Immunogenicity of Sars-Cov-2 Vaccines by Vaccine Type in Randomised Clinical Trials

Background: Currently five SARS-CoV-2 vaccines are approved in North America (FDA) and Europe (EMA). Across the world other vaccines have been developed but not approved in high-income countries. Of the approved vaccines, 2 are mRNA vaccines, 2 are viral vectored vaccines, and 1 is a protein subunit vaccine. As immunogenicity markers are increasingly being used by regulatory agencies as surrogate markers for vaccine efficacy to inform authorization decisions, this meta-analysis compared the size of immunogenicity responses response elicited by the different COVID-19 vaccine types (mRNA, protein subunit, inactivated virus, viral vectors) and approved and unapproved COVID-19 vaccines. Method(s): Systematic review of trial registers and databases identified RCTs for SARS-CoV-2 vaccines. Risk of bias analysis was conducted using the Cochrane Risk of Bias tool. High risk of bias studies were excluded from analysis. Meta-analysis of seroconversion rates and geometric antibody titers (GMT) for neutralising (NAb) and anti-spike antibodies was conducted, each compared with a placebo using random effects model Cochrane-Mantel Haenszel Tests. Result(s): All studies assessed immunogenicity of COVID-19 vaccines on healthy non-immunocompromised adults between the age of 18 and 59. Statistically significant difference was identified between the different vaccine types for NAb GMT, anti-spike GMT, NAb seroconversion, and anti-spike seroconversion (P< 0.00001 for all). Conversely, no statistical significant difference was identified between approved and unapproved vaccines for NAb seroconversion (P=0.39), Nab GMT (P=0.36), anti-spike seroconversion (P=0.07), and antispike GMT (P=0.54). mRNA vaccines had the best immunogenicity results for NAb seroconversion, GMT, and anti-spike seroconversion. Viral vector vaccines had the lowest results for NAb seroconversion and GMT, while inactivated viruses had the lowest result for anti-spike seroconversion and mRNA vaccines for anti-spike GMT. High heterogeneity was observed across the different studies. Conclusion(s): This metanalysis of 35 randomised trials in 33,813 participants showed approved and unapproved vaccines to be comparable in postvaccination GMT values and seroconversion for both NAb and anti-spike. However, while comparing COVID-19 vaccines by vaccine types, statistically significant differences are observed. Variations in study designs, populations enrolled, and infection prevalence during trial duration could have influenced results.

Parents' Perception of Changes in Learning Environment Due to Covid-19

The study analyzes the learning environment before and after the Covid-19 pandemic based on a survey among parents. The parents were asked to give their perceptions of the changes in their childrens learning behavior and the mode of teaching-learning due to the pandemic. The findings indicate that there is a significant change in the learning environment and that the post-pandemic situation is perceived unfavorably by parents.

RNA enigma: "From origin of life to novel Coronavirus-COVID-19".

Recent events of the viral catastrophe have shown the rapidity of spread of new disease through emergence of virulent strains. Proper control measures can be developed only through understanding the evolution of virulence in RNA viruses. To understand the evolution of this novel Coronavirus, COVID-19, it is imperative to delineate the evolution of RNA, its transformation into first life forms, the steady and continuous evolution and emergence through modification in their genome and nevertheless the natural selection. This review will throw light on these aspects to understand the possible origin of COVID-19 to control and eradicate this viral outbreak.

Covid-19 and Dynamic Changes in Learning Environment: A Perceptional Study (preprint)

De-addiction of mobile in students has become a challenge for both urban and rural parents. Students were forced to use mobile handsets and in-spite of the hybrid learning mode adopted and adapted by schools and colleges; due to Covid and its challenges. Covid has made things clearer to learn by distance and maintain the social distance. India is full of villages and most parents are unaware of what students are watching on their mobile. Children and students camouflage their parents by projecting as attending an online class. This has become a challenge to de-addict and bring them back to normal learning. The present study intends to analyses the dynamic changes in the learning environment during pre and post Covid learning environment. The outcome of the study indicated that the that there is significant difference in the learning environment and it also revealed that after covid the learning environment became unfavourable.

