Skip to main content

Our take —

While masks most likely prevent community spread of COVID-19, this highly flawed paper provides no evidence on mask effectiveness at the population level. The study also provides no information to demonstrate that airborne transmission — let alone “long-range airborne transmission” — is the dominant form of COVID-19 transmission. The claims made in this paper are not supported, and the journal editors should strongly consider retraction.

Study design

Other

Study population and setting

The objective of the study was to assess the impact of masks and other non-pharmaceutical interventions on COVID-19 transmission, as well to determine the predominant routes of viral spread (e.g., airborne versus droplet). The authors used linear regressions fit to case data from New York City and Italy to assess trends in cases occurring before and after implementation of various non-pharmaceutical interventions, particularly mask mandates in northern Italy on April 6, 2020 and in New York City on April 17, 2020. Qualitative comparisons were made to trends in Wuhan, China. Inference about the effectiveness of mask-wearing, and subsequently about the dominant route of SARS-CoV-2 transmission, was made on the basis of departures from linearity after the date of mask mandates.

Summary of Main Findings

This paper had two primary conclusions, neither of which were supported by the evidence presented. First, the authors concluded that mask mandates were the only factor that led to departures from the linear trend of case counts in Italy and New York City, and by implication, that no other non-pharmaceutical interventions (e.g., social distancing policies) were effective. Second, the authors concluded that airborne transmission is the major driver of COVID-19 spread. There were no measures of uncertainty reported.

Study Strengths

None

Limitations

The authors made two false statements, which were key assumptions underpinning their primary conclusions. The first statement, which was used to justify the conclusion that masks were the sole effective non-pharmaceutical intervention leading to reduction in the growth of new cases, was that, “after April 3, the only difference in regulatory measures between NYC and the United States lies in face coverings on April 17 in NYC”. This assertion is verifiably false based on publicly available resources (e.g., HIT-COVID) and represents a gross mischaracterization of the primary exposure variable (non-pharmaceutical interventions). Second, in justifying the conclusion that airborne transmission is the dominant mode of COVID-19 spread, they state that, “with social distancing, quarantine, and isolation in place worldwide and in the United States since the beginning of April, airborne transmission represents the only viable route for spreading the disease.” This statement is also verifiably false; many countries and jurisdictions were not in lockdown and did not have isolation and quarantine programs in place at the beginning of April (e.g., Sweden, parts of the US).

There were also serious methodological flaws, which may be broadly categorized as follows:

Exposure misclassification: the construct of interest is mask-wearing, but dates of mask mandates are poor proxies for behavior. No attempt was made to measure or describe actual mask-wearing behavior during the time periods and regions considered.

Confounding: the authors considered no other factors determining COVID-19 case counts that may have differed between time periods and regions. The time period under consideration in Italy and the United States saw sweeping, complex changes in a broad array of non-pharmaceutical interventions, personal behaviors, testing availability, and epidemic dynamics. None of these are included in the models. Similarly, the authors’ qualitative comparisons with Wuhan, China ignore substantive differences not only in the underlying populations, but in the intensity of non-pharmaceutical interventions such as case detection, contact tracing, and isolation.

Model misspecification: Linear models were fit to cumulative and daily COVID-19 case-count data, which do not follow linear growth patterns, except in specific circumstances for limited times. Infectious disease dynamics were entirely ignored by this simplistic approach. The analysis also did not account for the necessary lag between reduction in transmission (via mask-wearing, for example) and reduction in reported cases.

Measures of uncertainty: The authors reported no measures of uncertainty. The results include no p-values, confidence intervals, or any formal inference of any sort. This represents a departure from scientific orthodoxy and a gross oversight, particularly considering the strong conclusions the authors assert from their results.

Value added

None

Our take —

To date, there is no evidence from randomized trials regarding the effect of wearing face masks on the risk of acquiring infection from SARS-CoV-2. In the absence of this urgently needed data, this systematic review and meta-analysis provides evidence, with a low degree of certainty, that wearing face masks may strongly reduce the risk of acquiring infection from cases. Moreover, there is evidence that N95 respirators, which are fitted to the user’s face, confer greater protection in health-care settings than other unfitted masks; no evidence was presented regarding differential effectiveness of respirators in community settings. This study does not address any potential reductions in transmission risk from mask-wearing on the part of an infectious person. Risk appears to be considerably reduced by maintaining a physical distance from infected individuals greater than 1 meter, with further risk reductions as the distance increases. However, these data come from non-randomized observational studies, only a small number of which were specific to SARS-CoV-2 (the majority came from studies of SARS and MERS).

