Structural mechanism of SARS-CoV-2 neutralization by two murine antibodies targeting the RBD.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has necessitated the rapid development of antibody-based therapies and vaccines as countermeasures. Here, we use cryoelectron microscopy (cryo-EM) to characterize two protective anti-SARS-CoV-2 murine monoclonal antibodies (mAbs) in complex with the spike protein, revealing similarities between epitopes targeted by human and murine B cells. The more neutralizing mAb, 2B04, binds the receptor-binding motif (RBM) of the receptor-binding domain (RBD) and competes with angiotensin-converting enzyme 2 (ACE2). By contrast, 2H04 binds adjacent to the RBM and does not compete for ACE2 binding. Naturally occurring sequence variants of SARS-CoV-2 and corresponding neutralization escape variants selected in vitro map to our structurally defined epitopes, suggesting that SARS-CoV-2 might evade therapeutic antibodies with a limited set of mutations, underscoring the importance of combination mAb therapeutics. Finally, we show that 2B04 neutralizes SARS-CoV-2 infection by preventing ACE2 engagement, whereas 2H04 reduces host cell attachment without directly disrupting ACE2-RBM interactions, providing distinct inhibitory mechanisms used by RBD-specific mAbs.

Clinical Features of Patients With COVID-19 With Nonalcoholic Fatty Liver Disease.

Previous studies reported that coronavirus disease 2019 (COVID-19) was likely to result in liver injury. However, few studies investigated liver injury in patients with COVID-19 with chronic liver diseases. We described the clinical features in patients with COVID-19 with nonalcoholic fatty liver disease (NAFLD). Confirmed patients with COVID-19 from hospitals in 10 cities of Jiangsu Province, China, were retrospectively included between January 18, 2020, and February 26, 2020. The hepatic steatosis index (HSI) was used to defined NAFLD. A total of 280 patients with COVID-19 were enrolled. Eighty-six (30.7%) of 280 patients with COVID-19 were diagnosed as NAFLD by HSI. One hundred (35.7%) patients presented abnormal liver function on admission. The median alanine aminotransferase (ALT) levels (34.5 U/L vs. 23.0 U/L; P < 0.001) and the proportion of elevated ALT (>40 U/L) (40.7% vs. 10.8%; P < 0.001) were significantly higher in patients with NAFLD than in patients without NAFLD on admission. The proportion of elevated ALT in patients with NAFLD was also significantly higher than patients without NAFLD (65.1% vs. 38.7%; P < 0.001) during hospitalization. Multivariate analysis showed that age over 50 years (odds ratio [OR], 2.077; 95% confidence interval [CI], 1.183, 3.648; P = 0.011) and concurrent NAFLD (OR, 2.956; 95% CI, 1.526, 5.726; P = 0.001) were independent risk factors of ALT elevation in patients with COVID-19, while the atomized inhalation of interferon α-2b (OR, 0.402; 95% CI, 0.236, 0.683; P = 0.001) was associated with a reduced risk of ALT elevation during hospitalization. No patient developed liver failure or death during hospitalization. The complications and clinical outcomes were comparable between patients with COVID-19 with and without NAFLD. Conclusion: Patients with NAFLD are more likely to develop liver injury when infected by COVID-19. However, no patient developed severe liver-related complications during hospitalization.

A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope.

With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here, we developed a panel of neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) that bound the receptor binding domain of the spike protein at distinct epitopes and blocked virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Although several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by ancestral SARS-CoV-2 strains, others induced escape variants in vivo or lost neutralizing activity against emerging strains. One mAb, SARS2-38, potently neutralized all tested SARS-CoV-2 variants of concern and protected mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engaged a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of neutralizing antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants.

Clinical and virological course of patients with coronavirus disease 2019 in Jiangsu province, China: a retrospective, multi-center cohort study.

