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.

Lewis, H.C.; et al.

SARS-CoV-2 infection in Africa: A systematic review and meta-analysis of standardized seroprevalence studies, from January 2020 to December 2021

Medrxiv.org, https://www.medrxiv.org/content/10.1

CONTENUTO E COMMENTO : Questa meta-analisi (ancora non peer reviewed) stima che la sieroprevalenza complessiva sia ora elevata in Africa (65,1% [56,3-73,0%] nel terzo trimestre 2021), notevolmente aumentato nel tempo (dal 3,0% nel secondo trimestre 2020) e caratterizzato da forti incrementi dopo la comparsa delle varianti Beta e Delta. La sieroprevalenza è altamente eterogenea tra:

- aree urbane e rurali (minore sieroprevalenza per le aree geografiche rurali) ;

-  bambini e adulti (i bambini tra 0-9 anni anni hanno avuto la sieroprevalenza più bassa);

- paesi e subregioni africane (orientale, occidentale, e regioni dell'Africa centrale associate a una maggiore sieroprevalenza).

Compatibilmente con i numerosi limiti metodologici dello studio (ad esempio molti studi sono condotti a livello locale e dunque non rappresentativi di interi stati, ridotta numerosità di dati da alcune aree geografiche), si evidenzia un incremento della sieroprevalenza per SARS-CoV-2 in Africa. La grande eterogeneità presente tra le varie regioni africane giustificherebbe interventi mirati in termini di vaccinazione nelle aree a minor sieroprevalenza. 

Scozzari G et al.

Prevalence, Persistence, and Factors Associated with SARS-CoV-2 IgG Seropositivity in a Large Cohort of Healthcare Workers in a Tertiary Care University Hospital in Northern Italy

Viruses, https://www.mdpi.com/1999-4915/13/6/1064

CONTENUTO E COMMENTO : Questo studio retrospettivo osservazionale condotto su 8769 operatori sanitari della “Città della Salute e della Scienza” e 1185 dipendenti dell’Università degli Studi di Torino. In totale, la sieroprevalenza tra gli operatori sanitari è stata del 7.6%, mentre la sieroprevalenza tra i dipendenti universitari del 3.3% e, complessivamente, il 27% dei soggetti sieropositivi non ha mai riportato sintomi. All’analisi multivariata, i contatti sul posto di lavoro hanno rappresentato un eccesso di rischio del 69%, mentre prestare servizio in un reparto COVID un eccesso di rischio del 24%, ma i contatti in ambiente extra-lavorativo hanno rappresentato un aumento del rischio del 500%. Curiosamente, essere fumatore attivo è risultato inversamente associato a sieroconversione.

Baker MA et al.;

Rapid control of hospital-based SARS-CoV-2 Omicron clusters through daily testing and universal use of N95 respirators

Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac113/6523822

CONTENUTO E COMMENTO : Studio osservazionale condotto in un ospedale di Boston, Stati Uniti, in cui, a partire da dicembre 2021, sono stati identificati numerosi di cluster di COVID-19 tra il personale sanitario. Un caso di trasmissione nosocomiale, in questo studio, è stato definito con il riscontro di tampone PCR + consecutivo ad almeno 2 tamponi PCR -. In questo lavoro, gli autori ipotizzano che l’aumento dell’incidenza dei casi di COVID-19 tra il personale rifletta, da un lato, una maggiore diffusione dell’infezione a livello comunitario, una maggiore infettività della variante Omicron e, di conseguenza, un maggiore numero di casi di COVID-19 asintomatico tra il personale sanitario.

Nei due cluster Omicron così identificati, autori riportano come siano stati rapidamente abbattuti anche grazie all’utilizzo dei respiratori N95, che offrono al contempo una maggiore controllo della diffusione delle particelle virali dei soggetti infetti e una maggiore protezione dei soggetti non infetti.

Konig S. et al.;

A Comparative Analysis of In-Hospital Mortality per Disease Groups in Germany Before and During the COVID-19 Pandemic From 2016 to 2020



CONTENUTO E COMMENTO : Studio cross-sectional analizzante i dati di quasi sei milioni di pazienti ricoverati, tra gennaio 2016 e dicembre 2020 in 87 ospedali tedeschi, al fine di identificare un eventuale eccesso di mortalità patologia-specifico intercorso con l’arrivo della pandemia.

In termini di incidenza, il 2020, se paragonato agli anni 2016-1029, si è caratterizzato da un aumento delle diagnosi di malattie respiratorie, affiancato da una riduzione dell’incidenza di patologie di altra natura. Tuttavia, una volta esclusi i pazienti COVID dall’analisi, la mortalità nel 2020 è risultata inferiore sia per l’intera coorte che nel sottogruppo delle patologie respiratorie.

Chaguza C. et al.


Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons

medRxiv preprint

doi: https://doi.org/10.1101/2022.01.22.22269660

e commento su Nature

How well can Omicron evade immunity from COVID vaccines?


CONTENUTO: Studio analitico condotto tramite un programma di sorveglianza nel sud del Connecticut (USA) per investigare l’emergenza di Omicron tramite una combinazione tra spike-gene target failure (SGTF) polymerase chain reaction (PCR) signatures (definito come gene target  ORF1ab PCR cycle threshold (Ct) < 30 e gene target spike « non rilevato ») e sequenziamento. Il primo riscontro di Omicron (ceppo BA.1) si e’ verificato in questa catchment area il 4 dicembre del 2021, fino a diventare la variante dominante della coorte il 20 dicembre: i casi Omicron sono raddoppiati ogni 3,2 giorni (95% confidence interval (CI): 3.0-3.5), tempo di raddoppiamento 3.7 volte piu’ corto di quello di Delta nel periodo di emergenza di quest’ultima variante (18 Aprile- 26 Maggio 2021 (11.9 giorni [95% CI: 10.7-13.3]). 34,980 unique persons that tested for SARS-CoV-2 (37,877 nasal swab eseguiti tra il 12-26 dicembre quando il numero di probabili infezioni Delta ed Omicron erano relativamente simili (Delta = 1463/2987, 49.0%; Omicron = 1524/2987, 51.0%). Il tasso di positivita’ nelle persone non vaccinate della coorte era maggiore per Delta (5.2% [95% CI: 4.9-5.6%]) che per Omicron (4.5 [95% CI: 4.2-4.7%]). Omicron era responsabile di tassi di positivita’ maggiori che Delta tra coloro che avevano ricevuto due dosi entro 5 mesi (Omicron = 4.7% [95% CI: 3.5-5.8%] vs. Delta = 2.6% [95% CI: 1.8-3.5%]), 2 dosi da piu’ di 5 mesi (4.2% [95% CI: 3.9-4.6%] vs. 2.9% [95% CI:2.5-3.2%]), e 3 dosi di vaccino (2.2% [95% CI: 1.7-2.7%] vs. 0.9% [95% CI: 0.5-1.2%]). I tassi di positivita’ per Omicron nei partecipanti con una o due dosi non erano significativamente piu’ bassi nelle persone non vaccinate ma 49.7% piu’ basse dopo 3 dosi. La riduzione dei tassi di positivita’ per Delta tra non vaccinati e i partecipanti con 2 dosi era 45.6-49.6% e con 3 dosi di vaccino 83.2%. 91.2% (1401/1524) dei partecipanti con infezioni Omicron erano eleggibili per 1 o piu’ dosi di vaccino al tempo del test PCR. Calcolando gli odds tra il rischio di test positivo per Omicron rispetto a Delta tramite modello logistico lineare generalizzato (GEE), per i pazienti vaccinati, si e’ assistito a un maggior rischio di infezione con Omicron (vs Delta) e gli odds aumentavano con l’incrementare delle dosi di vaccino. I valori Ct erano simili tra le dosi di vaccino, ma piu’ alti nelle infezioni Omicron che Delta, riflettenti quindi una piu’ bassa carica virale.

LIMITAZIONI : DATI NON PEER REVIEWED ; non sequenziati tutti i campioni ricavati tramite SGTF ; esclusi i partecipanti con informazione vaccinale incompleta ; non studiato impatto reinfezioni ; non analizzata indicazione per il test (motivi altri che malattia da COVID, non possibile quindi inferire sulla patogenicita’ di Omicron nei vaccinati)

COMMENTO : Un’analisi retrospettiva che suggerisce che, data la scarsa diversita’ genetica del virus circolante tra i vaccinati, i vaccini non promuovano nuove mutazioni. Nonostante l’escape immune della variante, i booster sono comunque efficaci nel ridurre il rischio di infezione Omicron del 50%. Rafforza inoltre l’idea dell’utilita’ di un vaccino specifico per Omicron, anche se esiste sempre il rischio dell’emergenza di nuove varianti.

Murray CJL.

COVID-19 will continue but the end of the pandemic is near

Lancet, https://www.thelancet.com/action/showPdf?pii=S0140-6736%2822%2900100-3

CONTENUTO E COMMENTO: Secondo l’autore di questo articolo nuove varianti di SARS-CoV-2 emergeranno sicuramente e alcune potrebbero essere più gravi di omicron. L’immunità, sia da infezione che da vaccinazione svanirà, creando le condizioni affinchè la trasmissione di SARS-CoV-2 continui. Data la stagionalità, inoltre, ci si potrebbe aspettare una maggiore trasmissione potenziale nei mesi invernali. Tuttavia l’autore conclude anche che l’impatto sulla salute della futura trasmissione di SARS-CoV-2 sarà inferiore a causa dell'ampia precedente esposizione al virus, dell’adeguamento dei vaccini alle nuove varianti, dell'avvento di nuovi antivirali e della consapevolezza che i più vulnerabili possono proteggersi durante le ondate future, quando necessario, utilizzando mascherine  di alta qualità e il distanziamento fisico.

