effects. To this end, each essay takes a past, present, and future framework to truly highlight how concerted policy change is the only way out of deep-rooted systems of inequity that continue to exploit and exclude the same communities. It becomes increasingly evident that Black and Latinx populations suffered illnesses and job loss at much higher rates than the general White populace. The book is split into four sections, each made up of between two and four essays, allowing a variance and consolidation of the topics discussed. The first section outlines ‘COVID-19 in context’, the second ‘COVID-19 and institutions’, the third ‘COVID-19 and financial restrictions’, and the last ‘COVID-19 and educational disparities’. Much of the merit of this book lies in the fact that not every essay and subsection is overtly academic. In ‘Race, religion, family and community during the COVID-19 pandemic’ Sandra Barnes adopts an engaging and familiar tone, whilst following the case study of one multi- generational black family, reconciling the risk of public worship with the exposure in their public facing jobs. It is noted that those members of the family participating in the study, received no renumeration for doing so. This only makes the facts Barnes includes all the more startling and prescient. In 2020 both The Lancet Public Health and The New England Journal of Medicine published reports about overcrowded prisons exacerbating the risks of a potentially deadly airborne virus in places where ventilation was minimal and interaction unavoidable. Arvind Krishamurthy, observes in ‘COVID19, race, and mass incarceration’ that structural determinants such as ‘the racial American carceral state and the ‘racial inequality of healthcare access’ meant the ‘likelihood of contracting COVID-19 inside prison are 3·67 times more than the likelihood of contracting it outside of prison’. When the population of both prisons and jails are disproportionately non-White, and the fact as of January 2022, 716 546 incarcerated people tested positive for the virus, it is no wonder such a large proportion of the populace are at risk of the virus. Krishnamurthy cites another non-profit organisation, Worth Rises, which found that more than fourty states used prisoners to manufacture hand sanitiser and personal protective equipment whilst they were denied access to the same basic equipment when making the products, as state laws relied on the cheap, consistent turnover of prison labour. These studies prove the inequities are remarkably easy to trace, when the data is readily available. The Federal Bureau of Prisons however was not forthcoming with the Marshall Project's weekly request for data. The pandemic divide should appeal to anyone with an interest in social and cultural politics, and moreover policy. In a world that is continually racialised and then derided for being so, this book is an urgent reminder of how deep rooted systems operate in sinister ways to continually exploit, undermine, and undervalue whole swathes of the population.

Fischer C et al.

Gradual emergence followed by exponential spread of the SARS-CoV-2 Omicron variant in Africa

Science, December 2022; doi/10.1126/science.add8737


The geographic and evolutionary origins of the SARS-CoV-2 Omicron variant (BA.1), which was first detected mid-November 2021 in Southern Africa, remain unknown. We tested 13,097 COVID-19 patients sampled between mid-2021 to early 2022 from 22 African countries for BA.1 by real-time RT-PCR. By November-December 2021, BA.1 had replaced the Delta variant in all African sub-regions following a South-North gradient, with a peak Rt of 4.1. Polymerase chain reaction and near-full genome sequencing data revealed genetically diverse Omicron ancestors already existed across Africa by August 2021. Mutations, altering viral tropism, replication and immune escape, gradually accumulated in the spike gene. Omicron ancestors were therefore present in several African countries months before Omicron dominated transmission. These data also indicate that travel bans are ineffective in the face of undetected and widespread infection.

Msemburi W. et al.

The WHO estimates of excess mortality associated with the COVID-19 pandemic

Nature, December 2022; doi.org/10.1038/s41586-022-05522-2


The World Health Organization has a mandate to compile and disseminate statistics on mortality, and we have been tracking the progression of the COVID-19 pandemic since the beginning of 20201. Reported statistics on COVID-19 mortality are problematic for many countries owing to variations in testing access, differential diagnostic capacity and inconsistent certification of COVID-19 as cause of death. Beyond what is directly attributable to it, the pandemic has caused extensive collateral damage that has led to losses of lives and livelihoods. Here we report a comprehensive and consistent measurement of the impact of the COVID-19 pandemic by estimating excess deaths, by month, for 2020 and 2021. We predict the pandemic period all-cause deaths in locations lacking complete reported data using an overdispersed Poisson count framework that applies Bayesian inference techniques to quantify uncertainty. We estimate 14.83 million excess deaths globally, 2.74 times more deaths than the 5.42 million reported as due to COVID-19 for the period. There are wide variations in the excess death estimates across the six World Health Organization regions. We describe the data and methods used to generate these estimates and highlight the need for better reporting where gaps persist. We discuss various summary measures, and the hazards of ranking countries’ epidemic responses.

Fauci A.S.

It Ain’t Over Till It’s Over…but It’s Never Over — Emerging and Reemerging Infectious Diseases

NEJM, December 2022,  DOI: 10.1056/NEJMp2213814


I prepare to step down from my dual positions at the National Institute of Allergy and Infectious Diseases (NIAID), where I have been a physician-scientist for 54 years and the director for 38 years, a bit of reflection is inevitable. As I think back over my career, what stands out most is the striking evolution of the field of infectious diseases and the changing perception of the importance and relevance of the field by both the academic community and the public.

I completed my residency training in internal medicine in 1968 and decided to undertake a 3-year combined fellowship in infectious diseases and clinical immunology at NIAID. Unbeknownst to me as a young physician, certain scholars and pundits in the 1960s were opining that with the advent of highly effective vaccines for many childhood diseases and a growing array of antibiotics, the threat of infectious diseases — and perhaps, with it, the need for infectious-disease specialists — was fast disappearing.1 Despite my passion for the field I was entering, I might have reconsidered my choice of a subspecialty had I known of this skepticism about the discipline’s future. Of course, at the time, malaria, tuberculosis, and other diseases of low- and middle-income countries were killing millions of people per year. Oblivious to this inherent contradiction, I happily pursued my clinical and research interests in host defenses and infectious diseases.

When I was several years out of my fellowship, I was somewhat taken aback when Dr. Robert Petersdorf, an icon in the field of infectious diseases, published a provocative article in the Journal suggesting that infectious diseases as a subspecialty of internal medicine was fading into oblivion.2 In an article entitled “The Doctors’ Dilemma,” he wrote regarding the number of young physicians entering training in the various internal medicine subspecialties, “Even with my great personal loyalties to infectious disease, I cannot conceive a need for 309 more infectious-disease experts unless they spend their time culturing each other.”

Of course, we all aspire to be part of a dynamic field. Was my chosen field now static? Dr. Petersdorf (who would become my friend and part-time mentor as we and others coedited Harrison’s Principles of Internal Medicine) gave voice to a common viewpoint that lacked a full appreciation of the truly dynamic nature of infectious diseases, especially regarding the potential for newly emerging and reemerging infections. In the 1960s and 1970s, most physicians were aware of the possibility of pandemics, in light of the familiar precedent of the historic influenza pandemic of 1918, as well as the more recent influenza pandemics of 1957 and 1968. However, the emergence of a truly new infectious disease that could dramatically affect society was still a purely hypothetical concept.

That all changed in the summer of 1981 with the recognition of the first cases of what would become known as AIDS. The global impact of this disease is staggering: since the start of the pandemic, more than 84 million people have been infected with HIV, the virus that causes AIDS, of whom 40 million have died. In 2021 alone, 650,000 people died from AIDS-related conditions, and 1.5 million were newly infected. Today, more than 38 million people are living with HIV.

Although a safe and effective HIV vaccine has not yet been developed, scientific advances led to the development of highly effective antiretroviral drugs that have transformed HIV infection from an almost-always-fatal disease to a manageable chronic disease associated with a nearly normal life expectancy. Given the lack of global equity in the accessibility of these lifesaving drugs, HIV/AIDS continues, exacting a terrible toll in morbidity and mortality, 41 years after it was first recognized.

If there is any silver lining to the emergence of HIV/AIDS, it is that the disease sharply increased interest in infectious diseases among young people entering the field of medicine. Indeed, with the emergence of HIV/AIDS, we sorely needed those 309 infectious-disease trainees that Dr. Petersdorf was concerned about — and many more. To his credit, years after his article was published, Dr. Petersdorf readily admitted that he had not fully appreciated the potential impact of emerging infections and became something of a cheerleader for young physicians to pursue careers in infectious diseases and specifically in HIV/AIDS practice and research.

Selected Landmark Events in Infectious-Disease Emergence Leading up to and during the Author’s Four-Decade Tenure as NIAID Director.

Of course, the threat and reality of emerging infections did not stop with HIV/AIDS. During my tenure as NIAID director, we were challenged with the emergence or reemergence of numerous infectious diseases with varying degrees of regional or global impact (see timeline). Included among these were the first known human cases of H5N1 and H7N9 influenza; the first pandemic of the 21st century (in 2009) caused by H1N1 influenza; multiple outbreaks of Ebola in Africa; Zika in the Americas; severe acute respiratory syndrome (SARS) caused by a novel coronavirus; Middle East respiratory syndrome (MERS) caused by another emergent coronavirus; and of course Covid-19, the loudest wake-up call in more than a century to our vulnerability to outbreaks of emerging infectious diseases.