Impact of the COVID-19 pandemic on personal networks and neurological outcomes of people with multiple sclerosis: a case-control cross-sectional and longitudinal analysis

Introduction: Personal social networks impact the quality of life of people living with multiple sclerosis (pwMS). Objective / Aims: To evaluate the dynamic associations between personal network features and neurological function in pwMS and control participants during the COVID-19 pandemic and compare with the pre-pandemic period. Method(s): We first analyzed data collected from 8 cohorts of pwMS and control participants during the COVID-19 pandemic from March-December 2020. We then leveraged data collected between 2017-2019 in 3 of the 8 cohorts for longitudinal comparison. Participants completed a personal network questionnaire, which quantified the structure and composition of each person's personal network, including the health behaviors of network members. Neurological disability was quantified by three interrelated patient-reported outcomes: Patient Determined Disease Steps (PDDS), Multiple Sclerosis Rating Scale-Revised (MSRS-R), and Patient Reported Outcomes Measurement Information System (PROMIS)-Physical Function. We identified the network features associated with neurologic disability using paired t-tests and covariate-adjusted regressions. Result(s): In the cross-sectional analysis of the pandemic data from 1130 pwMS and 1250 control participants, percentage of network members perceived to have a negative health influence was associated with greater neurological symptom burden in pwMS (MSRS-R: Beta[95% CI]=2.181[1.082, 3.279], p<.001) and worse physical function in control participants (PROMIS-Physical Function: Beta[95% CI]=-5.707[-7.405, -4.010], p<.001). In the longitudinal analysis of 230 pwMS and 136 control participants, the percentage of people contacted weekly or less (p<.001) decreased during the COVID-19 pandemic for both pwMS (0.30+/-0.26 v. 0.19+/-0.22) and controls (0.23+/-0.25 v. 0.15+/-0.21) when compared to the pre-pandemic period. PwMS further experienced a greater reduction in network size (p<.001), increase in constraint (a measure of close ties of the network, p<.001) and decrease in maximum degree (highest number of ties of a network member, p<.001) than controls during the COVID-19 pandemic. These changes in network features were not associated with worsening neurological disability. Conclusion(s): Our findings suggest that negative health influences in personal networks are associated with worse disability in all participants and COVID-19 pandemic led to contraction of personal networks to a greater extent for pwMS than controls.

Changes in alcohol consumption during the COVID-19 pandemic and associations with alcohol response, perceived stress, and loss of control over drinking

Background: Previous reports on alcohol consumption during the COVID-19 pandemic have been varied. To better understand this heterogeneity, we examined measures of alcohol response, perceived stress, and loss of control over drinking and their associations with changes in alcohol consumption during the COVID-19 pandemic across Alcohol Use Disorder (AUD) and non-AUD groups. Method(s): Alcohol response measures included Self-Report of the Effects of Alcohol Scale (SRE), Anticipated-Biphasic Alcohol Effects Scale (A-BAES), and Penn Alcohol Craving Scale (PACS). Additionally, we collected the Perceived Stress Scale (PSS) and the Impaired Control Scale (ICS). Alcohol consumption was measured using Alcohol Use Disorder Identification Test Consumption (AUDIT-C) and collected pre- and during pandemic. Participants were categorized into three groups based on their AUDIT-C score change: no change (n = 147), decrease (n = 128), or increase (n = 115). We also examined the full AUDIT score and categorized participants in those with a score below 8, or 8+. Participants (n = 390;mean age = 43.7 years;52.0% male) previously enrolled in the NIAAA Natural History Protocol were recruited for a follow-up longitudinal survey study. Result(s): Data were analyzed using general linear models covarying for history of AUD, sex, age, enrollment phase, and time since screened in the natural history protocol. Participants reporting an increase in AUDIT scores from pre-pandemic had significantly higher scores on alcohol response (PACS, p < 0.001;A-BAES, p < 0.001, SRE, p < 0.001), PSS (p < 0.001), and ICS failed attempts to control drinking (p < 0.001) during the pandemic than those with a decrease or no change in AUDIT scores. History of AUD was significant in all models (all p's < 0.01). Participants with AUDIT scores 8 or greater also reported greater scores on alcohol response measures, stress, and failed attempts to control drinking (all p's < 0.001). Conclusion(s): An increase in AUDIT scores from pre-pandemic to during the pandemic and those who met criteria for harmful alcohol consumption were associated with higher scores in measures of alcohol response, stress and impaired control than those with a decrease or no change in their AUDIT scores. These associations were stronger in those with a history of AUD and highlight potential biobehavioral correlates of vulnerability of those with a history of AUD and those at risk for heavier drinking.

