O. Puhach et al.

Infectious viral load in unvaccinated and vaccinated individuals infected with ancestral, Delta or Omicron SARS-CoV-2. 

Nature Medicine, April (2022); doi.org/10.1038/s41591-022-01816-0

Abstract

Infectious viral load (VL) expelled as droplets and aerosols by infected individuals partly determines SARS-CoV-2 transmission. RNA VL measured by qRT-PCR is only a weak proxy for infectiousness. Studies on the kinetics of infectious VL are important to understand the mechanisms behind the different transmissibility of SARS-CoV-2 variants and the effect of vaccination on transmission, which allows to guide public health measures. In this study we quantified infectious VL in SARS-CoV-2 infected individuals during the first 5 symptomatic days by in vitro culturability assay in unvaccinated or vaccinated individuals infected with pre-variant of concern (pre-VOC) SARS-CoV-2, Delta, or Omicron. Unvaccinated individuals infected with pre-VOC SARS-CoV-2 had lower infectious VL compared to Delta-infected unvaccinated individuals. Full vaccination (defined as >2weeks after reception of 2nd dose during primary vaccination series) significantly reduced infectious VL for Delta breakthrough cases compared to unvaccinated individuals. For Omicron breakthrough cases, reduced infectious VL was only observed in boosted but not in fully vaccinated individuals compared to unvaccinated subjects. In addition, infectious VL was lower in fully vaccinated Omicron- compared to fully vaccinated Delta-infected individuals, suggesting that other mechanisms than increased infectious VL contribute to the high infectiousness of SARS-CoV-2 Omicron. Our findings indicate that vaccines may lower transmission risk and therefore have a public health benefit beyond the individual protection from severe disease.

D. Lewis

Perché l'OMS ha impiegato due anni per dire che COVID-19 si trasmette per via aerea

Nature, 12 aprile 2022

Abstract

All'inizio della pandemia, l'Organizzazione mondiale della Sanità ha dichiarato che SARS-CoV-2 non si trasmetteva attraverso l'aria. Quell'errore e il prolungato processo di correzione hanno seminato confusione e sollevano domande su che cosa accadrà nella prossima emergenza pandemica.

Kolodziej LM et al.

SARS-CoV-2 transmission risk upon return to work in RNA-positive healthcare workers

J Hosp Infect.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8916832/pdf/main.pdf

CONTENUTO E COMMENTO : In questo studio prospettico osservazionale viene valutata la capacità di trasmissione del virus SARS-CoV-2 di operatori sanitari che rientrano a lavoro dopo l’infezione da SARS-CoV-2. Sono stati arruolati operatori sanitari non vaccinati per SARS-CoV-2 (da maggio a settembre 2020) con un tampone nasofaringeo molecolare positivo. Al rientro a lavoro (dopo almeno 24 ore dalla risoluzione dei sintomi respiratori, in accordo con le procedure interne dell’ospedale di riferimento) è stato ripetuto il tampone nasofaringeo molecolare per SARS-CoV-2. Per gli operatori sanitari risultati positivi al tampone nasofaringeo di controllo sono state effettuate analisi filogenetiche per valutare possibili trasmissioni sul posto di lavoro. Sessantuno (84.7%) partecipanti hanno avuto un tampone di controllo positivo (mediana 13 giorni dall’esordio dei sintomi), il 49.1% dei quali con una mediana di cicli soglia di 29.2. Undici colleghi diretti di sei partecipanti con tampone positivo al rientro con cicli soglia <30 sono risultati positivi; tuttavia le analisi epidemiologiche e filogenetiche non hanno mostrato alcuna trasmissione legata al partecipante indice.

Stabilire la contagiosità di un soggetto con recente infezione da SARS-CoV-2 è una questione di fondamentale importanza e numerosi studi hanno dimostrato la scarsa capacità del tampone molecolare nel decretare la fine del periodo di contagiosità. L’approccio basato sulla assenza di sintomatologia per stabilire il rientro a lavoro degli operatori sanitari proposto dagli autori dello studio dovrebbe tuttavia essere integrato con un test di laboratorio, come ad esempio il tampone antigenico che sembrerebbe più accurato del tampone molecolare nello stabilire il periodo di infettività.

Ma, Q.; et al.

Global Percentage of Asymptomatic SARS-CoV-2 Infections Among the Tested Population and Individuals With Confirmed COVID-19 Diagnosis A Systematic Review and Meta-analysis

JAMA, file:///C:/Users/00122705/Downloads/ma_2021_oi_211054_1638886091.86274.pdf

CONTENUTO E COMMENTO: In questa revisione sistematica e meta-analisi di 95 studi unici con 29.776.306 individui sottoposti a test (soltanto però fino a febbraio 2021), la percentuale aggregata di infezioni asintomatiche era dello 0,25% tra la popolazione testata e del 40,5% tra la popolazione con COVID-19 confermato. L'elevata percentuale di infezioni asintomatiche in questo studio evidenzia il potenziale rischio di trasmissione del virus nella comunità.