The devastation that Covid-19 has inflicted globally is truly historic and highlights the world’s overall lack of public health preparedness for an outbreak of this magnitude. One highly successful element of the response to Covid-19, however, was the rapid development — enabled by years of investment in basic and applied research — of highly adaptable vaccine platforms such as mRNA (among others) and the use of structural biology tools to design vaccine immunogens. The unprecedented speed with which safe and highly effective Covid-19 vaccines were developed, proven effective, and distributed resulted in millions of lives saved.3 Over the years, many subspecialties of medicine have benefited greatly from breathtaking technological advances. The same can now be said of the field of infectious diseases, particularly with the tools we now have for responding to emerging infectious diseases, such as the rapid and high-throughput sequencing of viral genomes; the development of rapid, highly specific multiplex diagnostics; and the use of structure-based immunogen design combined with novel platforms for vaccines.4

If anyone had any doubt about the dynamic nature of infectious diseases and, by extension, the discipline of infectious diseases, our experience over the four decades since the recognition of AIDS should have completely dispelled such skepticism. Today, there is no reason to believe that the threat of emerging infections will diminish, since their underlying causes are present and most likely increasing. The emergence of new infections and the reemergence of old ones are largely the result of human interactions with and encroachment

on nature. As human societies expand in a progressively interconnected world and the human–animal interface is perturbed, opportunities are created, often aided by climate changes, for unstable infectious agents to emerge, jump species, and in some cases adapt to spread among humans.

An inevitable conclusion of my reflections on the evolution of the field of infectious diseases is that the pundits of years ago were incorrect and that the discipline is certainly not static; it is truly dynamic. In addition to the obvious need to continue to improve on our capabilities for dealing with established infectious diseases such as malaria and tuberculosis, among others, it is now clear that emerging infectious diseases are truly a perpetual challenge. As one of my favorite pundits, Yogi Berra, once said, “It ain’t over till it’s over.” Clearly, we can now extend that axiom: when it comes to emerging infectious diseases, it’s never over. As infectious-disease specialists, we must be perpetually prepared and able to respond to the perpetual challenge.

Abdelrahman ElTohamy et al.

Association Between College Course Delivery Model and Rates of Psychological Distress During the COVID-19 Pandemic

JAMA, November 2022; doi:10.1001/jamanetworkopen.2022.44270


Importance College students in the US have been heavily affected by the COVID-19 pandemic. In addition to increased rates of depression and anxiety, college students have faced unprecedented stressors, such as geographic relocation and abrupt conversion from in-person classes to online classes.

Objective To study the association between course delivery model and psychological distress among US college students.

Design, Setting, and Participants This cross-sectional analysis used national data from the American College Health Association–National College Health Assessment III data set. Data were gathered from a web-based survey administered from January to early June 2021 to full-time US college students attending 4-year programs.

Exposure Course delivery model was self-reported.

Main Outcomes and Measures Psychological distress was measured using the Kessler Screening Scale for Psychological Distress.

Conclusions and Relevance The findings of this study suggest that mental health professionals may wish to consider the association of course delivery models with mental health outcomes when working with college students. Colleges should be aware of the mental health burden associated with attending fully online classes and consider possible in-person components and supports for students.

Bowes D.A. et al.

Leveraging an established neighbourhood-level, open access wastewater monitoring network to address public health priorities: a population-based study

Lancet, December 2022; doi.org/10.1016/S2666-5247(22)00289-0



Before the COVID-19 pandemic, the US opioid epidemic triggered a collaborative municipal and academic effort in Tempe, Arizona, which resulted in the world's first open access dashboard featuring neighbourhood-level trends informed by wastewater-based epidemiology (WBE). This study aimed to showcase how wastewater monitoring, once established and accepted by a community, could readily be adapted to respond to newly emerging public health priorities.


In this population-based study in Greater Tempe, Arizona, an existing opioid monitoring WBE network was modified to track SARS-CoV-2 transmission through the analysis of 11 contiguous wastewater catchments.


Lessons learned from leveraging an existing neighbourhood-level WBE reporting dashboard include: (1) community buy-in is key, (2) public data sharing is effective, and (3) sub-ZIP-code (postal code) data can help to pinpoint populations at risk, track intervention success in real time, and reveal the effect of local clinical testing capacity on WBE's early warning capability. This successful demonstration of transitioning WBE efforts from opioids to COVID-19 encourages an expansion of WBE to tackle newly emerging and re-emerging threats (eg, mpox and polio).

Fischer C. et al.

Gradual emergence followed by exponential spread of the SARS-CoV-2 Omicron variant in Africa

Science, December 2022; DOI:10.1126/science.add8737


The geographic and evolutionary origins of the SARS-CoV-2 Omicron variant (BA.1), which was first detected mid-November 2021 in Southern Africa, remain unknown. Omicron ancestors were therefore present in several African countries months before Omicron dominated transmission. These data also indicate that travel bans are ineffective in the face of undetected and widespread infection.

Hualei Xin et al.

Hospitalizations and mortality during the first year of the COVID-19 pandemic in Hong Kong, China: An observational study

The Lancet, November 2022; doi.org/10.1016/j.lanwpc.2022.100645



Hong Kong followed a strict COVID-19 elimination strategy in 2020. We estimated the impact of the COVID-19 pandemic responses on all-cause and cause-specific hospitalizations and deaths in 2020.


The COVID-19 pandemic might have caused indirect impact on population morbidity and mortality likely through changed healthcare seeking particularly in youngest and oldest individuals and those with cardiovascular diseases. Better healthcare planning is needed during public health emergencies with disruptions in healthcare services.

Min Woo Sun et al.

Do Public Health Efforts Matter? Explaining Cross-Country Heterogeneity in Excess Death During the COVID-19 Pandemic

MedRxiv, November 2022; doi.org/10.1101/2022.11.21.22282563


The COVID-19 pandemic has taken a devastating toll around the world. Since January 2020, the World Health Organization estimates 14.9 million excess deaths have occurred globally. Despite this grim number quantifying the deadly impact, the underlying factors contributing to COVID-19 deaths at the population level remain unclear. Prior studies indicate that demographic factors like proportion of population older than 65 and population health explain the cross-country difference in COVID-19 deaths. However, there has not been a holistic analysis including variables describing government policies and COVID-19 vaccination rate. Furthermore, prior studies focus on COVID-19 death rather than excess death to assess the impact of the pandemic. Through a robust statistical modeling framework, we analyze 80 countries and show that actionable public health efforts beyond just the factors intrinsic to each country are necessary to explain the cross-country heterogeneity in excess death.

McGowan V.J., Bambra C. et al.

COVID-19 mortality and deprivation: pandemic, syndemic, and endemic health inequalities

The Lancet, November 2022; doi.org/10.1016/S2468-2667(22)00223-7


Summary COVID-19 has exacerbated endemic health inequalities resulting in a syndemic pandemic of higher mortality and morbidity rates among the most socially disadvantaged. We did a scoping review to identify and synthesise published evidence on geographical inequalities in COVID-19 mortality rates globally. We included peer-reviewed studies, from any country, written in English that showed any area-level (eg, neighbourhood, town, city, municipality, or region) inequalities in mortality by socioeconomic deprivation (ie, measured via indices of multiple deprivation: the percentage of people living in poverty or proxy factors including the Gini coefficient, employment rates, or housing tenure). 95 papers from five WHO global regions were included in the final synthesis. A large majority of the studies (n=86) found that COVID-19 mortality rates were higher in areas of socioeconomic disadvantage than in affluent areas. The subsequent discussion reflects on how the unequal nature of the pandemic has resulted from a syndemic of COVID-19 and endemic inequalities in chronic disease burden.

Urashima M et al.

Association Between Life Expectancy at Age 60 Years Before the COVID-19 Pandemic and Excess Mortality During the Pandemic in Aging Countries

JAMA, October 2022; doi:10.1001/jamanetworkopen.2022.37528


Older age is one of the factors associated with the greatest increase in risk of COVID-19 deaths. Japan has the highest aging ratio in the world but it was able to keep Excess Mortality low during the pandemic. To investigate this contradiction, the authors explored associations of health, well-being, population, and economic factors before the pandemic with EM during the pandemic.

A. Sharifi

An overview and thematicanalysis of research on cities and the COVID-19 pandemic: toward just, resilient, and sustainableurban planning and design

iScience, October 2022; doi: 10.1016/j.isci.2022.105297


Since 2020, researchershave made efforts to study variousissuesrelated to cities and the pandemic. Despite the wealth of research on thistopic, there are only a few review articlesthatexplore multiple issuesrelated to it. In the present study the authorsrely on bibliometricanalysis techniques to gain an overview of the knowledge structure and map key themes and trends of research on cities and the pandemic. Based on the findings, theydiscuss major lessonsthat can be learned from the pandemic and highlight key areasthatneedfurtherresearch.

Montasir Ahmed Osman

COVID-19 transmission in Africa: estimating the role of meteorologicalfactors

Helion, September 2022; doi.org/10.1016/j.heliyon.2022.e10901


Climatevariables play a criticalrole in COVID-19’s spread. Thisresearchaims to analyze the effect of average temperature and relative humidity on the propagation of COVID-19 in Africa's first fouraffected countries (South Africa, Morocco, Tunisia, and Ethiopia).

A. Ho et al.

SARS-CoV-2: can isolation be limited to thosewho are trulyinfectious?

Lancet Respiratory Medicine, October2022; doi: 10.1016/S2213-2600(22)00272-7


At the beginningof the COVID-19 pandemic, public health restrictionsincluding self-isolation of positive cases and their close contactswerevital to reduce onward transmission of SARS-CoV-2.Thesemeasureshad an enormous impact on individuals. Understanding the viralkinetics of SARS-CoV-2 infectionis key to optimal self-isolation policies, whichneed to strike a balance betweenpreventingonward transmission and avoidingunnecessaryisolation.

