M. Borna et al.

A correlational analysis of COVID-19 incidence and mortality and urban determinants of vitamin D status across the London boroughs

Nature Scientific Reports, July 2022; doi.org/10.1038/s41598-022-15664-y


One of the biggest challenges of the COVID-19 pandemic is the heterogeneity in disease severity exhibited amongst patients. Among multiple factors, latest studies suggest vitamin D deficiency and pre-existing health conditions to be major contributors to death from COVID-19. It is known that certain urban form attributes can impact sun exposure and vitamin D synthesis. Also, long-term exposure to air pollution can play an independent role in vitamin D deficiency. We conducted a correlational analysis of urban form and air quality in relation to the demographics and COVID-19 incidence and mortality across 32 London boroughs between March 2020 and January 2021. We found total population, number of residents of Asian ethnicity, 4-year average PM10 levels and road length to be positively correlated with COVID-19 cases and deaths. We also found percentage of households with access to total open space to be negatively correlated with COVID-19 deaths. Our findings link COVID-19 incidence and mortality across London with environmental variables linked to vitamin D status. Our study is entirely based on publicly available data and provides a reference framework for further research as more data are gathered and the syndemic dimension of COVID-19 becomes increasingly relevant in connection to health inequalities within large urban areas.

G.A. Herman et al.

Efficacy and safety of a single dose of casirivimab and imdevimab for the prevention of COVID-19 over an 8-month period: a randomised, double-blind, placebo-controlled trial

eco, controllato con placebo

The Lancet Infectious Diseases, July 2022; doi.org/10.1016/S1473-3099(22)00416-9



There is an unmet need for COVID-19 prevention in patient populations who have not mounted or are not expected to mount an adequate immune response to complete COVID-19 vaccination. We previously reported that a single subcutaneous 1200 mg dose of the monoclonal antibody combination casirivimab and imdevimab (CAS + IMD) prevented symptomatic SARS-CoV-2 infections by 81·4% in generally healthy household contacts of SARS-CoV-2-infected individuals over a 1-month efficacy assessment period. Here we present additional results, including the 7-month follow-up period (months 2–8), providing additional insights about the potential for efficacy in pre-exposure prophylaxis settings.


This was a randomised, double-blind, placebo-controlled trial done in the USA, Romania, and Moldova in 2020–2021, before the emergence of omicron (B.1.1.529) and omicron-lineage variants. Uninfected and unvaccinated household contacts of infected individuals, judged by the investigator to be in good health, were randomly assigned (1:1) to receive 1200 mg CAS + IMD or placebo by subcutaneous injection according to a central randomisation scheme provided by an interactive web response system; randomisation was stratified per site by the test results of a local diagnostic assay for SARS-CoV-2 and age group at baseline. COVID-19 vaccines were prohibited before randomisation, but participants were allowed to receive COVID-19 vaccination during the follow-up period. Participants who developed COVID-19 symptoms during the follow-up period underwent RT-PCR testing. Prespecified endpoints included the proportion of previously uninfected and baseline-seronegative participants (seronegative-modified full analysis set) who had RT-PCR-confirmed COVID-19 in the follow-up period (post-hoc for the timepoints of months 2–5 and 6–8 only) and underwent seroconversion (ie, became seropositive, considered a proxy for any SARS-CoV-2 infections [symptomatic and asymptomatic]; prespecified up to day 57, post-hoc for all timepoints thereafter). We also assessed the incidence of treatment-emergent adverse events.


From July 13, 2020, to Oct 4, 2021, 2317 participants who were RT-PCR-negative for SARS-CoV-2 were randomly assigned, of whom 1683 (841 assigned to CAS + IMD and 842 assigned to placebo) were seronegative at baseline. During the entirety of the 8-month study, CAS + IMD reduced the risk of COVID-19 by 81·2% (nominal p<0·0001) versus placebo (prespecified analysis). During the 7-month follow-up period, protection was greatest during months 2–5, with a 100% relative risk reduction in COVID-19 (nominal p<0·0001; post-hoc analysis). Efficacy waned during months 6–8 (post-hoc analysis). Seroconversion occurred in 38 (4·5%) of 841 participants in the CAS + IMD group and in 181 (21·5%) of 842 in the placebo group during the 8-month study (79·0% relative risk reduction vs placebo; nominal p<0·0001). Six participants in the placebo group were hospitalised due to COVID-19 versus none who received CAS + IMD. Serious treatment-emergent adverse events (including COVID-19) were reported in 24 (1·7%) of 1439 participants receiving CAS + IMD and in 23 (1·6%) of 1428 receiving placebo. Five deaths were reported, none of which were due to COVID-19 or related to the study drugs.


CAS + IMD is not authorised in any US region as of Jan 24, 2022, because data show that CAS + IMD is not active against omicron-lineage variants. In this study, done before the emergence of omicron-lineage variants, a single subcutaneous 1200 mg dose of CAS + IMD protected against COVID-19 for up to 5 months of community exposure to susceptible strains of SARS-CoV-2 in the pre-exposure prophylaxis setting, in addition to the post-exposure prophylaxis setting that was previously shown.

T.D. Ngo

Bad COVID Public Health Messaging Is Blocking Our Path to a ‘New Normal’

Scientific American, June 2022: https://www.scientificamerican.com/article/bad-covid-public-healthmessaging-is-blocking-our-path-to-a-new-normal/


The U.S. has no clear vision of how to reach a postpandemic world. Over the past two years, we have developed extraordinary scientific tools for the mitigation, treatment and prevention of COVID. But we’ve stumbled badly in implementing them. Many of these failures happened because our public health messages were not clear about how to use those tools, which include vaccines, masks, tests, antiviral drugs and temporary activity restrictions. The result is confusion among the public that has left us vulnerable to the disease and unable to respond to new and more transmissible variants such as BA.2 and its sublineages, which are infecting a rising number of people across the nation.

E. Arcà et al.

Death by austerity? The impact of cost containment on avoidable mortality in Italy

Health Economics, August 202; doi.org/10.1002/hec.4147


Does austerity in health care affect health and healthcare outcomes? We examine the intended and unintended effects of the Italian austerity policy Piano di Rientro aimed at containing the cost of the healthcare sector. Using an instrumental variable strategy that exploits the temporal and geographical variation induced by the policy rollout, we find that the policy was successful in alleviating deficits by reducing expenditure, mainly in the southern regions, but also resulted in a 3% rise in avoidable deaths among both men and women, a reduction in hospital capacity and a rise in south-to-north patient migration. These findings suggest that—even in a high-income country with relatively low avoidable mortality like Italy—spending cuts can hurt survival.

