Right-left digit ratios, a novel form of asymmetry: Patterns of instability in children and relationships to platelet counts and hospitalization in adults with COVID-19.

High right minus left (R-L) asymmetry of digit ratios has been reported to be linked to hospitalization for COVID-19. Here we examined the developmental patterns of this novel form of asymmetry in children and further explored their relationships to platelet counts and hospitalization for COVID-19 in adult patients. We considered ratios calculated from four digits (2D, 3D, 4D, 5D) in: (i) a sample of healthy participants aged 2 years to 18 years (n = 680, 340 males) and (ii) 96 adult patients (42 males) hospitalized for COVID-19 and 100 controls (53 males). The protocol for (ii) included a questionnaire and laboratory test results. In sample (i) of the six unsigned digit ratio asymmetries, those which included 5D had the highest mean asymmetry with the greatest between-individual variation and they were unstable over the age range of 2 years to 18 years. In sample (ii) patients showed higher asymmetries than controls in four ratios (2D:4D, 2D:5D, 3D:5D, 4D:5D) and a sum of asymmetries of the two independent ratios (2D:4D+3D:5D) correlated positively with platelet counts and hospitalization. Conclusion: Means and SDs of digit ratio asymmetry that include the 5th digit are high and age-unstable. Digit ratio asymmetry, particularly 5th digit ratio asymmetry and a composite measure of 2D:4D + 3D:5D asymmetry, may be positively linked to high platelet counts in COVID-19 patients and to an elevated risk of hospitalization.

Unbiased approach to identify and assess efficacy of human SARS-CoV-2 neutralizing antibodies.

Coronavirus disease 2019 (COVID-19) continues to significantly impact the global population, thus countermeasure platforms that enable rapid development of therapeutics against variants of SARS-CoV-2 are essential. We report use of a phage display human antibody library approach to rapidly identify neutralizing antibodies (nAbs) against SARS-CoV-2. We demonstrate the binding and neutralization capability of two nAbs, STI-2020 and STI-5041, against the SARS-CoV-2 WA-1 strain as well as the Alpha and Beta variants. STI-2020 and STI-5041 were protective when administered intravenously or intranasally in the golden (Syrian) hamster model of COVID-19 challenged with the WA-1 strain or Beta variant. The ability to administer nAbs intravenously and intranasally may have important therapeutic implications and Phase 1 healthy subjects clinical trials are ongoing.

Salicylanilides Reduce SARS-CoV-2 Replication and Suppress Induction of Inflammatory Cytokines in a Rodent Model.

SARS-CoV-2 virus has recently given rise to the current COVID-19 pandemic where infected individuals can range from being asymptomatic, yet highly contagious, to dying from acute respiratory distress syndrome. Although the world has mobilized to create antiviral vaccines and therapeutics to combat the scourge, their long-term efficacy remains in question especially with the emergence of new variants. In this work, we exploit a class of compounds that has previously shown success against various viruses. A salicylanilide library was first screened in a SARS-CoV-2 activity assay in Vero cells. The most efficacious derivative was further evaluated in a prophylactic mouse model of SARS-CoV-2 infection unveiling a salicylanilide that can reduce viral loads, modulate key cytokines, and mitigate severe weight loss involved in COVID-19 infections. The combination of anti-SARS-CoV-2 activity, cytokine inhibitory activity, and a previously established favorable pharmacokinetic profile for the lead salicylanilide renders salicylanilides in general as promising therapeutics for COVID-19.

Understanding COVID-19: A hypothesis regarding digit ratio (2D:4D), ACE I/D polymorphism, oxygen metabolism and national case fatality rates.

OBJECTIVE: Male digit ratio (2D:4D) correlates positively with the national case fatality rate (CFR) for COVID-19. The severity of COVID-19 may be influenced by a counterbalance between the angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2). SARS-CoV2 cleaves with ACE2 and enters cells leaving an unopposed effect of ACE in the lungs. Both 2D:4D and the ACE I/D polymorphism are covariates of oxygen metabolism. COVID-19 leads to lung damage and a reduction in oxygen saturation of the blood. Here, we examine the interrelationships between 2D:4D, ACE polymorphism, and COVID-19 CFR. METHODS: National frequencies/rates were obtained for 2D:4D from the BBC Internet study (n = 41), published values of ACE I/II (n = 39), and COVID-19 CFR from three World Health Organization situation reports (n = 41). RESULTS: 2D:4D was negatively associated with national ACE I/II frequencies. However, there was a positive relationship between male 2D:4D and CFR (right and left 2D:4D, two, and three situation reports respectively). The relationships between ACE I/II and CFR were non-significant. Relationships between male 2D:4D and CFR's were independent of female 2D:4D and ACE I/II. CONCLUSIONS: The ACE I/D polymorphism may influence 2D:4D such that ACE II individuals have lower 2D:4D than ACE DD individuals. Low 2D:4D and ACE II individuals show efficient oxygen metabolism. Therefore, low 2D:4D and ACE II together may protect against COVID-19 severity. The sex-dependent positive correlation between male 2D:4D and CFR is independent of ACE I/II, suggesting that the sex-dependent variation in the ACE2 gene may also influence the 2D:4D phenotype.

Understanding COVID-19: Digit ratio (2D:4D) and sex differences in national case fatality rates

Background The reported national case fatality rates (CFRs) for coronavirus disease 2019 (COVID-19) shows a sex bias with males > females. The relative lengths of the index (2D) and ring (4D) fingers (digit ratio;2D:4D) is a sexually dimorphic (males < females) proxy of fetal sex steroids (low 2D:4D indicates high prenatal testosterone/low prenatal estrogen). Aim To examine sex-specific relationships of 2D:4D per nation with national values of COVID-19 CFRs. Study design: COVID-19 CFRs and the percent of male deaths were related to mean national (self-reported) 2D:4D by sex and hand from a large online survey (the BBC Internet Study). Subjects 103,482 men and 83,366 women. Outcome measures Relationships of mean national 2D:4D with CFRs from 41 countries and with national male death rates from 16 countries. Results Male right and left hand 2D:4D showed positive relationships with CFR. These relationships remained significant after removing the influence of female 2D:4D. A positive association of male right and left 2D:4D was detected with the percentage of male deaths. Conclusions At the national level, high mean 2D:4D (indicating low prenatal testosterone/high prenatal estrogen) is associated with high CFRs and percent male mortality. At the individual level, high 2D:4D may be a risk factor for severity of COVID-19 in males. We speculate that male 2D:4D is a negative correlate for expression of the SARS-CoV2 receptor (ACE2).