Transcriptome Wide Association Study of Individually Imputed Genetically Regulated Gene Expression in the Million Veteran Program

Background: Most neuropsychiatric disorders are moderately heritable but characterized by many genetic risk variants with weak effects. As such, it is difficult to point to direct causes or elucidate mechanisms of action. Despite the ease in gathering genetic data from humans, genetic data does not easily explain mechanistic effects. Gene expression on the other hand, which can more easily explain mechanistic effects, is harder to gather, especially in brain regions that are critical to the understanding of neuropsychiatric disease. To address this, we developed methods to impute genetically regulated gene expression (GReX) from genotypes and imputed GReX in over 440,000 European individuals in the Million Veteran Program (MVP) for a wide variety of tissues and cell types. Method(s): We use EpiXcan (based on PrediXcan) to develop machine learning models from training genotype, expression, and epigenetic data. We use custom scripts to impute individual GReX and perform a variety of downstream association analyses, including GReX Phenome Wide Association Studies (PheWAS) and Transcriptome Wide Association Studies (TWAS). Result(s): Results show an overlap in Schizophrenia genes identified by individual level TWAS and those identified by summary level TWAS informed by GWAS. TWASs for neuropsychiatric phenotypes identify genes established in the literature, but also novel targets. Inverse-variance meta-analyzed single gene imputation efforts across ancestries confirm clinical results obtained from COVID-19 positive individuals in both IL10RB and IFNAR2. GReX PheWAS for these particular genes using a novel negative binomial distribution for phecodes confirm COVID-19 related phenotypes. Finally, we describe various enriched pathways found in a COVID-19 TWAS, including immunological pathways. Discussion(s): GReX presents a unique solution to integrate effects across the genome and increase sample size in gene expression analyses. We are pursuing the creation of additional EpiXcan models, improved statistical methods for downstream association analyses, and replication efforts across biobanks. We plan to perform these analyses in all ancestries, available EpiXcan and PrediXcan models, and phenotypes. Disclosure: Nothing to disclose. Copyright © 2022

Integrated treatment strategies and prosthetic rehabilitation for COVID-19-associated mucormycosis

Mucormycosis is a life-threatening opportunistic infection caused by the fungi belonging to the order Mucorales. Mucormycosis commonly develops in patients with diabetes mellitus having a background of immunosuppression. An integrative approach in the management of COVID-19-associated mucormycosis can be more effective and beneficial to the patients, as the delay in diagnosis and treatment is commonly associated with COVID-19. The rehabilitation of the resected facial structures in these patients would be very crucial in sustaining the quality of life. Thus, our review aims in providing insights into management strategies across different fields of medicine and the various rehabilitation methods. © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

EXAMINING CHANGES IN AUDIT SCORE DURING THE COVID-19 PANDEMIC AND ASSOCIATED MEASURES THROUGH THE ADDICTIONS NEUROCLINICAL ASSESSMENT FRAMEWORK

