COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors.

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.

Kinetics of IgM and IgG antibody specific to SARS-CoV-2 nucleocapsid and spike proteins

：Objective To study the kinetics of IgM and IgG antibodies based on nucleocapsid（N） and spike（S） protein of SARS-Co V2-in COVID-19 patients. Methods Immunofluorescent kits were used to detect N and S protein specific IgM and IgG antibodies from Jan.21 to Feb.11, 2020 for the 60 hospitalized COVID-19 patients（48 mild, 12 severe cases） with a total of 290 plasma samples collected 9 weeks after the onset of the disease. Results The level of antibodies specific for S protein varied significantly with the course of disease（Ig M from 27.32 to 110.10 TU/ml, IgG from 56.85 to 135.00 TU/ml）, but not for N protein.Higher level of Ig M/Ig G antibodies specific to S protein was observed during the 2-7 week than that to N protein.The seropositive rate of antibodies gradually increased during the early stage of disease.IgM/IgG antibodies specific to N protein changed from 12.50% at the first week to peak level（51.72% and 86.21% respectively） at the 4 th week and those for S protein from 25.00% and 14.58% to 100.00%, and then declined.The seropositive rate of Ig M antibody specific to S protein was higher than that for N protein during 2-8 th week and that for Ig G antibody at 2, 3, 4, 6 and 7 th week.The seropositive rate of Ig G antibody specific to N protein in severe patients at the third week was higher than that in mild patients（100.00% vs 59.52%,χ2=9.67, P=0.001 9）, and the same as to Ig G antibody for S protein at the second week after disease onset（80.00% vs 46.58%, χ2=5.57, P=0.018 2）. Conclusions SARS-Co V2-S protein can induc stronger antibody response than N protein, and the antibody level was related to the severity of the disease.

Kinetics of SARS-CoV-2 antibodies in COVID-19 patients and relationship with severity of disease

Objective To study the kinetics of SARS-CoV-2 antibodies in COVID-19 patients and the correlation with disease severity. Methods A total of 290 plasma samples were collected from 60 hospitalized patients including 48 mild cases and 12 severe cases within 63 days after disease onset in Guangzhou Eighth People′s Hospital affiliated to Guangzhou Medical University during January 21 to April 11, 2020.SARS-CoV-2 specific antibodies were determined by four commercial colloidal gold serologic reagents validated by National Medical Products Administration in China. Results The seropositive rate ranged from 19.23% to 34.62% by four assays within one week after disease onset, and rapidly increased within the following two weeks.The seropositive rates were 52.27% to 68.18% and 83.05% to 98.31%, respectively.IgM antibody peaked within the fourth week and maintained high level for 1 to 2 weeks, and decreased significantly until the 9 th week.But no obvious decreasing trend of the seropositive rate of IgG antibody was observed during two months after disease onset.The seropositive rates of antibodies between mild and severe cases showed no statistical difference.Four assays demonstrated a sensitivity of 78.33%to 91.67%in 60 COVID-19 patients.The difference was statistically significant between the highest and the lowest values（χ2=4.183,P=0.041）． Conclusions The colloidal gold serologic reagents show good sensitivity during the late stage of disease but not at the early stage.There is no correlation between seropositive and disease severity.The sensitivity of different reagents is different

Author Correction: Temporal dynamics in viral shedding and transmissibility of COVID-19.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Temporal dynamics in viral shedding and transmissibility of COVID-19.

We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 25-69%) of secondary cases were infected during the index cases' presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.

Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity.

The novel coronavirus (2019-nCoV) infection caused pneumonia. we retrospectively analyzed the virus presence in the pharyngeal swab, blood, and the anal swab detected by real-time PCR in the clinical lab. Unexpectedly, the 2109-nCoV RNA was readily detected in the blood (6 of 57 patients) and the anal swabs (11 of 28 patients). Importantly, all of the 6 patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity (p-value = 0.0001). Meanwhile, 8 of the 11 patients with annal swab virus-positive was in severe clinical stage. However, the concentration of viral RNA in the anal swab (Ct value = 24 + 39) was higher than in the blood (Ct value = 34 + 39) from patient 2, suggesting that the virus might replicate in the digestive tract. Altogether, our results confirmed the presence of virus RNA in extra-pulmonary sites.