Asymptomatic infection and atypical manifestations of COVID-19: Comparison of viral shedding duration Dear Editor,Coronavirus disease 2019 (COVID-19) bears several challenging problems, including insidious symptom onset, subclinical manifestations and highly transmissible property during early stage of infection. 1 In the recent study by Huang et al., SARS-CoV-2infection presented strong infectivity during the incubation period with rapid transmission. 2 Some patients with COVID-19 are asymptomatic, while others complain of atypical symptoms including loss of smell and taste sense. 3 However, there is insufficient data on the prevalence of asymptomatic infection and atypical manifestations of COVID-19. In this study, we aimed to evaluate the prevalence of asymptomatic infection, anosmia (smell loss) and ageusia (taste loss) among patients with mild COVID-19 in a residential treatment center (RTC). We also compared the duration of SARS-CoV-2 viral shedding between groups with different clinical manifestations.An observational cohort study was conducted for 199 patients with COVID-19 in a RTC at Gyeongju, Gyeongsangbuk province, Republic of Korea (ROK). The RTC was introduced to care patients with mild COVID-19 for the efficient distribution of limited medical resources during large epidemic in early March 2020. Data on demographic findings, symptoms, and duration of viral shedding were collected. The patients were interviewed about initial symptoms and their duration in detail. Real-time PCR (RT-PCR) to detect SARS-CoV-2 was performed every 2-7 days. Duration of viral shedding was considered as time from diagnosis date to the day before first negative conversion of two consecutive negative results of RT-PCR. RT-PCR was conducted using Allplex 2019-nCoV assay (Seegene, Seoul, South Korea). Statistical analyses were performed using SPSS 20.0 program. Mann-Whitney U test was performed to compare the duration of viral shedding between groups with different clinical manifestations. P -value < 0.05 was considered statistically significant. This study was approved by the Institutional Review Board of Korea University Guro Hospital (approval number: 2020GR0135).Among 199 patients with COVID-19, male was 34.7% and mean age of the patients was 38.0 years ( Table 1 ). Most patients (187, 94.0%) were healthy without chronic medical conditions. Among 199 patients, 26.6% were asymptomatic. In the early study, asymptomatic cases accounted for 10.7% (3/28) of COVID-19 cases in the ROK. 1 Asymptomatic proportion of COVID-19 was estimated as 17.9% (95% credible interval, 15.5-20.2%) on the Diamond Princess cruise ship, Japan. 4 Among clinical manifestations, cough (41.2%) was most common, followed by rhinorrhea and nasal stuffiness (30.2%). Of note, 26.1% (52/199) of patients presented anosmia, and 22.6% (45/199) complained of ageusia. Thirty-eight (19.1%) patients complained of both anosmia and ageusia. Duration of anosmia and Duration of viral shedding (days, mean ± SD) p value Asymptomatic 22.6 ± 4.0 < 0.01 * Symptomatic 25.2 ...

Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population.

Mounting evidence suggests that the gut-to-lung axis is critical during respiratory viral infections. We herein hypothesized that disruption of gut homeostasis during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may associate with early disease outcomes. To address this question, we took advantage of the Syrian hamster model. Our data confirmed that this model recapitulates some hallmark features of the human disease in the lungs. We further showed that SARS-CoV-2 infection associated with mild intestinal inflammation, relative alteration in intestinal barrier property and liver inflammation and altered lipid metabolism. These changes occurred concomitantly with an alteration of the gut microbiota composition over the course of infection, notably characterized by a higher relative abundance of deleterious bacterial taxa such as Enterobacteriaceae and Desulfovibrionaceae. Conversely, several members of the Ruminococcaceae and Lachnospiraceae families, including bacteria known to produce the fermentative products short-chain fatty acids (SCFAs), had a reduced relative proportion compared to non-infected controls. Accordingly, infection led to a transient decrease in systemic SCFA amounts. SCFA supplementation during infection had no effect on clinical and inflammatory parameters. Lastly, a strong correlation between some gut microbiota taxa and clinical and inflammation indices of SARS-CoV-2 infection severity was evidenced. Collectively, alteration of the gut microbiota correlates with disease severity in hamsters making this experimental model valuable for the design of interventional, gut microbiota-targeted, approaches for the control of COVID-19. Abbreviations: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; COVID-19, coronavirus disease 2019; SCFAs, short-chain fatty acids; dpi, day post-infection; RT-PCR, reverse transcription polymerase chain reaction; IL, interleukin. ACE2, angiotensin converting enzyme 2; TMPRSS2, transmembrane serine protease 2.