COVID-19 and membranous nephropathy: observational and Mendelian randomization analyses (preprint)

Membranous nephropathy (MN) imposes a substantial burden of illness and death. However, a systematic assessment of the impact of the COVID-19 pandemic on MN incidence has not yet been conducted. This research is an observational cohort study conducted retrospectively. The kidney biopsy results of two medical institutions, including our hospital, were reviewed for the period between January 2016 and May 2023. Relevant statistical analysis of different glomerular diseases was performed based on the corresponding pathological diagnoses. The aim was to compare the incidence changes of different glomerular diseases before and during the COVID-19 pandemic. Our focus was on investigating the changes in the incidence rate of MN and attempting to uncover the causal effects between varying degrees of COVID-19 and MN utilizing bidirectional Mendelian randomization (MR) using GWAS data from European and Asian ancestry. We found that the incidence of MN decreased by 3.6% during the COVID-19 pandemic compared to the period before the onset of the COVID-19 pandemic(P = 0.026). However, after Bonferroni correction, the change in incidence did not reach a significant p-value(P > 0.05/2), and the overall incidence of glomerular diseases did not show a significant change (P = 0.364). Additionally, the Mendelian randomization analysis indicated no significant causality between COVID-19 (critical illness, susceptibility, severe infection, hospitalization, and severity) and MN (no significance, PBonferroni>0.05).The results of this preliminary study suggest that the incidence rate of MN remained relatively stable during the COVID-19 pandemic. Furthermore, our genetic perspective Mendelian randomization analysis has furnished additional evidence contradicting any causal relationship between varying degrees of COVID-19 infection and MN.

Clarifying real receptor binding site between coronavirus HCoV-HKU1 and 9-O-Ac-Sia based on molecular docking.

HCoV-HKU1 is a [Formula: see text]-coronavirus with low pathogenicity, which usually leads to respiratory diseases. At present, a controversial issue is that whether the receptor binding site (RBS) of HCoV-HKU1 is located in the N-terminal domain (NTD) or the C-terminal domain (CTD) in the HCoV-HKU1 S protein. To address this issue, we used molecular docking technology to dock the NTD and CTD with 9-oxoacetylated sialic acid (9-O-Ac-Sia), respectively, with the results showing that the RBS of HCoV-HKU1 is located in the NTD (amino acid residues 80-95, 25-32). Our findings clarified the structural basis and molecular mechanism of the HCoV-HKU1 infection, providing important information for the development of therapeutic antibody drugs and the design of vaccines.

Molecular evolutionary characteristics of SARS-CoV-2 emerging in the United States.

SARS-CoV-2 is a newly discovered beta coronavirus at the end of 2019, which is highly pathogenic and poses a serious threat to human health. In this paper, 1875 SARS-CoV-2 whole genome sequences and the sequence coding spike protein (S gene) sampled from the United States were used for bioinformatics analysis to study the molecular evolutionary characteristics of its genome and spike protein. The MCMC method was used to calculate the evolution rate of the whole genome sequence and the nucleotide mutation rate of the S gene. The results showed that the nucleotide mutation rate of the whole genome was 6.677 × 10-4 substitution per site per year, and the nucleotide mutation rate of the S gene was 8.066 × 10-4 substitution per site per year, which was at a medium level compared with other RNA viruses. Our findings confirmed the scientific hypothesis that the rate of evolution of the virus gradually decreases over time. We also found 13 statistically significant positive selection sites in the SARS-CoV-2 genome. In addition, the results showed that there were 101 nonsynonymous mutation sites in the amino acid sequence of S protein, including seven putative harmful mutation sites. This paper has preliminarily clarified the evolutionary characteristics of SARS-CoV-2 in the United States, providing a scientific basis for future surveillance and prevention of virus variants.

Progressive liver injury and increased mortality risk in COVID-19 patients: A retrospective cohort study in China.

BACKGROUND: Liver injury is common and also can be fatal, particularly in severe or critical patients with coronavirus disease 2019 (COVID-19). AIM: To conduct an in-depth investigation into the risk factors for liver injury and into the effective measures to prevent subsequent mortality risk. METHODS: A retrospective cohort study was performed on 440 consecutive patients with relatively severe COVID-19 between January 28 and March 9, 2020 at Tongji Hospital, Wuhan, China. Data on clinical features, laboratory parameters, medications, and prognosis were collected. RESULTS: COVID-19-associated liver injury more frequently occurred in patients aged ≥ 65 years, female patients, or those with other comorbidities, decreased lymphocyte count, or elevated D-dimer or serum ferritin (P < 0.05). The disease severity of COVID-19 was an independent risk factor for liver injury (severe patients: Odds ratio [OR] = 2.86, 95% confidence interval [CI]: 1.78-4.59; critical patients: OR = 13.44, 95%CI: 7.21-25.97). The elevated levels of on-admission aspartate aminotransferase and total bilirubin indicated an increased mortality risk (P < 0.001). Using intravenous nutrition or antibiotics increased the risk of COVID-19-associated liver injury. Hepatoprotective drugs tended to be of assistance to treat the liver injury and improve the prognosis of patients with COVID-19-associated liver injury. CONCLUSION: More intensive monitoring of aspartate aminotransferase or total bilirubin is recommended for COVID-19 patients, especially patients aged ≥ 65 years, female patients, or those with other comorbidities. Drug hepatotoxicity of antibiotics and intravenous nutrition should be alert for COVID-19 patients.