BACKGROUND: The clinical and virological course of patients with coronavirus disease 2019 (COVID-19) are lacking. We aimed to describe the clinical and virological characteristics of COVID-19 patients from 10 designated hospitals in 10 cities of Jiangsu province, China. The factors associated with the clearance of SARS-CoV-2 were investigated. METHODS: A total of 328 hospitalized patients with COVID-19 were retrospectively recruited. The epidemiological, clinical, laboratory, radiology and treatment data were collected. The associated factors of SARS-CoV-2 clearance were analyzed. RESULTS: The median duration of hospitalization was 16.0 days (interquartile range [IQR] 13.0-21.0 days). On multivariate Cox regression analysis, age > 60 years (hazard ratio [HR] 0.643, 95% confidence interval [CI] 0.454-0.911, P = 0.013) was associated with the delayed SARS-CoV-2 clearance, while the atomized inhalation of interferon α-2b could improve the clearance of SARS-CoV-2 (HR, 1.357, 95% CI 1.050-1.755, P = 0.020). Twenty-six (7.9%) patients developed respiratory failure and 4 (1.2%) patients developed ARDS. Twenty (6.1%) patients were admitted to the ICU, while no patient was deceased. CONCLUSIONS: Our study found that age > 60 years was associated with the delayed SARS-CoV-2 clearance, while treated with atomized inhalation of interferon α-2b could promote the clearance of SARS-CoV-2.

Risk of severe illness of COVID-19 patients with NAFLD and increased NAFLD fibrosis scores.

BACKGROUND: There is still little knowledge about the association of liver fibrosis with the clinical outcomes of COVID-19 patients with non-alcoholic fatty liver disease (NAFLD). The aim of the study was to determine the association of NAFLD fibrosis score (NFS)-determined liver fibrosis with clinical outcomes of COVID-19 patients with NAFLD. METHODS: The NAFLD was diagnosed by the Hepatic Steatosis Index (HSI) in the absence of other causes of chronic liver diseases. NFS was used to evaluate the severity of liver fibrosis. RESULTS: A total of 86 COVID-19 patients with NAFLD were included. The median age was 43.5 years, and 58.1% of patients were male. Thirty-eight (44.2%) patients had advanced liver fibrosis according to the NFS. Multivariate analysis indicated that concurrent diabetes (odds ratio [OR] 8.264, 95% confidence interval [CI] 1.202-56.830, p = 0.032) and advanced liver fibrosis (OR 11.057, 95% CI 1.193-102.439, p = 0.034) were independent risk factors of severe illness in COVID-19 patients with NAFLD. CONCLUSION: NAFLD patients with NFS-determined advanced liver fibrosis are at higher risk of severe COVID-19.

A single intranasal or intramuscular immunization with chimpanzee adenovirus-vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters.

The development of an effective vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), is a global priority. Here, we compare the protective capacity of intranasal and intramuscular delivery of a chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (chimpanzee adenovirus [ChAd]-SARS-CoV-2-S) in Golden Syrian hamsters. Although immunization with ChAd-SARS-CoV-2-S induces robust spike-protein-specific antibodies capable of neutralizing the virus, antibody levels in serum are higher in hamsters vaccinated by an intranasal compared to intramuscular route. Accordingly, against challenge with SARS-CoV-2, ChAd-SARS-CoV-2-S-immunized hamsters are protected against less weight loss and have reduced viral infection in nasal swabs and lungs, and reduced pathology and inflammatory gene expression in the lungs, compared to ChAd-control immunized hamsters. Intranasal immunization with ChAd-SARS-CoV-2-S provides superior protection against SARS-CoV-2 infection and inflammation in the upper respiratory tract. These findings support intranasal administration of the ChAd-SARS-CoV-2-S candidate vaccine to prevent SARS-CoV-2 infection, disease, and possibly transmission.

A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques.