Study design

Other

Study population and setting

This systematic review and meta-analysis included studies of SARS-CoV, MERS-CoV, and SARS-CoV-2 that assessed the effects of physical distancing, face masks, and eye protection on disease transmission. The review included 172 studies, 44 of which were comparative (including a total of 25,697 patients in health-care, household, and community settings) and were therefore used in pooled effect estimates in meta-analysis. Of these 44 studies, 7 were specific to SARS-CoV-2; pooled effect estimates were calculated separately for each coronavirus and combined into weighted averages across all studies. The authors used Cochrane and GRADE methods for the systematic review and assessment, and reported results using PRISMA and MOOSE guidelines. Risk of bias for each study was assessed via the Newcastle-Ottawa scale.

Summary of Main Findings

Across 10 adjusted studies and 29 unadjusted studies that included both health-care and non-health-care settings, wearing any type of face mask was associated with a lower risk of infection (unadjusted RR: 0.34, 95% CI: 0.26 to 0.45; adjusted OR: 0.15, 95% CI: 0.07 to 0.34). A stronger protective effect in health-care settings was observed with N95 respirators relative to other mask types (adjusted ORs of 0.04 vs. 0.33, p=0.09 for interaction). Wearing eye protection was associated with a lower risk of infection (unadjusted RR: 0.34, 95% CI: 0.22 to 0.52; adjusted RR: 0.25, 95% CI: 0.14 to 0.43). Physical distance of greater than 1 meter was associated with a lower risk of disease transmission relative to less than 1 meter (adjusted OR: 0.18, 95% CI: 0.09 to 0.38; risk difference: -10.2%, 95% CI: -11.5% to -7.5%). Increased distance was associated with lower viral transmission risk. The certainty of the results, according to the GRADE scale, was deemed to be moderate for distance and low for both face masks and eye protection. Risk of bias was deemed to be low-to-moderate. Across 24 studies examining attitudes and contextual factors regarding interventions, face mask use of multiple types was generally considered to be acceptable and feasible, despite reported challenges including discomfort.

Study Strengths

The systematic review was conducted according to established and transparent protocols. The meta-analyses used appropriate statistical techniques, and authors tested their results with well-described sensitivity analyses. Results were reported with a high degree of disaggregation and detail.

Limitations

The number of extant studies, particularly those specific to SARS-CoV-2, was small, and these studies were non-randomized. Mask use by an index case and its effect on transmissibility, on one hand, and mask use by contacts of the index case and its effect on susceptibility, on the other, are not distinguished as separate issues in either the analysis or the discussion. Mask types and usage were heterogeneous in the underlying studies, and the role of mask fit was not discussed, despite a potentially large impact on effectiveness. Measurement of interventions often relied on self-report and these data are subject to recall bias. Distance measurements in underlying studies were heterogeneous and imprecise. The duration of exposure was not assessed as a risk factor for transmission or as an effect modifier.

Value added

This review and meta-analysis provides the best available evidence for the possible protective effects of face masks, eye protection, and physical distancing on the risk of SARS-CoV-2 infection.

Our take —

In a large study from the US, Canada, and Spain, patients with cancer and COVID-19 had a high likelihood of severe disease and death. A history of smoking, increased age, and the presence of active cancer were risk factors for severe disease and death. Further study is needed to better understand how active cancer treatment is associated with disease progression.

Study design

Other

Study population and setting

The study included 928 adult patients (median age 66 years; 50% male) with current or past invasive cancer and with laboratory-confirmed COVID-19 treated at participating facilities in the United States, Canada, or Spain. Baseline information on SARS-CoV-2-infected patients was entered between March 17 and April 16, 2020, with follow-up through May 7, 2020. Median follow-up duration was 21 days. Logistic regression was used to examine associations between patient factors and outcomes (primary outcome: death within 30 days of COVID-19 diagnosis; secondary outcomes: hospital admission, ICU admission, mechanical ventilation, supplemental oxygen).

Summary of Main Findings

Overall, by the end of follow-up, 13% of patients died within 30 days of COVID-19 diagnosis; and 26% of patients experienced the composite outcome of death, ICU admission, or mechanical ventilation. Mortality among those admitted to the hospital was 23%. Factors associated with increased mortality included older age, male sex, history of smoking, more comorbidities, current or progressing disease (versus remission), and treatment with azithromycin and hydroxychloroquine. There was no observed impact of race/ethnicity, obesity, and cancer type on mortality.

