BACKGROUND & AIMS: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gastrointestinal tissues, little is known about the roles of gut commensal microbes in susceptibility to and severity of infection. We investigated changes in fecal microbiomes of patients with SARS-CoV-2 infection during hospitalization and associations with severity and fecal shedding of virus. METHODS: We performed shotgun metagenomic sequencing analyses of fecal samples from 15 patients with Coronavirus Disease 2019 (COVID-19) in Hong Kong, from February 5 through March 17, 2020. Fecal samples were collected 2 or 3 times per week from time of hospitalization until discharge; disease was categorized as mild (no radiographic evidence of pneumonia), moderate (pneumonia was present), severe (respiratory rate !30/min, or oxygen saturation 93% when breathing ambient air), or critical (respiratory failure requiring mechanical ventilation, shock, or organ failure requiring intensive care). We compared microbiome data with those from 6 subjects with communityacquired pneumonia and 15 healthy individuals (controls). We assessed gut microbiome profiles in association with disease severity and changes in fecal shedding of SARS-CoV-2. RESULTS: Patients with COVID-19 had significant alterations in fecal microbiomes compared with controls, characterized by enrichment of opportunistic pathogens and depletion of beneficial commensals, at time of hospitalization and at all timepoints during hospitalization. Depleted symbionts and gut dysbiosis persisted even after clearance of SARS-CoV-2 (determined from throat swabs) and resolution of respiratory Gastroenterology 2020;159:944-955 BASIC AND TRANSLATIONAL AT symptoms. The baseline abundance of Coprobacillus, Clostridium ramosum, and Clostridium hathewayi correlated with COVID-19 severity; there was an inverse correlation between abundance of Faecalibacterium prausnitzii (an antiinflammatory bacterium) and disease severity. Over the course of hospitalization, Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis, and Bacteroides ovatus, which downregulate expression of angiotensin-converting enzyme 2 (ACE2) in murine gut, correlated inversely with SARS-CoV-2 load in fecal samples from patients. CONCLUSIONS: In a pilot study of 15 patients with COVID-19, we found persistent alterations in the fecal microbiome during the time of hospitalization, compared with controls. Fecal microbiota alterations were associated with fecal levels of SARS-CoV-2 and COVID-19 severity. Strategies to alter the intestinal microbiota might reduce disease severity.

Despite infection control measures, breakthrough transmission of severe acute respiratory syndrome (SARS) occurred for many hospital workers in Hong Kong. We conducted a case-control study of 72 hospital workers with SARS and 144 matched controls. Inconsistent use of goggles, gowns, gloves, and caps was associated with a higher risk for SARS infection (unadjusted odds ratio 2.42 to 20.54, p < 0.05). The likelihood of SARS infection was strongly associated with the amount of personal protection equipment perceived to be inadequate, having <2 hours of infection control training, and not understanding infection control procedures. No significant differences existed between the case and control groups in the proportion of workers who performed high-risk procedures, reported minor protection equipment problems, or had social contact with SARS-infected persons. Perceived inadequacy of personal protection equipment supply, infection control training <2 hours, and inconsistent use of personal protection equipment when in contact with SARS patients were significant independent risk factors for SARS infection.

To control the COVID-19 pandemic and prevent its resurgence in areas preparing for a return of economic activities, a method for a rapid, simple, and inexpensive point-of-care diagnosis and mass screening is urgently needed. We developed and evaluated a one-step colorimetric reverse-transcriptional loop-mediated isothermal amplification assay (COVID-19-LAMP) for detection of SARS-CoV-2, using SARS-CoV-2 isolate and respiratory samples from patients with COVID-19 (n = 223) and other respiratory virus infections (n = 143). The assay involves simple equipment and techniques and low cost, without the need for expensive qPCR machines, and the result, indicated by color change, is easily interpreted by naked eyes. COVID-19-LAMP can detect SARS-CoV-2 RNA with detection limit of 42 copies/reaction. Of 223 respiratory samples positive for SARS-CoV-2 by qRT-PCR, 212 and 219 were positive by COVID-19-LAMP at 60 and 90 min (sensitivities of 95.07% and 98.21%) respectively, with the highest sensitivities among nasopharyngeal swabs (96.88% and 98.96%), compared to sputum/deep throat saliva samples (94.03% and 97.02%), and throat swab samples (93.33% and 98.33%). None of the 143 samples with other respiratory viruses were positive by COVID-19-LAMP, showing 100% specificity. Samples with higher viral load showed shorter detection time, some as early as 30 min. This inexpensive, highly sensitive and specific COVID-19-LAMP assay can be useful for rapid deployment as mobile diagnostic units to resource-limiting areas for point-of-care diagnosis, and for unlimited high-throughput mass screening at borders to reduce cross-regional transmission.

Background Self-collected specimens has been advocated to avoid infectious exposure to healthcare workers. Self-induced sputum in those with a productive cough, and saliva in those without a productive cough have been proposed, but sensitivity remains uncertain. Methods We performed a prospective study in two regional hospitals in Hong Kong Results We prospectively examined 563 serial samples collected during the virus shedding periods of 50 patients: 150 deep-throat saliva (DTS), 309 pooled-nasopharyngeal (NP) and throat swabs, and 104 sputum. DTS had the lowest overall RT-PCR positive rate (68.7% vs. 89.4% [sputum] and 80.9% [pooled NP and throat swabs]), and the lowest viral RNA concentration (mean log copy/mL 3.54 vs. 5.03 [sputum] and 4.63 [pooled NP and throat swabs]). Analyses with respect to time from symptom onset and severity also revealed similar results. Virus yield of DTS correlated with that of sputum (Pearson correlation index [95% CI]: 0.76 [0.62 – 0.86]). We estimated the overall false-negative rate of DTS could be 31.3%, and increased 2.7 times among patients without sputum. Conclusion DTS produced the lowest viral RNA concentration and RT-PCR positive rate compared to conventional respiratory specimens in all phases of illness. Self-collect sputum should be the choice for patients with sputum.