The deployment of a vaccine that limits transmission and disease likely will be required to end the coronavirus disease 2019 (COVID-19) pandemic. We recently described the protective activity of an intranasally administered chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike (S) protein (ChAd-SARS-CoV-2-S [chimpanzee adenovirus-severe acute respiratory syndrome-coronavirus-2-S]) in the upper and lower respiratory tracts of mice expressing the human angiotensin-converting enzyme 2 (ACE2) receptor. Here, we show the immunogenicity and protective efficacy of this vaccine in non-human primates. Rhesus macaques were immunized with ChAd-Control or ChAd-SARS-CoV-2-S and challenged 1 month later by combined intranasal and intrabronchial routes with SARS-CoV-2. A single intranasal dose of ChAd-SARS-CoV-2-S induces neutralizing antibodies and T cell responses and limits or prevents infection in the upper and lower respiratory tracts after SARS-CoV-2 challenge. As ChAd-SARS-CoV-2-S confers protection in non-human primates, it is a promising candidate for limiting SARS-CoV-2 infection and transmission in humans.

Seroprevalence of SARS-CoV-2 Antibodies in Children and Adults in St. Louis, Missouri, USA.

Reported coronavirus disease 2019 (COVID-19) case counts likely underestimate the true prevalence because mild or asymptomatic cases often go untested. Here, we use a sero-survey to estimate the seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the St. Louis, MO, metropolitan area in a symptom-independent manner. Five hundred three adult and 555 pediatric serum/plasma samples were collected from patients presenting to Barnes-Jewish Hospital or St. Louis Children's Hospital between 14 April 2020 and 12 May 2020. We developed protocols for in-house enzyme-linked immunosorbent assays (ELISAs) using spike and nucleoprotein and used the assays to estimate a seroprevalence rate based on our samples. Overall IgG seropositivity was estimated to be 1.71% (95% credible interval [CI], 0.04% to 3.38%) in pediatric samples and 3.11% (95% CI, 0.92% to 5.32%) in adult samples. Seropositivity was significantly lower in children under 5 years of age than in adults, but rates between adults and children aged 5 or older were similar. Of the 176 samples tested from children under 4 years of age, none were positive.IMPORTANCE This study determined the percentages of both children and adult samples from the greater St. Louis metropolitan area who had antibodies to SARS-CoV-2 in late April to early May 2020. Approximately 1.7 to 3.1% of the tested individuals had antibodies, indicating that they had previously been infected by SARS-CoV-2. These results demonstrate that the extent of infection was about 10 times greater than the number of confirmed cases at that time. Furthermore, it demonstrated that by 5 years of age, children were infected to an extent similar to that of adults.

Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization.

Neutralizing antibodies against the SARS-CoV-2 spike (S) protein are a goal of COVID-19 vaccines and have received emergency use authorization as therapeutics. However, viral escape mutants could compromise efficacy. To define immune-selected mutations in the S protein, we exposed a VSV-eGFP-SARS-CoV-2-S chimeric virus, in which the VSV glycoprotein is replaced with the S protein, to 19 neutralizing monoclonal antibodies (mAbs) against the receptor-binding domain (RBD) and generated 50 different escape mutants. Each mAb had a unique resistance profile, although many shared residues within an epitope of the RBD. Some variants (e.g., S477N) were resistant to neutralization by multiple mAbs, whereas others (e.g., E484K) escaped neutralization by convalescent sera. Additionally, sequential selection identified mutants that escape neutralization by antibody cocktails. Comparing these antibody-mediated mutations with sequence variation in circulating SARS-CoV-2 revealed substitutions that may attenuate neutralizing immune responses in some humans and thus warrant further investigation.

Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion.

Cholesterol 25-hydroxylase (CH25H) is an interferon (IFN)-stimulated gene that shows broad antiviral activities against a wide range of enveloped viruses. Here, using an IFN-stimulated gene screen against vesicular stomatitis virus (VSV)-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses, we identified CH25H and its enzymatic product 25-hydroxycholesterol (25HC) as potent inhibitors of SARS-CoV-2 replication. Internalized 25HC accumulates in the late endosomes and potentially restricts SARS-CoV-2 spike protein catalyzed membrane fusion via blockade of cholesterol export. Our results highlight one of the possible antiviral mechanisms of 25HC and provide the molecular basis for its therapeutic development.