Sood N et al.

Seroprevalence of Antibodies Specific to Receptor Binding Domain of SARS-CoV-2 and Vaccination Coverage Among Adults in Los Angeles County, April 2021: The LA Pandemic Surveillance Cohort Study

JAMA, https://jamanetwork.com/journals/jama/fullarticle/2788408

CONTENUTO E COMMENTO: Studio cross-sectional esplorante la sieroprevalenza di anticorpi diretti contro il receptor-binding domain (RBD) su un campione di popolazione residente a Los Angeles statisticamente rappresentativo. Sulla base di questa analisi è risultato che il 72% degli adulti residenti a LA possiedono una potenziale immunità protettiva nei confronti di SARS-CoV2, con percentuali significativamente inferiori per afroamericani e comunità economicamente deprivate.

Henry NJ et al.

Variation in excess all-cause mortality by age, sex, and province during the first wave of the COVID-19 pandemic in Italy

Scientific Reports,


CONTENUTO E COMMENTO : Primo studio applicante un nuovo modello di calcolo dell’eccesso di mortalità, aggiustata, sesso, area geografica ed età, durante i mesi della prima ondata in Italia (marzo-maggio 2020). Tale studio stima che in questo periodo di tempo sia deceduto un eccesso di 53,200 individui, a confronto delle 35,500 morti registrate come COVID-associate. Inoltre, il 97% di questi decessi ha riguardato individui con età al di sopra dei 60 anni.

De Nadai et al.

The impact of control and mitigation strategies during the second wave of coronavirus infections in Spain and Italy

Nature Scientific Reports, https://www.nature.com/articles/s41598-022-05041-0

CONTENUTO E COMMENTO : Survey sull’efficacia della strategia « Test, Trace and Isolate » in Italia e Spagna durante la seconda ondata della pandemia (giugno – dicembre 2020). Tale analisi ha rilevato diverse debolezze critiche : il 40% degli intervistati ha dovuto attendere almeno 48h per ricevere un test diagnostico, solo 29% dei contatti stretti ha riportato di essere stato contattato, e più del 45% degli intervistati ha riportato di non essere in grado di implementare l’isolamento domiciliare. Tuttavia, in Italia, nonostante queste criticità, il 20% dei contatti stretti sono stati efficacemente prevenuti.

European Centre for Disease Prevention and Control

Guidance on quarantine of close contacts to COVID-19 cases and isolation of COVID-19 cases, in the current epidemiological situation, 7 January 2022


CONTENUTO E COMMENTO: Queste sono le nuove indicazioni dell’ECDC riguardo la gestione dei contatti stretti di casi di COVID-19. Tali indicazioni tengono conto della possibile presenza di contesti con pressione sul sistema sanitario più elevata o addirittura « estrema«. In risposta a esigenze legate ad una maggiore pressione sui sistemi sanitari la quarantena per i soggetti vaccinati è stata molto ridimensionata sia in termini di durata che di misure. 

O. M. Manda S., et al.

A Spatial Analysis of COVID-19 in African Countries:Evaluating the Effects of Socio-Economic Vulnerabilitiesand Neighbouring

International Journal of Environmental Research and Public Health, file:///C:/Users/00122705/Downloads/ijerph-18-10783-v2.pdf

CONTENUTO: PIL pro capite, trasparenza del governo e proporzione della popolazione di età≥ 65 anni risulta associata a una maggiore prevalenzadi COVID-19 in Africa. Ci vengono fornite le possibili spiegazioni di questo fenomeno.

COMMENTO : Gli autori analizzano le due ondate epidemiche maggiori in Africa usando un modello di regressione logistica spaziale.La prevalenza del Covid in una regione africana era fortemente dipendente da quella dei paesi africani vicini, nonché dalla sua ricchezza economica, trasparenza e percentuale della popolazione di età pari o superiore a 65 anni.Un elevato onere COVID-19 nei paesi con una migliore trasparenza e l'aumento della ricchezza economica sono sorprendenti e controintuitivi.Gli autori ipotizzano che questa sia una riflessione sulle differenze nella capacità di test COVID-19, che è per lo più  elevata nei paesi più sviluppati, o sulla modifica dei dati da parte di governi meno trasparenti.

Nichols G.L., et al.

Coronavirus seasonality, respiratoryinfections and weather

BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/s12879-021-06785-2.pdf

CONTENUTO: Uno studio sulle somiglianze e le differenze tra influenza, altri virus respiratori e coronavirus per valutare la stagionalità e capire se anche questo fattore contribuisce alla diffusione. Anche per SARS-CoV-2 potrebbe esserci una stagionalità al pari degli altri coronavirus.

COMMENTO: Gli autori hanno esaminato la stagionalità delle infezioni respiratorie in Inghilterra e Galles e le associazioni tra paramentri meteorologici e casi stagionali da coronavirus. Utilizzando una metodologia che prevede l’uso di un data-base per la sorveglianza routinaria, trovano che le dinamiche dei coronavirus stagionali riflettono i driver immunologici, meteorologici, sociali e di movimento dei soggetti infetti. Le prove provenienti da studi su diversi tipi di coronavirus suggeriscono che la bassa temperatura e la bassa radiazione / luce solare favoriscono la sopravvivenza dei virus. Ciò implica che un aumento stagionale di SARS-CoV-2 può verificarsi nei paesi con un clima di questo tipo.

Acosta AM et al.

Racial and Ethnic Disparities in Rates of COVID-19–Associated Hospitalization, Intensive Care Unit Admission, and In-Hospital Death in the United States From March 2020 to February 2021

JAMA Netw Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2785325?resultClick=1

CONTENUTO : Importante studio cross-sectional esplorante la composizione etnico-demografica dei pazienti ricoverati in reparti di degenza ordinaria negli Stati Uniti, tra il 1° marzo 2020 e il 28 febbraio 2021. In questa casistica di 153.692 pazienti, se confrontati con individui bianchi non-ispanici, persone di origine indio-americana, nativi dell’Alaska, ispanici, afro-americani, persone di origine asiatica o delle isole del pacifico hanno presentato un rischio significativamente maggiore, aggiustato per età, di essere ricoverati in un reparto di degenza ordinaria, di essere ricoverati in terapia intensiva o di morire.

COMMENTO: Questo ampio studio, condotto fra marzo 2020 e aprile 2021 in 14 stati degli USA, consente importanti considerazioni data la elevata prevalenza di popolazioni a rischio incluse nello studio: soggetti di età >50 anni, di sesso maschile e con notevole differenziazione etnica. Raffrontati con la popolazione di etnia bianca soprattutto gli indiani d’America e i nativi dell’Alaska, seguiti dai latini e dai neri americani, presentavano più elevati tassi di ospedalizzazione, di ricovero in ICU e di mortalità. Il rischio relativo, aggiustato per sesso e per età, appare inferiore per gli asiatici e i nativi delle isole del Pacifico. Queste differenze etniche sono verosimilmente correlate a condizioni di disagio socio-economico nelle relative popolazioni.

Gianino M.M., et al.

Evaluation of the Strategies to Control COVID-19 Pandemic in Four European Countries

Front. Public Health, file:///C:/Users/a264791/AppData/Local/Temp/fpubh-09-700811.pdf

CONTENUTO E COMMENTO: Questo interessante studio valuta il nesso di causalità tra misure specifiche di controllo della diffusione di SARS-CoV-2 e casi incidenti.

Lo studio sottolinea come l'efficacia dei singoli interventi può essere influenzata dal contesto socio-economico, da atteggiamenti culturali e norme comportamentali.

In questo studio gli autori indagano sulla possibile correlazione tra casi incidenti di covid e e specifiche misure di public health strategicamente adottate.

Lo studio osservazionaleusa tredici differenti indicatori epidemiologici in 4 differenti paesi europei.

Dal modello statistico utilizzato non sembra esserci questo tipo di correlazione in molti degli indicatori e solo un lock-down strtetto e il divieto di riunione private sembra essere correlato con una diminuzione dell’incidenza.

Nielsen J, et al.

Sex-differences in COVID-19 associated excess mortality is not exceptional for the COVID-19 pandemic

Scientific reports, https://www.nature.com/articles/s41598-021-00213-w

CONTENUTO : Studio utilizzante i dati provenienti dal registro ufficiale dell’Unione Europea, relativi a 27 paesi europei, dimostrante che la mortalità per COVID-19 è significativamente aumentata per il sesso maschile.

COMMENTO: Con riferimento alla prima ondata di COVID-19 in Europa fra febbraio e maggio 2020 rispetto alla stagione pre-COVID 2016/2017 e 2018/2019, si evidenzia un eccesso di mortalità nel sesso maschile di 52.7 per 100.000 persone/anno rispetto al sesso femminile. Questo dato veromisilmente può essere riferito a una più elevata prevalenza di co-morbidità nel sesso maschile, che condiziona una maggiore severità della Malattia.

Brosseau LM et al

SARS-CoV-2 Dose, Infection, and Disease Outcomes for COVID-19 – A Review

Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab903/6397523

CONTENUTO : Review sulla relazione tra dose di SARS-CoV-2, infezione e gravità della malattia COVID-19, sia nell’uomo che sul modello animale. Sia nell’animale che nell’uomo, la gravità della malattia è correlata a fattori legati all’ospite, quali età, sesso, comorbidità, fumo e gravidanza. I dati epidemiologici suggeriscono un’associazione tra dose di virus e capacità infettante, mentre i dati sull’associazione tra dose del virus e gravità della malattia sono scarsi.