Aregu, M.B.; et al.

Safe water supply challenges for hand hygiene in the prevention of COVID-19 in Southern Nations, Nationalities, and People's Region (SNNPR), Ethiopia

Heliyon,

https://www.cell.com/action/showPdf?pii=S2405-8440%2821%2902533-0

CONTENUTO E COMMENTO: Questo studio Etiope mette in luce come un gesto banale, ma fondamentale per la prevenzione della trasmissione di SARS-CoV-2 come il lavaggio delle mani sia gravato da minacce per la salute in contesti come quello Africano dove l’acqua, quando disponibile, spesso non è sicura.

Behzadinasab S., et al.

SARS-CoV-2 virus transfers to skin through contact with contaminated solids

Sci Rep, https://www.nature.com/articles/s41598-021-00843-0.pdf

CONTENUTO E COMMENTO: Questo studio dimostra un sostanziale trasferimento del virus SARS-CoV-2 da una varietà di solidi contaminati da droplet ad an dito artificiale dopo una forza breve, leggera e senza sfregamento. Il trasferimento è inferiore (3-9% vs. 13-16%) ma ancora possibile dopo che la gocciolina ha essiccato. Quando la goccia penetra in un solido poroso, come legno o tessuto, il trasferimento è basso. Ovviamente questo non è uno studio sulla trasmissione di SARS-CoV-2 perchè la trasmissione richiede un ulteriore passaggio che è quello dalle mani alle vie aeree.

Bae S et al.

Dynamics of Viral Shedding and Symptoms in Patients with Asymptomatic or Mild COVID-19

Viruses, https://www.mdpi.com/1999-4915/13/11/2133

CONTENUTO : Studio di coorte prospettica che ha reclutato operatori sociali sudcoreani tra il 10 gennaio e il 22 febbraio 2021, di cui 89 hanno sviluppato infezione da COVID-19. In questo studio, nelle fasi iniziali della malattia gli individui asintomatici hanno presentato carica virale simile agli individui sintomatici, che però è andata incontro ad una più rapida riduzione e ad una conseguente più rapida scomparsa dell’infettività. Sempre negli individui asintomatici, il virus è risultato non coltivabile dopo soli 3 giorni dal suo iniziale rilevamento.

COMMENTO: In questo studio prospettico, condotto nel corso della seconda ondata epidemica di gennaio-febbraio 2021, è stato indagato il rapporto fra carica virale, viral shedding e stato clinico. Mentre nella fase acuta dell’infezione la carica virale non era dissimile fra soggetti asintomatici e pazienti sintomatici, si assisteva nei soggetti asintomatici ad un rapido decremento della carica virale e alla scomparsa di virus rilevabile nelle colture cellulari già in 3° giornata. La persistenza di viral shedding e quindi della infettività risulta pertanto correlata alla gravità della malattia sintomatica. Determinare l’entità della quota di pazienti sintomatici e affetti da malattia grave appare quindi importante per valutare il grado di trasmissibilità in una comunità residenziale.

European Centre for Disease Prevention and Control

Contact tracing in the European Union: public health management of persons, including healthcare workers, who have had contact with COVID-19 cases – fourth update, 28 October 2021

https://www.ecdc.europa.eu/sites/default/files/documents/contact-tracing-guidance-fourth-update.pdf

CONTENUTO: In questo documento di ECDC si trovano informazioni aggiornate riguardo la gestione dei contatti alla luce delle nuove evidenze sulla trasmissibilità della variante Delta e sull’efficacia del vaccino su di essa. Inoltre vi si trovano raccomandazioni per il tracciamento nelle scuole.

COMMENTO : Un articolo che sottolinea l’importanza del tracciamento in Sanità Pubblica come una delle armi per combattere la diffusione del virus

L’importanza e maggiore nelle scuole per evitare inutili chiusure e mettere in quarantena certa solo i contatti veri con il caso indice. Il tracciamento ribadiscono gli autori nell’articolo cheil tracciamento  è importante indipendentemente dall’essere o. o vaccinati

European Centre for Disease Prevention and Control. Contact tracing in the European Union: public health

management of persons, including healthcare workers, who have had contact with COVID-19 cases – fourth update, 28 October 2021.

Yang Ge MS, et al.

COVID-19 Transmission Dynamics Among Close Contacts of Index Patients With COVID-19 A Population-Based Cohort Study in Zhejiang Province, China

JAMA Intern Med, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2783099

CONTENUTO: Grosso studio di coorte investigante l’associazione tra la severità della presentazione clinica e il rischio di trasmettere l’infezione da SARS-CoV2 a un contatto stretto. Analizzando i dati di 730 casi di COVID-19 e 8872 contatti, lo studio ha rilevato che il massimo rischio di trasmettere l’infezione si ha tra due giorni prima e tre giorni dopo l’esordio dei sintomi, con picco al giorno di esordio. Inoltre, i casi di COVID-19 con sintomi lievi o moderati si sono dimostrati particolarmente a rischio di trasmettere il virus mentre, al contrario, i contatti di casi asintomatici hanno registrato un rischio minore di sviluppare la malattia.