R. Hamad et al.

The role of health care systems in bolstering the social safety net to address health inequities in the wake of the covid-19 pandemic

JAMA, June 2022; doi:10.1001/jama.2022.10160


For  hundreds of years, US health has been characterized by vast inequities in health achievement across groups. For example, at least since the 1800s, disparities in tuberculosis were known to be associated with overcrowded housing, poor ventilation, and malnutrition. The earliest evaluations of the Framingham Heart Study documented disparities in cardiovascular disease by educational attainment. Today, advantaged groups in the US have a 20-year greater life expectancy than disadvantaged groups, while racial and ethnic minority populations and those with lower income and education (among other types of disadvantage) have a greater burden of disease than more advantaged groups. As the scholarship examining these health outcomes has evolved, it has become clearer that these inequities are caused by foundational social and structural forces, stemming from historical structural conditions that carry to the present day.

P. Marks et al.

COVID-19 Vaccination—Becoming Part of the New Normal

JAMA, May 2022; doi:10.1001/jama.2022.7469


As the US emerges from the recent Omicron surge of the COVID-19 pandemic following close to a million deaths in the country attributable to COVID-19, many people are hoping that the worst is over. Widespread vaccine- and infection-induced immunity, combined with the availability of effective therapeutics, could blunt the effects of future outbreaks. Nonetheless, it is time to accept that the presence of SARS-CoV-2, the virus that causes COVID-19, is the new normal. It will likely circulate globally for the foreseeable future, taking its place alongside other common respiratory viruses such as influenza. And it likely will require similar annual consideration for vaccine composition updates in consultation with the US Food and Drug Administration (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC). A recent meeting of the VRBPAC on April 6, 2022, resulted in a lively discussion and agreement on many considerations for planning for upcoming approaches to COVID-19 vaccine strain composition decision-making, development, and recommendations.

M.J. Levin et al.

Intramuscular AZD7442 (Tixagevimab–Cilgavimab) for Prevention of Covid-19

N Engl J Med., April;  doi: 10.1056/NEJMoa2116620


Background: The monoclonal-antibody combination AZD7442 is composed of tixagevimab and cilgavimab, two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that have an extended half-life and have been shown to have prophylactic and therapeutic effects in animal models. Pharmacokinetic data in humans indicate that AZD7442 has an extended half-life of approximately 90 days.

Methods: In an ongoing phase 3 trial, we enrolled adults (≥18 years of age) who had an increased risk of an inadequate response to vaccination against coronavirus disease 2019 (Covid-19), an increased risk of exposure to SARS-CoV-2, or both. Participants were randomly assigned in a 2:1 ratio to receive a single dose (two consecutive intramuscular injections, one containing tixagevimab and the other containing cilgavimab) of either 300 mg of AZD7442 or saline placebo, and they were followed for up to 183 days in the primary analysis. The primary safety end point was the incidence of adverse events after a single dose of AZD7442. The primary efficacy end point was symptomatic Covid-19 (SARS-CoV-2 infection confirmed by means of reverse-transcriptase-polymerase-chain-reaction assay) occurring after administration of AZD7442 or placebo and on or before day 183.

Results: A total of 5197 participants underwent randomization and received one dose of AZD7442 or placebo (3460 in the AZD7442 group and 1737 in the placebo group). The primary analysis was conducted after 30% of the participants had become aware of their randomized assignment. In total, 1221 of 3461 participants (35.3%) in the AZD7442 group and 593 of 1736 participants (34.2%) in the placebo group reported having at least one adverse event, most of which were mild or moderate in severity. Symptomatic Covid-19 occurred in 8 of 3441 participants (0.2%) in the AZD7442 group and in 17 of 1731 participants (1.0%) in the placebo group (relative risk reduction, 76.7%; 95% confidence interval [CI], 46.0 to 90.0; P<0.001); extended follow-up at a median of 6 months showed a relative risk reduction of 82.8% (95% CI, 65.8 to 91.4). Five cases of severe or critical Covid-19 and two Covid-19-related deaths occurred, all in the placebo group.

Conclusions: A single dose of AZD7442 had efficacy for the prevention of Covid-19, without evident safety concerns. (Funded by AstraZeneca and the U.S. government; PROVENT ClinicalTrials.gov number, NCT04625725.).

S. Vardhana et al.

Understanding T-cell responses to COVID-19 is essential for informing public health strategies

Science Immunology, March 2022; doi: 10.1126/sciimmunol.abo1303


Durable T-cell responses to SARS-CoV-2 antigens after infection or vaccination improve immune-mediated viral clearance. To date, population-based surveys of COVID-19 adaptive immunity have focused on testing for IgG antibodies that bind spike protein and/or neutralize the virus. Deployment of existing methods for measuring T-cell immunity could provide a more complete profile of immune status, informing public health policies and interventions.

Bartsch S.M. et al.

Maintaining face mask use before and after achieving different COVID-19 vaccination coverage levels: a modelling study

The Lancet, https://www.thelancet.com/action/showPdf?pii=S2468-2667%2822%2900040-8

CONTENUTO E COMMENTO : Studio con modello-simulato computazionale finalizzato a comparare cosa accade se le mascherine vengono utilizzate vs. non utilizzate in attesa del raggiungimento di differenti livelli di copertura vaccinale della popolazione considerati nello studio (70-90%). La simulazione ha mostrato che indossare la mascherina, in tutti i contesti analizzati, risultava conveniente in termini di costi e in molti casi portava ad un risparmio sia per la società ed i singoli individui che per le assicurazioni sanitarie. Tali benefici sono stati riscontrati calcolando come costo unitario della mascherina 1.25 dollari al massimo. In tutti gli scenari è risultato conveniente indossare tale dspositivo di protezione anche dalle 2 alle 10 settimane dopo il raggiungimento della copertura vaccinale considerata, con un prolungamento di tale periodo se il target di è stato raggiunto nella stagione invernale. Tutti i fattori che possono incrementare la trasmissibilità del virus (nuove varianti, riduzione dell’efficacia del vaccino) non fanno che aumentare il cost-saving e il cost-effectiveness derivante dal mantenimento di tale DPI. Ovviamente essendo un modello costituisce una semplificazione della realtà, concedendo comunque informazioni utili per una migliore organizzazione della società nella gestione della pandemia. 