COMMENTO: Questa revisione sistematica completa e molto ben redatta riguarda un argomento che ha interessato il ruolo eventuale che ha, per condizionare trasmissione e gravità la presenza di una quantità minore o maggiore di virus.I dati al momento non sono ancora definitivi ma certamente questo rappresenta un aspetto non secondario sia sotto il profilo epidemiologico che clinico.Vengono peraltro raccomandati animali che potrebbero essere utilizzati per questo fine.

Kossi A. et al.

A model of COVID-19 pandemic evolution in African countries

Scientific African,


CONTENUTO : Analisi di dodici mesi di dati sull’epidemia di COVID-19 in paesi Africani (Camerun, Ghana, Kenya, Madagascar, Mozambico, Ruanda, Sudafrica, Togo e Zambia).

COMMENTO : Finalmente un lavoro sulla situazione Africana dell’evoluzione della pandemia da COVID-19, tenendo conto di casi attivi di mortalità e di casi di ricovero. Gli autori hanno stimato il valore di R0 stimato in <=4all’inizio della pandemia ad un anno per avere una chiara situazionne che possa determinare una strategia  vaccinale.

Deng X et al

Breakthrough Infections with Multiple Lineages of SARS-CoV-2 Variants Reveals Continued Risk of Severe Disease in Immunosuppressed Patients

Viruses, https://www.mdpi.com/1999-4915/13/9/1743/htm

CONTENUTO : Report di 14 re-infezioni da SARS-CoV-2 in individui vaccinati, con forme cliniche variabili da asintomatica a grave ed alte cariche virali (Ct medio 19.6), indipendentemente dalla gravità clinica. Gli individui immunodepressi avevano una maggiore probabilità di essere ricoverati. Questo studio evidenzia che anche pazienti asintomatici con re-infezione da SARS-CoV-2 possono raggiungere alte cariche virali e sottolinea la vulnerabilità di individui immunosoppressi all’infezione da SARS-CoV-2.

COMMENTO: Le reinfezioni causate da diverse varianti di SARS-CoV-2 che avvengono in soggetti immunodepressi, ancora una volta sottolineano l’importanza di effetuare un richiamo vaccinale in questa popolazione ed il mantenimento, in questa fase della pandemia, dei mezzi di protezione individuale per aumentare il livello di sicurezza.

Choowe Muzymba

Global Heath Reserch and Policy

Local characterization of the COVID-19 response: the case of a lockdown in Lusaka, Zambia

Global Heath Reserch and Policy , https://ghrp.biomedcentral.com/articles/10.1186/s41256-021-00220-4

CONTENUTO: L’articolo pubblicato esamina tramite interviste telefoniche ad alcuni abitanti di Lusaka, capitale dello Zambia, l’impatto del lockdown, evidenziandone aspetti positivi e negativi, in particolare nel contesto del paese africano. L’autore sottolinea l‘importanza del dialogo tra i cittadini e i governi, cercando di adattare le misure di contenimento dell’infezione al contesto specifico e locale.

COMMENTO: un lavoro importante, sebbene limitato dal numero degli intervistati. Ma serve a capire la complessità delle risposte al COVID in Africa. Anche relativamente ai lockdown, che ovviamente son stati implementati anche nei Paesi Africani, con conseguenze positive sulla circolazione del virus, ma con effetti devastanti a livello socio-economico. E’ evidente che la strada sarà di vaccinare il mondo !!!!

Keehner J. et al.

N Engl J Med.

Resurgence of SARS-CoV-2 Infection in a Highly Vaccinated  Health System Workforce

 N Engl J Med, https://www.nejm.org/doi/pdf/10.1056/NEJMc2112981?articleTools=true

CONTENUTO: Studio effettuato a San Diego (California) sul calo dell’efficacia dei vaccini anti-SARS-CoV-2. L'efficacia del vaccino ha superato il 90% da marzo a giugno, ma è scesa al 65,5% a luglio. Questo è probabilmente dovuto sia all'emergere della variante delta che alla diminuzione dell'immunità nel tempo, aggravata dal maggiore rischio di esposizione nella comunità derivante dal termine dell’obbligo di portare la mascherina da metà giugno.

COMMENTO : Un ottimo lavoro che ci da prova della durata della protezione vaccinale. Inoltre lo studio ben fatto  evidenzia come togliere la mas herina quando circola una variante contagiosa quanto la varicella è una sconsiderata azione che porta solo a danni.

Kofman A et al

Potential COVID-19 Endgame Scenarios Eradication, Elimination, Cohabitation, or Conflagration?

JAMA, July 2021 ; doi:10.1001/jama.2021.11042

COMMENTO : [W]here on the endgame spectrum individual countries end up will dépend on both the collective choices and realities of the global community and the oft-inscrutable and perhaps unpredictable dynamics of SARS-CoV-2.

Dorigatti I et al

SARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo’

Nature, July 2021 ; doi.org/10.1038/s41467-021-24622-7

COMMENTO : In February and March 2020, two mass swab testing campaigns were conducted in Vo’, Italy. In May 2020, we tested 86% of the Vo’ population with three immuno-assays detecting antibodies against the spike and nucleocapsid antigens, a neutralisation assay and Polymerase Chain Reaction (PCR). Subjects testing positive to PCR in February/March or a serological assay in May were tested again in November. Here we report on the results of the analysis of the May and November surveys. We estimate a seroprevalence of 3.5% (95% Credible Interval (CrI): 2.8–4.3%) in May. In November, 98.8% (95% Confidence Interval (CI): 93.7–100.0%) of sera which tested positive in May still reacted against at least one antigen; 18.6% (95% CI: 11.0–28.5%) showed an increase of antibody or neutralisation reactivity from May. Analysis of the serostatus of the members of 1,118 households indicates a 26.0% (95% CrI: 17.2–36.9%) Susceptible-Infectious Transmission Probability. Contact tracing had limited impact on epidemic suppression.

Chu VT et al

Household Transmission of SARS-CoV-2 from Children and Adolescents

NEJM, July 2021 ; DOI: 10.1056/NEJMc2031915

COMMENTO : Of 526 household contacts of these index patients, 377 (72%) were tested for SARS-CoV-2, and 46 (12%) of those who were tested had positive results. An additional 2 secondary cases of infection were identified according to clinical and epidemiologic criteria.4 A total of 38 of the 48 secondary cases (79%) occurred in households where the index patient had become symptomatic after returning home from camp; the median serial interval (i.e., the interval between the onset of symptoms in the index patient and the onset of symptoms in the household contacts infected by that patient) was 5.0 days (95% confidence interval [CI], 4.0 to 6.5). Transmission occurred in 35 of 194 households (18%); in these households, the secondary attack rate was 45% (95% CI, 36 to 54) (48 of 107 households). Among the household contacts who became infected and who were at least 18 years of age, 4 of 41 (10%) were hospitalized (length of hospital stay, 5 to 11 days); none of the 7 persons with a secondary case of infection who were younger than 18 years were hospitalized.

Buckee C et al

Thinking clearly about social aspects of infectious disease transmission

Nature, June 2021 ; doi.org/10.1038/s41586-021-03694-x

COMMENTO : Social and cultural forces shape almost every aspect of infectious disease transmission in human populations, as well as our ability to measure, understand, and respond to epidemics. For directly transmitted infections, pathogen transmission relies on human-to-human contact, with kinship, household, and societal structures shaping contact patterns that in turn determine epidemic dynamics. Social, economic, and cultural forces also shape patterns of exposure, health-seeking behaviour, infection outcomes, the likelihood of diagnosis and reporting of cases, and the uptake of interventions. Although these social aspects of epidemiology are hard to quantify and have limited the generalizability of modelling frameworks in a policy context, new sources of data on relevant aspects of human behaviour are increasingly available. Researchers have begun to embrace data from mobile devices and other technologies as useful proxies for behavioural drivers of disease transmission, but there is much work to be done to measure and validate these approaches, particularly for policy-making. Here we discuss how integrating local knowledge in the design of model frameworks and the interpretation of new data streams offers the possibility of policy-relevant models for public health decision-making as well as the development of robust, generalizable theories about human behaviour in relation to infectious diseases.

Woolf SH et al

Effect of the covid-19 pandemic in 2020 on life expectancy across populations in the USA and other high income countries: simulations of provisional mortality data

BMJ, June 2021; DOI: 10.1136/bmj.n1343

COMMENTO: Objective To estimate changes in life expectancy in 2010-18 and during the covid-19 pandemic in 2020 across population groups in the United States and to compare outcomes with peer nations.

Design Simulations of provisional mortality data.

Setting US and 16 other high income countries in 2010-18 and 2020, by sex, including an analysis of US outcomes by race and ethnicity.

Population Data for the US and for 16 other high income countries from the National Center for Health Statistics and the Human Mortality Database, respectively.

Main outcome measures Life expectancy at birth, and at ages 25 and 65, by sex, and, in the US only, by race and ethnicity. Analysis excluded 2019 because life table data were not available for many peer countries. Life expectancy in 2020 was estimated by simulating life tables from estimated age specific mortality rates in 2020 and allowing for 10% random error. Estimates for 2020 are reported as medians with fifth and 95th centiles.