J.D. Ford J.D. et al.

Interactions betweenclimate and COVID-19

Lancet Planet Health, October2022; doi: 10.1016/S2542-5196(22)00174-7


With their personal view, the authorsexplain the ways thatclimatic risks affect the transmission, perception, response, and livedexperience of COVID-19. The climaticconditions can lead to vulnerability, resilience, transformation, or collapse of health systems, communities, and livelihoodsthroughoutvaryingtimescales. Itisimportantthat recovery measuresconsiderclimatic risks, especially in locations that are susceptible to climateextremes.

P.D. Rhys et al.

Using multiple sampling strategies to estimate SARS-CoV-2 epidemiological parameters from genomic sequencing data

Nature Communications, September 2022; doi.org/10.1038/s41467-022-32812-0


The choice of viral sequences used in genetic and epidemiological analysis is important as it can induce biases that detract from the value of these rich datasets. This raises questions about how a set of sequences should be chosen for analysis. The authors provide insights on these largely understudied problems using SARS-CoV-2 genomic sequences from Hong Kong, China, and the Amazonas State, Brazil. They consider multiple sampling schemes which were used to estimate Rt and rt as well as related R0 and date of origin parameters.

G.E. Martin et al.

Maintaining genomic surveillance using whole-genome sequencing of SARSCoV-2 from rapid antigen test devices

Lancet Infectious Diseases, October 2022;doi.org/10.1016/S1473-3099(22)00512-6


Genomic sequencing of SARS-CoV-2 has had a major role in the public health response to the COVID-19 pandemic, enabling mapping of viral transmission at global and local levels, informing infection control measures, and identifying and tracking the emergence of new SARS-CoV-2 variants.The rapid detection and characterisation of new variants is crucial for informing the potential efficacy of vaccines andtherapeutics.

Soo Limand Minji Sohn

How to cope with emerging viral diseases: Lessons from South Korea’s strategy for COVID-19, and collateral damage to cardiometabolic health

The Lancet Regional Health - Western Pacific, September 2022;

doi.org/10.1016/j. lanwpc.2022.100581


From February 2020, the South Korean government adopted active epidemiological investigations, strict isolation of affected patients, and extensive public lockdowns, which were helpful in controlling spread until the end of 2021. This stable situation in South Korea has changed dramatically since the Omicron variant—reportedly less severe but more infective than the original strain—became dominant from January 2022. In June 2022, the COVID-19 situation in South Korea is improving. The COVID-19 pandemic and its preventive measures have had a negative influence on cardiometabolic profiles in the country. Considering the likelihood of another novel variant of SARS-CoV-2 or new infectious disease emerging in the future, understanding the situation in South Korea and the strategies flexibly adopted by its government could be beneficial for many countries.

C. Webber et al.

Cognitive Decline in Long-term Care Residents Before and During the COVID-19 Pandemic in Ontario, Canada

JAMA, September2022;doi: 10.1001/jama.2022.17214


Long-term care (LTC) home residents experienced high infection and mortality during the COVID-19 pandemic. There is concern that public health restrictions to limit COVID-19 spread may have negatively affected resident cognition through increased social isolation.We compared the 1-year incidence of cognitive decline among LTC residents in Ontario, Canada, before and during the COVID-19 pandemic.

H. Wang et al.

The amount of SARS-CoV-2 RNA in wastewater relates to the development of the pandemic and its burden on the health system

iScience, September2022;doi: 10.1016/j.isci.2022.105000


Virus surveillance in wastewater can be a useful indicator of the development of the COVID-19 pandemic in communities. However, knowledge about how the amount of SARS-CoV-2 RNA in wastewater relates to different data on the burden on the health system is still limited. Herein, the authors monitored the amount of SARS-CoV-2 RNA and the spectrum of virus variants in weekly pooled wastewater samples for two years from mid-February 2020 and compared them with several clinical data. The two-year monitoring showed the weekly changes in the amount of viral RNA in wastewater preceded the hospital care needs for COVID-19 and the number of acute calls on adult acute respiratory distress by 1-2 weeks during the first three waves of COVID-19. This study demonstrates that virus surveillance in wastewater can predict the development of a pandemic and its burden on the health system, regardless of society's test capacity and possibility of tracking infected cases.

M.D. Solomon et al.

Risk of severe COVID-19 infection among adults with prior exposure to children

PNAS, August 2022; doi: 10.1073/pnas.2204141119


Susceptibility and severity of COVID-19 infection vary widely. Prior exposure to endemic coronaviruses, common in young children, may protect against SARS-CoV-2. We evaluated risk of severe COVID-19 among adults with and without exposure to young children in a large, integrated healthcare system. Adults with children 0-5 years were matched 1:1 to adults with children 6-11 years, 12-18 years, and those without children based upon a COVID-19 propensity score and risk factors for severe COVID-19. COVID-19 infections, hospitalizations, and need for intensive care unit (ICU) were assessed in 3,126,427 adults, of whom 24% (N = 743,814) had children 18 years or younger, and 8.8% (N = 274,316) had a youngest child 0-5 years. After 1:1 matching, propensity for COVID-19 infection and risk factors for severe COVID-19 were well balanced between groups. Rates of COVID-19 infection were slightly higher for adults with exposure to older children (incident risk ratio, 1.09, 95% confidence interval, [1.05-1.12] and IRR 1.09 [1.05-1.13] for adults with children 6-11 and 12-18, respectively), compared to those with children 0-5 years, although no difference in rates of COVID-19 illness requiring hospitalization or ICU admission was observed. However, adults without exposure to children had lower rates of COVID-19 infection (IRR 0.85, [0.83-0.87]) but significantly higher rates of COVID-19 hospitalization (IRR 1.49, [1.29-1.73]) and hospitalization requiring ICU admission (IRR 1.76, [1.19-2.58]) compared to those with children aged 0-5. In a large, real-world population, exposure to young children was associated with less severe COVID-19 illness. Endemic coronavirus cross-immunity may play a role in protection against severe COVID-19.

Islam Momin et al.

Correlation between COVID-19 and weather variables: A meta-analysis

Heliyon, August 2022; doi.org/10.1016/j.heliyon.2022.e10333


Background: COVID-19 has significantly impacted humans worldwide in recent times. Weather variables have a remarkable effect on COVID-19 spread all over the universe.

Objectives: The aim of this study was to find the correlation between weather variables with COVID-19 cases and COVID-19 deaths.

Conclusion: This meta-analysis disclosed significant correlations between weather and COVID-19 cases and deaths. The findings of this analysis would help policymakers and the health professionals to reduce the cases and fatality rate depending on weather forecast techniques and fight this pandemic using restricted assets.

Q. S. Wang et al.

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

Nature communications, August 2022; doi: 10.1038/s41467-022-32276-2


Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.

M. Sadarangani et al.

Safety of COVID-19 vaccines in pregnancy: a Canadian National Vaccine Safety (CANVAS) network cohort study

Lancet Infect Dis, August 2022; doi: 10.1016/S1473-3099(22)00426-1


Background: Pregnant individuals have been receiving COVID-19 vaccines following pre-authorisation clinical trials in non-pregnant people. This study aimed to determine the frequency and nature of significant health events among pregnant females after COVID-19 vaccination, compared with unvaccinated pregnant controls and vaccinated non-pregnant individuals.

Methods: We did an observational cohort study, set in seven Canadian provinces and territories including Ontario, Quebec, British Columbia, Alberta, Nova Scotia, Yukon, and Prince Edward Island. Eligibility criteria for vaccinated individuals were a first dose of a COVID-19 vaccine within the previous 7 days; an active email address and telephone number; ability to communicate in English or French; and residence in the aforementioned provinces or territories. Study participants were pregnant and non-pregnant females aged 15-49 years. Individuals were able to participate as controls if they were unvaccinated and fulfilled the other criteria. Data were collected primarily by self-reported survey after both vaccine doses, with telephone follow-up for those reporting any medically attended event. Participants reported significant health events (new or worsening of a health event sufficient to cause work or school absenteeism, medical consultation, or prevent daily activities) occurring within 7 days of vaccination or within the past 7 days for unvaccinated individuals. We employed multivariable logistic regression to examine significant health events associated with mRNA vaccines, adjusting for age group, previous SARS-CoV-2 infection, and trimester, as appropriate.

Findings: As of Nov 4, 2021, 191 360 women aged 15-49 years with known pregnancy status had completed the first vaccine dose survey and 94 937 had completed the second dose survey. 180 388 received one dose and 94 262 received a second dose of an mRNA vaccine, with 5597 pregnant participants receiving dose one and 3108 receiving dose two, and 174 765 non-pregnant participants receiving dose one and 91 131 receiving dose two. Of 6179 included unvaccinated control participants, 339 were pregnant and 5840 were not pregnant. Overall, 226 (4·0%) of 5597 vaccinated pregnant females reported a significant health event after dose one of an mRNA vaccine, and 227 (7·3%) of 3108 after dose two, compared with 11 (3·2%) of 339 pregnant unvaccinated females. Pregnant vaccinated females had an increased odds of a significant health event within 7 days of the vaccine after dose two of mRNA-1273 (adjusted odds ratio [aOR] 4·4 [95% CI 2·4-8·3]) compared with pregnant unvaccinated controls within the past 7 days, but not after dose one of mRNA-1273 or any dose of BNT162b2. Pregnant vaccinated females had decreased odds of a significant health event compared with non-pregnant vaccinated females after both dose one (aOR 0·63 [95% CI 0·55-0·72]) and dose two (aOR 0·62 [0·54-0·71]) of any mRNA vaccination. There were no significant differences in any analyses when restricted to events which led to medical attention.

