Better safe than sorry-Whole-genome sequencing indicates that missense variants are significant in susceptibility to COVID-19.

Undoubtedly, genetic factors play an important role in susceptibility and resistance to COVID-19. In this study, we conducted the GWAS analysis. Out of 15,489,173 SNPs, we identified 18,191 significant SNPs for severe and 11,799 SNPs for resistant phenotype, showing that a great number of loci were significant in different COVID-19 representations. The majority of variants were synonymous (60.56% for severe, 58.46% for resistant phenotype) or located in introns (55.77% for severe, 59.83% for resistant phenotype). We identified the most significant SNPs for a severe outcome (in AJAP1 intron) and for COVID resistance (in FIG4 intron). We found no missense variants with a potential causal function on resistance to COVID-19; however, two missense variants were determined as significant a severe phenotype (in PM20D1 and LRP4 exons). None of the aforementioned SNPs and missense variants found in this study have been previously associated with COVID-19.

Gene Variants Related to Cardiovascular and Pulmonary Diseases May Correlate with Severe Outcome of COVID-19.

Background: Severe outcomes of COVID-19 account for up to 15% of all cases. The study aims to check if any gene variants related to cardiovascular (CVD) and pulmonary diseases (PD) are correlated with a severe outcome of COVID-19 in a Polish cohort of COVID-19 patients. Methods: In this study, a subset of 747 samples from unrelated individuals collected across Poland in 2020 and 2021 was used and whole-genome sequencing was performed. Results: The GWAS analysis of SNPs and short indels located in genes related to CVD identified one variant significant in COVID-19 severe outcome in the HADHA gene, while for the PD gene panel, we found two significant variants in the DRC1 gene. In this study, both potentially protective and risk variants were identified, of which variants in the HADHA gene deserve the most attention. Conclusions: This is the first study reporting the association between the HADHA and DRC1 genetic variants and COVID-19 severe outcome based on the cohort WGS analysis. Although all the identified variants are localised in introns, they may be correlated and therefore inherited along with other risk variants, potentially causative to severe outcome of COVID-19 but not discovered yet.

Beyond GWAS-Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19?

COVID-19 infections pose a serious global health concern so it is crucial to identify the biomarkers for the susceptibility to and resistance against this disease that could help in a rapid risk assessment and reliable decisions being made on patients' treatment and their potential hospitalisation. Several studies investigated the factors associated with severe COVID-19 outcomes that can be either environmental, population based, or genetic. It was demonstrated that the genetics of the host plays an important role in the various immune responses and, therefore, there are different clinical presentations of COVID-19 infection. In this study, we aimed to use variant descriptive statistics from GWAS (Genome-Wide Association Study) and variant genomic annotations to identify metabolic pathways that are associated with a severe COVID-19 infection as well as pathways related to resistance to COVID-19. For this purpose, we applied a custom-designed mixed linear model implemented into custom-written software. Our analysis of more than 12.5 million SNPs did not indicate any pathway that was significant for a severe COVID-19 infection. However, the Allograft rejection pathway (hsa05330) was significant (p = 0.01087) for resistance to the infection. The majority of the 27 SNP marking genes constituting the Allograft rejection pathway were located on chromosome 6 (19 SNPs) and the remainder were mapped to chromosomes 2, 3, 10, 12, 20, and X. This pathway comprises several immune system components crucial for the self versus non-self recognition, but also the components of antiviral immunity. Our study demonstrated that not only single variants are important for resistance to COVID-19, but also the cumulative impact of several SNPs within the same pathway matters.

Heart rate variability comparison between young males after 4–6 weeks from the end of SARS-CoV-2 infection and controls

Due to the prolonged inflammatory process induced by infection of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), indices of autonomic nervous system dysfunction may persist long after viral shedding. Previous studies showed significant changes in HRV parameters in severe (including fatal) infection of SARS-CoV-2. However, few studies have comprehensively examined HRV in individuals who previously presented as asymptomatic or mildly symptomatic cases of COVID-19. In this study, we examined HRV in asymptomatic or mildly symptomatic individuals 5–7 weeks following positive confirmation of SARS-CoV-2 infection. Sixty-five ECG Holter recordings from young (mean age 22.6 ± 3.4 years), physically fit male subjects 4–6 weeks after the second negative test (considered to be the start of recovery) and twenty-six control male subjects (mean age 23.2 ± 2.9 years) were considered in the study. Night-time RR time series were extracted from ECG signals. Selected linear as well as nonlinear HRV parameters were calculated. We found significant differences in Porta’s symbolic analysis parameters V0 and V2 (p < 0.001), α2 (p < 0.001), very low-frequency component (VLF;p = 0.022) and respiratory peak (from the PRSA method;p = 0.012). These differences may be caused by the changes of activity of the parasympathetic autonomic nervous system as well as by the coupling of respiratory rhythm with heart rate due to an increase in pulmonary arterial vascular resistance. The results suggest that the differences with the control group in the HRV parameters, that reflect the functional state of the autonomic nervous system, are measurable after a few weeks from the beginning of the recovery even in the post-COVID group—a young and physically active population. We indicate HRV sensitive markers which may be used in long-term monitoring of patients after recovery.