Yang Y; et al.

Longitudinal analysis of antibody dynamics in COVID-19 convalescents reveals neutralizing responses up to 16 months after infection

Nature Microbiology,


CONTENUTO E COMMENTO : Studio esplorante le dinamiche della risposta anticoprale in una coorte di 214 pazienti sopravvissuti all’infezione da SARS-CoV2, non ri-esposti al virus o alla vaccinazione, in un periodo di tempo compreso tra 1 e 480 giorni dall’esordio dei sintomi.

In questo studio, il picco di risposta anticorpale è stato raggiunto al giorno 120 dall’esordio dei sintomi, per poi andare incontro a una progressiva riduzione. Tuttavia, nonostante tale declino, i ricercatori hanno osservato una persistente attività neutralizzante di tipo IgG fino a 480 giorni dopo l’esordio dei sintomi, rilevata sia nei casi di infezioni lievi (85.6%), sia nei casi di infezione asintomatica (50%). L’attività neutralizzante di tali anticorpi si è rivelata però rignificativamente inferiore nei confronti delle varianti Beta, Delta e Mu.

Zou J.; et al.

Neutralization against Omicron SARS-CoV-2 from previous non-Omicron infection

Nature Communications,


CONTENUTO E COMMENTO: Studio in vitro, analizzante l’attività neutralizzante degli anticorpi prodotti in risposta a un’infezione da variante non Omicron nei confronti della proteina Spike caratteristica della variante Omicron, sintetizzata in laboratorio e inserendola nel DNA della variante USA-WA1/2020, isolata a gennaio 2020. In questo modo, sono stati determinati i titoli anticorpali neutralizzanti, definiti come la massima diluizione in grado di neutralizzare il 50% dei virioni infettivi, in campioni di siero di pazienti convalescenti da COVID-19, raccolti a distanza di 1 – 6 mesi dalla diagnosi.

Nel corso di tale periodo di tempo, i titoli neutralizzanti contro USA-WA1/2020 sono scesi da 601 a 142, mentre i titoli neutralizzanti contro Omicron sono rimasti stabilmente bassi, tra 38 e 32. Tale risultato dimostra la bassa reattività anticorpale crociata, da una precedente infezione da variante non-Omicron, nei confronti di Omicron.

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 : Revisione della letteratura sull’efficacia delle mascherine a livello di comunità, in considerazione della diffusione della variante Omicron.

Tale documento conclude che una policy di utilizzo della mascherina è raccomandato in tutti i contesti in cui si ha un’evidenza di circolazione virale a livello della comunità. Un’opzione alternativa potrebbe essere quella di utilizzare la mascherina in contesti in cui si ha una elevata concentrazione di individui fragili e/o particolarmente esposti allo sviluppo di COVID severo, come le case di riposo. Il documento ricorda inoltre che le mascherine, per essere realmente efficaci, devono essere utilizzate correttamente, ricoprendo interamente il volto dalla piramide nasale al mento. Inoltre, le mascherine filtranti tipo FFP2/3 è probabile che siano più efficaci, nel ridurre la diffusione del virus, rispetto alle mascherine chirurgiche o altri tipi di mascherine.

Olivera Mesa D.; et al.

Modelling the impact of vaccine hesitancy in prolonging the need for Non-Pharmaceutical Interventions to control the COVID-19 pandemic

Communications Medicine, https://www.nature.com/articles/s43856-022-00075-x

CONTENUTO E COMMENTO : Studio esplorante il l’impatto dell’esitazione vaccinale nel prolungamento degli interventi non farmacologici di controllo della pandemia. Tale analisi, effettuata costruendo un modello matematico con dati epidemiologici e dati di esitazione vaccinale estratti da survey di popolazione, conclude che, nei paesi coi più alti tassi di esitazione vaccinale, in un periodo di tempo di 2 anni e in un contesto di generale rilassamento delle restrizioni, la mortalità COVID-relata potrebbe essere fino a 7.6 volte maggiore rispetto a paesi con livelli ideali di aderenza vaccinale.

Questo modello sottolinea pertanto quanto, per quanto sottoporsi a vaccinazione sia una scelta individuale, l’esitazione vaccinale ha un impatto significativo sulla traiettoria della pandemia, in grado di mettere in difficoltà gli sforzi messi in atto fino ad ora per contrastare la COVID-19.

Klompas, M.; Karan, A.

Preventing SARS-CoV-2 Transmission in Health Care Settings in the Context of the Omicron Variant

JAMA, file:///C:/Users/00122705/Downloads/jama_klompas_2022_vp_220006_1643401941.87023.pdf

CONTENUTO E COMMENTO: Il lavoro analizza separatamente tre misure fondamentali per ridurre la diffusione della variante Omicron all’interno degli ospedali, evento che purtroppo pone a rischio le strutture di focolai all’interno dei reparti nonchè di numerose e improvvise assenze da parte del personale sanitario. Le misure analizzate sono :

- il booster negli operatori ;

- lo screening frequente degli asintomatici (Il rischio stimato di infezione per un paziente ricoverato in una stanza condivisa con un vettore SARS-CoV-2 positivo occulto va dal 30% al 40%).

-Le mascherine N95 (l’equivalente certificazione americana della mascherina FFP2 europea).

Dheda, K.; et al.

A position statement and practical guide to the use of particulate filtering facepiece respirators (N95, FFP2, or equivalent) for South African health workers exposed to respiratory pathogens including Mycobacterium tuberculosis and SARS-CoV-2

Afr J Thorac Crit Care Med,


CONTENUTO E COMMENTO: Linea guida Sudafricana sull’uso delle FFP2 nei contesti ad elevata trasmissione di SARS-CoV-2 e M. tuberculosis.  Contiene una sintesi sulle raccomandazioni sudafricane e internazionali per l'uso di maschere e respiratori da parte degli operatori sanitari. SARS-CoV-2 è trasmesso anche per via aerosolica. I respiratori FFP offrono prestazioni migliori in termini di protezione dagli aerosol infettivi rispetto alle mascherine chirurgiche, e dunque sono consigliati per l'uso da parte di tutti gli operatori sanitari in contesti con tassi elevati di TB e COVID-19.

Yang B et al.