Interpretation: COVID-19 mRNA vaccines have a good safety profile in pregnancy. These data can be used to appropriately inform pregnant people regarding reactogenicity of COVID-19 vaccines during pregnancy, and should be considered alongside effectiveness and immunogenicity data to make appropriate recommendations about best use of COVID-19 vaccines in pregnancy.

J. S. Faust et al.

Uncoupling of all-cause excess mortality from COVID-19 cases in a highly vaccinated state

 Lancet Infect Dis, August 2022; doi: 10.1016/S1473-3099(22)00547-3


Since March, 2020, excess mortality— the number of all-cause deaths exceeding the baseline number of expected deaths—has been observed in waves coinciding with COVID-19 outbreaks in the USA and worldwide. However, after February, 2022, the reported number of COVID-19-associated deaths decreased despite a notable spring wave of infections primarily due to omicron subvariants (BA.2, BA.2.12.1, BA.4, BA.5). Until now, it has been unknown whether the spring, 2022, COVID-19 wave in Massachusetts, USA, was associated with all-cause excess mortality.

J.E. Pekar et al.

The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2

Science, July 2022; doi: 10.1126/science.abp8337


Understanding the circumstances that lead to pandemics is important for their prevention. Here, we analyze the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic. We show that SARS-CoV-2 genomic diversity before February 2020 likely comprised only two distinct viral lineages, denoted A and B. Phylodynamic rooting methods, coupled with epidemic simulations, reveal that these lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October-8 December), while the separate introduction of lineage A likely occurred within weeks of this event. These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans prior to November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events.

S.K. Byeon et al.

Development of a multiomics model for identification of predictive biomarkers for COVID-19 severity: a retrospective cohort study

Lancet Digit Health, July 2022; doi: 10.1016/S2589-7500(22)00112-1


Background: COVID-19 is a multi-system disorder with high variability in clinical outcomes among patients who are admitted to hospital. Although some cytokines such as interleukin (IL)-6 are believed to be associated with severity, there are no early biomarkers that can reliably predict patients who are more likely to have adverse outcomes. Thus, it is crucial to discover predictive markers of serious complications.

Methods: In this retrospective cohort study, we analysed samples from 455 participants with COVID-19 who had had a positive SARS-CoV-2 RT-PCR result between April 14, 2020, and Dec 1, 2020 and who had visited one of three Mayo Clinic sites in the USA (Minnesota, Arizona, or Florida) in the same period. These participants were assigned to three subgroups depending on disease severity as defined by the WHO ordinal scale of clinical improvement (outpatient, severe, or critical). Our control cohort comprised of 182 anonymised age-matched and sex-matched plasma samples that were available from the Mayo Clinic Biorepository and banked before the COVID-19 pandemic. We did a deep profiling of circulatory cytokines and other proteins, lipids, and metabolites from both cohorts. Most patient samples were collected before, or around the time of, hospital admission, representing ideal samples for predictive biomarker discovery. We used proximity extension assays to quantify cytokines and circulatory proteins and tandem mass spectrometry to measure lipids and metabolites. Biomarker discovery was done by applying an AutoGluon-tabular classifier to a multiomics dataset, producing a stacked ensemble of cutting-edge machine learning algorithms. Global proteomics and glycoproteomics on a subset of patient samples with matched pre-COVID-19 plasma samples was also done.

Findings: We quantified 1463 cytokines and circulatory proteins, along with 902 lipids and 1018 metabolites. By developing a machine-learning-based prediction model, a set of 102 biomarkers, which predicted severe and clinical COVID-19 outcomes better than the traditional set of cytokines, were discovered. These predictive biomarkers included several novel cytokines and other proteins, lipids, and metabolites. For example, altered amounts of C-type lectin domain family 6 member A (CLEC6A), ether phosphatidylethanolamine (P-18:1/18:1), and 2-hydroxydecanoate, as reported here, have not previously been associated with severity in COVID-19. Patient samples with matched pre-COVID-19 plasma samples showed similar trends in muti-omics signatures along with differences in glycoproteomics profile.

Interpretation: A multiomic molecular signature in the plasma of patients with COVID-19 before being admitted to hospital can be exploited to predict a more severe course of disease. Machine learning approaches can be applied to highly complex and multidimensional profiling data to reveal novel signatures of clinical use. The absence of validation in an independent cohort remains a major limitation of the study.

F. Amman et al.

Viral variant-resolved wastewater surveillance of SARS-CoV-2 at national scale

Nat Biotechnol, July 2022; doi: 10.1038/s41587-022-01387-y


SARS-CoV-2 surveillance by wastewater-based epidemiology is poised to provide a complementary approach to sequencing individual cases. However, robust quantification of variants and de novo detection of emerging variants remains challenging for existing strategies. We deep sequenced 3,413 wastewater samples representing 94 municipal catchments, covering >59% of the population of Austria, from December 2020 to February 2022. Our system of variant quantification in sewage pipeline designed for robustness (termed VaQuERo) enabled us to deduce the spatiotemporal abundance of predefined variants from complex wastewater samples. These results were validated against epidemiological records of >311,000 individual cases. Furthermore, we describe elevated viral genetic diversity during the Delta variant period, provide a framework to predict emerging variants and measure the reproductive advantage of variants of concern by calculating variant-specific reproduction numbers from wastewater. Together, this study demonstrates the power of national-scale WBE to support public health and promises particular value for countries without extensive individual monitoring.

A.A. Cohen et al.

Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models

Science, August 2022; doi: 10.1126/science.abq0839


To combat future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD nanoparticles in mice and macaques and observed stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains, including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants, including Omicrons, and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest that mosaic-8 RBD nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.

L. Marsden et al.

Daily testing of contacts of SARS-CoV-2 infected cases as an alternative to quarantine for key workers in Liverpool: A prospective cohort study

eClinicalMedicine, July 2022; doi.org/10.1016/j.eclinm.2022.101519


Background Covid-19 test-to-release from quarantine policies affect many lives. The SMART Release pilot was the foundation of these policies and an element of the world’s largest population cohort study of community-wide, SARS-CoV-2 rapid antigen testing. The objective of the study was to evaluate daily lateral flow testing (LFT) as an alternative to 10-14 days quarantine for key worker contacts of known Covid-19 (or SARS-CoV-2 infection) cases.

Methods Prospective cohort study incorporating quantitative and qualitative research methods to consider how serial LFT compares with PCR testing to detect SARS-CoV-2 infections and to understand experiences/compliance with testing and the viability of this quarantine harm-reduction strategy. Participants were residents of the Liverpool area who were key workers at participating fire, police, NHS and local government organisations in Liverpool, and who were identified as close contacts of cases between December 2020 and August 2021. Thematic qualitative analysis was used to evaluate stakeholder meetings.

Findings Compliance with the daily testing regime was good across the three main organisations in this study with 96¢9%, 93¢7% and 92¢8% compliance for Merseyside Police, Merseyside Fire & Rescue Service and Alder Hey Children’s Hospital respectively. Out of 1657 participants, 34 positive Covid-19 cases were identified and 3 undetected by the daily LFT regime. A total of 8291 workdays would have been lost to self-isolation but were prevented due to negative daily tests. Organisations reported that daily contact testing proved useful, flexible and well-tolerated initiative to sustain key worker services.

Interpretation Compliance with daily testing among key workers was high, helping sustain service continuity during periods of very high risk of staffing shortage. Services reported that the pilot was a “lifeline” and its successful delivery in Liverpool has been replicated elsewhere.

S.F. Nilsson et al.

Adverse SARS-CoV-2-associated outcomes among people experiencing social marginalisation and psychiatric vulnerability: A population-based cohort study among 4,4 million people

The Lancet Regional Health - Europe; June 2022; doi.org/10.1016/j.lanepe.2022.100421



Knowledge of the adverse problems related to SARS-CoV-2 infection in marginalised and deprived groups may help to prioritise more preventive efforts in these groups. We examined adverse outcomes associated with SARS-CoV-2 infection among vulnerable segments of society.


Using health and administrative registers, a population-based cohort study of 4.4 million Danes aged at least 15 years from 27 February 2020 to 15 October 2021 was performed. People with 1) low educational level, 2) homelessness, 3) imprisonment, 4) substance abuse, 5) supported psychiatric housing, 6) psychiatric admission, and 7) severe mental illness were main exposure groups. Chronic medical conditions were included for comparison. COVID-19-related outcomes were: 1) hospitalisation, 2) intensive care, 3) 60-day mortality, and 4) overall mortality. PCR-confirmed SARS-CoV-2 infection and PCR-testing were also studied. Poisson regression analysis was used to compute adjusted incidence and mortality rate ratios (IRRs, MRRs).


Using health and administrative registers, we performed a population-based cohort study of 4,412,382 individuals (mean age 48 years; 51% females). In all, 257,450 (5·8%) individuals had a PCR-confirmed SARS-CoV-2 infection. After adjustment for age, calendar time, and sex, we found that especially people experiencing homelessness had high risk of hospitalisation (IRR 4·36, 95% CI, 3·09-6·14), intensive care (IRR 3·12, 95% CI 1·29-7·52), and death (MRR 8·17, 95% CI, 3·66-18·25) compared with people without such experiences, but increased risk was found for all studied groups. Furthermore, after full adjustment, including for status of vaccination against SARS-CoV-2 infection, individuals with experiences of homelessness and a PCR-confirmed SARS-CoV-2 infection had 41-times (95% CI, 24·84-68·44) higher risk of all-cause death during the study period compared with individuals without. Supported psychiatric housing was linked to almost 3-times higher risk of hospitalisation and 60-day mortality following SARS-CoV-2 infection compared with the general population with other living circumstances.