Study Strengths

The study included a large sample of patients with cancer. Geographically diverse study sites increase generalizability of findings.

Limitations

Because the study relied on providers to input information into the database on cancer patients with COVID-19, those with severe disease may be more likely to be entered. Patients with mild or asymptomatic disease may not have presented for care or would be less likely to trigger data entry. This would result in overestimation of the likelihood of severe disease and death. Those who present with severe disease may have been more likely to be administered azithromycin/hydroxychloroquine; thus, we cannot conclude that use of the drug combination itself is independently associated with severe disease (confounding by indication). Patients with current cancer may have considerably different exposure-outcome relationships from those whose cancer was in remission or was successfully treated; if so, analysis with stratification would be more appropriate.

Value added

This is one of largest studies to date on COVID-19 in patients with cancer.

Our take —

This study utilized contact-tracing surveillance data collected from January 28 to March 15, 2020 in Guangzhou, China to characterize secondary transmission of COVID-19 among contacts of pre-symptomatic cases. The overall secondary attack rate was 3.3% (95% CI 1.9%–5.6%), and varied by eventual symptomatic status of index-cases, including 0.8% (0.2–5.6) among contacts of asymptomatic cases, and from 3.5% to 5.7% among cases who became symptomatic. Although the number of secondary cases, and thus power, were limited (n=12), this study supports secondary transmission to contacts of both pre-symptomatic and asymptomatic cases.

Study design

Other

Study population and setting

This study utilized contact-tracing surveillance data collected from January 28 to March 15, 2020 in Guangzhou, China. These data included a total of 359 confirmed COVID-19 cases, and 369 close contacts of those cases to estimate the secondary attack rate based on the proportion of COVID-19 incidence among close contacts of pre-symptomatic cases. The eventual symptomatic status of the pre-symptomatic cases was determined based on the person’s clinical course assessed by a physician as of March 30, 2020.

Summary of Main Findings

Overall, among the 369 close contacts, 12 secondary cases were identified through diagnostic testing, resulting in a secondary attack rate of 3.3% (95% CI 1.9%–5.6%), with estimates of 16.1% among household members, 1.5% among contacts with friends or family, 1.1% among social contact with strangers, and 0% among workplace contacts. Secondary attack rates varied by eventual symptomatic status of index cases, including 0.8% among contacts of asymptomatic cases, 3.5% to 5.7% among contact of pre-symptomatic index cases who eventually became symptomatic.

Study Strengths

This study incorporates both pre-symptomatic and asymptomatic index cases in the analyses of onward transmission to contacts.

Limitations

This study is limited to close contacts who were able to be reached, and therefore may be subject to selection bias. The study may have missed asymptomatic index cases and contacts, who therefore may not be represented. Close contacts who were exposed to more than two confirmed COVID-19 cases were excluded from this study. Because there were a limited number of secondary cases (n=12), confidence intervals were wide when comparing the relative risk of secondary infection based on index case symptoms, suggesting that a larger sample size is necessary to ascertain patterns between symptom severity and secondary transmission.

Value added

This study considers the eventual clinical presentation of index cases in onward transmission to secondary cases during the pre-symptomatic period.

Our take —

This study, published as a preprint and thus not yet peer-reviewed, shows nearly perfect correlation between trends in viral SARS-CoV-2 RNA measured in sewage sludge in New Haven, Connecticut, and both trends in hospital admissions and community cases testing positive for COVID-19. These results are may be useful for surveillance activities, particularly early warning systems. Further work must be done to validate these findings, and ensure they are generalizable to other settings.

Study design

Other

Study population and setting

The study was conducted in the metropolitan area of New Haven, Connecticut from March 19 to May 1, 2020, with daily primary sludge collected from the East Shore Water Pollution Abatement Facility, which serves an estimated 200,000 people. The study also used Yale New Haven admission data and community SARS-CoV-2 testing data from the Connecticut Department of Public Health.

Summary of Main Findings

SARS-CoV-2 was found in all sludge samples, however 96.5% of all SARS-CoV-2 viral RNA tested samples had concentrations that were less than the detection threshold indicated for this method. Among samples testing positive, the viral RNA level peaked 3 days before hospital admissions, and 7 days before COVID-19 case counts. When shifting the viral RNA data forward by 3 days, there was high correlation with hospital admissions (R=0.996), and when shifted forward by 7 days, there was a high correlation with COVID-19 case counts (R=0.994).