Universal community nucleic acid testing for COVID-19 in Hong Kong reveals insights into transmission dynamics: a cross-sectional and modelling study

Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab925/6413763

CONTENUTO : Studio esponente i risultati di un programma di screening universale messo in atto ad Hong Kong tra giugno e settembre 2020. Degli 1.8 milioni di soggetti coinvolti (il 24% dell’intera popolazione di Hong Kong) il programma di screening universale ha identificato una quota significativamente più alta di casi sporadici rispetto al più classico approccio di sorveglianza pubblica (62% vs 27%). Tale approccio, per quanto sicuramente più impegnativo, dimostra in questo studio di essere più efficiente nell’identificazione di casi e cluster occulti.

COMMENTO : Nella fase calante della terza ondata dell’epidemia a Hong Kong, il sistema di sorveglianza pubblica condotto sulla base dei dati clinici, ha evidenziato il 27% di tutti i casi di infezione occorsi nel periodo dello studio da Luglio a Settembre 2020. Parallelamente una quota significativamente più elevata di casi sporadici e di cluster è stata rilevata da un esperimento di screening universale di popolazione. Il dato fa riflettere su quanto siano sottostimati i casi notificati dalla sorveglianza pubblica. Lo screening universale è estremamente più efficace ma comporta un tale dispendio di mezzi che ne limita l’impiego eventuale solo alle fasi calanti dell’ondata epidemica quando l’obiettivo non è solo il controllo ma l’eliminazione dell’epidemia.

McNamara L. A. et al.

Estimating the early impact of the US COVID-19 vaccination programme on COVID-19 cases, emergency department visits, hospital admissions, and deaths among adults aged 65 years and older: an ecological analysis of national surveillance data

The Lancet, https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2902226-1

CONTENUTO : : Studio osservazionale, condotto negli Stati Uniti, volto a valutare l’impatto della prima fase della campagna vaccinale contro Sars-CoV2, prendendo in considerazione come variabili i casi di COVID-19, gli accessi in Pronto Soccorso, i ricoveri ospedalieri e i decessi negli over 65, comparati inoltre ai dati inerenti la popolazione tra i 50-64 aa nello stesso periodo. Sono stati utilizzati i dati delle agenzie federali degli Stati Uniti, nel lasso di tempo tra il 1 novembre 2020 ed il 10 aprile 2021, riguardanti appunto i casi di COVID-19, accessi in PS, ricoveri e decessi COVID-relati nella popoazione over 50. Sono state valutate le variazioni relative nell’incidenza di tali eventi tra i due gruppi divisi per età, pre-vaccinazione e post-vaccinazione. Il tasso di variazioni relative riguardanti l’incidenza dei casi tra il periodo pre e post vaccino ha mostrato una riduzione dei casi di COVID-19 del 53% tra i 65-74 aa e del 62% dai 75aa in su, rispetto al gruppo tra i 54-64 aa. Una riduzione del 61% (65-74aa) e del 77% (età> o = 75 aa) si è osservata anche per gli accessi in PS. I ricoveri ospedalieri si sono ridotti del 39% nella fascia di età 60-69, del 60% tra i 70-79 aa e del 68% dagli 80 aa in su, paragonati ad una popolazione adulta tra i 50-59 aa. Infine anche i decessi COVID-relati hanno dimostrato una riduzione, seppur meno chiara ed affiidabile rispetto alle restanti variabili considerate.

COMMENTO : Il paper è interessante soprattutto nel riportare dati «reali» dell’impatto dei vaccini usati nella prima fase di vaccinazione (adulti a rischio, anziani ed operatori sanitari) nel contrastare le varie fasi di COVID-19 negli Stati Uniti. L’effetto protettivo della vaccinazione è stato maggiore per i soggetti più anziani e critici a dimostrazione della correttezza nella scelta di rendere prioritaria la vaccinazione per questi soggetti. Notare che l’impatto reale della vaccinazione, per esempio sull’ospedalizzazione, pur variabile nei vari gruppi di popolazione, è piuttosto lontano dalla relativa efficacia vaccinale come da trial clinico.

Lalwani P, et al.

High anti-SARS-CoV-2 antibody seroconversion rates before the second wave in Manaus, Brazil, and the protective effect of social behaviour measures: results from the prospective DETECTCoV-19 cohort

The Lancet Global Health, https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00355-7/fulltext

CONTENUTO: Grosso studio di coorte esplorante il tasso di sieroconversione per SARS-CoV2 prima della grande ondata epidemica che ha colpito Manaus, in Brasile. In un intervallo di tempo di 4 settimane, il tasso di sieroprevalenza è aumentato dal 27.7% al 34.3%, con una prevalenza di infezioni asintomatiche del 48%. I Fattori di rischio per la sieroconversione identificati dallo studio sono stati una scarsa compliance con il distanziamento fisico e l’indossare la mascherina, e avere un familiare positivo per SARS-CoV2. Lo smartworking si è invece dimostrato un fattore protettivo.

COMMENTO: L’importanza di questo studio, condotto on-line in Manaus (Brasile), consiste nell’avere correlato positivamente l’incidenza pre-epidemica dei tassi di sieroconversione per SARS-CoV-2 con le co-variate socio demografiche e la compliance alle misure di mitigazione adottate e negativamente con lo smartworking. Questo offre un dato a sostegno della validità delle strategie individuali e sociali di protezione anche in ambienti “difficili” nei confronti del contrasto all’epidemia.

Motta FC, et al.

Assessment of Simulated Surveillance Testing and Quarantine in a SARS-CoV-2–Vaccinated Population of Students on a University Campus

JAMA Health Forum, https://jamanetwork.com/journals/jama-health-forum/fullarticle/2784740

CONTENUTO: Modello matematico stimante l’incidenza di infezioni in un campus universitario di 5000 studenti vaccinati, simulando l’efficacia delle misure di sorveglianza rispetto a diversi scenari di efficacia vaccinale (90%, 75% e 50%). In questa simulazione, anche in uno scenario di elevata efficacia vaccinale, l’esecuzione di un tampone di sorveglianza settimanale si è tradotto in una significativa riduzione dell’incidenza di infezioni. Al contrario, nel modello, la quarantena dei contatti stretti si è rivelata non strettamente necessaria, in quanto ad efficacia paragonabile ad un aumento della frequenza di test diagnostici nel limitare la diffusione delle infezioni.

