The Association of Previous Vaccination with Live-Attenuated Varicella Zoster Vaccine and COVID-19 Positivity: An Israeli Population-Based Study.

The Bacillus Calmette-Guérin (BCG) vaccine affords indirect protection against COVID-19, which is presumably due to priming of the innate immune system. It was hypothesized that the live attenuated Varicella Zoster (LAVZ) vaccine, recommended for the elderly population, would also protect against COVID-19 infection. A retrospective population-based cross-sectional study was conducted using the Leumit Health Services (LHS) database. LAVZ-vaccinated patients were matched with controls based on a propensity score model using 1:9 nearest-neighbor matching. Matching was based on age, gender, and the presence of some chronic disorders, which were selected according to their association with COVID-19 infection. Multivariate logistic regression analyses, adjusted for sex, age, smoking status, comorbidities, and chronic medications associated with COVID-19 risk, were used to estimate the association between LAVZ vaccination and COVID-19 RT-PCR results. Subjects (625) vaccinated with LAVZ and RT-PCR-tested for COVID-19 were identified. After 1:9 matching of subjects who received the LAVZ vaccine, 6250 subjects were included in the study. Multivariate logistic regression analysis demonstrated a significant and independent negative association between having received the LAVZ vaccine and the likelihood of COVID-19 infection (adjusted OR = 0.47 (95% CI 0.33-0.69, p < 0.001)). This association was further strengthened after separate analysis based on the time of LAVZ vaccination before COVID-19 RT-PCR testing. Individuals aged ≥50 years vaccinated with LAVZ had a decreased likelihood of being tested positive for COVID-19.

Specific Susceptibility to COVID-19 in Adults with Down Syndrome.

The current SARS-CoV-2 outbreak, which causes COVID-19, is particularly devastating for individuals with chronic medical conditions, in particular those with Down Syndrome (DS) who often exhibit a higher prevalence of respiratory tract infections, immune dysregulation and potential complications. The incidence of Alzheimer's disease (AD) is much higher in DS than in the general population, possibly increasing further the risk of COVID-19 infection and its complications. Here we provide a biological overview with regard to specific susceptibility of individuals with DS to SARS-CoV-2 infection as well as data from a recent survey on the prevalence of COVID-19 among them. We see an urgent need to protect people with DS, especially those with AD, from COVID-19 and future pandemics and focus on developing protective measures, which also include interventions by health systems worldwide for reducing the negative social effects of long-term isolation and increased periods of hospitalization.

Seasonal UV exposure and vitamin D: association with the dynamics of COVID-19 transmission in Europe.

Several recent studies have demonstrated that low plasma 25(OH) vitamin D levels are associated with the risk of COVID-19 infection. The primary source of vitamin D production in humans is environmental UV radiation. In many viral respiratory diseases, peak infection rates are observed during winter due to reduced UV exposure and low temperatures. In Europe, the second wave of COVID-19 began early in the winter of 2020. Investigating the impact of seasonal temperature and UV exposure on COVID-19 transmission could thus aid in prevention and intervention. As such, we first performed a comprehensive meta-analysis of all related published literature based on the association between vitamin D and COVID-19, which supported the hypothesis that the low vitamin D level is a critical risk factor for COVID-19 infection. Next, to understand the potential impact of seasonal UV and temperature levels on COVID-19 cases, we analyzed meteorological data and daily COVID-19 cases per million in the populations of 26 European countries. We observed that low temperature, UV index, and cloud-free vitamin D UV dose (UVDVF) levels are negatively correlated with COVID-19 prevalence in Europe. Furthermore, a distributed lag nonlinear model was used to assess the nonlinear delayed effects of individual seasonal factors on COVID-19 cases. Such analysis highlighted the significantly delayed impact of UVDVF on the cumulative relative risk of COVID-19 infection. The findings of this study suggest that low UV exposure can affect the required production of vitamin D in the body, which substantially influences the dynamics of COVID-19 transmission and severity.

Non-optimal codon usage preferences of coronaviruses determine their promiscuity for infecting multiple hosts.

Circulating animal coronaviruses occasionally infect humans. The SARS-CoV-2 is responsible for the current worldwide outbreak of COVID-19 that has resulted in 2 112 844 deaths as of late January 2021. We compared genetic code preferences in 496 viruses, including 34 coronaviruses and 242 corresponding hosts, to uncover patterns that distinguish single- and 'promiscuous' multiple-host-infecting viruses. Based on a codon usage preference score, promiscuous viruses were shown to significantly employ nonoptimal codons, namely codons that involve 'wobble' binding to anticodons, as compared to single-host viruses. The codon adaptation index (CAI) and the effective number of codons (ENC) were calculated for all viruses and hosts. Promiscuous viruses were less adapted hosts vs single-host viruses (P-value = 4.392e-11). All coronaviruses exploit nonoptimal codons to infect multiple hosts. We found that nonoptimal codon preferences at the beginning of viral coding sequences enhance the translational efficiency of viral proteins within the host. Finally, coronaviruses lack endogenous RNA degradation motifs to a significant degree, thereby increasing viral mRNA burden and infection load. To conclude, we found that promiscuously infecting coronaviruses prefer nonoptimal codon usage to remove degradation motifs from their RNAs and to dramatically increase their viral RNA production rates.