COMMENTO: Lo studio offre dati importanti che potrebbero essere usati per contrastare l’obiezione di chi è contrario alla vaccinazione con la motivazione che questa non evita completamente il rischio di contrarre l’infezione. I risultati dello studio infatti possono essere trasferiti, con ribaltamento, applicandoli alla fattispecie dei casi indice vaccinati: è vero che possono contrarre la COVID ma hanno una modesta probabilità di trasmettere l’infezione e i loro contatti infetti hanno una elevata probabilità di restare asintomatici.

Adenaiye OO, et al.

Infectious SARS-CoV-2 in Exhaled Aerosols and Efficacy of Masks During Early Mild Infection

Clinical Infectious Diseases,

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab797/6370149

CONTENUTO: Studio analizzante la presenza di materiale genetico di SARS-CoV2 in campioni di sangue, saliva e aereosol prodotti da pazienti all’esordio dei sintomi. Tra i 49 soggetti reclutati, i campioni di aereosol appartenenti a pazienti infetti da variante alpha hanno presentato una quantità di RNA virale significativamente maggiore, e l’utilizzo delle mascherine chirurgiche è stato in grado di ridurre la quantità di RNA virale del 48%. Tali evidenze sottolineano il ruolo fondamentale delle mascherine e suggeriscono che il virus stia evolvendo verso una sempre maggiore efficienza di trasmissione per via aerea.

COMMENTO: Lo studio evidenzia nei campioni di aereosol la maggiore quantità di RNA virale associata alla variante (VOC) alpha, che ne giustifica la maggiore trasmissibilità. Possiamo presumere che questo sarà tanto più vero per la variante delta, oggi assolutamente prevalente. Altro dato importante è il riscontro della non differente efficacia protettiva delle mascherine facciali chirurgiche e di tessuto. Riteniamo che questo aspetto vada approfondito e discusso perché esistono molti dati contrastanti sull’efficacia delle mascherine di tessuto.

Maogui H. et al.

Risk of SARS-CoV-2 Transmission among Air Passengers in China

Clin Infect Dis, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab836/6373518

CONTENUTO:  Studio sulla trasmissione di SARS-CoV-2 sugli aerei di linea.

Il rischio complessivo è relativamente basso (ad es. per la ridotta probabilità che soggetti sintomatici viaggino, ma anche per la presenza di filtri dell’aria).

Tale rischio è maggiore per i vicini di posto del caso indice e in generale per chi è seduto nella stessa fila. Il soggetto affetto da COVID-19 che viaggia risulta più infettante se seduto in un posto centrale (rispetto al lato finestrino/corridoio). Il rischio di contagio aumenta se la durata del viaggio supera le 2 ore.

COMMENTO :

Questo articolo ribadisce due cose importanti

Uno che i protocolli di sicurezza cosi come il ri circolo dell’aria negli aerei funziona

Due : si ripassano noti principi di tracciamento epidemiologico che normalmente si fa negli aerei in caso di presenza di un caso di infezione trasmissibile

Lee JH, et al.

Effectiveness of portable air filtration on reducing indoor aerosol transmission: preclinical observational trials.

J Hosp Infect,

https://reader.elsevier.com/reader/sd/pii/S0195670121003364?token=5B801D9E6BE450976BDDBABB4736587386B55804A31E8508B96D88AC5CF24742E28D042B42D49638CD018A59B5BD70FF&originRegion=eu-west-1&originCreation=20210930155631

CONTENUTO: Vi sono prove crescenti che la trasmissione di SARS-CoV-2 avvenga anche attraverso l’inalazione di particelle di aerosol e che questa via di trasmissione svolga un ruolo dominante soprattutto negli ambienti chiusi in cui la ventilazione è scarsa.

I dispositivi portatili per la pulizia dell'aria possono migliorare l'eliminazione dell'aerosol in ambienti chiusi.

Gli autori negano ovviamente conflitti di interesse ed interessi commerciali

COMMENTO : l’articolo parla e solleva un vecchio problema di questa pandemia

La stabilita del virus in aerosol e quindi la sua trasmissione per questa via

Ovviamente nei setting ad alto rischio purificatori di aria e filtri sono assolutamente necessari oltre ai protocolli di sicurezza.

Jung J. et al

Clustering and multiple-spreading events of nosocomial severe acute respiratory syndrome coronavirus 2 infection

Journal of Hospital Infection, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384763/pdf/main.pdf

CONTENUTO: Studio sulla trasmissione nosocomiale di SARS-CoV-2 condotto in Corea del Sud da cui emerge che la maggior parte dei casi di infezione non darebbe origine a casi secondari. Più della metà dei cluster ospedalieri sono generati da pochi individui (18%) che si comportano pertanto da super-diffusori. La principale causa potrebbe essere il maggior tempo intercorso tra l’esordio dei sintomi e la conferma diagnostica.