Socially marginalised and psychiatrically vulnerable individuals had substantially elevated risks of adverse health outcomes following SARS-CoV-2 infection. The results highlight that pandemic preparedness should address inequalities in health, including infection prevention and vaccination of vulnerable groups.

H. Schwandt et al.

Changes in the Relationship Between Income and Life Expectancy Before and During the COVID-19 Pandemic, California, 2015-2021

JAMA, July 2022; doi:10.1001/jama.2022.10952


Objective  To measure changes in life expectancy in 2020 and 2021 and the relationship between income and life expectancy by race and ethnicity.

Design, Setting, and Participants  Retrospective ecological analysis of deaths in California in 2015 to 2021 to calculate state- and census tract–level life expectancy. Tracts were grouped by median household income (MHI), obtained from the American Community Survey, and the slope of the life expectancy-income gradient was compared by year and by racial and ethnic composition.

Exposures  California in 2015 to 2019 (before the COVID-19 pandemic) and 2020 to 2021 (during the COVID-19 pandemic).

Main Outcomes and Measures  Life expectancy at birth.

Results  California experienced 1 988 606 deaths during 2015 to 2021, including 654 887 in 2020 to 2021. State life expectancy declined from 81.40 years in 2019 to 79.20 years in 2020 and 78.37 years in 2021. MHI data were available for 7962 of 8057 census tracts (98.8%; n = 1 899 065 deaths). Mean MHI ranged from $21 279 to $232 261 between the lowest and highest percentiles. The slope of the relationship between life expectancy and MHI increased significantly, from 0.075 (95% CI, 0.07-0.08) years per percentile in 2019 to 0.103 (95% CI, 0.098-0.108; P < .001) years per percentile in 2020 and 0.107 (95% CI, 0.102-0.112; P < .001) years per percentile in 2021. The gap in life expectancy between the richest and poorest percentiles increased from 11.52 years in 2019 to 14.67 years in 2020 and 15.51 years in 2021. Among Hispanic and non-Hispanic Asian, Black, and White populations, life expectancy declined 5.74 years among the Hispanic population, 3.04 years among the non-Hispanic Asian population, 3.84 years among the non-Hispanic Black population, and 1.90 years among the non-Hispanic White population between 2019 and 2021. The income–life expectancy gradient in these groups increased significantly between 2019 and 2020 (0.038 [95% CI, 0.030-0.045; P < .001] years per percentile among Hispanic individuals; 0.024 [95% CI: 0.005-0.044; P = .02] years per percentile among Asian individuals; 0.015 [95% CI, 0.010-0.020; P < .001] years per percentile among Black individuals; and 0.011 [95% CI, 0.007-0.015; P < .001] years per percentile among White individuals) and between 2019 and 2021 (0.033 [95% CI, 0.026-0.040; P < .001] years per percentile among Hispanic individuals; 0.024 [95% CI, 0.010-0.038; P = .002] years among Asian individuals; 0.024 [95% CI, 0.011-0.037; P = .003] years per percentile among Black individuals; and 0.013 [95% CI, 0.008-0.018; P < .001] years per percentile among White individuals). The increase in the gradient was significantly greater among Hispanic vs White populations in 2020 and 2021 (P < .001 in both years) and among Black vs White populations in 2021 (P = .04).

Conclusions and Relevance  This retrospective analysis of census tract–level income and mortality data in California from 2015 to 2021 demonstrated a decrease in life expectancy in both 2020 and 2021 and an increase in the life expectancy gap by income level relative to the prepandemic period that disproportionately affected some racial and ethnic minority populations. Inferences at the individual level are limited by the ecological nature of the study, and the generalizability of the findings outside of California are unknown.

H. Tegally et al.

Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa

Nature Medicine, June 2022; doi.org/10.1038/s41591-022-01911-2


Three lineages (BA.1, BA.2 and BA.3) of the SARS-CoV-2 Omicron variant of concern predominantly drove South Africa’s fourth COVID-19 wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and comparable to BA.2 except for the addition of 69-70del (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild type amino acid at Q493.The two lineages only differ outside of the spike region. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature . BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimate growth advantages for BA.4 and BA.5 of 0.08 (95% CI: 0.08 - 0.09) and 0.10 (95% CI: 0.09 - 0.11) per day respectively over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus.

C.D. Mathers et al.

Projections of Global Mortality and Burden of Disease from 2002 to 2030

PLoS Med., November 2006; doi: 10.1371/journal.pmed.0030442



Global and regional projections of mortality and burden of disease by cause for the years 2000, 2010, and 2030 were published by Murray and Lopez in 1996 as part of the Global Burden of Disease project. These projections, which are based on 1990 data, continue to be widely quoted, although they are substantially outdated; in particular, they substantially underestimated the spread of HIV/AIDS. To address the widespread demand for information on likely future trends in global health, and thereby to support international health policy and priority setting, we have prepared new projections of mortality and burden of disease to 2030 starting from World Health Organization estimates of mortality and burden of disease for 2002. This paper describes the methods, assumptions, input data, and results.

Methods and Findings

Relatively simple models were used to project future health trends under three scenarios—baseline, optimistic, and pessimistic—based largely on projections of economic and social development, and using the historically observed relationships of these with cause-specific mortality rates. Data inputs have been updated to take account of the greater availability of death registration data and the latest available projections for HIV/AIDS, income, human capital, tobacco smoking, body mass index, and other inputs. In all three scenarios there is a dramatic shift in the distribution of deaths from younger to older ages and from communicable, maternal, perinatal, and nutritional causes to noncommunicable disease causes. The risk of death for children younger than 5 y is projected to fall by nearly 50% in the baseline scenario between 2002 and 2030. The proportion of deaths due to noncommunicable disease is projected to rise from 59% in 2002 to 69% in 2030. Global HIV/AIDS deaths are projected to rise from 2.8 million in 2002 to 6.5 million in 2030 under the baseline scenario, which assumes coverage with antiretroviral drugs reaches 80% by 2012. Under the optimistic scenario, which also assumes increased prevention activity, HIV/AIDS deaths are projected to drop to 3.7 million in 2030. Total tobacco-attributable deaths are projected to rise from 5.4 million in 2005 to 6.4 million in 2015 and 8.3 million in 2030 under our baseline scenario. Tobacco is projected to kill 50% more people in 2015 than HIV/AIDS, and to be responsible for 10% of all deaths globally. The three leading causes of burden of disease in 2030 are projected to include HIV/AIDS, unipolar depressive disorders, and ischaemic heart disease in the baseline and pessimistic scenarios. Road traffic accidents are the fourth leading cause in the baseline scenario, and the third leading cause ahead of ischaemic heart disease in the optimistic scenario. Under the baseline scenario, HIV/AIDS becomes the leading cause of burden of disease in middle- and low-income countries by 2015.


These projections represent a set of three visions of the future for population health, based on certain explicit assumptions. Despite the wide uncertainty ranges around future projections, they enable us to appreciate better the implications for health and health policy of currently observed trends, and the likely impact of fairly certain future trends, such as the ageing of the population, the continued spread of HIV/AIDS in many regions, and the continuation of the epidemiological transition in developing countries. The results depend strongly on the assumption that future mortality trends in poor countries will have a relationship to economic and social development similar to those that have occurred in the higher-income countries.

K.R. McCarthy

Catching the breadth of broadly protective antibodies to SARS-CoV-2

Nature Immunology, June 2022; doi.org/10.1038/s41590-022-01225-y


Broadly protective antibodies to SARS-CoV-2 inform vaccine improvements and are directly used for treatment and prevention. New technologies are enabling the recovery of thousands of antibody examples, and workflows to rapidly identify the most potent examples are accelerating discovery.

Pandemics often emerge and spread in the absence of pre-existing population-level immunity. Immunity can be built through infection or vaccination and delivered as prophylactic or therapeutic monoclonal antibodies. Viruses can then evolve to evade immunity, which erodes protection conferred through these mechanisms. 

W.C. Kirby

Zeroing out on zero-COVID

Science, June 2022;doi: 10.1126/science.add1891


There is no such thing as “ zero-COVID.” As the Omicron variant spreads to China’s capital city, Beijing, the question is not if, but when and how, China will begin to “live with COVID-19” rather than continue to impose endless lockdowns. The problem is that under China’s stifling political climate, this notion cannot be uttered, let alone debated. How did a country with a history of deep respect for science and a laser focus on becoming a global powerhouse in technology and innovation fall into such isolation from the rest of the world?

C. del Rio et al.

COVID-19 in 2022—The Beginning of the End or the End of the Beginning?

Jama, May 2022; doi:10.1001/jama.2022.9655


Now in the third year of the coronavirus pandemic, well after the Omicron variant surge, both in the US and globally the number of daily cases had been declining to their lowest levels in more than 6 months. While it seemed that SARS-CoV-2 was moving toward endemicity, US infections are again rising in May 2022, and the reported number of cases is likely a gross underestimate of actual infections because many infections are unreported with increasing at-home testing. Several factors help explain the current trends: The emergence of the BA.2 subvariant of Omicron and the more recently identified subvariant called BA.2.12.1, the limited durability of protection from infection both from vaccination and prior infection, and lifting of mandates (such as mask use) and other restrictions across the country.

