No Causal Association Between Cholelithiasis and COVID-19: A Bidirectional Mendelian Randomization Study (preprint)

Background: Gallstone diseases and cholecystectomy are possibly associated with the severity of COVID-19 bidirectionally, yet the casual association remains unclear. Method: Applying genome-wide association study summary statistics of primarily European individuals, we utilized 2-sample Mendelian randomization to estimate the bidirectional causal effects of cholelithiasis, cholecystitis and cholecystectomy on three COVID-19 phenotypes: SARS-CoV-2 infection, COVID-19 hospitalization and severe COVID-19. Results: Inverse variance weighted Mendelian randomization results from the FinnGen consortium showed that none of cholelithiasis, cholecystitis and cholecystectomy was not causally associated with COVID-19 phenotypes, and vice versa. In addition, other methods including MR-Egger, weighted median, weight mode and simple mode exhibited approximate tendency as IVW. These results were all robust to sensitivity analysis. Conclusion:  The forward MR analysis showed no causally significant impact of cholelithiasis, cholecystitis and cholecystectomy on COVID-19 phenotypes. Similarly, reverse MR results also showed no causal association between COVID-19 and cholelithiasis events.

Human Brain Organoids as an In Vitro Model System of Viral Infectious Diseases

Brain organoids, or brainoids, have shown great promise in the study of central nervous system (CNS) infection. Modeling Zika virus (ZIKV) infection in brain organoids may help elucidate the relationship between ZIKV infection and microcephaly. Brain organoids have been used to study the pathogenesis of SARS-CoV-2, human immunodeficiency virus (HIV), HSV-1, and other viral infections of the CNS. In this review, we summarize the advances in the development of viral infection models in brain organoids and their potential application for exploring mechanisms of viral infections of the CNS and in new drug development. The existing limitations are further discussed and the prospects for the development and application of brain organs are prospected.

Cross-neutralization antibodies against SARS-CoV-2 and RBD mutations from convalescent patient antibody libraries (preprint)

The emergence of coronavirus disease 2019 (COVID-19) pandemic led to an urgent need to develop therapeutic interventions. Among them, neutralizing antibodies play crucial roles for preventing viral infections and contribute to resolution of infection. Here, we describe the generation of antibody libraries from 17 different COVID-19 recovered patients and screening of neutralizing antibodies to SARS-CoV-2. After 3 rounds of panning, 456 positive phage clones were obtained with high affinity to RBD (receptor binding domain). Then the positive clones were sequenced and reconstituted into whole human IgG for epitope binning assays. After that, all 19 IgG were classified into 6 different epitope groups or Bins. Although all these antibodies were shown to have ability to bind RBD, the antibodies in Bin2 have more superiority to inhibit the interaction between spike protein and angiotensin converting enzyme 2 receptor (ACE2). Most importantly, the antibodies from Bin2 can also strongly bind with mutant RBDs (W463R, R408I, N354D, V367F and N354D/D364Y) derived from SARS-CoV-2 strain with increased infectivity, suggesting the great potential of these antibodies in preventing infection of SARS-CoV-2 and its mutations. Furthermore, these neutralizing antibodies strongly restrict the binding of RBD to hACE2 overexpressed 293T cells. Consistently, these antibodies effectively neutralized pseudovirus entry into hACE2 overexpressed 293T cells. In Vero-E6 cells, these antibodies can even block the entry of live SARS-CoV-2 into cells at only 12.5 nM. These results suggest that these neutralizing human antibodies from the patient-derived antibody libraries have the potential to become therapeutic agents against SARS-CoV-2 and its mutants in this global pandemic.

Discussion on the Management of Fever Clinic during the Epidemic Period of Corona Virus Disease 2019 / 中华急诊医学杂志

Objective@#To investigate the role of epidemiological history in the screening of Corona Virus Disease 2019 (COVID-19) in fever clinic, to improve the efficiency in fever clinic and reduce the incidence of cross infection.@*Methods@#This is a retrospective study. Patients who were admitted to the fever clinic in West China Hospital of Sichuan University from January 23th, 2020 to February 11th, 2020 included the study. According to epidemiological history, the patients were divided into epidemiological history group (the experimental group) and no epidemiological history group (the control group). The two groups of patients were admitted and treated separately. The clinical data, NEWS score, etiology results, viral pneumonia showed on CT, time of visit, COVID-19 patient ratio, and admission composition ratio were compared between the two groups. The measurement data were presented as the mean ± standard deviation (SD), and the numeration data were expressed as ratio or constituent ratio. The measurement data of normal distribution between the two groups were compared by independent sample t test. The measurement data of skewed distribution are expressed by the median (interquartile range), and the comparison between the two groups is tested by non-parameter. The differences between enumeration data were assessed by chi-square test. A P<0.05 was considered statistically significant.@*Results@#A total of 2423 patients were included, including 927 patients in the experimental group and 1296 patients in the control group. There were no significant differences in gender, NEWS score and clinical symptoms between the two groups (P> 0.05). The age (35.00 ± 12.80 vs 38.13 ± 15.57 years) , the proportion of fever patients (28.80% vs 32.75%) and waiting time (31.72 vs 58.08 min) of the experimental group were lower than the control group, the difference was statistically significant (P <0.05). The CT examination ratio (37.54% vs 20.39%), viral pneumonia ratio showed on CT (9.77% vs 2.95%), ratio of examined COVID-19 nucleic acid test (85.44% vs 56.75%), and the admission ratio (16.72% vs 9.63%) of the experimental group were higher than the control group, and the differences were statistically significant (P <0.05); There was no significant difference in the positive rates of influenza virus and rhinovirus between the two groups (P> 0.05).@*Conclusion@#It is necessary to adjust the management mode of fever clinic during the Corona Virus Disease 2019, and to manage the patients according to the epidemiological history which can improve the screening efficiency and reduce the risk of cross infection.