COMMENTO : Finalmente uno studio che riguarda e conferma come un ospedale se non ha gli adeguati protocolli di sicurezza puo essere un amplificatore di infezioni virali ed innescare casi da uno o piu casi che fanno da super diffusori. Lo studio e anche un buon esempio di contact tracing nosocomiale interamente epidemiologico.

Cevik M et al

Networks of SARS-CoV-2 transmission

Science, July 2021 ; DOI: 10.1126/science.abg0842

COMMENTO : The basic reproduction number, R0 (the number of infections caused by a case in a homogeneously susceptible population), for a particular infection is dependent on the epidemiological triad of the biological characteristics of the pathogen, the environment, and the characteristics of the population (1). Even for diseases with similar transmission characteristics, R0 varies by population owing to differential opportunities for onward transmission according to the contact patterns and the size of the transmission network of an infected individual (1). Although transmission can happen in many settings, some factors facilitate a greater risk of infection because of compounded risks often driven by network dynamics (frequent contacts, close proximity, and prolonged contact) and structural-level determinants (such as poverty, occupation, and household size) (2–4). Understanding drivers of transmission risks and heterogeneity could be used to improve modeling and guide population- and setting-specific mitigation strategies.

Muyldermans A et al

SARS-CoV-2 RNA and antibodies in tear fluid

BMJ Open Ophtalmology, April 2021; DOI: 10.1136/bmjophth-2021-000733

COMMENTO : Background/aims: SARS-CoV-2 is highly contagious. More evidence concerning extrapulmonary transmission routes such as the eyes is urgently needed. Although the humoral immune response is important in the viral containment, the local response in tears has not yet been studied. The aim of our study was twofold: to assess the prevalence of both SARS-CoV-2 RNA and antibodies in tear fluid. Methods: In a first series, nasopharyngeal sampling and tear sampling by Schirmer test strips were performed in 26 acutely ill patients with COVID-19 to assess the presence of SARS-CoV-2 RNA by reverse transcription PCR. In a second series, IgG and IgA responses to SARS-CoV-2 spike protein in serum and tear fluid of convalescent individuals (n=22) were compared with control individuals (n=15) by ELISA. Results: SARS-CoV-2 RNA was detected in tears of 7/26 (26.9%) patients with COVID-19. None of them had ocular symptoms. Convalescent individuals displayed a significant higher ratio of IgG (p<0.0001) and IgA (p=0.0068) in tears compared with control individuals. A sensitivity of 77.3% and specificity of 93.3% was observed for IgG, and 59.1% and 100% for IgA. Conclusions: Our results demonstrate the presence of SARS-CoV-2 RNA and a local IgG and IgA immune response in tear fluid. These data confirm the possibility of SARS-CoV-2 transmission through tear fluid and the importance of the eye as a first defence against SARS-CoV-2, indicating the potential of tears as a non-invasive surrogate for serum in monitoring the host immune response.

Karan A et al

The Risk of SARS-CoV-2 Transmission from Patients with Undiagnosed Covid-19 to Roommates in a Large Academic Medical Center

CID, June 2021; doi.org/10.1093/cid/ciab564

COMMENTO : We assessed SARS-CoV-2 transmission between patients in shared rooms in an academic hospital between September 2020-April 2021. 11,290 patients were admitted to shared rooms, of whom 25 tested positive. Among 31 exposed roommates, 12 (39%) tested positive within 14 days. Transmission was associated with PCR cycle thresholds ≤21.

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, July 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.

Xiao X et al

Animal sales from Wuhan wet markets immediately prior to the COVID-19 pandemic

Scientific Reports, June 2021 ; doi.org/10.1038/s41598-021-91470-2

COMMENTO : Here we document 47,381 individuals from 38 species, including 31 protected species sold between May 2017 and November 2019 in Wuhan’s markets. We note that no pangolins (or bats) were traded, supporting reformed opinion that pangolins were not likely the spillover host at the source of the current coronavirus (COVID-19) pandemic. While we caution against the misattribution of COVID-19’s origins, the wild animals on sale in Wuhan suffered poor welfare and hygiene conditions and we detail a range of other zoonotic infections they can potentially vector. Nevertheless, in a precautionary response to COVID-19, China’s Ministries temporarily banned all wildlife trade on 26th Jan 2020 until the COVID-19 pandemic concludes, and permanently banned eating and trading terrestrial wild (non-livestock) animals for food on 24th Feb 2020. These interventions, intended to protect human health, redress previous trading and enforcement inconsistencies, and will have collateral benefits for global biodiversity conservation and animal welfare.

