Mendelian randomization study of obesity and type 2 diabetes in hospitalized COVID-19 patients.

BACKGROUND: Both obesity and type 2 diabetes (T2D) are reported to be highly enriched in hospitalized COVID-19 patients. Due to the close correlation between obesity and T2D, it is important to examine whether obesity and T2D are independently related to COVID-19 hospitalization. OBJECTIVE: To examine the causal effect of obesity and T2D in hospitalized COVID-19 patients using Mendelian randomization (MR). RESEARCH DESIGN AND METHODS: This two-sample MR analysis applied genetic markers of obesity identified in the genome wide association study (GWAS) by the GIANT Consortium as instrumental variables (IVs) of obesity; and genetic markers of T2D identified by the DIAGRAM Consortium as IVs of T2D. The MR analysis was performed in hospitalized COVID-19 patient by the COVID-19 Host Genetics Initiative using the MR-Base platform. RESULTS: All 3 classes of obesity (Class 1/2/3) were shown as the causal risk factors of COVID-19 hospitalization; however, T2D doesn't increase the risk of hospitalization or critically ill COVID-19 as an independent factor. CONCLUSIONS: Obesity, but not T2D, is a primary risk factor of COVID-19 hospitalization.

Expression Pattern of the SARS-CoV-2 Entry Genes ACE2 and TMPRSS2 in the Respiratory Tract.

To address the expression pattern of the SARS-CoV-2 receptor ACE2 and the viral priming protease TMPRSS2 in the respiratory tract, this study investigated RNA sequencing transcriptome profiling of samples of airway and oral mucosa. As shown, ACE2 has medium levels of expression in both small airway epithelium and masticatory mucosa, and high levels of expression in nasal epithelium. The expression of ACE2 is low in mucosal-associated invariant T (MAIT) cells and cannot be detected in alveolar macrophages. TMPRSS2 is highly expressed in small airway epithelium and nasal epithelium and has lower expression in masticatory mucosa. Our results provide the molecular basis that the nasal mucosa is the most susceptible locus in the respiratory tract for SARS-CoV-2 infection and consequently for subsequent droplet transmission and should be the focus for protection against SARS-CoV-2 infection.

Serum levels of the IgA isotype switch factor TGF-ß1 are elevated in patients with COVID-19.

We previously observed enhanced immunoglobulin A (IgA) responses in severe COVID-19, which might confer damaging effects. Given the important role of IgA in immune and inflammatory responses, the aim of this study was to investigate the dynamic response of the IgA isotype switch factor TGF-ß1 in COVID-19 patients. We observed, in a total of 153 COVID-19 patients, that the serum levels of TGF-ß1 were increased significantly at the early and middle stages of COVID-19, and correlated with the levels of SARS-CoV-2-specific IgA, as well as with the APACHE II score in patients with severe disease. In view of the genetic association of the TGF-ß1 activator THBS3 with severe COVID-19 identified by the COVID-19 Host Genetics Initiative, this study suggests TGF-ß1 may play a key role in COVID-19.

Heparin-binding protein levels correlate with aggravation and multiorgan damage in severe COVID-19.

BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients may suffer persistent systemic inflammation and multiple organ failure, leading to a poor prognosis. RESEARCH QUESTION: To examine the relevance of the novel inflammatory factor heparin-binding protein (HBP) in critically ill COVID-19 patients, and evaluate the correlation of the biomarker with disease progression. STUDY DESIGN AND METHODS: 18 critically ill COVID-19 patients who suffered from respiratory failure and sepsis, including 12 cases who experienced a rapidly deteriorating clinical condition and six cases without deterioration, were investigated. They were compared with 15 age- and sex- matched COVID-19-negative patients with respiratory failure. Clinical data were collected and HBP levels were investigated. RESULTS: HBP was significantly increased in critically ill COVID-19 patients following disease aggravation and tracked with disease progression. HBP elevation preceded the clinical manifestations for up to 5 days and was closely correlated with patients' pulmonary ventilation and perfusion status. INTERPRETATION: HBP levels are associated with COVID-19 disease progression in critically ill patients. As a potential mediator of disease aggravation and multiple organ injuries that are triggered by continuing inflammation and oxygen deficits, HBP warrants further study as a disease biomarker and potential therapeutic target.

COVID-19: Look to the Future, Learn from the Past.

There is a current pandemic of a new type of coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of confirmed infected cases has been rapidly increasing. This paper analyzes the characteristics of SARS-CoV-2 in comparison with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and influenza. COVID-19 is similar to the diseases caused by SARS-CoV and MERS-CoV virologically and etiologically, but closer to influenza in epidemiology and virulence. The comparison provides a new perspective for the future of the disease control, and offers some ideas in the prevention and control management strategy. The large number of infectious people from the origin, and the highly infectious and occult nature have been two major problems, making the virus difficult to eradicate. We thus need to contemplate the possibility of long-term co-existence with COVID-19.

The Infection Rate of COVID-19 in Wuhan, China: Combined Analysis of Population Samples.

BACKGROUND: The coronavirus disease (COVID-19) pandemic began in Wuhan, China, in December 2019. Wuhan had a much higher mortality rate than the rest of China. However, a large number of asymptomatic infections in Wuhan may have never been diagnosed, contributing to an overestimated mortality rate. OBJECTIVE: This study aims to obtain an accurate estimate of infections in Wuhan using internet data. METHODS: In this study, we performed a combined analysis of the infection rate among evacuated foreign citizens to estimate the infection rate in Wuhan in late January and early February. RESULTS: Based on our analysis, the combined infection rate of the foreign evacuees was 0.013 (95% CI 0.008-0.022). Therefore, we estimate the number of infected people in Wuhan to be 143,000 (range 88,000-242,000), which is significantly higher than previous estimates. Our study indicates that a large number of infections in Wuhan were not diagnosed, which has resulted in an overestimated case fatality rate. CONCLUSIONS: Increased awareness of the original infection rate of Wuhan is critical for proper public health measures at all levels, as well as to eliminate panic caused by overestimated mortality rates that may bias health policy actions by the authorities.