J.S. Faust et al.

Excess Mortality in Massachusetts During the Delta and Omicron Waves of COVID-19

Jama, May 2022; doi:10.1001/jama.2022.8045


The COVID-19 pandemic has produced excess deaths, the number of all-cause fatalities exceeding the expected number in any period.Given reports that the Omicron variant may confer less risk than prior variants, we compared excess mortality in Massachusetts, a highly vaccinated state, during the Delta and initial Omicron periods.3


We applied autoregressive integrated moving average (ARIMA) models to US Census populations (2014-2019) and seasonal ARIMA (sARIMA) models to Massachusetts Department of Health all-cause mortality statistics (from January 5, 2015, through February 8, 2020) to account for prepandemic age and mortality trends and to project the age-stratified (0-17, 18-49, 50-64, and ≥65 years) weekly population and the weekly number of expected deaths in Massachusetts during the pandemic period (February 9, 2020, through February 20, 2022), focusing on the Delta (June 28, 2021, through December 5, 2021), the Delta-Omicron transition (December 6-26, 2021), and Omicron COVID-19 periods (December 27, 2021, through February 20, 2022). Period barriers were determined by variant dominance in regional wastewater.4

The population of Massachusetts is approximately 6.9 million individuals. We corrected expected deaths for the decreased population owing to cumulative pandemic-associated excess deaths (eAppendix in the Supplement). Population covariates were used to calculate 95% CIs for expected deaths. Excess mortality for each period was defined as the difference between the observed deaths and point estimate for sARIMA-determined expected deaths. Incident rate ratios were calculated to compare the Omicron and Delta periods. According to the Massachusetts Department of Health, deaths recorded from 2020 to 2022 were considered provisional. Excess mortality for individuals aged 0 to 17 years was determined and included in the overall analysis, but not presented separately because the death rates were considered too small to be reliable.

Analyses were conducted with R version 4.1.2. Statistical significance was defined as a 95% CI that did not include 0. This study used publicly available data and was not subject to institutional review board approval according to the Massachusetts Registry of Vital Records and Statistics.


During the 23-week Delta period, 1975 all-cause excess deaths occurred (27 265 observed; 25 290 expected; 95% CI, 671-3297 excess deaths). During the 8-week Omicron period, 2294 excess deaths occurred (12 231 observed; 9937 expected; 95% CI, 1795-2763 excess deaths). The per-week Omicron to Delta incident rate ratio for excess mortality was 3.34 (95% CI, 3.14-3.54) (Table).

Statistically significant excess mortality occurred in all adult age groups at various times during the study period and in each period overall (FigureTable). For all adult age groups, the ratio of observed to expected excess mortality increased during the Omicron period compared with the Delta period (Table).


More all-cause excess mortality occurred in Massachusetts during the first 8 weeks of the Omicron period than during the entire 23-week Delta period. Although numerically there were more excess deaths in older age groups, there was excess mortality in all adult age groups, as recorded in earlier waves, including in younger age groups. Moreover, the ratio of observed to expected all-cause deaths was similar in all age groups, and increased during the Omicron period compared with the Delta period.

Others have reported that the Omicron variant may cause milder COVID-19. If true, increased all-cause excess mortality observed during the Omicron wave in Massachusetts may reflect a higher mortality product (ie, a moderately lower infection fatality rate multiplied by far higher infection rate).

This observational study was limited by use of preliminary data, although mortality reporting for the study period in Massachusetts is more than 99% complete. Also, during the early Omicron period, a small number of deaths may have been caused by Delta infections that occurred several weeks earlier. Nevertheless, the present findings indicate that a highly contagious (although relatively milder) SARS-CoV-2 variant can quickly confer substantial excess mortality, even in a highly vaccinated and increasingly immune population.

G. Nattino et al.

Association Between SARS-CoV-2 Viral Load inWastewater and Reported Cases, Hospitalizations, and Vaccinations in Milan, March 2020 to November 2021

JAMA, April 2022; doi:10.1001/jama.2022.4908


Several studies have demonstrated that wastewater surveillance can be used to monitor SARS-CoV-2 incidence. This surveillance intends to overcome the limitations of traditional surveillance indicators, such as the number of positive tests, which depends on test availability and indications, or COVID-19–related hospitalizations, which occur weeks after the spread of SARS-CoV-2 and do not include mild or asymptomatic cases. This study evaluated the association between SARS-CoV-2 load in urban wastewater and surveillance indicators of infection prevalence and severity in Milan, Italy.


Sewage samples were collected approximately once a week from March 2020 to November 2021 in the Nosedo wastewater treatment plant, serving about 50% of the Milan population. SARS-CoV-2 RNA was measured in wastewater by amplifying the nucleocapsid gene, and viral load was calculated correcting for daily wastewater flow and population (eMethods in the Supplement). Aggregate epidemiological data about Milan were supplied by the Lombardy Region and included daily numbers of SARS-CoV-2–positive cases, COVID-19 hospitalizations, and individuals completing the vaccination cycle (2 doses for 2-dose vaccines or 1 for Ad26.COV2.S [Janssen/Johnson & Johnson]) by age group and sex. According to Italian legislation, informed consent and ethics committee approval were not required because the analyzed data were anonymous.

The SARS-CoV-2 load in wastewater was graphically compared with surveillance indicators of infection prevalence. Local polynomial regression was conducted and 95% confidence intervals calculated to assess trends in SARS-CoV-2 loads. Positive cases and COVID-19 hospitalizations in Milan were used to estimate the prevalence of infection and severe infection, assuming a 15-day viral excretion for each positive or hospitalized individual (eMethods in the Supplement). The daily proportion of vaccinated individuals was computed and standardized by age and sex to the population of patients with COVID-19 hospitalized before the vaccination campaign started. Such standardization was performed to measure the coverage of individuals at higher risk of hospitalization after SARS-CoV-2 infection. Analyses were performed with R version 4.0.2.


Figure 1 presents positive cases and hospitalizations over the study period. Figure 2 presents wastewater SARS-CoV-2 loads. The vaccination campaign began in January 2021 and coverage progressively increased, reaching 75% (>85% for individuals at increased risk of hospitalization) in November 2021. The curves for wastewater load and hospitalized patients are similar until the increase in vaccination coverage. The curves for wastewater load and positive cases also are similar except during the first wave, which was characterized by a shortage of tests. Curves for positive cases and hospitalizations diverge from the curve for wastewater load as vaccination coverage increased, with decreases in cases and hospitalizations and increases in wastewater viral load. On November 30, 2021, despite the limited number of positive cases (n = 4672) and hospitalizations (n = 252), the wastewater load was 7.25 × 109copies/d/1000 people (95% CI, 2.43-24.80 × 109), comparable with values observed during the second wave (November 10, 2020; 12.30 × 109copies/d/1000 people, 95% CI, 4.71-22.31 × 109), before the vaccination campaign started.


In Milan, high wastewater SARS-CoV-2 loads were found when vaccination coverage was high and traditional surveillance indicators suggested limited SARS-CoV-2 prevalence. This result suggests that there was significant circulating virus in the population during this period, including among vaccinated individuals. The SARS-CoV-2 circulation among vaccinated individuals may create modest evolutionary pressure toward resistance to the host’s immune response, making variants with significant transmission advantages more competitive. The current spread of the Omicron variant supports this theory.

This study is limited by the difficulty in translating SARS-CoV-2 wastewater loads into infection prevalence because the variability of loads is affected by factors that can be controlled only partially.Nonetheless, the magnitude of the observed trends supports the value of wastewater surveillance to monitor the spread of SARS-CoV-2. In addition, the study was limited to a single city.

The results suggest that vaccines are effective in protecting against symptomatic and severe disease, but that, with high vaccination rates, standard surveillance metrics may not accurately estimate the spread of SARS-CoV-2. Thus, wastewater surveillance may be important as an early warning of virus circulation. These results strengthen the scientific basis of the recommendations from the Centers for Disease Control and Prevention National Wastewater Surveillance System and European Commission to establish systematic SARS-CoV-2 wastewater surveillance networks.

M.E.K. Niemi et al.

The human genetic epidemiology of COVID-19

Nature reviews genetic, May 2022; doi.org/10.1038/s41576-022-00478-5


Human genetics can inform the biology and epidemiology of coronavirus disease 2019 (COVID-19) by pinpointing causal mechanisms that explain why some individuals become more severely affected by the disease upon infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Large-scale genetic association studies, encompassing both rare and common genetic variants, have used different study designs and multiple disease phenotype definitions to identify several genomic regions associated with COVID-19. Along with a multitude of follow-up studies, these findings have increased our understanding of disease aetiology and provided routes for management of COVID-19. Important emergent opportunities include the clinical translatability of genetic risk prediction, the repurposing of existing drugs, exploration of variable host effects of different viral strains, study of inter-individual variability in vaccination response and understanding the long-term consequences of SARS-CoV-2 infection. Beyond the current pandemic, these transferrable opportunities are likely to affect the study of many infectious diseases.

J.R. Horwitz et al.

Not Ready for the End Game — Why Ending Federal Covid-19 Emergency Declarations Will Harm Access to Care

New England J Medicine, April 2022; doi: 10.1056/NEJMp2203468


Increasing demands that President Joe Biden “end the emergency” reflect political symbolism and understandable longing for normal life. But responding literally, by abruptly terminating federal emergency declarations, will backfire. Doing so will not eliminate the mask, vaccination, and quarantine requirements some Americans oppose — many of which are being discontinued anyway. Moreover, rushed terminations of federal emergency declarations will eliminate regulatory flexibility and financial supports for patients, providers, and the health care system.