COMMENTO: Le ripercussioni dei risultati di questo studio sono importanti al fine di guidare le decisioni sulle modalità di prevenzione da attuare nella collettività, per esempio nelle scuole. In sostanza, assumendo che l’efficienza dei vaccini approvati in Italia sia almeno del 90%, l’attuazione di strategie di mitigazione basate sulla ripetizione settimanale di test consente una riduzione solo marginale di casi positivi. Lo stesso vale per l’adozione di misure di quarantena di 10 giorni dei contatti. Queste misure offrono importanti risultati di riduzione del rischio solo nel caso di vaccini la cui efficienza sia fra il 50 e il 75%: potrebbe essere il caso della vaccinazione con Sputnik-1 a San Marino.

Revollo B et al.

Same-day SARS-CoV-2 antigen test screening in an indoor mass-gathering live music event: a randomised controlled trial

Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00268-1/fulltext

CONTENUTO: Trial randomizzato esplorante l’efficacia di un intervento composito per prevenire la diffusione di SARS-CoV2 in un evento musicale al chiuso. I risultati suggeriscono che la combinazione di screening con test antigenico rapido, aderenza all’uso della mascherina filtrante (N95) e adeguato sistema di ventilazione possa essere una valida strategia per prevenire la diffusione del virus nell’ambito di un grosso evento musicale al chiuso.

COMMENTO: Lo studio è di rilevante attuale pratico. Con la vaccinazione dell’80% della popolazione oltre i 12 anni, si pone urgente il problema di programmare la riapertura delle attività e degli accessi a spettacoli al chiuso, inclusi concerti dal vivo e discoteche, che rappresentano luoghi ad elevato rischio di trasmissione di SARS-CoV-2. Questa proposta di modello di prevenzione è di alto interesse poiché di dimostrata efficacia. Certamente pone problemi organizzativi, in particolare nell’attuazione di screening tempestivi a grandi masse affollate di partecipanti.

Seung-Ji Kng et al.

Successful control of COVID-19 outbreak through tracing, testing, and isolation: Lessons learned from the outbreak control efforts made in a metropolitan city of South Korea

Journal of Infection and Public Health, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276554/pdf/main.pdf

CONTENUTO : Lo studio pubblicato analizza l’efficacia della strategia di contact-tracing in una città della Corea del Sud anche tramite l’utilizzo di strumenti informatici.

 Kathy Leung  1 , Joseph T Wu  2 , Gabriel M Leung

Effects of adjusting public health, travel, and social measures during the roll-out of COVID-19 vaccination: a modelling study

Lancet Public Health, https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(21)00167-5/fulltext

CONTENUTO: Lo studio analizza mediante un modello predittivo l’impatto della mitigazione delle misure sociali e di sanità pubblica e delle restrizioni dei viaggi internazionail sulla diffusione dell’infezione da SARS-CoV-2 e del carico sulle strutture ospedaliere alla luce dei diversi livelli di copertura vaccinale.

Kiang MV et al

Routine asymptomatic testing strategies for airline travel during the COVID-19 pandemic: a simulation study

The Lancet, July 2021 ; doi.org/10.1016/S1473-3099(21)00134-1

COMMENTO : Background

Routine viral testing strategies for SARS-CoV-2 infection might facilitate safe airline travel during the COVID-19 pandemic and mitigate global spread of the virus. However, the effectiveness of these test-and-travel strategies to reduce passenger risk of SARS-CoV-2 infection and population-level transmission remains unknown.


In this simulation study, we developed a microsimulation of SARS-CoV-2 transmission in a cohort of 100 000 US domestic airline travellers using publicly available data on COVID-19 clinical cases and published natural history parameters to assign individuals one of five health states of susceptible to infection, latent period, early infection, late infection, or recovered. We estimated a per-day risk of infection with SARS-CoV-2 corresponding to a daily incidence of 150 infections per 100 000 people. We assessed five testing strategies: (1) anterior nasal PCR test within 3 days of departure, (2) PCR within 3 days of departure and 5 days after arrival, (3) rapid antigen test on the day of travel (assuming 90% of the sensitivity of PCR during active infection), (4) rapid antigen test on the day of travel and PCR test 5 days after arrival, and (5) PCR test 5 days after arrival. Strategies 2 and 4 included a 5-day quarantine after arrival. The travel period was defined as 3 days before travel to 2 weeks after travel. Under each scenario, individuals who tested positive before travel were not permitted to travel. The primary study outcome was cumulative number of infectious days in the cohort over the travel period without isolation or quarantine (population-level transmission risk), and the key secondary outcome was the number of infectious people detected on the day of travel (passenger risk of infection).


We estimated that in a cohort of 100 000 airline travellers, in a scenario with no testing or screening, there would be 8357 (95% uncertainty interval 6144–12831) infectious days with 649 (505–950) actively infectious passengers on the day of travel. The pre-travel PCR test reduced the number of infectious days from 8357 to 5401 (3917–8677), a reduction of 36% (29–41) compared with the base case, and identified 569 (88% [76–92]) of 649 actively infectious travellers on the day of flight; the addition of post-travel quarantine and PCR reduced the number of infectious days to 2520 days (1849–4158), a reduction of 70% (64–75) compared with the base case. The rapid antigen test on the day of travel reduced the number of infectious days to 5674 (4126–9081), a reduction of 32% (26–38) compared with the base case, and identified 560 (86% [83–89]) actively infectious travellers; the addition of post-travel quarantine and PCR reduced the number of infectious days to 3124 (2356–495), a reduction of 63% (58–66) compared with the base case. The post-travel PCR alone reduced the number of infectious days to 4851 (3714–7679), a reduction of 42% (35–49) compared with the base case.


Routine asymptomatic testing for SARS-CoV-2 before travel can be an effective strategy to reduce passenger risk of infection during travel, although abbreviated quarantine with post-travel testing is probably needed to reduce population-level transmission due to importation of infection when travelling from a high to low incidence setting.

Gostin LO et al

Mandatory SARS-CoV-2 Vaccinations in K-12 Schools, Colleges/Universities, and Businesses

JAMA, June 2021; doi:10.1001/jama.2021.9342

COMMENTO: The Centers for Disease Control and Prevention (CDC) recently issued guidance that fully vaccinated individuals can safely remove masks and end social distancing in most indoor settings.1 Educational facilities and businesses are faced with whether and how to differentiate between vaccinated and unvaccinated individuals, including requiring proof of vaccination. Mandatory vaccination has historically served as a tool to reach and sustain high immunization coverage and to prevent transmission in K-12 schools, colleges/universities, and health care facilities. Vaccine mandates could extend to workers and customers in businesses to ensure safer environments. This Viewpoint examines the epidemiologic, public health, and legal considerations for mandatory SARS-CoV-2 vaccinations in each setting.

