Disrupted chromatin architecture in olfactory sensory neurons: looking for the link from COVID-19 infection to anosmia.

We tackle here genomic mechanisms of a rapid onset and recovery from anosmia-a potential diagnostic indicator for early-stage COVID-19 infection. Based on previous observations on how olfactory receptor (OR) gene expression is regulated via chromatin structure in mice, we hypothesized that the disruption of the OR gene expression and, respectively, deficiency of the OR function can be caused by chromatin reorganization taking place upon SARS-CoV-2 infection. We obtained chromatin ensemble reconstructions from COVID-19 patients and control samples using our original computational framework for the whole-genome 3D chromatin ensemble reconstruction. Specifically, we used megabase-scale structural units and effective interactions between them obtained in the Markov State modelling of the Hi-C contact network as an unput in the stochastic embedding procedure of the whole-genome 3D chromatin ensemble reconstruction. We have also developed here a new procedure for analyzing fine structural hierarchy with (sub)TAD-size units in local chromatin regions, which we apply here to parts of chromosomes containing OR genes and corresponding regulatory elements. We observed structural modifications in COVID-19 patients on different levels of chromatin organization, from the alteration of whole genome structure and chromosomal intermingling to reorganization of contacts between chromatin loops at the level of topologically associating domains. While complementary data on known regulatory elements point to potential pathology-associated changes within the overall picture of chromatin alterations, further investigation using additional epigenetic factors mapped on 3D reconstructions with improved resolution will be required for better understanding of anosmia caused by SARS-CoV-2 infection.

Higher benefit-risk ratio of COVID-19 vaccination in patients with schizophrenia and major depressive disorder versus patients with bipolar disorder when compared to controls.

Patients with major psychiatric disorders (MPD) that include schizophrenia (SCH), bipolar disorder (BP), and major depressive disorder (MDD) are at increased risk for coronavirus disease 2019 (COVID-19). However, the safety and efficacy of COVID-19 vaccines in MPD patients have not been fully evaluated. This study aimed to investigate adverse events (AEs)/side effects and efficacy of COVID-19 vaccines in MPD patients. This retrospective study included 2034 patients with SCH, BP, or MDD who voluntarily received either BBIBP-CorV or Sinovac COVID-19 vaccines, and 2034 matched healthy controls. The incidence of AEs/side effects and the efficacy of COIVD-19 vaccinations among the two groups were compared. The risk ratio (RR) of side effects in patients with MPD was 0.60 (95% confidence interval [CI]: 0.53-0.68) after the first dose and 0.80 (95% CI: 0.65-0.99) following the second dose, suggesting a significantly lower risk in the MPD group versus healthy controls. The RRs of AEs did not differ between patients and controls. Notably, fully vaccinated patients exhibited a decreased risk of influenza with or without fever compared with controls (RR=0.38, 95% CI: 0.31-0.46; RR=0.23, 95% CI: 0.17-0.30; respectively). Further subgroup comparisons revealed a significantly lower risk of influenza with fever in MDD (RR=0.13, 95% CI: 0.08-0.21) and SCH (RR=0.24, 95% CI: 0.17-0.34) than BP (RR=0.85, 95% CI: 0.69-1.06) compared to controls. We conclude that the benefit-risk ratio of COVID-19 vaccination was more favorable in SCH or MDD versus BP when compared with controls. These data indicate that COVID-19 vaccines are safe and protective in patients with MPD from COVID-19.

Disrupted chromatin architecture in olfactory sensory neurons: A missing link from COVID-19 infection to anosmia (preprint)

AO_SCPLOWBSTRACTC_SCPLOWWe tackle here genomic mechanisms of a rapid onset and recovery from anosmia - a useful diagnostic indicator for early-stage COVID-19 infection. On the basis of earlier observed specifics of olfactory receptors (ORs) regulation in the mice chromatin structures, we hypothesized that the disruption of OR function can be caused by chromatin reorganization taking place upon SARS-CoV-2 infection. We reconstructed the chromatin ensembles of ORs obtained from COVID-19 patients and control samples using our original computational framework for the whole-genome chromatin ensemble 3D reconstruction. We have also developed here a new procedure for the analysis of fine structural hierarchy in local, megabase scale, parts of chromosomes containing the OR genes and corresponding epigenetic factors. We observed structural modifications in COVID-19 patients on different levels of chromatin organization, from alteration of the whole genome structure and chromosomal intermingling to reorganization of contacts between the chromatin loops at the level of topologically associating domains. While complementary data on known regulatory elements point to pathology-associated changes within the overall picture of chromatin alterations, further investigation using additional epigenetic factors mapped on 3D reconstructions with improved resolution will be required for better understanding of anosmia caused by SARS-CoV-2 infection.

Protocol for a retrospective cohort study for evaluating the early antibiotics use in non-severe COVID-19 patients (preprint)

The use of antibiotics is common in the treatment of COVID-19, but adequate evaluation is lacking. We aimed to evaluate the efficacy of antibiotic use in non-severe COVID-19 patients, particularly in patients admitted with low risk of bacterial infection. This is a multi-center retrospective cohort study. Patients are screened strictly according to the inclusion/exclusion criteria and are divided into two groups based on antibiotics exposure. The exposure is defined as the treatment of antibiotics prescribed within 48 hours after admission, with a course of treatment≥3 days; and patients in this group are classified as early antibiotic use group. Otherwise, patients are classified as the non early antibiotic use group. The primary end point of the study is progressing from non-severe type COVID-19 into severe type. This is the first protocol to put a focus on the transformation of the severity of the disease, based on a multi-center retrospective cohort design.

Evaluation of early antibiotics use in non-severe COVID-19 patients admitted with low risk of bacterial infection (preprint)

The use of antibiotics is common in the treatment of COVID-19, but adequate evaluation is lacking. This study aimed to evaluate the effect of early antibiotic use in non-severe COVID-19 patients admitted with low risk of bacterial infection. The multi-center retrospective cohort study included 1613 non-severe COVID-19 inpatients admitted with low risk of bacterial infection. During the follow-up of 30 days, the proportion of patients progressed into severe type COVID-19 in the early antibiotics use group was almost 1.5 times than that of the comparision group. In the mixed-effect model, the early use of antibiotics was associated with higher probability of developing severe type, staying in the hospital for over 15 days, and secondary infection. However, it was not significant association with mortality rate. Analysis with propensity score-matched cohort displayed similar results. It is suggested that antibiotic use should be avoided unless absolutely necessary in non-severe COVID-19 patients, particularly in the early stages.