Results Between 2010 and 2018, the gap in life expectancy between the US and the peer country average increased from 1.88 years (78.66 v 80.54 years, respectively) to 3.05 years (78.74 v 81.78 years). Between 2018 and 2020, life expectancy in the US decreased by 1.87 years (to 76.87 years), 8.5 times the average decrease in peer countries (0.22 years), widening the gap to 4.69 years. Life expectancy in the US decreased disproportionately among racial and ethnic minority groups between 2018 and 2020, declining by 3.88, 3.25, and 1.36 years in Hispanic, non-Hispanic Black, and non-Hispanic White populations, respectively. In Hispanic and non-Hispanic Black populations, reductions in life expectancy were 18 and 15 times the average in peer countries, respectively. Progress since 2010 in reducing the gap in life expectancy in the US between Black and White people was erased in 2018-20; life expectancy in Black men reached its lowest level since 1998 (67.73 years), and the longstanding Hispanic life expectancy advantage almost disappeared.

Conclusions The US had a much larger decrease in life expectancy between 2018 and 2020 than other high income nations, with pronounced losses among the Hispanic and non-Hispanic Black populations. A longstanding and widening US health disadvantage, high death rates in 2020, and continued inequitable effects on racial and ethnic minority groups are likely the products of longstanding policy choices and systemic racism.

Althoff KN et al

Antibodies to SARS-CoV-2 in All of Us Research Program Participants, January 2-March 18, 2020

CID, June 2021; DOI: 10.1093/cid/ciab519

COMMENTO : Background : With limited SARS-CoV-2 testing capacity in the US at the start of the epidemic (January – March), testing was focused on symptomatic patients with a travel history throughout February, obscuring the picture of SARS-CoV-2 seeding and community transmission. We sought to identify individuals with SARS-CoV-2 antibodies in the early weeks of the US epidemic.

Methods : All of Us study participants in all 50 US states provided blood specimens during study visits from January 2 to March 18, 2020. A participant was considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies on the Abbott Architect SARS-CoV-2 IgG ELISA and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. Sensitivity and specificity of the Abbott and EUROIMMUNE ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated with 95% confidence intervals.

Results : The estimated sensitivity of Abbott and EUROIMMUN was 100% (107/107 [96.6%, 100%]) and 90.7% (97/107 [83.5%, 95.4%]), respectively. The estimated specificity of Abbott and EUROIMMUN was 99.5% (995/1,000 [98.8%, 99.8%]) and 99.7% (997/1,000 [99.1%, 99.9%), respectively. The net sensitivity and specificity of our sequential testing algorithm was 90.7% (97/107 [83.5%, 95.4%]) and 100.0% (1,000/1,000 [99.6%, 100%]), respectively. Of the 24,079 study participants with blood specimens from January 2 to March 18, 2020, 9 were seropositive, 7 of whom were seropositive prior to the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi.

Conclusions : Our findings indicate SARS-CoV-2 infections weeks prior to the first recognized cases in 5 US states.

Food and Drug Administration

Antibody Testing Is Not Currently Recommended to Assess Immunity After COVID-19 Vaccination: FDA Safety Communication


COMMENTO : The U.S. Food and Drug Administration (FDA) is reminding the public and health care providers that results from currently authorized SARS-CoV-2 antibody tests should not be used to evaluate a person’s level of immunity or protection from COVID-19 at any time, and especially after the person received a COVID-19 vaccination.

Xin H et al

The incubation period distribution of coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis

CID, June 2021 ; DOI: 10.1093/cid/ciab501

COMMENTO : Incubation period is an important parameter to inform quarantine period and to study transmission dynamics of infectious diseases. We conducted a systematic review and meta-analysis on published estimates of the incubation period distribution of COVID-19, and showed that the pooled median of the point estimates of the mean, median and 95 th percentile for incubation period are 6.3 days (range: 1.8 to 11.9 days), 5.4 days (range: 2.0 to 17.9 days) and 13.1 days (range: 3.2 to 17.8 days) respectively. Estimates of the mean and 95 th percentile of the incubation period distribution were considerably shorter before the epidemic peak in China compared to after the peak, and variation was also noticed for different choices of methodological approach in estimation. Our findings implied that corrections may be needed before directly applying estimates of incubation period into control of or further studies on emerging infectious diseases.

Salyer SJ et al

The first and second waves of the COVID-19 pandemic in Africa: a cross-sectional study

The Lancet, April 2021; DOI: 10.1016/S0140-6736(21)00632-2

COMMENTO:  Background : Although the first wave of the COVID-19 pandemic progressed more slowly in Africa than the rest of the world, by December, 2020, the second wave appeared to be much more aggressive with many more cases. To date, the pandemic situation in all 55 African Union (AU) Member States has not been comprehensively reviewed. We aimed to evaluate reported COVID-19 epidemiology data to better understand the pandemic's progression in Africa.

Methods : We did a cross-sectional analysis between Feb 14 and Dec 31, 2020, using COVID-19 epidemiological, testing, and mitigation strategy data reported by AU Member States to assess trends and identify the response and mitigation efforts at the country, regional, and continent levels. We did descriptive analyses on the variables of interest including cumulative and weekly incidence rates, case fatality ratios (CFRs), tests per case ratios, growth rates, and public health and social measures in place.

Findings : As of Dec 31, 2020, African countries had reported 2 763 421 COVID-19 cases and 65 602 deaths, accounting for 3·4% of the 82 312 150 cases and 3·6% of the 1 798 994 deaths reported globally. Nine of the 55 countries accounted for more than 82·6% (2 283 613) of reported cases. 18 countries reported CFRs greater than the global CFR (2·2%). 17 countries reported test per case ratios less than the recommended ten to 30 tests per case ratio range. At the peak of the first wave in Africa in July, 2020, the mean daily number of new cases was 18 273. As of Dec 31, 2020, 40 (73%) countries had experienced or were experiencing their second wave of cases with the continent reporting a mean of 23 790 daily new cases for epidemiological week 53. 48 (96%) of 50 Member States had five or more stringent public health and social measures in place by April 15, 2020, but this number had decreased to 36 (72%) as of Dec 31, 2020, despite an increase in cases in the preceding month.

Interpretation : Our analysis showed that the African continent had a more severe second wave of the COVID-19 pandemic than the first, and highlights the importance of examining multiple epidemiological variables down to the regional and country levels over time. These country-specific and regional results informed the implementation of continent-wide initiatives and supported equitable distribution of supplies and technical assistance. Monitoring and analysis of these data over time are essential for continued situational awareness, especially as Member States attempt to balance controlling COVID-19 transmission with ensuring stable economies and livelihoods.

Wymant C et al

The epidemiological impact of the NHS COVID-19 App

Nature, May 2021; doi.org/10.1038/s41586-021-03606-z

COMMENTO : The COVID-19 pandemic has seen digital contact tracing emerge around the world to help prevent spread of the disease. A mobile phone app records proximity events between app users, and when a user tests positive for COVID-19, their recent contacts can be notified instantly. Theoretical evidence has supported this new public health intervention1–6, but its epidemiological impact has remained uncertain7. Here we investigated the impact of the NHS COVID-19 app for England and Wales, from its launch on 24 September 2020 through to the end of December 2020. It was used regularly by approximately 16.5 million users (28% of the total population), and sent approximately 1.7 million exposure notifications: 4.4 per index case consenting to contact tracing. Weestimatedthat the fraction of app-notifiedindividualssubsequentlyshowingsymptoms and testing positive (the secondaryattack rate, SAR) was 6.0%, comparable to the SAR for manuallytraced close contacts. Weestimated the number of cases averted by the app usingtwocomplementaryapproaches. Modellingbased on the notifications and SAR gave 284,000 (108,000-450,000), and statisticalcomparison of matchedneighbouring local authorities gave 594,000 (317,000-914,000). Roughly one case wasaverted for each case consenting to notification of their contacts. Weestimatedthat for every percentage point increase in app users, the number of cases can bereduced by 0.8% (modelling) or 2.3% (statisticalanalysis). Thesefindingsprovideevidence for continueddevelopment and deployment of such apps in populations that are awaiting full protection from vaccines.

Vivier E et al

Specific exposure of ICU staff to SARS-CoV-2 seropositivity: a wide seroprevalence study in a French city-center hospital

Annals of Intensive Care, May 2021; doi.org/10.1186/s13613-021-00868-8

COMMENTO: BACKGROUND: Most hospital organizations have had to face the burden of managing the ongoing COVID-19 outbreak. One of the challenges in overcoming the influx of COVID-19 patients is controlling patient-to-staff transmission. Measuring the specific extent of ICU caregiver exposure to the virus and identifying the associated risk factors are, therefore, critical issues. We prospectively studied SARS-CoV-2 seroprevalence in the staff of a hospital in Lyon, France, several weeks after a first epidemic wave. Risk factors for the presence of SARS-CoV-2 antibodies were identified using a questionnaire survey. RESULTS: The overall seroprevalence was 9% (87/971 subjects). Greater exposure was associated with higher seroprevalence, with a rate of 3.2% [95% CI 1.1-5.2%] among non-healthcare staff, 11.3% [8.9-13.7%] among all healthcare staff, and 16.3% [12.3-20.2%] among healthcare staff in COVID-19 units. The seroprevalence was dramatically lower (3.7% [1.0-6.7%]) in the COVID-19 ICU. Risk factors for seropositivity were contact with a COVID-19-confirmed household (odds ratio (OR), 3.7 [1.8-7.4]), working in a COVID-19 unit (OR, 3.5 [2.2-5.7], and contact with a confirmed COVID-19 coworker (OR, 1.9 [1.2-3.1]). Conversely, working in the COVID-19-ICU was negatively associated with seropositivity (OR, 0.33 [0.15-0.73]). CONCLUSIONS: In this hospital, SARS-CoV-2 seroprevalence was higher among staff than in the general population. Seropositivity rates were particularly high for staff in contact with COVID-19 patients, especiallythose in the emergency department and in the COVID-19 unit, but were much lower in ICU staff.