Risk factors of liver injury in patients with coronavirus disease 2019 in Jiangsu, China: A retrospective, multi-center study.

We aimed to describe liver injury and identify the risk factors of liver injury in coronavirus disease (COVID-19) patients without chronic liver diseases (CLD). The clinical data of 228 confirmed COVID-19 patients without CLD were retrospectively collected from ten hospitals in Jiangsu, China. Sixty-seven (29.4%) of 228 patients without CLD showed abnormal liver function on admission, including increased alanine aminotransferase (ALT) (25 [11.0%]) U/L, aspartate aminotransferase (AST) 30 [13.2%]) U/L, gamma-glutamyl transferase (GGT) 28 [12.4%]) U/L, total bilirubin (Tbil) 16 [7.0%] µmol/L, and alkaline phosphatase (ALP) 10 [4.5%]) U/L. During hospitalization, 129 (56.3%) of 228 patients showed abnormal liver function, including elevated ALT (84 [36.8%]), AST (58 [25.4%]), GGT (67 [29.5%]), and Tbil (59 [25.9%]). Age over 50 years (odds ratio [OR], 2.086; 95% confidence interval [CI], 1.030-4.225; p = .041), male sex (OR, 2.737; 95% CI, 1.418-5.284; p = .003), and lopinavir-ritonavir (OR, 2.504; 95% CI, 1.187-5.283; p = .016) were associated with higher risk of liver function abnormality, while the atomized inhalation of interferon α-2b (OR, 0.256; 95% CI 0.126-0.520; p < .001) was associated with reduced risk of liver function abnormality during hospitalization. Mild to moderate liver injury was common in COVID-19 patients in Jiangsu, China. Age over 50 years, male sex, and lopinavir-ritonavir were the independent risk factors of liver impairment in COVID-19 patients during hospitalization.

Overweight and Obesity are Risk Factors of Severe Illness in Patients with COVID-19.

OBJECTIVE: This study aimed to observe the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with overweight and obesity. METHODS: Consecutive patients with COVID-19 from 10 hospitals of Jiangsu province, China, were enrolled. RESULTS: A total of 297 patients with COVID-19 were included, and 39.39% and 13.47% of patients had overweight and obesity, respectively. The proportions of bilateral pneumonia (92.50% vs. 73.57%, P = 0.033) and type 2 diabetes (17.50% vs. 3.57%, P = 0.006) were higher in patients with obesity than lean patients. The proportions of severe illness in patients with overweight (12.82% vs. 2.86%, P = 0.006) and obesity (25.00% vs. 2.86%, P < 0.001) were significantly higher than lean patients. More patients with obesity developed respiratory failure (20.00% vs. 2.86%, P < 0.001) and acute respiratory distress syndrome (5.00% vs. 0%, P = 0.024) than lean patients. The median days of hospitalization were longer in patients with obesity than lean patients (17.00 days vs. 14.00 days, P = 0.029). Overweight (OR, 4.222; 95% CI: 1.322-13.476; P = 0.015) and obesity (OR, 9.216; 95% CI: 2.581-32.903; P = 0.001) were independent risk factors of severe illness. Obesity (HR, 6.607; 95% CI: 1.955-22.329; P = 0.002) was an independent risk factor of respiratory failure. CONCLUSIONS: Overweight and obesity were independent risk factors of severe illness in COVID-19 patients. More attention should be paid to these patients.

Corticosteroid therapy is associated with the delay of SARS-CoV-2 clearance in COVID-19 patients.