Study Strengths

The study integrated multiple data sources to understand how viral RNA in sewage was associated with COVID outcomes in the community over time. By using sewage sludge rather than wastewater, there is a higher solid content of the material, which often leads to increased detection compared to wastewater.

Limitations

Further validation of using sewage sludge viral RNA data as a proxy for COVID-19 cases must be done, and while the correlation coefficient provides evidence of a linear relationship between the two, further statistics should be calculated. These results also may not be generalizable to other areas given they sampled from one city. In addition, this study was conducted during the stay-at-home order in Connecticut, and may not be as applicable when the stay-at-home order is lifted as people travel again.

Value added

This study provides promising results that sewage sludge analysis could be useful for COVID-19 disease surveillance activities, especially when testing capacity may be limited.

Our take —

This retrospective cross-sectional study examined the correlation between SARS-CoV-2 RT-PCR results (RNA testing) from Canada, and time since symptom onset with virus culture in vitro. While they used the largest sample size to date of non-epidemiologically linked samples to assess these associations, they do not assess actual infectivity in vivo, and the sample size per day since symptom onset is very limited. They also do not assess the relationship between RNA testing and infectiousness in asymptomatic or pre-symptomatic individuals, who may be contributing a significant amount to viral spread in the real-world. Given the limited sample size, we recommend caution when interpreting the peak infectivity.

Study design

Cross-Sectional; Other

Study population and setting

Nasopharangeal (NP) and endotracheal (ETT) samples collected as part of routine care and surveillance in Manitoba, Canada, were tested for SARS-CoV-2 RNA using RT-PCR targeting the viral envelope at the provincial public health laboratory (n=90 total samples). Samples were linked with epidemiological data including time from symptom onset to test (STT). Researchers assessed the relationship between RT-PCR cycle threshold (Ct), which has an inverse relationship with viral concentration, STT, and infectivity of Vero cells in vitro.

Summary of Main Findings

Overall, 26/90 (28.9%) of the samples were deemed infectious, though none past day 8 STT. Infectious samples were more likely to have a lower Ct (<24) and a lower STT (<8 days) than non-infectious samples. Ct was found to be statistically associated with positive culture (infectivity) (OR 0.64 [95% CI: 0.49 – 0.84])—which can be interpreted as for each 1 unit increase in Ct value the odds of infectivity decreased by 32%. Similarly, STT was associated with culture as well (OR 0.63 [95% CI: 0.42 – 0.94]). The peak probability of infectivity was on day 3 STT and decreased thereafter.

Study Strengths

The study used the largest sample size to date collected from epidemiologically unrelated individuals to examine the relationship between test result and infectivity. They integrated PCR results, with epidemiological data and in-vitro infectivity data.

Limitations

Although the largest sample to date, 26 infectious cases remains limited and it is not clear how many samples were available by day, potentially leading to a misinterpretation of results that infectiousness is highest at Day 3 STT given limited sample sizes. In vitro culture is not directly equivalent to in vivo infectivity, especially with respect to actual factors related to transmission events. All individuals were symptomatic, part of the criteria for testing in Manitoba, so the relationship between PCR results and infectivity remains unknown in asymptomatic individuals who have been shown to be infectious. Ct values can vary by assay and lab even when using the same assay. Ct values can be converted into a viral load with a properly run standard curve, which may be more useful in drawing hypotheses across platforms and laboratories about viral PCR results and infectiousness.

Value added

This study links epidemiologic, laboratory, and diagnostic data using a large and epidemiologically unrelated sample set to examine the relationship between RNA testing, time since symptom onset, and potential infectiousness (in vitro).

Our take —

During the first seven weeks of a symptom monitoring program for inbound travelers to the United States from China and Iran, the California Department of Health reviewed and forwarded 12,061 traveler records, many containing errors or omissions, to 51 health jurisdictions, generating 1,694 additional person-hours of labor and only three matches to confirmed COVID-19 cases in California. Traveler symptom monitoring is a resource- and time-intensive intervention which, independent of other mitigation activities, may be insufficient for containing COVID-19 transmission in community settings.