The response to Covid-19 does not hinge on a single emergency declaration. Overlapping federal, state, and local declarations have triggered executive emergency powers to spend money and issue, suspend, and alter regulations. Most state and local governments have now terminated the declarations that allowed governors and mayors to order travel and business restrictions and mask and quarantine mandates without legislative action.1 At the federal level, several distinct emergency declarations remain active, but their primary effect is to remove regulatory barriers and address liability concerns that would otherwise impede access to health care and medical countermeasures, not to impose mandates.

D. Goldblatt

SARS-CoV-2: from herd immunity to hybrid immunity

Nature Reviews Immunology, April 2022; doi.org/10.1038/s41577-022-00725-0


Herd immunity, where a pathogen can no longer efficiently spread in a population, is achieved when a large proportion of the population becomes immune, making the spread of infection from person to person unlikely and protecting those without immunity. Despite the global spread of SARS-CoV-2, the failure of virus- and vaccine-induced immunity to prevent transmission, combined with the emergence of antigenically distinct variants, has made herd immunity to SARS-CoV-2 unachievable thus far. Wheredoesthisleaveus?

T. Burki

Dynamic zero COVID policy in the fight against COVID

The Lancet, Respiratory Medicine, April 2022; doi.org/10.1016/S2213-2600(22)00142-4


On April 11, 2022, the authorities in Shanghai, China, announced that they would ease the citywide lockdown. Residents in zones that have reported no new cases of COVID-19 for 2 weeks were granted permission to leave their homes, on condition that they restrict their movements to specific areas. “After a long period of lockdown, it is understandable that people want to go out and get some air, and they need to go shopping for food and medicine and go for medical treatment”, stated city health official Wu Qianyu. “But if lots of people gather in a disorderly way, it will cause hidden dangers to our epidemic prevention work.”

N. Brusselaers et al.

Evaluation of science advice during the COVID-19 pandemic in Sweden

Humanities and Social Sciences Communications, March 2022; doi.org/10.1057/s41599-022-01097-5


Sweden was well equipped to prevent the pandemic of COVID-19 from becoming serious. Over 280 years of collaboration between political bodies, authorities, and the scientific community had yielded many successes in preventive medicine. Sweden’s population is literate and has a high level of trust in authorities and those in power. During 2020, however, Sweden had ten times higher COVID-19 death rates compared with neighbouring Norway. In this report, we try to understand why, using a narrative approach to evaluate the Swedish COVID-19 policy and the role of scientific evidence and integrity. We argue that that scientific methodology was not followed by the major figures in the acting authorities—or the responsible politicians—with alternative narratives being considered as valid, resulting in arbitrary policy decisions. In 2014, the Public Health Agency merged with the Institute for Infectious Disease Control; the first decision by its new head (Johan Carlson) was to dismiss and move the authority’s six professors to Karolinska Institute. With this setup, the authority lacked expertise and could disregard scientific facts. The Swedish pandemic strategy seemed targeted towards “natural” herd-immunity and avoiding a societal shutdown. The Public Health Agency labelled advice from national scientists and international authorities as extreme positions, resulting in media and political bodies to accept their own policy instead. The Swedish people were kept in ignorance of basic facts such as the airborne SARS-CoV-2 transmission, that asymptomatic individuals can be contagious and that face masks protect both the carrier and others. Mandatory legislation was seldom used; recommendations relying upon personal responsibility and without any sanctions were the norm. Many elderly people were administered morphine instead of oxygen despite available supplies, effectively ending their lives. If Sweden wants to do better in future pandemics, the scientific method must be re-established, not least within the Public Health Agency. It would likely make a large difference if a separate, independent Institute for Infectious Disease Control is recreated. We recommend Sweden begins a self-critical process about its political culture and the lack of accountability of decision-makers to avoid future failures, as occurred with the COVID-19 pandemic.

M. Avolio et al.

Epidemiology of respiratory virus before and during COVID-19 pandemic

Infezioni in Medicina, 2022; doi: 10.53854/liim-3001-12


The COVID pandemic has forcefully turned the spotlight on the importance of the diagnosis of respiratory virus infections. Viruses have always been a frequent and common cause of respiratory tract infections. Rapid molecular diagnostics applied to the diagnostics of respiratory virus infections has revolutionized microbiology laboratories only a few years ago. Few studies illustrate the epidemiology of respiratory viruses, and fewer still those that have compared the pre-pandemic to the pandemic period. During the first year of the pandemic (2020–2021) it was clear to everyone to witness a sudden disappearance of the circulation of all the other respiratory viruses, especially those typically isolated during the winter time, such as RSV and Influenza virus. In our study we wanted to verify this phenomenon and to study the epidemiology of our local reality, analyzing three consecutive flu seasons (2018–2019, 2019–2020, 2020–2021). The results lead us to note that the prevalence of positivity to respiratory virus infections went from 49.8% (2018–2019) and 39% (2019–2020) to 13.4% (2020–2021). This decrease is at least partly attributable to the security measures adopted (social distancing and mask), but it certainly opens up new scenarios when the restriction measures will be terminated. We believe such studies can provide real-world evidence of the effectiveness of public health interventions implemented during current and future pandemics.

C. Crudo Blackburn 

COVID is here to stay? How do we live with it?

Scientific American, 1 marzo 2022


COVID-19 will continue in pandemic form, surging in one or more regions and disrupting daily life, until the world reaches herd immunity. With that, most scientists say, the SARS-CoV-2 virus will become endemic—always present but transmitted among people at modest, predictable rates. After several years the infamous 1918 influenza pandemic made that transition, and the virus is still circulating, 104 years later, in mutated strains. Almost all influenza A infections since 1918 have descended from that strain.

As the endemic stage arrives, people of all ages will be eligible for the COVID vaccine, and hospitals and pharmacies will be well supplied with effective treatments for infection. At that point, it might be wise for public health officials to treat COVID as a respiratory disease that is more dangerous than a cold, similar to how we handle influenza and cytomegalovirus (CMV)—by evaluating distribution of a seasonal vaccine, tracking hospitalization rates and educating the public about current risk. We don’t yet know if COVID will lead to higher rates of long-term complications than those diseases do, so other precautions may be necessary.

In this future, routine testing might become part of everyday life. People with imperceptible symptoms who test positive would know to wear masks and isolate from others. If we could develop similar tests for influenza and CMV and make them cheaply available to everyone, everywhere, society could end up even safer against infectious respiratory diseases than it was before COVID arrived.


Even if COVID cases declined significantly, it’s unlikely the virus would burn out. As long as it was still spreading in animals, it could spill over into humans at another time. Nature is always surprising us. A future, reemergent SARS-CoV-2 could be either less or more transmissible, less or more lethal. The Omicron variant that spread this winter taught us to expect the unexpected. Our world still has much to do to become better prepared for new variants—as well as whatever novel virus emerges next.

ECDC Technical Report

Considerations for the use of face masks in the community in the context of the SARS-CoV-2 Omicron variant of concern


CONTENUTO E COMMENTO: Report aggiornato dell’ECDC sull’uso delle mascherine in comunità nel contesto epidemiologico attuale e dunque durante la diffusione della variante Omicron. 

Nelle aree in cui l'obiettivo di salute pubblica è quello di ridurre la trasmissione comunitaria del COVID-19, indossare una maschera facciale dovrebbe essere considerata come una delle possibili misure di prevenzione in spazi pubblici ristretti, come negozi, supermercati, snodi di trasporto

(es. porti, aeroporti, stazioni di treni/autobus) e quando si usano i trasporti pubblici.

Indossare una maschera facciale dovrebbe essere considerato in ambienti esterni affollati dove non è possibile il distanziamento fisico quando l'obiettivo di salute pubblica è quello di limitare la trasmissione comunitaria.

Sulla base di dati sperimentali sull'efficacia delle maschere filtranti (FFP), è stato stimato che quando sia la fonte che la persona esposta indossano un respiratore ben aderente, il tempo per raggiungere la dose infettante aumenta da 15’ (quando nè la fonte, nè l’esposto indossano una maschera facciale) a 25 ore. Tuttavia,  sebbene le maschere filtranti sembrino più efficaci delle mascherine chirurgiche in ambito di studi sperimentali, le evidenze di real life sull'efficacia dei filtranti facciali rispetto alle mascherine chirurgiche in termini di riduzione della trasmissione di SARS-CoV-2 in contesti comunitari rimane molto limitata e inconcludente.

Cohen. C.; et al.

SARS-CoV-2 incidence, transmission, and reinfection in a rural and an urban setting: results of the PHIRST-C cohort study, South Africa, 2020–21

Lancet Infect Dis , https://www.thelancet.com/action/showPdf?pii=S1473-3099%2822%2900069-X

CONTENUTO E COMMENTO: Studio prospettico condotto in Sud Africa per studiare la  trasmissione intra-familiare di SARS-CoV-2.Lo studio conclude che questo fenomeno è stato centrale nelle tre ondate di COVID nel paese. Nonostante oltre l’85% dei casi sia rimasto asintomatico durante tutta l’infezione (che durava in media circa 11 giorni), questo non ha influenzato l’HCIR, ovvero rapporto tra il numero di contatti familiari contagiati e il numero di membri familiari suscettibili. Inoltre viene sottolineato un aspetto interessante: i soggetti HIV+ non virologicamente soppressi hanno un maggior rischio di avere una infezione sintomatica e di rilasciare il virus più a lungo rispetto alla controparte sieronegativa.Lo studio ha evidenziato i limiti del fare affidamento esclusivamente su interventi non farmacologici. La vaccinazione rimane uno degli strumenti più importanti nella prevenzione della trasmissione.