Heart rate variability comparison between young males after 4-6 weeks from the end of SARS-CoV-2 infection and controls.

Due to the prolonged inflammatory process induced by infection of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), indices of autonomic nervous system dysfunction may persist long after viral shedding. Previous studies showed significant changes in HRV parameters in severe (including fatal) infection of SARS-CoV-2. However, few studies have comprehensively examined HRV in individuals who previously presented as asymptomatic or mildly symptomatic cases of COVID-19. In this study, we examined HRV in asymptomatic or mildly symptomatic individuals 5-7 weeks following positive confirmation of SARS-CoV-2 infection. Sixty-five ECG Holter recordings from young (mean age 22.6 ± 3.4 years), physically fit male subjects 4-6 weeks after the second negative test (considered to be the start of recovery) and twenty-six control male subjects (mean age 23.2 ± 2.9 years) were considered in the study. Night-time RR time series were extracted from ECG signals. Selected linear as well as nonlinear HRV parameters were calculated. We found significant differences in Porta's symbolic analysis parameters V0 and V2 (p < 0.001), α2 (p < 0.001), very low-frequency component (VLF; p = 0.022) and respiratory peak (from the PRSA method; p = 0.012). These differences may be caused by the changes of activity of the parasympathetic autonomic nervous system as well as by the coupling of respiratory rhythm with heart rate due to an increase in pulmonary arterial vascular resistance. The results suggest that the differences with the control group in the HRV parameters, that reflect the functional state of the autonomic nervous system, are measurable after a few weeks from the beginning of the recovery even in the post-COVID group-a young and physically active population. We indicate HRV sensitive markers which may be used in long-term monitoring of patients after recovery.

The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design.

BACKGROUND: COVID-19, a disease caused by infection with the SARS-CoV-2 virus, is asymptomatic or mildly symptomatic in most cases. Some patients, usually burdened with risk factors develop acute respiratory failure and other organ dysfunction. In such cases, the mortality rate is very high despite the use of intensive therapy. Amantadine has complex activity including antiviral, antiinflammatory and dopaminergic effects. This clinical trial will assess the efficacy and safety of amantadine in the prevention of COVID-19 progression toward acute respiratory failure and neurological complications. METHODS AND RESULTS: The trial will enroll 200 patients who are positive for SARS-CoV-2 infection and have one or more risk factors for worsening the disease. These patients will be included as hospitalized or ambulatory subjects for early treatment of illness. The recruitment will take place in 8 centers covering different regions of Poland. For 14 days they will be given either 200 mg of amantadine a day or placebo. Our hypothesis is a considerable reduction in the number of patients with progression toward respiratory insufficiency or neurological complications thanks to the treatment of amantadine. CONCLUSIONS: Demonstrating the efficacy and safety of amantadine treatment in improving the clinical condition of patients diagnosed with COVID-19 is of great importance in combating the effects of the pandemic. It has potential to influence on the severity and course of neurological complications, which are very common and persist long after the infection as long-COVID syndrome. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov identification no. NCT04854759; Eudra CT number: 2021-001144-98 (dated 27 February 2021).

Convalescent plasma treatment is associated with lower mortality and better outcomes in high-risk COVID-19 patients - propensity-score matched case-control study.

OBJECTIVE: This study aimed to investigate the efficacy and safety of convalescent plasma (CP) transfusion in a group of high-risk COVID-19 patients. METHODS: This prospective study included 204 patients from a single tertiary-care hospital, hospitalized with COVID-19, of whom 102 were treated with CP administration and standard care (PG) and 102 others who received standard care only (CG). The CG was selected from 336 hospitalized patients using the propensity-score matching (PSM) technique using age, MEWS score, and comorbidities. The primary outcome was mortality rate; secondary outcomes were the requirement of a ventilator, length of ventilator need, length of intensive care unit (ICU) stay, and length of overall hospital confinement. Additionally, parameters predicting death in COVID-19 patients were identified. RESULTS: Findings confirmed a significantly lower mortality rate in the PG versus the CG (13.7% vs. 34.3 %, p = 0.001) and a significant difference in the cumulative incidence of death between the two groups (p < 0.001). CP treatment was associated with lower risk of death (OR = 0.25 CI95 [0.06; 0.91], p = 0.041). There were no significant differences in ICU stay, ventilator time, and hospitalization time between the two groups. CONCLUSIONS: A significantly lower mortality rate was observed in the group of patients treated with CP. Age, presence of cardiac insufficiency, active cancer, a ventilator requirement, and length of hospitalization significantly increased the risk of death in both groups. Our study shows that CP affords better outcomes when administrated in the earlier stage of high-risk COVID-19 disease.