Study design

Other

Study population and setting

The study reviews the implementation of California Department of Health’s (CDPH) symptom monitoring program for travelers arriving from China and Iran to 51 local health jurisdictions between February 3 and March 17, 2020. On February 3, 2020, the United States directed all inbound flights from China to 11 airports for streamlined COVID-19 entry screening, whereby travelers’ information was collected and distributed to state health departments in the jurisdiction of the travelers’ final destination. Guidelines were expanded on March 5, 2020 to include individuals with recent (14 days) travel to Iran. Customs and Border Protection agents implemented secondary screening of inbound travelers, assessed travelers for signs and symptoms of COVID-19, and directed all travelers to quarantine and/or self-monitor (based on CDC risk assessment criteria) for two weeks following their last potential exposure to COVID-19. Where possible, local health jurisdictions were directed to contact travelers residing in their jurisdictions and collect daily reports on developing signs or symptoms, using information transmitted from Customs and Border Protection to health departments via CDC’s Epi-X system. Traveler records transmitted and local health jurisdiction person-hours implementing symptom monitoring between February 3 and March 17, 2020 were aggregated for descriptive analysis.

Summary of Main Findings

Of the 2,266 Epi-X notifications processed by CDPH (corresponding to 12,061 individual travelers) between February 3 and March 17, 2020, 13% had identifiable errors: 75% contained incorrect U.S. telephone numbers, 40% were duplicates, and 32% were untraceable or resided outside California. Of the 11,574 travelers for whom records were distributed by CDPH to 51 local health jurisdictions, three had a confirmed COVID-19 diagnosis in California. 1,694 total person-hours of CDPH labor, 34% of which were outside ordinary business hours, were attributed to reviewing and disseminating Epi-X notifications to local health jurisdictions.

Study Strengths

The study descriptively summarizes input and process indicators (i.e., number of traveler records disseminated and person-hours of labor) to appraise the feasibility of a symptom monitoring program.

Limitations

The study did not aggregate person-hours of implementation labor from local health jurisdictions or compare these estimated labor inputs with labor availability (i.e., number of staff available in each jurisdiction to conduct traveler symptom monitoring). Other relevant process level indicators, like program-associated costs and traveler lost-to-follow-up rates during symptom monitoring, were also not enumerated.

Value added

This is among the first studies to descriptively assess the feasibility of implementing a symptom monitoring program in a U.S. destination (i.e., California) with high inbound traveler volume from COVID-19-impacted origins.

Our take —

This study reports 86% (32 of 37) of reporting jurisdictions report at least COVID-19 case among US correctional and detention facilities. There were 4,893 detected cases among incarcerated or detained people, and 2,778 cases among facility staff. This is an important case count, however only 69% of jurisdictions responded to the CDC request for data, and facilities did not use a universal testing strategy, therefore the numbers are likely an undercount. More granular data from facilities are needed to help understand the situation within these vulnerable populations.

Study design

Ecological; Other

Study population and setting

The study consisted of aggregate data of COVID-19 cases in correctional and detention facilities from 37 state and territorial health department jurisdictions (out of 54 jurisdictions requested) from April 22 to 28, 2020, and laboratory-confirmed cases identified and reported from January 21 to April 21, 2020.

Summary of Main Findings

Of the 37 jurisdictions reporting, COVID-19 cases were reported from 32 (86%) jurisdictions and 420 facilities within these jurisdictions. Of these, 221 (53%) reported COVID-19 cases only among staff members. There were 4,893 total cases among incarcerated or detained persons, 491 (10%) hospitalizations, and 88 (2%) deaths due to COVID-19. Of 2,788 staff member cases, 79 (3%) were hospitalized, and 15 (1%) died due to COVID-19.

Study Strengths

This study is the first report of laboratory-confirmed COVID-19 cases among correctional and detention facilities. The study reported the number of cases due to detained and incarcerated people, as well as the number due to staff members; this disaggregation is important to describe risks among two very different populations that are both present in these facilities.

Limitations

The study only had data from 69% of the total 54 jurisdictions requested, therefore there may be selection bias and these results may not be generalizable across US facilities, and some jurisdictions only had state facility data, rather than local jails, federal, or private facilities. Also, most facilities do not provide universal testing to either incarcerated/detained people or to staff members, and therefore these numbers are likely undercounts. With aggregate numbers, none were disaggregated by state or region, or with any individual information, therefore it is unclear if these cases cluster in any particular area or among any particular population.

Value added

This is one of the first reports of the aggregate number of cases throughout the US in correctional and detention facilities.

Our take —

This study documented a significantly elevated incidence of Kawasaki-like disease among children in a northern Italian hospital during the COVID-19 epidemic, and detected SARS-CoV-2 antibodies in 80% of these cases. Compared to the prior 5-year period, children presenting with Kawasaki-like disease during the COVID-19 epidemic were older and had more severe clinical presentations, including cardiac involvement and macrophage activation syndrome. While additional evidence is needed to establish a causal association, these findings suggest that COVID-19 may subsequently trigger a severe form of Kawasaki disease among a small percentage of children, and are consistent with early reports from other settings.

