COVID-19 in twins: What can we learn from them

Investigations on the concordance in monozygotic (MZ) as compared to dizygotic (DZ) twins may reveal if there is a genetic component increasing the susceptibility or resistance against an infectious disease. Here, we compared the concordance rates of SARS-CoV-2 infection in MZ versus DZ young twins who shared the same bedrooms and were equally exposed to the virus. The concordance rate was higher in the MZ group supporting a complex multifactorial inheritance responsible for SARS-Cov-2 infection.

Men are the main COVID-19 transmitters: lessons from couples

BackgroundCOVID-19 has affected millions of people worldwide. Clinical manifestations range from severe cases with a lethal outcome to mild or asymptomatic cases. Although there is the same proportion of infected genders, men are more susceptible to severe COVID-19, with a higher risk of death than women. This sex-bias may be explained by biological pathways. MethodsWe performed an epidemiological survey from July 2020 to July 2021 including 1744 unvaccinated adult Brazilian couples with at least one infected spouse despite living together during the COVID-19 infection without protective measures. The presence or absence of infection was confirmed by RT-PCR and/or serology results. The couples were divided between groups where both partners were infected (concordant couples) or only one spouse remained asymptomatic despite the close contact with the infected one (discordant couples). Statistical analysis of the collected data was performed aiming to verify a differential transmitter potential between genders in household contact. ResultsThe combination of our data collected from concordant and discordant couples showed that the man is the first (or the only) affected in the major occurrences when compared to women. Our findings support other published surveys and are in concordance with previous studies of our group. ConclusionsThese observations support the hypothesis according to which male individuals are more efficient virus transmitters than females, independently of the use of protective masks. In short, the present study confirmed the existence of gender differences not only for susceptibility to infection and resistance to COVID-19 but also in the transmission rate. HIGHLIGHTSO_LIThere are sex differences in COVID-19 susceptibility and transmission between couples with direct contact without protective measures; C_LIO_LIMen are more efficient virus transmitters than women; C_LIO_LISex-bias in COVID-19 transmission can be explained by differences in viral load in saliva, immune response and also behavioural protective differences between genders. C_LI

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

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.

Monozygotic twins discordant for severe clinical recurrence of COVID-19 show drastically distinct T cell responses to SARS-Cov-2

BackgroundClinical recurrence of COVID-19 in convalescent patients has been reported, which immune mechanisms have not been thoroughly investigated. Presence of neutralizing antibodies suggests other types of immune response are involved. MethodsWe assessed the innate type I/III IFN response, T cell responses to SARS-CoV-2 with IFN{gamma} ELISPOT, binding and neutralizing antibody assays, in two monozygotic twin pairs with one COVID-19 recurrence case. ResultsIn pair 1, four months after a first mild episode of infection for both siblings, one displayed severe clinical recurrence of COVID-19. Twin pair 2 of siblings underwent non-recurring asymptomatic infection. All fours individuals presented similar overall responses, except for remarkably difference found in specific cellular responses. Recurring sibling presented a reduced number of recognized T cell epitopes as compared to the other three including her non-recurring sibling. ConclusionsOur results suggest that an effective SARS-CoV-2-specific T cell immune response is key for complete viral control and avoidance of clinical recurrence of COVID-19. Besides, adaptive immunity can be distinct in MZ twins. Given the rising concern about SARS-CoV-2 variants that evade neutralizing antibodies elicited by vaccination or infection, our study stresses the importance of T cell responses in protection against recurrence/reinfection. Key pointsImmune parameters leading to COVID-19 recurrence/reinfection are incompletely understood. A COVID-19 recurrence case in a monozygotic twin pair is described with an intact antibody and innate type I/III Interferon response and drastically reduced number of recognized SARS-CoV-2 T cell epitopes.