Talbot TR et al

COVID-19 Vaccination of Health Care Personnel as a Condition of Employment

A Logical Addition to Institutional Safety Programs

JAMA, June 2021 ;  DOI: 10.1001/jama.2021.8901

COMMENTO: As the SARS-CoV-2 vaccines move closer to full licensure and the data on their excellent effectiveness against both symptomatic and asymptomatic COVID-19 infection emerge, the question of whether to implement a SARS-CoV-2 vaccination policy for HCP as a condition of employment is becoming clearer. HCP should not inadvertently spread contagious infections like measles and influenza to their patients and other HCP. The time is coming to add COVID-19 to that list.

Folgueira MD et al

Prolonged SARS-CoV-2 cell culture replication in respiratory samples from patients with severe COVID-19

CMI, February 2021; doi.org/10.1016/j.cmi.2021.02.014

COMMENTO: Objectives

This study compares the infectivity of SARS-CoV-2 in respiratory samples from patients withmild COVID-19 withthosefromhospitalized patients withseverebilateralpneumonia. In severe COVID-19, we also analysed the presence of neutralizing activity in paired sera.


Weperformedcell cultures on 193 real-time reverse transcription polymerase chain reaction respiratory samples, positive for SARS-CoV-2, obtained from 189 patients at various times, from clinical diagnosis to follow-up. Eleven samples were obtained from asymptomatic individuals, 91 samples from 91 out patients with mildforms of COVID-19 and 91 samples from 87 in patients with severe pneumonia. In these patients, neutralizing activity was analysed in 30 paired sera collected after symptom onset >10 days.


We detected a cytopathic effect (CPE) in 91/193 (47%) samples. Viral viability was maintained for up to 10 days in patients with mild COVID-19. In patients with severe COVID-19, the virus remained viable for up to 32 days after the onset of symptoms. Patients with severe COVID-19 presented infectious virus at a significantly higher rate in the samples with moderate to low viral load (cycle threshold value ≥ 26): 32/75 (43%) versus 14/63 (22%) for mild cases (p < 0.01). We observed a positive CPE despite the presence of clear neutralizing activity (NT50 > 1:1024 in 10% (3/30) of samples.


Patients withsevere COVID-19 might shed viable virus duringprolongedperiods of up to 4 weeks after symptomonset, even when presenting high cycle threshold values in their respiratory samples and despite having developed high neutralizing antibody titres.

Patel MD et al

Association of Simulated COVID-19 Vaccination and Nonpharmaceutical Interventions With Infections, Hospitalizations, and Mortality

JAMA, June 2021; doi:10.1001/jamanetworkopen.2021.10782

COMMENTO : Importance  Vaccination against SARS-CoV-2 has the potential to significantly reduce transmission and COVID-19 morbidity and mortality. The relative importance of vaccination strategies and nonpharmaceutical interventions (NPIs) is not wellunderstood.

Objective  To assess the association of simulated COVID-19 vaccine efficacy and coverage scenarios with and without NPIs with infections, hospitalizations, and deaths.

Design, Setting, and Participants  An established agent-based decision analytical model was used to simulate COVID-19 transmission and progression from March 24, 2020, to September 23, 2021. The model simulated COVID-19 spread in North Carolina, a US state of 10.5 million people. A network of 1 017 720 agents wasconstructedfrom US Census data to represent the statewide population.

Exposures  Scenarios of vaccine efficacy (50% and 90%), vaccine coverage (25%, 50%, and 75% at the end of a 6-month distribution period), and NPIs (reduced mobility, school closings, and use of face masks) maintained and removed during vaccine distribution.

Main Outcomes and Measures  Risks of infection from the start of vaccine distribution and risk differences comparing scenarios. Outcome means and SDs were calculated acrossreplications.

Results  In the worst-case vaccination scenario (50% efficacy, 25% coverage), a mean (SD) of 2 231 134 (117 867) new infections occurred after vaccination began with NPIs removed, and a mean (SD) of 799 949 (60 279) new infections occurred with NPIs maintained during 11 months. In contrast, in the best-case scenario (90% efficacy, 75% coverage), a mean (SD) of 527 409 (40 637) new infections occurredwithNPIsremoved and a mean (SD) of 450 575 (32 716) new infections occurredwithNPIsmaintained. WithNPIsremoved, lowerefficacy (50%) and highercoverage (75%) reduced infection risk by a greater magnitude thanhigherefficacy (90%) and lowercoverage (25%) comparedwith the worst-case scenario (mean [SD] absoluteriskreduction, 13% [1%] and 8% [1%], respectively).

Conclusions and Relevance  Simulation outcomes suggest that removing NPIs while vaccines are distributed may result in substantial increases in infections, hospitalizations, and deaths. Furthermore, as NPIs are removed, higher vaccination coveragewithlessefficacious vaccines can contribute to a largerreduction in risk of SARS-CoV-2 infection comparedwith more efficacious vaccines at lowercoverage. These findings highlight the need for well-resourced and coordinated efforts to achieve high vaccine coverage and continuedadherence to NPIs before many prepandemic activities can beresumed.

Chia WN et al

Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study

The Lancet, March 2021: doi.org/10.1016/S2666-5247(21)00025-2

COMMENTO : Background : Studies have found different waning rates of neutralising antibodies compared with binding antibodies against SARS-CoV-2. The impact of neutralising antibody waning rate at the individual patient level on the longevity of immunity remains unknown. We aimed to investigate the peaklevels and dynamics of neutralising antibody waning and IgG avidity maturation over time, and correlate this with clinical parameters, cytokines, and T-cellresponses.

Methods : We did a longitudinal study of patients who had recovered from COVID-19 up to day 180 post-symptomonset by monitoring changes in neutralising antibody levels using a previously validated surrogate virus neutralisation test. Changes in antibody avidities and other immune markers at different convalescent stages were determined and correlatedwith clinical features. Using a machine learning algorithm, temporal change in neutralising antibody levels was classified into five groups and used to predict the longevity of neutralising antibody-mediatedimmunity.

