“Immunogenetics of resistance to SARS-CoV-2 infection in discordant couples”

Abstract

BackgroundDespite the high number of individuals infected by SARS-CoV-2 who develop COVID-19 symptoms worldwide, many exposed individuals remain asymptomatic and/or stay uninfected. This could be explained by a combination of environmental (exposure, previous infection), epigenetic, and genetic factors. Aiming to identify genetic variants involved in SARS-CoV-2 resistance, we analyzed 86 discordant Brazilian couples where one was infected and symptomatic while the partner remained asymptomatic and seronegative despite sharing the same bedroom during the infection. The discordant partners had comparable ages, and genetic ancestry proportions.MethodsWhole-exome sequencing followed by a state-of-the-art method to call genotypes and haplotypes across the highly polymorphic MHC and LRC.ResultsWe observed a minor impact in antigen-presentation genes and KIR genes associated with resistance. Interestingly, genes related to immune modulation, mainly involved in NK cell killing activation/inhibition harbor variants potentially contributing to infection resistance. We hypothesize that individuals prone to produce higher amounts of MICA (possibly soluble), LILRB1, LILRB2, and low amounts of MICB, would be more susceptible to infection.ConclusionAccording to this hypothesis, quantitative differences in these NK activity-related molecules could contribute to resistance to COVID-19 down regulating NK cell cytotoxic activity in infected individuals but not in resistant partners.

A Novel Saliva RT-LAMP Workflow for Rapid Identification of COVID-19 Cases and Restraining Viral Spread

“…Notably, compared to age-matched males, young females (<38 years old) showed lower salivary viral load that increases with age, while no clear age-related effects were found in males. Clinical severity and immunological profiles seem to better correlate with viral load in saliva than in NOP swabs [38,39], so our findings could be attributed to distinct immune responses between genders leading to higher viral shedding and disease severity in males [40], and could also explain the higher proportion of asymptomatic females in couples positive for SARS-CoV-2 [41]. These observations further suggest that salivary viral load together with older age, male gender and other risk factors could be important to predict disease duration, severity and mortality [39,42].…”

“…This work not only provides recommendations to optimize viral detection, but it also indicates that saliva may provide clues to clarify the biological determinants of SARS-CoV-2 infection and transmission. Recent reports show that saliva has higher sensitivity than nasal/nasopharyngeal swabs for identifying asymptomatic cases [41], and that viral load distribution is equivalent in saliva from symptomatic and nonsymptomatic individuals [42]. Considering that a fraction of infected patients escape detection via NOP RT-PCR, and since saliva better correlates with transmissibility and clinical outcomes, rapid salivary diagnostics stands as an invaluable opportunity to efficiently tackle the COVID-19 pandemic.…”

Antigen Presentation of mRNA-Based and Virus-Vectored SARS-CoV-2 Vaccines

“…The authors found only a minor impact of classical MHC class I and class II genes associated with resistance. However, individuals producing higher amounts of MICA and low amounts of MICB were more susceptible to SARS-CoV-2 infection [91]. While these are preliminary data which need to be confirmed, it is interesting from the perspective that MICB can serve as an antigen-presenting molecule for γδ T cells.…”

An immunogenetic view of COVID-19

“…Thus, the analysis of non-Europeans and admixed populations is urgently needed to identify the COVID-19 causal variants and to evaluate their impact on COVID-19 in worldwide populations. To this end, several collaborative initiatives and consortia have been launched and the first results are emerging (for example, Castelli et al (2021);Castro et al (2021); and Rede Genômica IPEC).…”