Razani N et al

Clarification regarding Outdoor Transmission of SARS-CoV-2 and Other Respiratory Viruses, a Systematic Review

The Journal of Infectious Diseases, June 2021; DOI: 10.1093/infdis/jiab298

COMMENTO: On April 24, 2021, the Centers for Disease Control and Prevention (CDC) issued new guidance on outdoor activities. In subsequent testimony before the United States Senate, a number reported in our article, “Outdoor Transmission of SARS-CoV-2 and Other Respiratory Viruses: A Systematic Review,” was cited that the proportion of SARS-CoV-2 transmission occurring in outside settings is less than 10%. We are writing to clarify how we arrived at the less than ten percent summary number. Our abstract and results sections state that “five identified studies found a low proportion of reported global SARS-CoV-2 infections occurred outdoors (<10%).” Because of the small number of heterogeneous studies we  reviewed, as well as their methodological limitations, we could not provide a meta-analytically pooled estimate of the exact proportion of SARSCoV-2 transmissio. Ten percent was chosen as a conservative estimate based on the upper confidence limit of the proportion of cases attributable to outdoor settings reported in one of the studies we reviewedns that have occurred outdoors or the associated risk.

Jones TC et al

Estimating infectiousness throughout SARS-CoV-2 infection course

Science, May 2021 ; DOI: 10.1126/science.abi5273

COMMENTO : Two elementary parameters for quantifying viral infection and shedding are viral load and whether samples yield a replicating virus isolate in cell culture. We examined 25,381 German SARS-CoV-2 cases, including 6110 from test centres attended by pre-symptomatic, asymptomatic, and mildly-symptomatic (PAMS) subjects, 9519 who were hospitalised, and 1533 B.1.1.7 lineage infections. The youngest had mean log10 viral load 0.5 (or less) lower than older subjects and an estimated ~78% of the peak cell culture replication probability, due in part to smaller swab sizes and unlikely to be clinically relevant. Viral loads above 109 copies per swab were found in 8% of subjects, one-third of whom were PAMS, with mean age 37.6. We estimate 4.3 days from onset of shedding to peak viral load (8.1) and cell culture isolation probability (0.75). B.1.1.7 subjects had mean log10 viral load 1.05 higher than non-B.1.1.7, with estimated cell culture replication probability 2.6 times higher.

Jones L et al

Transmission of SARS-CoV-2 on a Patient Transport Van

Clinical Infectious Diseases, April 2021; doi.org/10.1093/cid/ciab347

COMMENTO : We report 2 episodes of potential SARS-CoV-2 transmission from infected van drivers to passengers despite masking and physical distancing. Who legenome  sequencing confirmed related ness of driver and passenger SARS-CoV-2. With the heater operating, fluorescent microspheres were transported by airflow>3 metersfrom the front to the back of the van.

Qiu X et al

The role of asymptomatic and pre-symptomatic infection in SARS-CoV-2 transmission—a living systematic review

Clinical Microbiology and Infection, April 2021; DOI: 10.1016/j.cmi.2021.01.011

COMMENTO : Background : Reports suggest that asymptomatic individuals (those with no symptoms at all throughout infection) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are infectious, but the extent of transmission based on symptom status requires further study.

Purpose : This living review aims to critically appraise available data about secondary attack rates from people with asymptomatic, pre-symptomatic and symptomatic SARS-CoV-2 infection.

Data sources : Medline, EMBASE, China Academic Journals full-text database (CNKI), and pre-print servers were searched from 30 December 2019 to 3 July 2020 using relevant MESH terms.

Study selection : Studies that report on contact tracing of index cases with SARS-CoV-2 infection in either English or Chinese were included.

Data extraction : Two authors independently extracted data and assessed study quality and risk of bias. We calculated the secondary attack rate as the number of contacts with SARS-CoV-2, divided by the number of contacts tested.

Data synthesis : Of 927 studies identified, 80 were included. Summary secondary attack rate estimates were 1% (95% CI 0%–2%) with a prediction interval of 0%–10% for asymptomatic index cases in ten studies, 7% (95% CI 3%–11%) with a prediction interval of 1%–40% for pre-symptomatic cases in 11 studies and 6% (95% CI 5%–8%) with a prediction interval of 5%–38% for symptomatic index cases in 40 studies. The highest secondary attack rates were found in contacts who lived in the same household as the index case. Other activities associated with transmission were group activities such as sharing meals or playing board games with the index case, regardless of the disease status of the index case.

Limitations : We excluded some studies because the index case or number of contacts were unclear.

Conclusion : Asymptomatic patients can transmit SARS-CoV-2 to others, but our findings indicate that such individuals are responsible for fewer secondary infections than people with symptoms.