Purpose: The Addictions Neuroclinical Assessment (ANA) is a neurobehavioral framework designed to better understand the heterogeneity of Alcohol Use Disorder (AUD). The aim of this analysis was to examine measures representing the ANA domains of incentive salience, negative emotionality, and executive function, and their associations with changes in alcohol problems related to the COVID-19 pandemic in AUD and non-AUD groups. Methods: Incentive salience measures included Self-Report of the Effects of Alcohol Scale (SRE), Anticipated-Biphasic Alcohol Effects Scale (A-BAES), and Penn Alcohol Craving Scale (PACS). Negative emotionality measures included Perceived Stress Scale (PSS), and executive function measures included Impaired Control Scale (ICS). All ANA domain measures were collected during the pandemic. Alcohol problems were measured using Alcohol Use Disorder Identification Test (AUDIT) and collected pre-and during pandemic. Participants were categorized into three groups based on their AUDIT score change: no change (n = 162), decrease (n = 141), or increase (n = 135). Data: Participants (n = 438;mean age = 44.8 years;52.0% male) previously enrolled in the NIAAA Natural History Protocol were recruited for a follow-up longitudinal survey study. Results: Data were analyzed using general linear models covarying for history of AUD, sex, age, enrollment phase, and time since screened in the natural history protocol. Participants reporting an increase in AUDIT scores from pre-pandemic had significantly higher scores on incentive salience (PACS, p <0.001;A-BAES sedation, p <0.001;trending for SRE, p = 0.06), negative emotionality (PSS, p <0.001), and executive function (ICS failed attempts to control drinking, p <0.005) during the pandemic than those with a decrease or no change in AUDIT scores. History of AUD was significant in all models (all p's<0.01). Age was negatively associated with negative emotionality, while males showed significantly higher scores on incentive salience measures. Finally, those enrolled in the early pandemic phase scored the highest on negative emotionality measures. Conclusions: An increase in AUDIT scores from pre-pandemic to during the pandemic was associated with higher scores in measures across all three ANA domains than those with a decrease or no change in their AUDIT scores. These associations were stronger in those with a history of AUD and highlight potential bio behavioral correlates of vulnerability of those with a history of AUD and those at risk for heavier drinking.

Ribavirin antiviral combination therapy in COVID 19, a single-center experience (preprint)

Background COVID 19 infection has a similar clinical spectrum of disease presentation such as SARS and MERS in the past. These led to the assumption of the possibility to treat COVID 19 infection with antivirals which had been used to treat SARS and MERS. Methods A retrospective analysis was done on the data of SEV COVID Trial in symptomatic adult patients of COVID 19 infection with objectives to explore whether ribavirin antiviral combinations reduces the need of both noninvasive and invasive ventilators in treatment of COVID 19 infections. Results The patients were categorized as Cohort A consisting of 40 patients and Cohort B of 61 patients as Cohort A being the group of patients who received the standard therapy and Cohort B the group of patients who received the ribavirin combination therapy. Conclusion The study concluded that there was no statistically significant difference in regard to the need of noninvasive ventilation and invasive ventilation and also the development of multiorgan dysfunction in between the two Cohorts. Also, with progress of time, the proportion of patients with single organ dysfunctions in the two cohorts showed gradual recovery without any statistically significant differences.

Geolocated twitter-based population mobility in victoria, australia, during the staged covid-19 restrictions

Using geotagged Twitter data in Victoria, we created a mobility index and studied the changes during the staged restrictions during the coronavirus disease 2019 (COVID-19) pandemic. We describe preliminary evidence that geotagged Twitter data may be used to provide real-time population mobility data and information on the impact of restrictions on such mobility. © 2020, College of Intensive Care Medicine. All rights reserved.

Adverse events reported from the COVID-19 vaccines: a descriptive study based on the WHO database (VigiBaseR)

The emergency approval of a few COVID-19 vaccines provided a ray of hope to fight the deadly pandemic. However, their approval was solely based on limited data from the clinical trials in a short period, thereby imposing a demand for post-marketing surveillance studies to monitor beneficial and adverse events (AEs). This study focuses on observing the serious adverse events (SAEs) data reported in the World Health Organization database. The data from VigiBaseR was analyzed. The duplicates in the data were removed and analyzed based on age, gender, and SAEs at the system organ classification level and the individual preferred term level. A total of 103,954 AEs were reported. The majority of them were seen as females (80%), from Europe (83%), and were between 18 and 64 years (80.74%) of age. The most-reported AEs were of the nervous system (19.1%), musculoskeletal (11.2%), and elderly (>65 years) people. The reported SAEs from the COVID-19 vaccines were in line with the data published in the clinical trial reports. These SAEs to vaccines will need causality analysis and review of individual reports.