Hamilton WL et al

Applying prospective genomic surveillance to support investigation of hospital-onset COVID-19

The Lancet, May 2021; doi.org/10.1016/S1473-3099(21)00251-6

COMMENTO : Here, we provide an update on our previous Article,which described the use of rapid SARS-CoV-2 genome sequencing to investigate hospital-acquired infections (HAIs) at Cambridge University Hospitals NHS Foundation Trust (CUH), Cambridge, UK. CUH experienced a substantial second wave of COVID-19 (figure). Between Nov 2, 2020, and Feb 7, 2021, 162 (14%) of 1178 patients with COVID-19 at CUH had a suspected or definite HAI (as previously defined), and 465 infected health-care workers (HCWs) were identified via the staff screening programme. Nanopore sequencing was attempted for 513 (44%) of 1178 patients, prioritising those with hospital-onset infections, and 324 (70%) of 465 HCWs; 252 (21%) of 1178 patients and 317 (68%) of 465 HCWs had SARS-CoV-2 genomes available after quality control filtering (as previously described). Patient coveragewaslowerthan in ourpreviousstudy and for HCWs, reflecting different diagnostic testing methods and limitations on sequencing capacity. The frequency of the B.1.1.7 PANGO-lineage increasedfrom 8% (nine of 109) in November, 2020, to 83% (257 of 311) in January, 2021.

Lee LYW et al

SARS-CoV-2 infectivity by viral load, S gene variants and demographic factors and the utility of lateral flow devices to prevent transmission

CID, April 2021; doi.org/10.1101/2021.03.31.21254687

COMMENTO : Background : How SARS-CoV-2 infectivity varies with viral load is incompletely understood. Whether rapid point-of-care antigenlateral flow devices (LFDs) detect most potential transmission sources despite imperfect clinical sensitivity is unknown.

Methods : We combined SARS-CoV-2 testing and contact tracing data from England between 01-September-2020 and 28-February-2021. We used multivariable logistic regression to investigate relationships between PCR-confirmed infection in contacts of community-diagnosed cases and index case viral load, S gene target failure (proxy for B.1.1.7 infection), demographics, SARS-CoV-2 incidence, social deprivation, and contact event type. Weused LFD performance to simulate the proportion of cases with a PCR-positive contact expected to bedetectedusing one of four LFDs.

Results : 231,498/2,474,066(9%) contacts of 1,064,004 index cases tested PCR-positive. PCR-positive results in contacts independently increased with higher case viral loads (lower Ct values) e.g., 11.7%(95%CI 11.5-12.0%) at Ct=15 and 4.5%(4.4-4.6%) at Ct=30. B.1.1.7 infection increased PCR-positive results by ~50%, (e.g. 1.55-fold, 95%CI 1.49-1.61, at Ct=20). PCR-positive results were most common in household contacts (at Ct=20.1, 8.7%[95%CI 8.6-8.9%]), followed by household visitors (7.1%[6.8-7.3%]), contacts at events/activities (5.2%[4.9-5.4%]), work/education (4.6%[4.4-4.8%]), and least common after outdoor contact (2.9%[2.3-3.8%]). Contacts of children were the least likely to test positive, particularly following contact outdoors or at work/education. The most and least sensitive LFDs would detect 89.5%(89.4-89.6%) and 83.0%(82.8-83.1%) of cases with PCR-positive contacts respectively.

Conclusions : SARS-CoV-2 infectivity varies by case viral load, contact event type, and age. Thosewith high viral loads are the mostinfectious. B.1.1.7 increased transmission by ~50%. The best performing LFDs detect most infectious cases.

Paul Sax

Some Colleges Require COVID-19 Vaccination — Why Don’t They All?

HIV and ID Observations – NEJM, https://blogs.jwatch.org/hiv-id-observations/index.php/some-colleges-require-covid-19-vaccination-why-dont-they-all/2021/05/03/

COMMENTO : Ever since the pandemic started, carefully done epidemiologic studies consistently show tha tolder teens and young adults have the highest incidence of infection. This factmight be counter intuitive, sinceolder people bear the disproportionate share of severe disease. As a result, the media quite regularly gets it wrong, by reporting each time when cases surgeane wthat “this time it’s different — it’s young adults.”

Babak D et al

Should masks be worn outdoors?

BMJ, April 2021 ; doi.org/10.1136/bmj.n1036

COMMENTO : Wearing face coverings outside should be normalised because it may reduce transmission of SARS-CoV-2 in some situations—and may encourage mask wearing indoors, where risks are greater—say Babak Javid, Dirk Bassler, and Manuel B Bryant. But Muge Cevik, Zeynep Tufekci, and Stefan Baral argue that outdoor transmission contributes very little to overall infection rates and that efforts should focus on reducing indoor transmission.

Barsky BA et al

Vaccination plus Decarceration — Stopping Covid-19 in Jails and Prisons

NEJM,  March 2021 ;  DOI: 10.1056/NEJMp2100609

COMMENTO: To protect the safety of incarcerated people, guards, and the general public, health experts have long called for large-scale decarceration. Decarceration measures that were used relatively early in the pandemic, though implemented in far too few jurisdictions to maximize public health benefit, have been shown to be safe — it is mass incarceration itself that threatens public safety — and have not been associated with increases in rearrest rates. Now, with the rollout of vaccines, public debate has increasingly shifted toward vaccination of incarcerated people. But several factors suggest that vaccination alone will not be enough to stop carceral outbreaks.

Bhuyan A et al

Experts criticise India's complacency over COVID-19

The Lancet, May 2021; doi.org/10.1016/S0140-6736(21)00993-4

COMMENTO: Mass gatherings have been permitted as cases soar and patients die, while experts criticise a lack of planning and flexibility in the COVID-19 response. Anoo Bhuyan reports from New Delhi.

India is battling a second wave of COVID-19, which has rapidly surpassed its first wave in 2020 in terms of the number of new cases and deaths per day. Currently, India has the second highest number of COVID-19 cases in the world after the USA. “The country is working day and night for hospitals, ventilators, and medicines”, said India's Prime Minister in his monthly national broadcast on April 25, 2021.

Taylor L

‘We are being ignored’: Brazil’s researchers blame anti-science government for devastating COVID surge

Nature, April 2021; doi.org/10.1038/d41586-021-01031-w

COMMENTO : More than a year after Brazil detected its first case of COVID-19, the country is facing its darkest phase of the pandemicyet. Researchers are devastated by the recentsurge in cases and saythat the government’sfailure to follow science-based guidance in responding to the pandemic has made the crisis much worse.

They add that President Jair Bolsonaro’s administration has publicly undermined science while refusing to implement protective national lockdowns and spreading misinformation.

Domingo P et a

Not all COVID-19 pandemic waves are alike

Clinical Microbiology and Infection, April 2021; doi.org/10.1016/j.cmi.2021.04.005

COMMENTO : Objective : Weaimed to assessdifferences in patients’ profiles in the first twosurges of the SARS-CoV-2 pandemic in Barcelona, Spain.

Methods : We prospectively collected data from all adult patients with SARS-CoV-2 infection diagnosed at the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. All the patients were diagnosed through nasopharyngealswab PCR. The first surges panned from March 1 to August 13, 2020, while surget woen compasses August 14 to December 8, 2020.

Results : There were 2479 and 852 patients with microbiologically proved SARS-CoV-2 infection in surge one and two, respectively. Patients from surge two were significantly younger (median age: 52 [IQR: 35] vs. 59 [40] years, respectively, P < 0.001), had fewer comorbidities (379/852, 44.5% vs. 1237/2479, 49.9%, P = 0.007), and a shorter interval between onset of symptoms-diagnosis (median: 3 [5] vs. 4 [5] days, P < 0.001). All-cause in-hospital mortality significantly decreased both for the whole population (24/852, 2.8% vs. 218/2479, 8.8%, P < 0.001) and hospitalized patients (20/302, 6.6% vs. 206/1570, 13.1%, P = 0.012). At adjusted logistic regression analysis, predictors of in-hospital mortality were older age (per year, adjusted odds ratio [aOR] 1.079, 95% CI: 1.063-1.094), male sex (aOR 1.476, 95% CI: 1.079-2.018), having comorbidities (aOR 1.414, 95% CI: 0.934-2.141), ICU admission (aOR 3.812, 95% CI: 1.875-7.751), mechanical ventilation (aOR 2.076, 95% CI: 0.968-4.454), and COVID-19 during surge one (with respect to surge two) (aOR 2.176, CI: 95% 1.286-3.680).

Conclusions : First wave SARS-CoV-2-infected patients had a more than two-foldhigher in-hospital mortality than second-wave patients. The causes are likely multifactorial.

Baumann M et al

A proactive approach to fight SARS-CoV-2 in Germany and Europe

Preprint – not peer reviewed, January 2021;


COMMENTO : This paper develops a sustainable way to deal with the Covid-19 pandemic. The strategy presented here aims to avoid new infections, deaths and more nationwide lockdowns. It consists of three core elements: First, a rapid reduction in the number of infections to zero. Second, the avoidance of transmissions/reintroduction of the virus into virus-free green zones through local travel restrictions, tests and quarantines. Third, rigorous outbreak management if new cases occur sporadically. In June/July of last year, Germany and many other European countries reached a situation of low incidence after a major struggle but failed to maintain it in the long run. In order to succeed this time, our countries need a concrete and uniform overall goal as well as a consistent strategy for reopening and the time thereafter. The NO-COVID target and the Green Zone strategy, for which we advocate, have already been applied successfully in several countries, thereby enabling their populations to return to a nearly normal life situation. For the Federal Republic of Germany and other European countries this path is both possible and optimal.