Schuit M et al

The stability of an isolate of the SARS-CoV-2 B.1.1.7 lineage in aerosols is similar to three earlier isolates

The Journal of Infectious Diseases, April 2021; DOI: 10.1093/infdis/jiab171

COMMENTO : Background : Our laboratory previous lyexamined the influence of environmental conditions on the stability of an earlyisolate of SARS-CoV-2 (hCoV-19/USA/WA-1/2020) in aerosolsgeneratedfrom culture medium or simulated saliva. However, geneticdifferences have emergedamong SARS-CoV-2 lineages, and itis possible thatthesedifferencesmay affect environmentalstability and the potential for aerosol transmission.

Methods : The influence of temperature, relative humidity, and simulated sunlight on the decay of four SARS-CoV-2 isolates in aerosols, including one belonging to the recentlyemerged B.1.1.7 lineage, werecompared in a rotatingdrumchamber. Aerosol swere generated from simulated respiratory tract liningfluid to represent aerosols originating from the deeplung.

Results : No differences in the stability of the isolates were observed in the absence of simulated sunlight at either 20°C or 40°C. However, a small but statistically significant difference in the stability was observed between some isolates in simulated sunlight at 20°C and 20% relative humidity. .

Conclusions : The stability of SARS-CoV-2 in aerosolsdoes not varygreatly among currently circulating lineages, including B.1.1.7, suggesting that the increasedtransmissibilityassociatedwithrecent SARS-CoV-2 lineagesis not due to enhancedsurvival in the environment.

Park M et al

Determining the communicable period of SARS-CoV-2: A rapid review of the literature, March to September 2020

Eurosurveillance, December 2020; doi.org/10.2807/1560-7917.ES.2021.26.14.2001506

COMMENTO : Introduction : Standard testing for infection withsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isbased on RT-PCR tests, but detection of viral geneticmaterialalonedoes not indicateongoinginfectiouspotential. The ability to isolatewhole virus represents a better proxy for infectivity.

Aim : The objective of thisstudywas to gain an understanding of the currentliterature and compare the reportedperiods of positive SARS-CoV-2 detectionfromstudiesthatconducted RT-PCR testing in addition to experimentsisolatingwhole virus.

Methods : Using a rapidreviewapproach, studiesreportingempirical data on the duration of positive RT-PCR results and/or successful viral isolation following SARS-CoV-2 infection in humanswereidentifiedthroughsearches of peer-reviewed and pre-printhealth sciences literature. Articles werescreened for relevance, then data wereextracted, analysed, and synthesised.

Results : Of the 160 studies included for qualitative analysis, 84% (n = 135) investigated duration of positive RT-PCR tests only, 5% (n = 8) investigated duration of successful viral isolations, while 11% (n = 17) included measurements on both. There was significant heterogeneity in reported data. There was a prolonged time to viral clearance when deduced from RT-PCR tests compared with viral isolations (median: 26 vs 9 days).

Discussion : Findingsfromthisreview support a minimum 10-day period of isolation but certain cases where virus wasisolatedafter 10 dayswereidentified. Given the extended time to viral clearance from RT-PCR tests, future researchshouldensure standard reporting of RT-PCR protocols and results to help informtestingpoliciesaimed at clearance from isolation.

Rasmussen AL et al

SARS-CoV-2 transmission without symptoms

Science, March 2021 ; DOI: 10.1126/science.abf9569

COMMENTO : Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a potentially long incubation period and spreads opportunistically among those who are unaware they are infected. Asymptomatic COVID-19 cases are those that do not develop symptoms for the duration of infection, whereas presymptomatic cases develop symptoms later in the course of infection, but both are crucial drivers of transmission. Transmission without symptoms poses specific challenges for determining the infectious timeline and potential exposures. Early in the pandemic, most transmission was from undocumented cases, suggesting that spread was driven by people who were either asymptomatic or experiencing such mild disease that it was not recognized as COVID-19. Contagious people without observable signs of illness make infection prevention efforts vulnerable to compliance with masking, distancing, hand hygiene, symptom screening, and ultimately, people staying home when possible. The lack of widespread testing in asymptomatic individuals further complicates COVID-19 mitigation and control efforts.

Schumm MA et al

Filtering Facepiece Respirator (N95 Respirator) Reprocessing: A Systematic Review

JAMA, March 2021; doi:10.1001/jama.2021.2531

COMMENTO : Importance  The COVID-19 pandemic has resulted in a persistent shortage of personal protective equipment; therefore, a need exists for hospitals to reprocess filtering facepiece respirators (FFRs), such as N95 respirators.

Objective  To perform a systematic review to evaluate the evidence on effectiveness and feasibility of different processes used for decontaminating N95 respirators.

Evidence Review  A search of PubMed and EMBASE (through January 31, 2021) was completed for 5 types of respirator-decontaminating processes including UV irradiation, vaporized hydrogen peroxide, moist-heat incubation, microwave-generated steam, and ethylene oxide. Data were abstracted on process method, pathogen removal, mask filtration efficiency, facial fit, user safety, and processing capability.