Study design

Case Series; Other

Study population and setting

The study population included all pediatric patients diagnosed with a Kawasaki-like disease (n=29, 48% male, mean age 4.9 years) at a single tertiary pediatric hospital in Bergamo, Italy from January 1, 2015 to April 20, 2020. Patients diagnosed during the COVID-19 epidemic (February 18, 2020 to April 20, 2020) were compared to those diagnosed during the preceding 5 years (January 1, 2015 to February 17, 2020). Patients presenting during the COVID-19 epidemic were tested for SARS-CoV-2 by PCR assay on nasopharyngeal and oropharyngeal swab samples; antibody response was assessed by serologic testing (IgG and IgM).

Summary of Main Findings

The incidence of Kawasaki-like disease was significantly higher during the COVID-19 epidemic. There were ten children (70% boys, mean age 7.5 years) diagnosed during the two months after the COVID-19 epidemic began, compared to 19 children (37% boys, mean age 3.5 years) diagnosed during the prior 5-year period. Among the 10 children diagnosed during the COVID-19 period, 8/10 tested positive for SARS-CoV-2 antibodies, of whom 2 also tested positive for SARS-CoV-2 via PCR; two tested negative for both. Severe disease was more prevalent during the COVID-19 period than the earlier period, including abnormal echocardiogram results (60% vs 10%), Kawasaki disease shock syndrome (50% vs. 0%), and macrophage activation syndrome (50% vs 0%); the mean age of children during the COVID-19 period was significantly higher. Children in both periods were successfully treated with intravenous immunoglobulin and aspirin, though during the COVID-19 period more children required steroid treatment (80% vs 16%); all were discharged without further complications.

Study Strengths

The cases were tested multiple times for SARS-CoV-2 infection and antibodies, demonstrating that most of the COVID-19 exposure would have been missed by PCR test alone at the time of admission for Kawasaki-like symptoms. Cases diagnosed prior to the COVID-19 epidemic were used as a comparison group.

Limitations

This study consists of a small number of cases from a single referral hospital. The incidence for the COVID-19 period appears to have been calculated using a smaller denominator of time (one month) than the seven-week period defined throughout the methods, inflating the incidence and incidence rate ratio reported, though the inference of a significant increase in cases during the COVID-19 epidemic stands nevertheless.

Value added

This was among the first published case series of Kawasaki-like disease in children during the COVID-19 epidemic.

Our take —

This study suggests that while SARS-CoV-2 does infect the intestinal epithelium cells, it is highly unlikely that it is transmitted via the fecal-oral route.

Study design

Other

Study population and setting

All human cell samples were derived from de-identified tissue collected with informed consent from healthy subjects who were undergoing colonoscopy at Stanford University or Washington University School of Medicine

Fecal samples were collected from patients with COVID-19. Patient populations are not described.

Summary of Main Findings

The authors demonstrated that angiotensin-converting enzyme 2 (ACE2), a known receptor for mediating SARS-CoV-2 entry, is expressed to high levels in cells in the small intestine in both humans and mice and that a Vesicular Stomatisi Virus pseudo-typed with SARS-CoV-2 S protein (which mediates entry via interaction with ACE2) as well as a clinical isolate of SARS-Cov-2 was able to infect these cells.

Additionally, it was demonstrated that the serine proteases TMPRSS2 and TMPRSS4 help to mediate SARS-CoV-2 entry.

The authors also demonstrated that while small levels of infectious SARS-CoV-2 were detectable following incubation in simulated gastric fluid, there was no detectable virus following incubation in simulation colonic fluid.

Importantly, while viral RNA was detected in 3 of 10 fecal samples from infected persons, no infectious virus was detected in any of the samples.

Study Strengths

This study provides extensive evidence using multiple methods that SARS-CoV-2 is able to infect the intestinal epithelium cells.

Limitations

While this study is highly suggestive that SARS-CoV-2 cannot be transmitted via the fecal-oral route, the patient population size of 10 id quite limited. Larger studies should be performed to confirm that infectious virus is not found in fecal material.

Value added

This study is highly suggestive that SARS-CoV-2 cannot be transmitted via the fecal-oral route,

Additionally, the serine proteases TMPRSS2 and TMPRSS4 may be new targets for therapeutics as they were identified here as important for efficient entry of SARV-CoV-2.