The impact of corticosteroid treatment on virological course of coronavirus disease 2019 (COVID-19) patients remains unclear. This study aimed to explore the association between corticosteroid and viral clearance in COVID-19. The clinical data of COVID-19 patients from 10 hospitals of Jiangsu, China, were retrospectively collected. Cox regression and Kaplan-Meier analysis were used to analyze the adverse factors of virus clearance. Of the 309 COVID-19 patients, eighty-nine (28.8%) patients received corticosteroid treatment during hospitalization. Corticosteroid group showed higher C-reactive protein (median 11.1 vs. 7.0 mg/l, P = 0.018) and lower lymphocytes (median 0.9 vs. 1.4 × 109/l, P < 0.001) on admission. Fever (93.3% vs. 65.0%, P < 0.001) and cough (69.7% vs. 57.3%, P = 0.043) were more common in corticosteroid group. The proportions of patients with severe illness (34.8% vs. 1.8%, P < 0.001), respiratory failure (25.8% vs. 1.4%, P < 0.001), acute respiratory distress syndrome (4.5% vs. 0%, P = 0.002), and admission to ICU (20.2% vs. 0.9%, P < 0.001) were significantly higher in corticosteroid group than non-corticosteroid group. The duration of virus clearance (median 18.0 vs. 16.0 days, P < 0.001) and hospitalization (median 17.0 vs. 15.0 days, P < 0.001) were also significantly longer in corticosteroid group than non-corticosteroid group. Treated with corticosteroid (Hazard ratio [HR], 0.698; 95% confidence interval [CI], 0.512 to 0.951; P = 0.023) was an adverse factor of the clearance of SARS-CoV-2, especially for male patients (HR, 0.620; 95% CI, 0.408 to 0.942; P = 0.025). The cumulative probability of SARS-CoV-2 clearance was lower in corticosteroid group (P < 0.001). Corticosteroid treatment may delay the SARS-CoV-2 clearance of COVID-19 patients and should be used with cautions.

A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2.

The coronavirus disease 2019 pandemic has made deployment of an effective vaccine a global health priority. We evaluated the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (ChAd-SARS-CoV-2-S) in challenge studies with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mice expressing the human angiotensin-converting enzyme 2 receptor. Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti-nucleoprotein antibodies after SARS-CoV-2 challenge. In contrast, a single intranasal dose of ChAd-SARS-CoV-2-S induces high levels of neutralizing antibodies, promotes systemic and mucosal immunoglobulin A (IgA) and T cell responses, and almost entirely prevents SARS-CoV-2 infection in both the upper and lower respiratory tracts. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission and curtailing pandemic spread.

Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections, and an effective vaccine is critical to mitigate coronavirus-induced disease 2019 (COVID-19). Previously, we developed a replication-competent vesicular stomatitis virus (VSV) expressing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Here, we show that vaccination with VSV-eGFP-SARS-CoV-2 generates neutralizing immune responses and protects mice from SARS-CoV-2. Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high antibody titers that neutralize SARS-CoV-2 and target the receptor binding domain that engages human angiotensin-converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice that expressed human ACE2 and were immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung, indicating protection against pneumonia. Passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals also protects naive mice from SARS-CoV-2 challenge. These data support development of VSV-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.

Neutralizing Antibody and Soluble ACE2 Inhibition of a Replication-Competent VSV-SARS-CoV-2 and a Clinical Isolate of SARS-CoV-2.

Antibody-based interventions against SARS-CoV-2 could limit morbidity, mortality, and possibly transmission. An anticipated correlate of such countermeasures is the level of neutralizing antibodies against the SARS-CoV-2 spike protein, which engages with host ACE2 receptor for entry. Using an infectious molecular clone of vesicular stomatitis virus (VSV) expressing eGFP as a marker of infection, we replaced the glycoprotein gene (G) with the spike protein of SARS-CoV-2 (VSV-eGFP-SARS-CoV-2) and developed a high-throughput-imaging-based neutralization assay at biosafety level 2. We also developed a focus-reduction neutralization test with a clinical isolate of SARS-CoV-2 at biosafety level 3. Comparing the neutralizing activities of various antibodies and ACE2-Fc soluble decoy protein in both assays revealed a high degree of concordance. These assays will help define correlates of protection for antibody-based countermeasures and vaccines against SARS-CoV-2. Additionally, replication-competent VSV-eGFP-SARS-CoV-2 provides a tool for testing inhibitors of SARS-CoV-2 mediated entry under reduced biosafety containment.