Findings : We approached 517 patients for participation in the study, of whom 288 consented for outpatient follow-up and collection of serial bloodsamples. 164 patients werefollowed up and hadadequatebloodsamplescollected for analysis, with a total of 546 serumsamplescollected, including 128 bloodsamplestaken up to 180 days post-symptomonset. Weidentified five distinctive patterns of neutralising antibodydy namics as follows: negative, individualswhodid not, at ourintervals of sampling, developneutralisingantibodies at the 30% inhibition level (19 [12%] of 164 patients); rapidwaning, individuals who had varyinglevels of neutralising antibodies from around 20 days after symptomonset, but seroreverted in lessthan 180 days (44 [27%] of 164 patients); slow waning, individuals whore mained neutralising antibody-positive at 180 days post-symptomonset (46 [28%] of 164 patients); persistent, although with varying peakneutralisinganti body levels, these individuals had minimal neutralisingantibodydecay (52 [32%] of 164 patients); and delayedresponse, a small group thatshowed an unexpectedincrease of neutralisingantibodiesduringlate convalescence (at 90 or 180 daysaftersymptomonset; three [2%] of 164 patients). Persistence of neutralisingantibodieswasassociatedwithdiseaseseverity and sustainedlevel of pro-inflammatory cytokines, chemokines, and growthfactors. By contrast, T-cellresponsesweresimilaramong the differentneutralisingantibodydynamics groups. On the basis of the different decaydynamics, we established a predictionalgorithm that revealed a wide range of neutralising antibody longevity, varyingfromaround 40 days to manydecades.

Interpretation : Neutralising antibody response dynamics in patients who have recovered from COVID-19 varygreatly, and prediction of immune longevity can only be accurately determined at the individuallevel. Our finding semphasise the importance of public health and social measures in the ongoingpandemicoutbreakresponse, and might have implications for longevity of immunityafter vaccination.

Wilson N et al

Estimating the impact of control measures to prevent outbreaks of COVID-19 associated with air travel into a COVID-19-free country

Scientific Report, May 2021 ; doi.org/10.1038/s41598-021-89807-y

COMMENTO : We aimed to estimate the risk of COVID-19 outbreaks associated with air travel to a COVID-19-free country [New Zealand (NZ)]. A stochastic version of the SEIR model CovidSIM v1.1, designed specifically for COVID-19 was utilised. We first considered historical data for Australia before it eliminated COVID-19 (equivalent to an outbreak generating 74 new cases/day) and one flight per day to NZ with no interventions in place. This gave a median time to an outbreak of 0.2 years (95% range of simulation results: 3 days to 1.1 years) or a mean of 110 flights per outbreak. However, the combined use of a pre-flight PCR test of saliva, three subsequent PCR tests (on days 1, 3 and 12 in NZ), and various other interventions (mask use and contact tracing) reduced this risk to one outbreak after a median of 1.5 years (20 days to 8.1 years). A pre-flight test plus 14 days quarantine was an even more effective strategy (4.9 years; 2,594 flights). For a much lower prevalence (representing only two new community cases per week in the whole of Australia), the annual risk of an outbreak with no interventions was 1.2% and had a median time to an outbreak of 56 years. In contrast the risks associated with travellers from Japan and the United States was very much higher and would need quarantine or other restrictions. Collectively, these results suggest that multi-layered interventions can markedly reduce the risk of importing the pandemic virus via air travel into a COVID-19-free nation. For some low-risk source countries, there is the potential to replace 14-day quarantine with alternative interventions. However, all approaches require public and policy deliberation about acceptable risks, and continuous careful management and evaluation.

Llaydon DJ et al

Modelling the impact of the tier system on SARS-CoV-2 transmission in the UK between the first and second national lockdowns

BMJ Open , April 2021; doi: 10.1136/bmjopen-2021-050346

COMMENTO: Objective To measure the effects of the tier system on the COVID-19 pandemic in the UK between the first and second national lockdowns, before the emergence of the B.1.1.7 variant of concern.

Design This is a modelling study combiningestimates of real-time reproduction numberRt (derivedfrom UK case, death and serologicalsurvey data) with publicly available data on regional non-pharmaceutical interventions. We fit a Bayesianhierarchical model with latent factors using the sequantities to account for broader national trends in addition to subnational effects from tiers.

Setting The UK at lower tier local authority (LTLA) level. 310 LTLAswereincluded in the analysis.

Primary and secondaryoutcomemeasures Reduction in real-time reproduction numberRt.

Results Nationally, transmission increased between July and lateSeptember, regional differences not with standing. Immediatelyprior to the introduction of the tier system, Rtaveraged 1.3 (0.9–1.6) acrossLTLAs, but declined to an average of 1.1 (0.86–1.42) 2 weekslater. Decline in transmission was not solelyattributable to tiers. Tier 1 hadnegligibleeffects. Tiers 2 and 3, respectively, reduced transmission by 6% (5%–7%) and 23% (21%–25%). 288 LTLAs (93%) would have begun to suppresstheirepidemics if every LTLA had gone into tier 3 by the second national lockdown, whereasonly 90 (29%) didso in reality.

Conclusions The relativelysmalleffect sizes found in thisanalysisdemonstratethat interventions at least as stringent as tier 3 are required to suppress transmission, especiallyconsidering more transmissible variants, at least until effective vaccination iswidespread or muchgreater population immunity has amassed.

Somekh I et al

Comparison of COVID-19 Incidence Rates Before and After School Reopening in Israel

JAMA, April 2021; doi:10.1001/jamanetworkopen.2021.7105

COMMENTO : Schoolsreopened in Israel on September 1, 2020, followingsummer vacation during active SARS-CoV-2 spread when the incidence of new cases of COVID-19 in Israelwas one of the highest in the world. DuringSeptember 2020, COVID-19 cases furthersurged in Israel, resulting in schoolclosure (September 14), and a countrywidelockdown. Schoolswerereopened on November 1. Weexamined the dynamics in infection rates in children and youthsaged 0 to 19 years compared with other age groups, with the goal of understanding whether school reopening was associated with SARS-CoV-2 infection in thoseaged 0 to 9 years.

Bartoszko JJ et al

Prophylaxis against COVID-19: living systematic review and meta-analysis

BMJ, April 2021; doi.org/10.1136/bmj.n949

COMMENTO : Objective To determine and compare the effects of drugprophylaxis on SARS-CoV-2 infection and covid-19.

Design Living systematicreview and network meta-analysis.

Data sources World HealthOrganization covid-19 database, a comprehensivemultilingual source of global covid-19 literature to 25 March 2021, and six additionalChinesedatabases to 20 February 2021.