Findings  Forty-two studies were included that examined 65 total types of masks. All were laboratory studies (no clinical trials), and 2 evaluated respirator performance and fit with actual clinical use of N95 respirators. Twenty-seven evaluated UV germicidal irradiation, 19 vaporized hydrogen peroxide, 9 moist-heat incubation, 10 microwave-generated steam, and 7 ethylene oxide. Forty-three types of N95 respirators were treated with UV irradiation. Doses of 1 to 2 J/cm2 effectively sterilized most pathogens on N95 respirators (>103 reduction in influenza virus [4 studies], MS2 bacteriophage [3 studies], Bacillus spores [2 studies], Escherichia virus MS2 [1 study], vesicular stomatitis virus [1 study], and Middle East respiratory syndrome virus/SARS-CoV-1 [1 study]) without degrading respirator components. Doses higher than 1.5 to 2 J/cm2 may be needed based on 2 studies demonstrating greater than 103 reduction in SARS-CoV-2. Vaporized hydrogen peroxide eradicated the pathogen in all 7 efficacy studies (>104 reduction in SARS-CoV-2 [3 studies] and >106 reduction of Bacillus and Geobacillus stearothermophilus spores [4 studies]). Pressurized chamber systems with higher concentrations of hydrogen peroxide caused FFR damage (6 studies), while open-room systems did not degrade respirator components. Moist heat effectively reduced SARS-CoV-2 (2 studies), influenza virus by greater than 104 (2 studies), vesicular stomatitis virus (1 study), and Escherichia coli (1 study) and preserved filtration efficiency and facial fit for 11 N95 respirators using preheated containers/chambers at 60 °C to 85 °C (5 studies); however, diminished filtration performance was seen for the Caron incubator. Microwave-generated steam (1100-W to 1800-W devices; 40 seconds to 3 minutes) effectively reduced pathogens by greater than 103 (influenza virus [2 studies], MS2 bacteriophage [3 studies], and Staphylococcus aureus [1 study]) and maintained filtration performance in 10 N95 respirators; however, damage was noted in least 1 respirator type in 4 studies. In 6 studies, ethylene oxide preserved respirator components in 16 N95 respirator types but left residual carcinogenic by-product (1 study).

Conclusions and Relevance  Ultraviolet germicidal irradiation, vaporized hydrogen peroxide, moist heat, and microwave-generated steam processing effectively sterilized N95 respirators and retained filtration performance. Ultraviolet irradiation and vaporized hydrogen peroxide damaged respirators the least. More research is needed on decontamination effectiveness for SARS-CoV-2 because few studies specifically examined this pathogen.

De Vries RD et al

Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets

Science, February 2021; DOI: 10.1126/science.abf4896

COMMENTO: Containment of the COVID-19 pandemic requires reducing viral transmission. SARS-CoV-2 infection isinitiated by membrane fusion between the viral and host cell membranes, mediated by the viral spike protein. We have designed lipopeptide fusion inhibitorsthat block thiscritical first step of infection, and based on in vitro efficacy and in vivo biodistributionselected a dimeri cform for evaluation in an animal model. Daily intranasal administration to ferrets completely prevented SARS-CoV-2 direct-contact transmission during 24-hour co-housing with infected animals, under stringent conditions that resulted in infection of 100% of untreated animals. These lipopeptides are highly stable and thus may readily translate into safe and effective intranasal prophylaxis to reduce transmission of SARS-CoV-2.

Rebeiro PF et al

The Impact of State Mask-Wearing Requirements on the Growth of COVID-19 Cases in the United States

Clinical Infectious Diseases, February 2021 ; doi.org/10.1093/cid/ciab101

COMMENTO: In our ecologic analysis of US states, piecewise multivariable models showed lower post- vs. pre-mask case-rate slopes, with -1.08% per 100,000 per day (95% CI: -1.48%, -0.67%) among early- and -0.37% per 100,000 per day (95% CI: -0.86%, 0.10%) among late- versus never-adopter states. Our findings support statewide mask requirements to mitigate COVID-19 transmission.

Qiu X et al

Defining the role of asymptomatic and pre-symptomatic SARS-CoV-2 transmission – a living systematic review

Clinical Microbiology and Infection, OCTOBER 2020; doi.org/10.1101/2020.09.01.20135194

COMMENTO : Background : Reports suggestthatasymptomaticindividuals (thosewith no symptoms at all throughout infection) withsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are infectious, but the extent of transmission based on symptomstatusrequiresfurtherstudy.

Purpose : This living reviewaims to criticallyappraiseavailable data about secondaryattack rates from people withasymptomatic, pre-symptomatic and symptomatic SARS-CoV-2 infection.

Data sources : Medline, EMBASE, China Academic Journals full-textdatabase (CNKI), and pre-print servers weresearchedfrom 30 December 2019 to 3 July 2020 using relevant MESH terms.