COVID-19 Excess Mortality Collaborators

Estimating excess mortality due to the COVID-19 pandemic: a systematic analysis of COVID-19-related mortality, 2020–21

The Lancet,  https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2902796-3

CONTENUTO E COMMENTO: Questo lavoro, finanziato tra gli altri dalla Bill & Melinda Gates Foundation ha lo scopo di valutare le morti in eccesso – ovvero la differenza tra il numero di decessi registrati per tutte le cause e il numero previsto in base alle tendenze passate – per avere una misura del vero bilancio delle vittime della pandemia. Le prime stime globali peer-reviewed delle morti in eccesso indicano che, al 31.12.2021, 18,2 milioni di persone potrebbero essere decedute a causa della pandemia di COVID-19, contro i 5,9 dichiarati. Con 5,3 milioni di decessi in eccesso, l'Asia meridionale ha registrato il numero più alto di morti in eccesso stimate per COVID-19, seguita dal Nord Africa e dal Medio Oriente (1,7 milioni) e dall'Europa orientale (1,4 milioni). Sono necessari ulteriori studi per comprendere la percentuale di decessi in eccesso dovuti direttamente al COVID-19 e gli effetti indiretti della pandemia, quali l'impatto sui servizi sanitari, i decessi per altre malattie e gli impatti economici più ampi.

COVID-19 Excess Mortality Collaborators*

Estimating excess mortality due to the COVID-19 pandemic: a systematic analysis of COVID-19-related mortality, 2020–21

The Lancet, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02796-3/fulltext

CONTENUTO E COMMENTO : L’eccesso di mortalità – definito come la differenza netta tra il numero di morti (per tutte le cause) registrato e/o stimato durante la pandemia, e il numero di morti “attese” sulla base dei trend di mortalità registrati negli anni precedenti – è un indicatore cruciale per stimare l’impatto della pandemia in termini di sanità pubblica. Tale valore si scosta dalla mortalità registrata perché, da un lato, non è influenzato dalla sottostima diagnostica (differenza tra numero di casi diagnosticati e reale numero di infezioni) e, dall’altro, tiene in considerazione anche dell’eccesso di mortalità determinato dallo stravolgimento dei sistemi sanitari secondario alla pandemia, e quindi del numero dei morti in eccesso per patologie diverse dalla COVID-19 che non sono state prese correttamente in carico nel periodo di pandemia.

I dati per questa analisi sono stati raccolti dai registri nazionali di 74, da gennaio 2008 fino a dicembre 2021, normalizzando le anomalie di mortalità dovute, ad esempio, ad ondate di calore. La mortalità attesa è stata quindi calcolata estrapolata dall’utilizzo di 6 modelli matematici differenti, applicando il modello predittivo anche a nazioni che non forniscono dati di mortalità.

Sulla base di tale analisi, sebbene le morti COVID-relate riportate ufficialmente nel periodo di tempo intercorrente tra il 1 gennaio 2020 e il 31 dicembre 2021 sono state 5,94 milioni, gli autori stimano che l’eccesso di mortalità rispetto all’atteso sia stato, in tutto il mondo, di 18 milioni di morti.

L’eccesso di mortalità per 100.000 unità di popolazione è risultato eterogeno, a seconda delle aree geografiche, raggiungendo i valori più alti in Asia Meridionale, Nord Africa, Medio Oriente e Est Europa. Le nazioni che hanno assistito all’eccesso di mortalità per 100.000 individui più elevato sono inoltre state, nell’ordine: Russia, Messico, Brasile e USA.

Questo studio mette in evidenzia il reale impatto della pandemia sulla mortalità mondiale, stimandolo circa 3 volte superiore ai report ufficiali.

Salo, J. et al.

Nature Communications

The indirect effect of mRNA-based COVID-19 vaccination on healthcare  workers’ unvaccinated household members


CONTENUTO E COMMENTO : La trasmissione intra-familiare di SARS-CoV-2 ha avuto un ruolo molto rilevante nella diffusione dei contagi. Questo studio valuta l'effetto dei vaccini a mRNA sulle trasmissioni secondarie di SARS-CoV-2 da parte di soggetti vaccinati a non vaccinati conviventi, inclusi i bambini. Coerentemente con i risultati ottenuti dopo la prima dose di vaccino, anche dopo la seconda dose gli effetti indiretti sui bambini e gli adolescenti di età compresa tra 3 e 18 anni sono statisticamente insignificanti e inferiori rispetto ai partner non vaccinati.

Hjorleifsson, K.E.; et al.

Reconstruction of a large-scale outbreak of SARS-CoV2 infection in Iceland informs vaccination strategies

Clinical Microbiology and Infection,


CONTENUTO E COMMENTO : Questo interessante studio condotto in Island adurante la terza ondata. Viene messo in evidenza come un programma di vaccinazione condotto seguendo un ordine di età crescente o random  avrebbe potuto ridurre maggiormente la trasmissione di SARS-CoV-2 rispetto a quello che è stato effettivamente messo in atto e dunque a partire dalle fasce di età più avanzata.

Madhi SA, et al.

Population Immunity and Covid-19 Severity with Omicron Variant in South Africa

NEJM,  https://www.nejm.org/doi/full/10.1056/NEJMoa2119658

CONTENUTO E COMMENTO: Grosso studio condotto in Sud Africa confrontando i dati di sieropravalenza, stato vaccinale, incidenza di COVID-19, ospedalizzazioni e mortalità nella provincia di Gauteng, in due diverse finestre temporali : prima della comparsa della variante omicron (da novembre 2020 a gennaio 2021) e durante l’ondata Omicron (descritta per la prima volta a novembre 2021).

Dall’analisi dei dati ottenuti da più di settemila partecipanti, la sieroprevalenza di IgG anti-SARS COV2 è risultata significativamente più alta per gli individui con più di 50 anni di età, vaccinati ma, soprattutto, è emerso che durante l’ondata Omicron si è assistito a una più rapida e ampia diffusione dell’infezione. Inoltre, nel corso di questa ondata si è assistito ad un disaccopiamento dei tassi di incidenza di infezione con i tassi di incidenza dei ricoveri e delle morti.

Lui AB.; et al.

Association of COVID-19 Quarantine Duration and Postquarantine Transmission Risk in 4 University Cohorts

JAMA, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2789427  

CONTENUTO E COMMENTO: Studio di coorte retrospettiva condotto in 4 università statunitensi, esaminante il rischio di trasmissione post-quarantena a seconda della durata della stessa.

Su un totale di 3641 partecipanti sottoposti a quarantena, 301 sono risultati positivi, e i tassi di positivizzazione sono risultati significativamente minori negli individui sottoposti a una quarantena più rigida (consegnando pasti a domicilio e assicurandosi che non ci siano contatti). In totale, tra gli individui positivi, il 13,7% è risultato negativo al settimo giorno. Sulla base di questi dati, gli autori dello studio suggeriscono che, per mantenere un rischio di trasmissione al di sotto del 5%, sia necessaria una quarantena di 10 giorni, o una più rigida di 8 giorni.

Madhi SA et al

Population Immunity and Covid-19 Severity with Omicron Variant in South Africa



CONTENUTO E COMMENTO : Sieroprevalenza di IgG per SARSC-CoV-2 in Sudafrica su circa 7000 partecipanti, di cui oltre 1300 vaccinati, nel periodo novembre 2020-gennaio 2021 (prima della diffusione della variante omicron : elevata presenza di IgG. Il rapido aumento di incidenza di infezione da SARS-CoV-2 durante la « quarta » ondata non è andato di pari passo con un aumento di ospedalizzazioni e morti, verosimilmente grazie alla diffusione della vaccinazione.

Bhattacharyya, R.P.;Hanage W.P.

Challenges in Inferring Intrinsic Severity of the SARS-CoV-2 Omicron Variant

NEJM, https://www.nejm.org/doi/pdf/10.1056/NEJMp2119682?articleTools=true

CONTENUTO E COMMENTO: Questo articolo sottolinea come anche altre variabili, differenti dall’intrinseca propensione di una variante di SARS-CoV-2 a dare forme severe di malattia, possano influenzare gli outcome clinici. Le differenze nell'immunità a livello di popolazione e nella propensione a infettare le persone con un'immunità preesistente infatti, confondono i confronti diretti del tasso di mortalità per infezione tra le varianti delta e omicron di SARS-CoV-2. I dati di questo lavoro  provengono dal Sud Africa: la variante delta ha attraversato il Sud Africa da giugno ad agosto 2021, quando l'immunità della popolazione era inferiore rispetto ad oggi. Al contrario, la variante omicron a novembre e dicembre 2021, ha incontrato una popolazione con un minor numero di persone non immuni a causa sia dell'infezione precedente (compresa quella da variante delta) che della vaccinazione, e sappiamo che omicron può infettare più facilmente le persone con immunità preesistente. Omicron quindi dovrebbe infettare molte più persone a basso rischio di esiti gravi a causa dell'immunità preesistente, il che ridurrà il tasso di mortalità per infezione osservato indipendentemente dalla gravità intrinseca della variante.

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