Y380Q novel mutation in receptor-binding domain of SARS-CoV-2 spike protein together with C379W interfere in the neutralizing antibodies interaction (preprint)

BackgroundThe emergence of SARS-CoV-2 variants is a current public health concern possibly impacting COVID-19 disease diagnosis, transmission patterns and vaccine effectiveness. ObjectivesTo describe the SARS-CoV-2 lineages circulating early pandemic among samples with S gene dropout and characterize a novel mutation in receptor-binding domain (RBD) of viral spike protein. Study designAdults and children older than 2 months with signs and symptoms of COVID-19 were prospectively enrolled from May to October 2020 in Porto Alegre, Brazil. All participants performed RT-PCR assays for diagnosing SARS-CoV-2, samples with S gene dropout and Ct < 30 (cycle threshold) were submitted to whole genome sequencing (WGS), and homology modeling and physicochemical properties analysis were performed. Results484/1,557 participants tested positive for SARS-CoV-2. The S gene dropout was detected in 7.4% (36/484) as early as May, and a peak was observed in early August. WGS was performed in 8 samples. The B.1.1.28, B.1.91 and B.1.1.33 lineages were circulating in early pandemic. The RBD novel mutation (Y380Q) was found in one sample occurring simultaneously with C379W and V395A, and the B.1.91 lineage in the spike protein. ConclusionMutations in the SARS-CoV-2 spike region were detected early in the COVID-19 pandemic in Southern Brazil, regarding the B.1.1.28, B.1.91 and B.1.1.33 lineages identified. The novel mutation (Y380Q) with C379W, modifies important RBD properties, which may interfere with the binding of neutralizing antibodies (CR3022, EY6A, H014, S304). HighlightsO_LICharacterization of novel mutation (Y380Q) in RBD of SARS-CoV-2 spike protein C_LIO_LIThe Y380Q and C379W modify important properties in the SARS-CoV-2 RBD region C_LIO_LIThe RBD mutations may interfere with the binding of neutralizing antibodies C_LIO_LIThe B.1.1.28, B.1.91 and B.1.1.33 lineages were circulating in early pandemic C_LI

Association between obesity and hospitalization in mild COVID-19 young adult outpatients in Brazil: a prospective cohort study (preprint)

Background/ObjectivesThe aim of this study was to evaluate the association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil. Subjects/MethodsAdults with signs and symptoms suggestive of acute SARS-CoV-2 infection who sought two hospitals (one public and one private) emergency department were prospectively enrolled. Patients with confirmed COVID-19 at inclusion were followed by phone calls at day (D) D7, D14 and D28. Multivariable logistic regression models were employed to explore the association between obesity and other potential predictors for hospitalization. ResultsA total of 1,050 participants were screened, 310 were diagnosed with COVID-19 by RT-PCR. Median age was 37.4 (IQR 29.8-45.0) years, and 186 (60.0%) were female. Duration of symptoms was 3.0 (IQR 2.0-5.0) days, and 10.0 (IQR 8.0-12.0) was the median number of symptoms at inclusion. A total of 98 (31.6%) were obese, and 243 (78.4%) had no previous medical conditions. Twenty three participants (23/310, 7.4%) required hospitalization during the period. After adjusting, obesity (BMI[≥]30.0 kg/m2) (OR=2.69, 95%CI 1.63-4.83, P<0.001) and older age (OR=1.05, 95%CI 1.01-1.09, P<0.001), were significantly associated with higher risks of hospitalization. ConclusionsObesity, followed by aging, was the main factor associated with hospital admission for COVID-19 in a young population in a low-middle income country. Our findings highlighted the need for actions to promote additional protection for obese population, such as vaccination, and to encourage lifestyle changes.

Infants have lower RT-PCR cycle threshold for SARS-CoV-2 in comparison with older children and adults (preprint)

BackgroundThe viral dynamics and the role of children in the spread of SARS-CoV-2 are not completely understood. Our aim was to evaluate how RT-PCR Ct values among children with confirmed SARS-CoV-2 compared with that of adult subjects. MethodsPatients (aged from 2 months to [≤]18 years, and adults) with signs and symptoms of acute SARS-CoV-2 infection for less than 7 days, were prospectively enrolled in the study from May to November 2020. All participants performed RT-PCR assay for SARS-CoV-2 detection; Ct values of ORF1ab, N, and S gene-targets, and the average of all the three probes were used as surrogates of viral load. ResultsOf the total of 376 participants with confirmed SARS-CoV-2 infection there were 21 infants, 62 children and 293 adults. The RT-PCR Ct values of children under 18 were not significantly different from that of adults, as observed by the analyzed probes (namely ORF1ab, N, and S), and by the mean of all 3 gene-targets. However, infants had significantly lower Ct values compared to children and adults (P = 0.044). DiscussionCt values for children were not significantly different than that of adults with positive SARS-CoV-2. Interestingly, infants had even lower Ct values when compared to older children and adults. Although viral load is not the only determinant of transmission, infants may play a significant role in the spread of SARS-CoV-2 in the community, especially if or when this population returns to regular daycare activities.

Strong anti-viral responses in pediatric COVID-19 patients in South Brazil (preprint)

Epidemiological evidence that COVID-19 manifests as a milder disease in children compared to adults has been reported by numerous studies, but the mechanisms underlying this phenomenon have not been characterized. It is still unclear how frequently children get infected, and/or generate immune responses to SARS-CoV-2. We have performed immune profiling of pediatric and adult COVID-19 patients in Brazil, producing over 38 thousand data points, asking if cellular or humoral immune responses could help explain milder disease in children. In this study, pediatric COVID-19 patients presented high viral titers. Though their non-specific immune profile was dominated by naive, non-activated lymphocytes, their dendritic cells expressed high levels of HLA-DR and were low in CX3CR1, indicating competence to generate immune responses that are not targeted to inflamed tissue. Finally, children formed strong specific antibody and T cell responses for viral structural proteins. Children s T cell responses differed from adults in that their CD8+ TNF+ T cell responses were low for S peptide but significantly higher against N and M peptide pools. Altogether, our data support a scenario in which SARS-CoV-2 infected children may contribute to transmission, though generating strong and differential responses to the virus that might associate with protection in pediatric COVID-19 presentation.