A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of infections and hundreds of thousands of deaths globally. There are no widely available licensed therapeutics against SARS-CoV-2, highlighting an urgent need for effective interventions. The virus enters host cells through binding of a receptor-binding domain within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. In this article, we describe the generation and characterization of a panel of murine mAbs directed against the receptor-binding domain. One mAb, 2B04, neutralized wild-type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/ml). In a murine model of SARS-CoV-2 infection, 2B04 protected challenged animals from weight loss, reduced lung viral load, and blocked systemic dissemination. Thus, 2B04 is a promising candidate for an effective antiviral that can be used to prevent SARS-CoV-2 infection.

Clinical findings of patients with coronavirus disease 2019 in Jiangsu province, China: A retrospective, multi-center study.

Limited data are available for clinical characteristics of patients with coronavirus disease 2019 (COVID-19) outside Wuhan. This study aimed to describe the clinical characteristics of COVID-19 and identify the risk factors for severe illness of COVID-19 in Jiangsu province, China. Clinical data of hospitalized COVID-19 patients were retrospectively collected in 8 hospitals from 8 cities of Jiangsu province, China. Clinical findings of COVID-19 patients were described and risk factors for severe illness of COVID-19 were analyzed. By Feb 10, 2020, 202 hospitalized patients with COVID-19 were enrolled. The median age of patients was 44.0 years (interquartile range, 33.0-54.0). 55 (27.2%) patients had comorbidities. At the onset of illness, the common symptoms were fever (156 [77.2%]) and cough (120 [59.4%]). 66 (32.7%) patients had lymphopenia. 193 (95.5%) patients had abnormal radiological findings. 11 (5.4%) patients were admitted to the intensive care unit and none of the patients died. 23 (11.4%) patients had severe illness. Severe illness of COVID-19 was independently associated with body mass index (BMI) ≥ 28 kg/m2 (odds ratio [OR], 9.219; 95% confidence interval [CI], 2.731 to 31.126; P<0.001) and a known history of type 2 diabetes (OR, 4.326; 95% CI, 1.059 to 17.668; P = 0.041). In this case series in Jiangsu Province, COVID-19 patients had less severe symptoms and had better outcomes than the initial COVID-19 patients in Wuhan. The BMI ≥ 28 kg/m2 and a known history of type 2 diabetes were independent risk factors of severe illness in patients with COVID-19.

Epidemiological and clinical features of asymptomatic patients with SARS-CoV-2 infection.

Few studies reported the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients with completely asymptomatic throughout the disease course. We investigated the epidemiological and clinical features of patients infected by SARS-CoV-2 without any symptoms. Patients with confirmed SARS-CoV-2 infection were retrospectively recruited. The demographic characteristics, clinical data, treatment, and outcomes of SARS-CoV-2 infected patients without any symptoms were analyzed. Fifteen (4.4%) of 342 SARS-CoV-2 infected patients did not develop any symptom during the course of the disease. The median time from exposure to diagnosis was 7.0 days (interquartile range [IQR]: 1.0-15.0 days). Of the 15 patients, 14 patients were diagnosed by tested positive for SARS-CoV-2 in throat swabs, while one patient was only tested positive for SARS-CoV-2 in anal swabs. During hospitalization, only 1 (6.7%) patient developed lymphopenia. Abnormalities of chest computed tomography examinations were detected in 8 (53.4%) patients on admission. As of 8 March 2020, all patients have been discharged. The median time of SARS-CoV-2 tested negative from admission was 7.0 days (IQR: 4.0-9.0 days). Patients without any symptoms but with SARS-CoV-2 exposure should be closely monitored and tested for SARS-CoV-2 both in anal and throat swabs to excluded the infection. Asymptomatic patients infected by SARS-CoV-2 have favorable outcomes.