Study selection Randomised trials of people at risk of covid-19 who were assigned to receive prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.

Methods Random effects bayesian network meta-analysis was performed after duplicate data abstraction. Included studies were assessed for risk of biasusing a modification of the Cochrane risk of bias 2.0 tool, and certainty of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach.

Results The first iteration of this living network meta-analysis includes nine randomised trials—six of hydroxychloroquine (n=6059 participants), one of ivermectin combined with iota-carrageenan (n=234), and two of ivermectin alone (n=540), all compared with standard care or placebo. Two trials (one of ramipril and one of bromhexine hydrochloride) did not meet the sample size requirements for network meta-analysis. Hydroxychloroquine has trivial to no effect on admission to hospital (risk difference 1 fewer per 1000 participants, 95% credible interval 3 fewer to 4 more; high certainty evidence) or mortality (1 fewer per 1000, 2 fewer to 3 more; high certainty). Hydroxychloroquine probably does not reduce the risk of laboratory confirmed SARS-CoV-2 infection (2 more per 1000, 18 fewer to 28 more; moderate certainty), probably increases adverse effects leading to drug discontinuation (19 more per 1000, 1 fewer to 70 more; moderate certainty), and may have trivial to no effect on suspected, probable, or laboratory confirmed SARS-CoV-2 infection (15 fewer per 1000, 64 fewer to 41 more; low certainty). Owing to seriousrisk of bias and very serious imprecision, and thusverylowcertainty of evidence, the effects of ivermectin combined with iota-carrageenan on laboratoryconfirmed covid-19 (52 fewer per 1000, 58 fewer to 37 fewer), ivermectinalone on laboratory confirmed infection (50 fewer per 1000, 59 fewer to 16 fewer) and suspected, probable, or laboratory confirmed infection (159 fewer per 1000, 165 fewer to 144 fewer) remain very uncertain.

Conclusions Hydroxychloroquine prophylaxis has trivial to no effect on hospital admission and mortality, probably increases adverse effects, and probably does not reduce the risk of SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, it is highly uncertain whether ivermectin combined with iota-carrageenan and ivermectinal one reduce the risk of SARS-CoV-2 infection.

Systematic review registration This reviewwas not registered. The protocol established a priori is included as a supplement.

Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Sickbert-Bennett EE et al

Fitted Filtration Efficiency of Double Masking During the COVID-19 Pandemic

JAMA, April 2021; doi:10.1001/jamainternmed.2021.2033

COMMENTO : Although global vaccination efforts against SARS-CoV-2 are underway, the public isurged to continue using face masks as a primary intervention to control transmission. Recently, US public healthofficials have also encouraged doubling masks as a strategy to counterelevated transmission associated with infectious SARS-CoV-2 variants. US Centers for Disease Control and Prevention investigators reported that doubling mask sincreased effectiveness, but their assessment was limited in type and combinations of maskstested, as well as by the use of head forms rather than humans. To address these limitations, this study compared the fitted filtration efficiency (FFE) of commonly available masks wornsingly, doubled, or in combinations.

Ji L et al

Disinfection spreads antimicrobial resistance

Science, 29 January 2021 ;  DOI: 10.1126/science.abg4380

COMMENTO : During the COVID-19 pandemic, the use of disinfectants, alcohol-based hand sanitizers, and antiseptic hand wash has surged. As a precaution, many authorities have also increased chlorine dosage in wastewater disinfection to achieve a free chlorine residual concentration greater than 6.5 mg/liter, despite evidence that a free chlorine residual of just above 0.5 mg/liter can completely inactivate human coronavirus. These chemicals can reach aquatic and terrestrial environments through direct discharge of wastewater into receiving waters. Disinfection protocols put in place to prevent COVID-19 should be limited to the minimum required to kill severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and weighed against their potential to increase antimicrobial resistance (AMR).

Lewis D

COVID-19 rarely spreads through surfaces. So why are we still deep cleaning?

Nature, 29 January 2021; doi.org/10.1038/d41586-021-00251-4

COMMENTO: Part of the problem is that specialists can’t rule out the possibility of fomite transmission, and the guidance from many health agencies about how to deal with surfaces has been unclear as the science has changed. In November, Chinese authorities introduced guidelines requiring disinfection of imported frozen-food packages. And the CDC directs people to a comprehensive list of agents that kill SARS-C0V-2 and says: “Frequent disinfection of surfaces and objects touched by multiple people is important.”

Smit M et al

Prophylaxis for COVID-19: a systematic review

Clinical Microbiology and Infection, 18 January; doi: 10.1016/j.cmi.2021.01.013

COMMENTO: Background : While the landscape of vaccine and treatment candidates against the novel coronavirus (COVID-19) has been reviewed systematically, prophylactic candidates remain unexplored.

Objectives : Map pre- and post-exposure prophylactic (PrEP and PEP) candidate for COVID-19.

Data sources : PubMed/Medline, Embase, International Committee of Medical Journal Editors and International Clinical Trials Registry Platform clinical trial registries and MedRxiv.

Study eligibility criteria and Participants : All studies in humans or animals and randomized clinical trials (RCTs) in humans reporting primary data on prophylactic candidates against COVID-19, excluding studies focused on key populations.

Interventions : PrEP and PEP candidate for COVID-19.

Methods : Systematic review (SR) and qualitative synthesis of COVID-19 PrEP and PEP studies and RCTs complemented by search of MedRxiv and PubMed and Embase for studies reporting RCTs outcomes since SR search completion.

Results : We identified 13 studies (out of 2,119 database records) and 117 RCTs (out of 5565 RCTs in the registries) meeting inclusion criteria. Non-RCT studies reported on cross-sectional studies using hydroxychloroquine (HCQ) in humans (n=2) or reported on animal studies (n=7) most of which used antibodies. All five completed RCTs focused on the use of HCQ as either PrEP or PEP and these and the cross-sectional studies reported no prophylactic effect. The majority of ongoing RCTs evaluated HCQ or other existing candidates including non-SARS-CoV-2 vaccines, anti(retro)virals, or use of vitamins and supplements.

Conclusions : The key message from completed studies and RCTs seems to be that HCQ does not work, there is little evidence regarding other compounds with all RCTs using candidates other than HCQ still ongoing. It remains to be seen if the portfolio of existing molecules being evaluated in RCTs will identify successful prophylaxis against COVID-19 or if there is a need for the development of new candidates.

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