StudyselectionStudiesthat report on contact tracing of index cases with SARS-CoV-2 infection in either English or Chinesewereincluded.

Data extraction : Two authors independently extracted data and assessed study quality and risk of bias. We calculated the secondary attack rate as the number of contacts with SARS-CoV-2, divided by the number of contacts tested. Data synthesis Of 927 studies identified, 80 were included. Summary secondary attack rate estimates were 1% (95% CI: 0%-2%) with a prediction interval of 0-10% for asymptomatic index cases in 10 studies, 7% (95% CI: 3%-11%) with a prediction interval of 1- 40% for pre-symptomatic cases in 11 studies and 6% (95% CI: 5%-8%) with a prediction interval of 5- 38% for symptomatic index cases in 40 studies. The highestsecondaryattack rates werefound in contacts wholived in the samehousehold as the index case. Otheractivitiesassociatedwith transmission were group activitiessuch as sharing meals or playingboardgameswith the index case, regardless of the diseasestatus of the index case.

Limitations : Weexcludedsomestudiesbecause the index case or number of contacts wereunclear.

Conclusion : Asymptomatic patients can transmit SARS-CoV-2 to others, but ourfindingsindicatethatsuchindividuals are responsible for fewersecondary infections than people withsymptoms.

Priesemann V et al

An action plan for pan-European defence against new SARS-CoV-2 variants

The Lancet, January 2021; doi.org/10.1016/S0140-6736(21)00150-1

COMMENTO : COVID-19 cases are very high across Europe. Currentmeasures are not reducing virus spread sufficiently, and new SARS-CoV-2 variants are emerging. The B.1.1.7 and B1.351 variants, first identified in the UK and South Africa, respectively, have spread to manyEuropean countries.Although the biologicalproperties of these variants are yet to becharacterised, epidemiological data suggestthey have a highertransmissibilitythan the original variant. These viral propertiescouldincrease the effective reproduction number R in the population. In the case of B.1.1.7, estimatessuggest R couldincreasefrom 1 to about 1.4 with no change in population behavior.If true, many countries that have succeeded in reducing R to 1 or lesswillbeconfrontedwith a novelwave of viral spread despite the currentmeasures.Once a more contagious variant has establisheditself, stabilising the number of new infections willbecomeincreasinglydifficult.

Samet JM et al

Airborne Transmission of SARS-CoV-2: What We Know

Clinical Infectious Diseases, January 2021 ; DOI: 10.1093/cid/ciab039

COMMENTO : We examine airborne transmission of SARS-CoV-2 potential using a source-to-dose framework beginning with generation of virus-containing droplets and aerosols and ending with virus deposition in the respiratory tract of susceptible individuals. By addressing four critical questions, we identify both gaps in addressing four critical questions with answers having policy implications.

Delikhoon M et al

Modes of Transmission of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) and Factors Influencing on the Airborne Transmission: A Review

International Journal fo Environmental Research and Public Health, 6 January 2021;  doi.org/10.3390/ijerph18020395

COMMENTO : The multiple modes of SARS-CoV-2 transmission including airborne, droplet, contact, and fecal-oral transmissions that cause coronavirus disease 2019 (COVID-19) contribute to a public threat to the lives of people worldwide. Herein, different databases are reviewed to evaluate modes of transmission of SARS-CoV-2 and study the effects of negative pressure ventilation, air conditioning system, and related protection approaches of this virus. Droplet transmission was commonly reported to occur in particles with diameter >5 microm that can quickly settle gravitationally on surfaces (1-2 m). Instead, fine and ultrafine particles (airborne transmission) can stay suspended for an extended period of time (>/=2 h) and be transported further, e.g., up to 8 m through simple diffusion and convection mechanisms. Droplet and airborne transmission of SARS-CoV-2 can be limited indoors with adequate ventilation of rooms, by routine disinfection of toilets, using negative pressure rooms, using face masks, and maintaining social distancing. Other preventive measures recommended include increasing the number of screening tests of suspected carriers of SARS-CoV-2, reducing the number of persons in a room to minimize sharing indoor air, and monitoring people's temperature before accessing a building. The work reviews a body of literature supporting the transmission of SARS-CoV-2 through air, causing COVID-19 disease, which requires coordinated worldwide strategies.

Meyerowitz EA et al

A defense of the classical model of transmission of respiratory pathogens

ClinicalInfectiousDiseases, January 2021 ; doi.org/10.1093/cid/ciab016

COMMENTO : We fully agree that an important lesson from the ongoing COVID-19 pandemic has been that the aerosol-droplet dichotomy for transmission of respiratory pathogens is oversimplified.However, it is remarkable that this model has held up surprisingly well in informing effective public health strategies to minimize spread. The over whelming evidence suggests that respiratory transmission is dominant and that, despite the flaws of the aerosol-droplet model, classical droplet (and in particular the infection control practices implied by it) is more important than aerosol transmission for SARSCoV-2. There are several points to consider.

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