Chan VW et al

Transmission of Severe Acute Respiratory Syndrome Coronavirus 1 and Severe Acute Respiratory Syndrome Coronavirus 2 During Aerosol-Generating Procedures in Critical Care A Systematic Review and Meta-Analysis of Observational Studies

Critical Care Medicine, March 2021; doi: 10.1097/CCM.0000000000004965

COMMENTO: Objectives: To assess the risk of coronavirus transmission to healthcare workers performing aerosol-generating procedures and the potential benefits of personal protective equipment during these procedures.

Data Sources: MEDLINE, EMBASE, and Cochrane CENTRAL were searched using a combination of related MeSH terms and keywords.

Study Selection: Cohort studies and case controls investigating common anesthetic and critical care aerosol-generating procedures and transmission of severe acute respiratory syndrome coronavirus 1, Middle East respiratory syndrome coronavirus, and severe acute respiratory syndrome coronavirus 2 to healthcare workers were included for quantitative analysis.

Data Extraction: Qualitative and quantitative data on the transmission of severe acute respiratory syndrome coronavirus 1, severe acute respiratory syndrome coronavirus 2, and Middle East respiratory syndrome coronavirus to healthcare workers via aerosol-generating procedures in anesthesia and critical care were collected independently. The Risk Of Bias In Non-randomized Studies - of Interventions tool was used to assess the risk of bias of included studies.

Data Synthesis: Seventeen studies out of 2,676 yielded records were included for meta-analyses. Endotracheal intubation (odds ratio, 6.69, 95% CI, 3.81–11.72; p < 0.001), noninvasive ventilation (odds ratio, 3.65; 95% CI, 1.86–7.19; p < 0.001), and administration of nebulized medications (odds ratio, 10.03; 95% CI, 1.98–50.69; p = 0.005) were found to increase the odds of healthcare workers contracting severe acute respiratory syndrome coronavirus 1 or severe acute respiratory syndrome coronavirus 2. The use of N95 masks (odds ratio, 0.11; 95% CI, 0.03–0.39; p < 0.001), gowns (odds ratio, 0.59; 95% CI, 0.48–0.73; p < 0.001), and gloves (odds ratio, 0.39; 95% CI, 0.29–0.53; p < 0.001) were found to be significantly protective of healthcare workers from contracting severe acute respiratory syndrome coronavirus 1 or severe acute respiratory syndrome coronavirus 2.

Conclusions: Specific aerosol-generating procedures are high risk for the transmission of severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2 from patients to healthcare workers. Personal protective equipment reduce the odds of contracting severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2.

Cassone A et al

Can reasoned mass testing impact covid-19 outcomes in wide community contexts? An evidence-based opinion

Pathogens and Global Health, July 2020; DOI: 10.21203/rs.3.rs-39944/v1

COMMENTO: We describe the early phases of a COVID-19 epidemic in two contiguous Italian regions, Lombardy and Veneto, which were heavily and simultaneously hit by SARS-CoV-2 in Italy but showed markedly different disease outcome in terms of case fatality rate, SARS-CoV-2-attributable mortality and hospitalization. We discuss data limitations together with similarities and differences of the regional context possibly affecting COVID-19 control in the two regions. We conclude that the better COVID-19 outcome in Veneto was due, at least in part, to the adoption of a strategy of active search of asymptomatic SARS-CoV-2 infections (Reasoned Mass Testing), instead of a strategy strictly based on the detection of symptomatic cases.

Van der Hurk K et al

Low awareness of past SARS-CoV-2 infection in healthy plasma donors

Cell Reports Medicine, March 2021; doi: 10.1016/j.xcrm.2021.100222

COMMENTO : Awareness of infection with SARS-CoV-2 is crucial for the effectiveness of COVID-19 control measures. Here, we investigate awareness of infection and symptoms in relation to antibodies against SARS-CoV-2 in healthy plasma donors.

We ask individuals donating plasma across the Netherlands between May 11th and 18th 2020 to report COVID-19 related symptoms and we test for antibodies indicative of a past infection with SARS-CoV-2. Among 3,676 with antibody and questionnaire data 239 (6.5%) are positive for SARS-CoV-2 antibodies. Of those, 48% suspect no COVID-19 despite the majority reporting symptoms. 11% of seropositive individuals report no, and 27% very mild symptoms at any time during the first peak of the epidemic. Anosmia/ageusia and fever are most strongly associated with seropositivity.

Almost half of seropositive individuals do not suspect SARS-CoV-2 infection. Improved recognition of COVID-19 symptoms, in particular anosmia/ageusia and fever, is needed to reduce widespread SARS-CoV-2 transmission.

Hashan MR et al

Epidemiology and clinical features of COVID-19 outbreaks in aged care facilities: A systematic review and meta-analysis

EClinicalMedicine, March 2021; doi.org/10.1016/j.eclinm.2021.100771

COMMENTO : Background : COVID-19 outbreaks in aged care facilities (ACFs) often have devastating consequences. However, epidemiologically these outbreaks are not well defined. We aimed to define such outbreaks in ACFs by systematically reviewing literature published during the current COVID-19 pandemic.

Methods : We searched 11 bibliographic databases for literature published on COVID-19 in ACFs between December 2019 and September 2020. Original studies reporting extractable epidemiological data as part of outbreak investigations or non-outbreak surveillance of ACFs were included in this systematic review and meta-analysis. PROSPERO registration: CRD42020211424.

Findings : We identified 5,148 publications and selected 49 studies from four continents reporting data on 214,380 residents in 8,502 ACFs with 25,567 confirmed cases of COVID-19. Aged care residents form a distinct vulnerable population with single-facility attack rates of 45% [95% CI 32–58%] and case fatality rates of 23% [95% CI 18–28%]. Of the cases, 31% [95% CI 28–34%] were asymptomatic. The rate of hospitalization amongst residents was 37% [95% CI 35–39%]. Data from 21 outbreaks identified a resident as the index case in 58% of outbreaks and a staff member in 42%. Findings from the included studies were heterogeneous and of low to moderate quality in risk of bias assessment.

Interpretation : The clinical presentation of COVID-19 varies widely in ACFs residents, from asymptomatic to highly serious cases. Preventing the introduction of COVID-19 into ACFs is key, and both residents and staff are a priority group for COVID-19 vaccination. Rapid diagnosis, identification of primary and secondary cases and close contacts plus their isolation and quarantine are of paramount importance.

Wilmes P et al

SARS-CoV-2 transmission risk from asymptomatic carriers: Results from a mass screening programme in Luxembourg

The Lancet, February 2021; doi.org/10.1016/j.lanepe.2021.100056

COMMENTO: Background : To accompany the lifting of COVID-19 lockdown measures, Luxembourg implemented a mass screening (MS) programme. The first phase coincided with an early summer epidemic wave in 2020.

Methods : rRT-PCR-based screening for SARS-CoV-2 was performed by pooling of samples. The infrastructure allowed the testing of the entire resident and cross-border worker populations. The strategy relied on social connectivity within different activity sectors. Invitation frequencies were tactically increased in sectors and regions with higher prevalence. The results were analysed alongside contact tracing data.

Findings : The voluntary programme covered 49% of the resident and 22% of the cross-border worker populations. It identified 850 index cases with an additional 249 cases from contact tracing. Over-representation was observed in the services, hospitality and construction sectors alongside regional differences. Asymptomatic cases had a significant but lower secondary attack rate when compared to symptomatic individuals. Based on simulations using an agent-based SEIR model, the total number of expected cases would have been 42·9% (90% CI [-0·3, 96·7]) higher without MS. Mandatory participation would have resulted in a further difference of 39·7% [19·6, 59·2].

Interpretation : Strategic and tactical MS allows the suppression of epidemic dynamics. Asymptomatic carriers represent a significant risk for transmission. Containment of future outbreaks will depend on early testing in sectors and regions. Higher participation rates must be assured through targeted incentivisation and recurrent invitation.

Murray CJL et al

The Potential Future of the COVID-19 Pandemic Will SARS-CoV-2 Become a Recurrent Seasonal Infection?

JAMA, March 2021 ; doi:10.1001/jama.2021.2828

COMMENTO: There is growing optimism and hope that by virtue of ongoing immunization efforts, seasonality (declining infections through August), and naturally acquired immunity, by spring and early summer 2021 in the US there will be a substantial decline in the number of deaths and hospitalizations related to COVID-19. However, this optimism must be tempered by several important factors. The likelihood of achieving herd immunity against SARS-CoV-2 is low simply because not all individuals in the US are eligible to be vaccinated and a quarter of eligible individuals will likely decline to be immunized. Moreover, the vaccines do not provide full immunity against infection, and the currently available vaccines are less effective against variant B.1.351, and possibly other variants. Accordingly, the public and health systems need to plan for the possibility that COVID-19 will persist and become a recurrent seasonal disease.

Klein H et al

Onset, duration and unresolved symptoms, including smell and taste changes, in mild COVID-19 infections. A cohort study in Israeli patients

COMMENTO: Objectives : This studyaims to characterize longitudinal symptoms of mild COVID-19 patients for a period of six months, and potentiallyaid in disease management.

Methods : Phone interviews wereconductedwith 103 mild COVID-19 patients in Israel, over a six-month period (April 2020 to October 2020). Patients were recruited via social media and word to mouth and were interviewed up to 4 times, depending on their unresolved symptoms reports. Inclusion criteria required participants to beIsraeliresidentsaged ≥18 years, with positive COVID-19 RT-PCR results and non-severesymptoms. Symptoms' onset, duration, severity, and resolution were analyzed.

