ABSTRACT
The B.1.1.529 (omicron) variant has rapidly supplanted most other SARS-CoV-2 variants. Using microfluidics-based antibody affinity profiling (MAAP), we have recently shown that current therapeutic monoclonal antibodies exhibit a drastic loss of affinity against omicron. Here, we have characterized affinity and IgG concentration in the plasma of 39 individuals with multiple trajectories of SARS-CoV-2 infection and/or vaccination as well as in 2 subjects without vaccination or infection. Antibody affinity in patient plasma samples was similar against the wild-type, delta, and omicron variants (KA ranges: 122{+/-}155, 159{+/-}148, 211{+/-}307 M-1, respectively), indicating a surprisingly broad and mature cross-clade immune response. We then determined the antibody iso- and subtypes against multiple SARS-CoV-2 spike domains and nucleoprotein. Postinfectious and vaccinated subjects showed different profiles, with IgG3 (p = 0.002) but not IgG1, IgG2 or IgG4 subtypes against the spike ectodomain being more prominent in the former group. Lastly, we found that the ELISA titers against the wildtype, delta, and omicron RBD variants correlated linearly with measured IgG concentrations (R=0.72) but not with affinity (R=0.29). These findings suggest that the wild-type and delta spike proteins induce a polyclonal immune response capable of binding the omicron spike with similar affinity. Changes in titers were primarily driven by antibody concentration, suggesting that B-cell expansion, rather than affinity maturation, dominated the response after infection or vaccination.
ABSTRACT
BackgroundWomen are overrepresented amongst individuals suffering from post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown. Methods and FindingsBy using Bayesian models comprising >200 co-variates, we assessed the impact of social context in addition to biological data on PASC in a multi-centre prospective cohort study of 2927 (46% women) individuals in Switzerland. Women more often reported at least one persistent symptom than men (43.5% vs 32.0% of men, p<0.001) six (IQR 5-9) months after SARS-CoV-2 infection. Adjusted models showed that women with personality traits stereotypically attributed to women were most often affected by PASC (OR 2.50[1.25-4.98], p<0.001), in particular when they were living alone (OR 1.84[1.25-2.74]), had an increased stress level (OR 1.06[1.03-1.09]), had undergone higher education (OR 1.30[1.08-1.54]), preferred pre-pandemic physical greeting over verbal greeting (OR 1.71[1.44-2.03]), and had experienced an increased number of symptoms during index infection (OR 1.27[1.22-1.33]). ConclusionBesides gender- and sex-sensitive biological parameters, sociocultural variables play an important role in producing sex differences in PASC. Our results indicate that predictor variables of PASC can be easily identified without extensive diagnostic testing and are targets of interventions aiming at stress coping and social support.
ABSTRACT
BackgroundRT-PCR of nasopharyngeal swabs (NPS) is the acknowledged gold standard for the detection of SARS-CoV-2 infection. Rising demands for repetitive screens and mass-testing necessitate, however, the development of additional test strategies. Saliva may serve as an alternative to NPS as its collection is simple, non-invasive and amenable for mass- and home-testing but rigorous validation of saliva particularly in children is missing. MethodsWe conducted a large-scale head-to-head comparison of SARS-CoV-2 detection by RT-PCR in saliva and nasopharyngeal swab (NPS) of 1270 adults and children reporting to outpatient test centers and an emergency unit for an initial SARS-CoV-2 screen. The saliva collection strategy developed utilizes common, low-cost plastic tubes, does not create biohazard waste at collection and was tailored for self-collection and suitability for children. ResultsIn total, 273 individuals were tested SARS-CoV-2 positive in either NPS or saliva. SARS-CoV-2 RT-PCR results in the two specimens showed a high agreement (Overall Percent Agreement = 97.8%). Despite lower viral loads in saliva of both adults and children, detection of SARS-CoV-2 in saliva compared well to NPS (Positive Percent Agreement = 92.5%). Importantly, in children, SARS-CoV-2 infections were more often detected in saliva than NPS (Positive Predictive Value = 84.8%), underlining that NPS sampling in children can be challenging. ConclusionsThe comprehensive parallel analysis reported here establishes saliva as a generally reliable specimen for the detection of SARS-CoV-2 with particular advantages for testing children that is readily applicable to increase and facilitate repetitive and mass-testing in adults and children. Article Summary Main PointsComparison with nasopharyngeal swabs in a large test center-based study confirms that saliva is a reliable and convenient material for the detection of SARS-CoV-2 by RT-PCR in adults and increases detection efficacy in children.
ABSTRACT
AO_SCPLOWBSTRACTC_SCPLOWA key parameter in epidemiological modeling which characterizes the spread of an infectious disease is the mean serial interval. There is increasing evidence supporting a prolonged viral shedding window for COVID-19, but the transmissibility in this phase is unclear. Based on this, we build a model including an additional compartment of infectious individuals who stay infectious for a longer duration than the reported serial interval, but with infectivity reduced to varying degrees. We find that such an assumption also yields a plausible model in explaining the data observed so far, but has different implications for the future predictions in case of a gradual easing on the lockdown measures. Considering the role of modeling in important decisions such as easing lockdown measures and adjusting hospital capacity, we believe that it is critically important to consider a chronically infectious population as an alternative modeling approach to better interpret the transmission dynamics of COVID-19.