COVID19 Drug Repository: text-mining the literature in search of putative COVID19 therapeutics.

The recent outbreak of COVID-19 has generated an enormous amount of Big Data. To date, the COVID-19 Open Research Dataset (CORD-19), lists ∼130,000 articles from the WHO COVID-19 database, PubMed Central, medRxiv, and bioRxiv, as collected by Semantic Scholar. According to LitCovid (11 August 2020), ∼40,300 COVID19-related articles are currently listed in PubMed. It has been shown in clinical settings that the analysis of past research results and the mining of available data can provide novel opportunities for the successful application of currently approved therapeutics and their combinations for the treatment of conditions caused by a novel SARS-CoV-2 infection. As such, effective responses to the pandemic require the development of efficient applications, methods and algorithms for data navigation, text-mining, clustering, classification, analysis, and reasoning. Thus, our COVID19 Drug Repository represents a modular platform for drug data navigation and analysis, with an emphasis on COVID-19-related information currently being reported. The COVID19 Drug Repository enables users to focus on different levels of complexity, starting from general information about (FDA-) approved drugs, PubMed references, clinical trials, recipes as well as the descriptions of molecular mechanisms of drugs' action. Our COVID19 drug repository provide a most updated world-wide collection of drugs that has been repurposed for COVID19 treatments around the world.

The use of aspirin for primary prevention of cardiovascular disease is associated with a lower likelihood of COVID-19 infection.

Acetylsalicylic acid (aspirin) is commonly used for primary and secondary prevention of cardiovascular diseases. Aspirin use is associated with better outcomes among COVID-19 positive patients. We hypothesized that the aspirin use for primary cardiovascular disease prevention might have a protective effect on COVID-19 susceptibility and disease duration. We conducted a retrospective population-based cross-sectional study, utilizing data from the Leumit Health Services database. The proportion of patients treated with aspirin was significantly lower among the COVID-19-positive group, as compared to the COVID-19-negative group [73 (11.03%) vs. 1548 (15.77%); P = 0.001]. Aspirin use was associated with lower likelihood of COVID-19 infection, as compared to nonusers (adjusted OR 0.71 (95% CI, 0.52 to 0.99; P = 0.041). Aspirin users were older (68.06 ± 12.79 vs. 56.63 ± 12.28 years of age; P < 0.001), presented a lower BMI (28.77 ± 5.4 vs. 30.37 ± 4.55; P < 0.0189), and showed higher prevalence of hypertension (56, 76.71%), diabetes (47, 64.38%), and COPD (11, 15.07%) than the aspirin nonusers (151, 25.64%, P < 0.001; 130, 22.07%, P < 0.001; and 43, 7.3%, P = 0.023, respectively). Moreover, COVID-19 disease duration (considered as the time between the first positive and second negative COVID-19 RT-PCR test results) among aspirin users was significantly shorter, as compared to aspirin nonusers (19.8 ± 7.8 vs. 21.9 ± 7.9 P = 0.045). Among hospitalized COVID-positive patients, a higher proportion of surviving subjects were treated with aspirin (20, 19.05%), as opposed to 1 dead subject (14.29%), although this difference was not significant (P = 0.449). In conclusion, we observed an inverse association between the likelihood of COVID-19 infection, disease duration and mortality, and aspirin use for primary prevention.

Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study.

Vitamin D deficiency is a worldwide pandemic. The aim of this study was to evaluate associations of plasma 25(OH)D levels with the likelihood of coronavirus disease 2019 (COVID-19) infection and hospitalization. The study population included the 14 000 members of Leumit Health Services, who were tested for COVID-19 infection from February 1st to April 30th , 2020, and who had at least one previous blood test for the plasma 25(OH)D level. 'Suboptimal' or 'low' plasma 25(OH)D level was defined as plasma 25-hydroxyvitamin D, or 25(OH)D, concentration below the level of 30 ng/mL. Of 7807 individuals, 782 (10.02%) were COVID-19-positive, and 7025 (89.98%) COVID-19-negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID-19 [19.00 ng/mL (95% confidence interval (CI) 18.41-19.59) vs. 20.55 (95% CI: 20.32-20.78)]. Univariate analysis demonstrated an association between the low plasma 25(OH)D level and increased likelihood of COVID-19 infection [crude odds ratio (OR) of 1.58 (95% CI: 1.24-2.01, P < 0.001)], and of hospitalization due to the SARS-CoV-2 virus [crude OR of 2.09 (95% CI: 1.01-4.30, P < 0.05)]. In multivariate analyses that controlled for demographic variables, and psychiatric and somatic disorders, the adjusted OR of COVID-19 infection [1.45 (95% CI: 1.08-1.95, P < 0.001)] and of hospitalization due to the SARS-CoV-2 virus [1.95 (95% CI: 0.98-4.845, P = 0.061)] were preserved. In the multivariate analyses, age over 50 years, male gender and low-medium socioeconomic status were also positively associated with the risk of COVID-19 infection; age over 50 years was positively associated with the likelihood of hospitalization due to COVID-19. We concluded that low plasma 25(OH)D levels appear to be an independent risk factor for COVID-19 infection and hospitalization.