Results : 44% (45/103), 41% (42/103), 39% (40/103) or 38% (39/103) of the patients experiencedheadache, fever, muscle ache, or dry cough as the first symptom respectively. Smell and taste changes wereexperienced 3.9 ± 5.4 and 4.6 ± 5.7 days (mean ± SD) after disease onset, respectively. Among prevalent symptoms, feverhad the shortest duration (5.8 ± 8.6 days), and taste and smell changes were the longest-lasting symptoms (17.2 ± 17.6 and 18.9 ± 19.7 days, durations censored at 60 days). Longer recovery of the sense of smellcorrelatedwith the extent of smell change. At the six-month follow-up, 46% (47/103) of the patients had at least one unresolved symptom, most commonly fatigue (22%, 23/103), smelland taste changes (15%, 15/103 and 8%, 8/103 respectively), and breathingdifficulties (8%, 8/103).

Conclusions : Long-lasting effects of mild COVID-19 manifested in almost half of the participants reporting at least one unresolved symptomafter six months.

Tan BI et al

Prevalence and Outcomes of SARS-CoV-2 Infection Among Migrant Workers in Singapore

JAMA, February 2021 ;  doi:10.1001/jama.2020.24071

COMMENTO: High-density communal residences are at elevated risk of large outbreaks of respiratory disease.After an initial nationwide outbreak of 231 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Singapore, which was contained as of March 24, 2020, a surge of 244 cases among migrant workers residing in dormitories, largely from Bangladesh and India, occurred from March 25 to April 7. A national task force was formed to coordinate Singapore’s outbreak response. A national lockdown from April 7 to June 1 enforced movement restriction and confined workers to their dormitories. Medical posts were deployed on-site in all dormitories, and testing capacity for testing and screening residents increased. All workers with a positive polymerase chain reaction (PCR) test result were admitted to health care facilities for isolation and treatment. We examined the prevalence and outcomes of SARS-CoV-2 infection among migrant workers in Singapore.

Steel K et al

Coronavirus (COVID-19) Infection Survey: characteristics of people testing positive for COVID-19 in England, 27 January 2021

Office for National Statistics.


COMMENTO : In recent weeks, there is evidence that the percentage testing positive for the coronavirus (COVID-19) has decreased in non-patient facing job roles but increased amongst those in patient-facing roles in England.

The largest differences in reported symptoms between the new variant compatible positives and those not compatible with the new UK variant were found in cough, sore throat, fatigue and myalgia.

The number of socially distanced and physical contacts that adults and school age children had with people outside their household decreased in January 2021.

Of those in school Year 12 to 24 years old, the highest percentage testing positive was among those who are employed.

Ren R et al

Asymptomatic SARS-CoV-2 Infections Among Persons Entering China From April 16 to October 12, 2020

JAMA, Febrary 2021 ; doi:10.1001/jama.2020.23942

COMMENTO: The magnitude of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a question of global concern. Individuals who test positive for SARS-CoV-2 infection via a polymerase chain reaction (PCR) test but lack coronavirus disease 2019 (COVID-19)–like symptoms must be followed up through the incubation period to distinguish individuals with asymptomatic infection from those with presymptomatic infection.

China successfully controlled its initial COVID-19 epidemic in March 20202 and has since focused on preventing importation of SARS-CoV-2 infection. Beginning April 1, 2020, persons entering China via air, sea, or land have been mandatorily tested for SARS-CoV-2 infection by PCR test at border checkpoints. Individuals who have tested positive have been hospitalized in isolation and those who have tested negative have been quarantined for 14 days at centralized facilities and then retested on day 13. We assessed the proportion of international entrants to China with asymptomatic SARS-CoV-2 infection.

Crane MA et al

Change in Reported Adherence to Nonpharmaceutical Interventions During the COVID-19 Pandemic, April-November 2020

JAMA, January 2021; doi:10.1001/jama.2021.0286

COMMENTO : Nonpharmaceutical interventions (NPIs) have been used to mitigate the effects of the coronavirus disease 2019 (COVID-19) pandemic. Reports describe an increasing attitude of apathy or resistancetowardadherence to NPIs, termedpandemic fatigue. To betterdescribethisphenomenon in the US, weused national surveillance data to analyzereporting of adherence to protective behaviorsidentified as NPIs.

Oran DP et al

The Proportion of SARS-CoV-2 Infections That Are Asymptomatic: A Systematic Review

Annals of Internal Medicine, January 2021; DOI: 10.7326/M20-6976

COMMENTO : Background:Asymptomatic infection seems to be a notable feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), but the prevalence is uncertain.

Purpose:To estimate the proportion of persons infected with SARS-CoV-2 who never develop symptoms.

Data Sources:

Searches of Google News, Google Scholar, medRxiv, and PubMed using the keywords antibodies, asymptomatic, coronavirus, COVID-19, PCR, seroprevalence, and SARS-CoV-2.

Study Selection:Observational, descriptive studies and reports of mass screening for SARS-CoV-2 that were either cross-sectional or longitudinal in design; were published through 17 November 2020; and involved SARS-CoV-2 nucleic acid or antibody testing of a target population, regardless of current symptomatic status, over a defined period.

Data Extraction:The authors collaboratively extracted data on the study design, type of testing performed, number of participants, criteria for determining symptomatic status, testing results, and setting.

Data Synthesis:Sixty-one eligible studies and reports were identified, of which 43 used polymerase chain reaction (PCR) testing of nasopharyngeal swabs to detect current SARS-CoV-2 infection and 18 used antibody testing to detect current or prior infection. In the 14 studieswith longitudinal data thatreported information on the evolution of symptomaticstatus, nearlythreequarters of personswhotested positive but had no symptoms at the time of testingremainedasymptomatic. The highest-qualityevidencecomesfromnationwide, representativeserosurveys of England (n = 365 104) and Spain (n = 61 075), whichsuggestthat at least one third of SARS-CoV-2 infections are asymptomatic.

Limitation:For PCR-based studies, data are limited to distinguish presymptomatic from asymptomatic infection. Heterogeneityprecludedformal quantitative syntheses.

Conclusion:Available data suggest that at least one third of SARS-CoV-2 infections are asymptomatic. Longitudinal studiessuggestthatnearlythreequarters of personswhoreceive a positive PCR test result but have no symptoms at the time of testingwillremainasymptomatic. Control strategies for COVID-19 shouldbealtered, takingintoaccount the prevalence and transmission risk of asymptomatic SARS-CoV-2 infection.

European Centers for Disease Prevention and Control

Updated rapid risk assessment from ECDC on the risk related to the spread of new SARS-CoV-2 variants of concern in the EU/EEA – first update

Eurosurveillance, January 2021; https://www.ecdc.europa.eu/en/publications-data/covid-19-risk-assessment-spread-new-variants-concern-eueea-first-update

COMMENTO : Virusesconstantly change through mutation and variations in the SARS-CoV-2 virus, due to evolution and adaptation processes, have been observedworldwide. Whilemostemerging mutations will not have a significant impact on the spread of the virus, some mutations or combinations of mutations mayprovide the virus with a selectiveadvantage, such as increasedtransmissibility or the ability to evade the host immune response. In this update we report new information on the spread of three virus variants (VOC 202012/01, 501Y.V2 and variant P.1). These variants are considered to be of concernbecause of mutations which have led to increasedtransmissibility and deterioratingepidemiological situations in the areas wherethey have recentlybecomeestablished.

Based on the new information, the riskassociatedwith the introduction and community spread of variants of concern has been increased to high/very high and the options for response have been adjusted to the current situation.

Kim MC et al

Duration of Culturable SARS-CoV-2 in Hospitalized Patients with Covid-19

NEJM, January 2021; DOI: 10.1056/NEJMc2027040

COMMENTO : SARS-CoV-2 wasculturedin 29 of the 89 samples (33%) (Figure 1). The median time fromsymptomonset to viral clearance in culture was 7 days (95% confidence interval [CI], 5 to 10), and the median time fromsymptomonset to viral clearance on real-time RT-PCR was 34 days (lowerboundary of the 95% CI, 24 days) (Fig. S1 and Table S4). The latest positive viral culture was 12 daysaftersymptomonset (in Patient 6). Viable virus wasidentifieduntil 3 daysafter the resolution in fever (in Patient 14). Viral culture was positive only in sampleswith a cycle-threshold value of 28.4 or less. The incidence of culture positivitydecreasedwith an increasing time fromsymptomonset and with an increasing cycle-threshold value.

Wang H et al

Performance of Nucleic Acid Amplification Tests for Detection of Severe Acute Respiratory Syndrome Coronavirus 2 in Prospectively Pooled Specimens

Emerging Infectious Diseases, Volume 27, Number 1—January 2021; DOI: 10.3201/eid2701.203379

COMMENTO: Pooled nucleic acid amplification tests for severe acute respiratory syndrome coronavirus 2 could increase availability of testing at decreased cost. However, the effect of dilution on analytical sensitivity through sample pooling has not been well characterized. We tested 1,648 prospectively pooled specimens by using 3 nucleic acid amplification tests for severe acute respiratory syndrome coronavirus 2: a laboratory-developed real-time reverse transcription PCR targeting the envelope gene, and 2 commercially available Panther System assays targeting open reading frame 1ab. Positive percent agreement (PPA) of pooled versus individualtestingrangedfrom 71.7% to 82.6% for pools of 8 and from 82.9% to 100.0% for pools of 4. We developed and validated an independent stochastic simulation model to estimate effects of dilution on PPA and efficiency of a 2-stage pooled real-time reverse transcription PCR testing algorithm. PPA was dependent on the proportion of tests with positive results, cycle threshold distribution, and assay limit of detection.

Li F et al

Household transmission of SARS-CoV-2 and risk factors for susceptibility and infectivity in Wuhan: a retrospective observational study

The Lancet, 18 January 2021; doi.org/10.1016/S1473-3099(20)30981-6

COMMENTO: Background : Wuhan was the first epicentre of COVID-19 in the world, accounting for 80% of cases in China during the first wave. We aimed to assess household transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and risk factors associated with infectivity and susceptibility to infection in Wuhan.

Methods : This retrospective cohort study included the households of all laboratory-confirmed or clinically confirmed COVID-19 cases and laboratory-confirmed asymptomatic SARS-CoV-2 infections identified by the Wuhan Center for Disease Control and Prevention between Dec 2, 2019, and April 18, 2020. We defined households as groups of family members and close relatives who did not necessarily live at the same address and considered households that shared common contacts as epidemiologically linked. We used a statistical transmission model to estimate household secondary attack rates and to quantify risk factors associated with infectivity and susceptibility to infection, accounting for individual-level exposure history. We assessed how intervention policies affected the household reproductive number, defined as the mean number of household contacts a case can infect.

Findings : 27 101 households with 29 578 primary cases and 57 581 household contacts were identified. The secondary attack rate estimated with the transmission model was 15·6% (95% CI 15·2–16·0), assuming a mean incubation period of 5 days and a maximum infectious period of 22 days. Individuals aged 60 years or older were at a higher risk of infection with SARS-CoV-2 than all other age groups. Infants aged 0–1 years were significantly more likely to be infected than children aged 2–5 years (odds ratio [OR] 2·20, 95% CI 1·40–3·44) and children aged 6–12 years (1·53, 1·01–2·34). Given the same exposure time, children and adolescents younger than 20 years of age were more likely to infect others than were adults aged 60 years or older (1·58, 1·28–1·95). Asymptomatic individuals were much less likely to infect others than were symptomatic cases (0·21, 0·14–0·31). Symptomatic cases were more likely to infect others before symptom onset than after (1·42, 1·30–1·55). After mass isolation of cases, quarantine of household contacts, and restriction of movement policies were implemented, household reproductive numbers declined by 52% among primary cases (from 0·25 [95% CI 0·24–0·26] to 0·12 [0·10–0·13]) and by 63% among secondary cases (from 0·17 [0·16–0·18] to 0·063 [0·057–0·070]).

Interpretation : Within households, children and adolescents were less susceptible to SARS-CoV-2 infection but were more infectious than older individuals. Presymptomatic cases were more infectious and individuals with asymptomatic infection less infectious than symptomatic cases. These findings have implications for devising interventions for blocking household transmission of SARS-CoV-2, such as timely vaccination of eligible children once resources become available.

Ranzani OT et al

Characterisation of the first 250 000 hospital admissions for COVID-19 in Brazil: a retrospective analysis of nationwide data

The Lancet, 15 January 2021; doi.org/10.1016/S2213-2600(20)30560-9

COMMENTO: Background : Most low-income and middle-income countries (LMICs) have little or no data integrated into a national surveillance system to identify characteristics or outcomes of COVID-19 hospital admissions and the impact of the COVID-19 pandemic on their national health systems. We aimed to analyse characteristics of patients admitted to hospital with COVID-19 in Brazil, and to examine the impact of COVID-19 on health-care resources and in-hospital mortality.

Methods : We did a retrospective analysis of all patients aged 20 years or older with quantitative RT-PCR (RT-qPCR)-confirmed COVID-19 who were admitted to hospital and registered in SIVEP-Gripe, a nationwide surveillance database in Brazil, between Feb 16 and Aug 15, 2020 (epidemiological weeks 8–33). We also examined the progression of the COVID-19 pandemic across three 4-week periods within this timeframe (epidemiological weeks 8–12, 19–22, and 27–30). The primary outcome was in-hospital mortality. We compared the regional burden of hospital admissions stratified by age, intensive care unit (ICU) admission, and respiratory support. We analysed data from the whole country and its five regions: North, Northeast, Central-West, Southeast, and South.

Findings : Between Feb 16 and Aug 15, 2020, 254 288 patients with RT-qPCR-confirmed COVID-19 were admitted to hospital and registered in SIVEP-Gripe. The mean age of patients was 60 (SD 17) years, 119 657 (47%) of 254 288 were aged younger than 60 years, 143 521 (56%) of 254 243 were male, and 14 979 (16%) of 90 829 had no comorbidities. Case numbers increased across the three 4-week periods studied: by epidemiological weeks 19–22, cases were concentrated in the North, Northeast, and Southeast; by weeks 27–30, cases had spread to the Central-West and South regions. 232 036 (91%) of 254 288 patients had a defined hospital outcome when the data were exported; in-hospital mortality was 38% (87 515 of 232 036 patients) overall, 59% (47 002 of 79 687) among patients admitted to the ICU, and 80% (36 046 of 45 205) among those who were mechanically ventilated. The overall burden of ICU admissions per ICU beds was more pronounced in the North, Southeast, and Northeast, than in the Central-West and South. In the Northeast, 1545 (16%) of 9960 patients received invasive mechanical ventilation outside the ICU compared with 431 (8%) of 5388 in the South. In-hospital mortality among patients younger than 60 years was 31% (4204 of 13 468) in the Northeast versus 15% (1694 of 11 196) in the South.

Interpretation : We observed a widespread distribution of COVID-19 across all regions in Brazil, resulting in a high overall disease burden. In-hospital mortality was high, even in patients younger than 60 years, and worsened by existing regional disparities within the health system. The COVID-19 pandemic highlights the need to improve access to high-quality care for critically ill patients admitted to hospital with COVID-19, particularly in LMICs.

Alteri C et al

Genomic epidemiology of SARS-CoV-2 reveals multiple lineages and early spread of SARS-CoV-2 infections in Lombardy, Italy

Nature, 19  January 2021; doi.org/10.1038/s41467-020-20688-x

COMMENTO: From February to April 2020, Lombardy (Italy) reported the highest numbers of SARS-CoV-2 cases worldwide. By analyzing 346 whole SARS-CoV-2 genomes, we demonstrate the presence of seven viral lineages in Lombardy, frequently sustained by local transmission chains and at least two likely to have originated in Italy. Six single nucleotide polymorphisms (five of them non-synonymous) characterized the SARS-CoV-2 sequences, none of them affecting N-glycosylation sites. The seven lineages, and the presence of local transmission clusters within three of them, revealed that sustained community transmission was underway before the first COVID-19 case had been detected in Lombardy.

Holler JG et al

First wave of COVID-19 hospital admissions in Denmark: a Nationwide population-based cohort study

BMC Infectious Diseases, 9 January 2021 ; doi: 10.1186/s12879-020-05717-w

COMMENTO : BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease coronavirus disease 2019 (COVID-19), is a worldwide emergency. Demographic, comorbidity and laboratory determinants of death and of ICU admission were explored in all Danish hospitalised patients. METHODS: National health registries were used to identify all hospitalized patients with a COVID-19 diagnosis. We obtained demographics, Charlson Comorbidity Index (CCI), and laboratory results on admission and explored prognostic factors for death using multivariate Cox proportional hazard regression and competing risk survival analysis. RESULTS: Among 2431 hospitalised patients with COVID-19 between February 27 and July 8 (median age 69 years [IQR 53-80], 54.1% males), 359 (14.8%) needed admission to an intensive care unit (ICU) and 455 (18.7%) died within 30 days of follow-up. The seven-day cumulative incidence of ICU admission was lower for females (7.9%) than for males (16.7%), (p < 0.001). Age, high CCI, elevated C-reactive protein (CRP), ferritin, D-dimer, lactate dehydrogenase (LDH), urea, creatinine, lymphopenia, neutrophilia and thrombocytopenia within +/-24-h of admission were independently associated with death within the first week in the multivariate analysis. Conditional upon surviving the first week, male sex, age, high CCI, elevated CRP, LDH, creatinine, urea and neutrophil count were independently associated with death within 30 days. Males presented with more pronounced laboratory abnormalities on admission. CONCLUSIONS: Advanced age, male sex, comorbidity, higher levels of systemic inflammation and cell-turnover were independent factors for mortality. Age was the strongest predictor for death, moderate to high level of comorbidity were associated with a nearly two-fold increase in mortality. Mortality was significantly higher in males after surviving the first week.

Gianotti R et al

COVID‐19 related dermatosis in November 2019. Could this case be Italy’s patient zero?

British Journal of Dermatology, 7 January 2021; doi.org/10.1111/bjd.19804

COMMENTO: Milan, the largest city in northern Italy, was one of the first European metropolitan areas to be affected by the COVID‐19 pandemic. We analyzed skin biopsies of patients from Milan with dermatoses and positive PCR swabs for SARS‐CoV‐2 at different stages of the infection. The results were compared to skin biopsies of 20 COVID‐19 non‐diagnosed patients with dermatoses, who were at high‐risk of COVID‐19 infection.

Harrington D et al

Confirmed Reinfection with SARS-CoV-2 Variant VOC-202012/01

Clinical Infectious Diseases, 9 January 2021; doi.org/10.1093/cid/ciab014

COMMENTO: We have detected a confirmed case of reinfection with SARS-CoV-2 with the second episode due to the ‘new variant’ VOC-202012/01 of lineage B.1.1.7. The initial infection occurred in the first wave of the pandemic in the UK and was a mild illness. 8 months later, during the second wave of the pandemic in the UK reinfection with the ‘new variant’ VOC-202012/01 was confirmed and caused a criticalillness.

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