Molecular epidemiology of invasive Group A Streptococcal infections before and after the COVID-19 pandemic in Switzerland (preprint)

Group A Streptococcus (GAS, aka Streptococcus pyogenes) poses a significant public health concern, causing a diverse spectrum of infections with high mortality rates. Following the COVID-19 pandemic, a resurgence of invasive GAS (iGAS) infections has been documented, necessitating efficient outbreak detection methods. Whole genome sequencing (WGS) serves as the gold standard for GAS molecular typing, albeit constrained by time and costs. This study aimed to characterize the postpandemic increased prevalence of iGAS on the molecular epidemiological level in order to assess whether new, more virulent variants have emerged, as well as to assess the performance of the rapid and cost-effective Fourier-transform infrared (FTIR) spectroscopy as an alternative to WGS for detecting and characterizing GAS transmission routes. A total of 66 iGAS strains isolated from nine Swiss hospitals during the COVID-19 post-pandemic increased GAS prevalence were evaluated and compared to 15 strains collected before and 12 during the COVID-19 pandemic. FT-IR measurements and WGS were conducted for network analysis. Demographic, clinical, and epidemiological data were collected. Skin and soft tissue infection was the most common diagnosis, followed by primary bacteremia and pneumonia. Viral co-infections were found in 25% of cases and were significantly associated with more severe disease requiring intensive care unit admission. WGS analysis did not reveal emerging GAS genetic distinct variants after the COVID-19 pandemic, indicating the absence of a pandemic-induced shift. FT-IR spectroscopy exhibited limitations in differentiating genetically distant GAS strains, yielding poor overlap with WGS-derived clusters. The emm1/ST28 gebotype was predominant in our cohort and was associated with five of the seven deaths recorded, in accordance with the molecular epidemiological data before the pandemic. Additionally, no notable shift in antibiotic susceptibility patterns was observed. Our data suggest that mainly non-pathogen related factors contributed to the recent increased prevalence of iGAS.

Contribution of endogenous and exogenous antibodies to clearance of SARS-CoV-2 during convalescent plasma therapy (preprint)

Neutralizing antibodies are considered a key correlate of protection by current SARS-CoV-2 vaccines. The ability of antibody-based therapies, including convalescent plasma, to affect established disease remains to be elucidated. Only few monoclonal therapies and only when used at a very early stage of infection have shown efficacy. Here, we conducted a proof-of-principle study of convalescent plasma therapy in a phase I trial in 30 COVID-19 patients including immunocompromised individuals hospitalized early after onset of symptoms. A comprehensive longitudinal monitoring of the virologic, serologic, and disease status of recipients in conjunction with detailed post-hoc seroprofiling of transfused convalescent plasma, allowed deciphering of parameters on which plasma therapy efficacy depends. Plasma therapy was safe and had a significant effect on viral clearance depending on neutralizing and spike SARS-CoV-2 antibody levels in the supplied convalescent plasma. Endogenous immunity had strong effects on virus control. Lack of endogenous neutralizing activity at baseline was associated with a higher risk of systemic viremia. The onset of endogenous neutralization had a noticeable effect on viral clearance but, importantly, even after adjusting for their endogenous neutralization status recipients benefitted from therapy with high neutralizing antibody containing plasma. In summary, our data demonstrate a clear impact of exogenous antibody therapy on the rapid clearance of viremia in the early stages of infection and provide directions for improved efficacy evaluation of current and future SARS-CoV-2 therapies beyond antibody-based interventions. Incorporating an assessment of the endogenous immune response and its dynamic interplay with viral production is critical for determining therapeutic effects. One Sentence SummaryThis study demonstrates the impact of exogenous antibody therapy by convalescent plasma containing high neutralizing titers on the rapid clearance of viremia in the early stages of SARS-CoV-2 infection.

Multifactorial SARS-CoV-2 seroprofiling dissects interdependencies with human coronaviruses and predicts neutralization activity (preprint)

Definition of SARS-CoV-2 antibody responses is essential to verify protective immunity following infection and vaccination. Here, we devised a versatile serological test, named ABCORA, that is based on a multifactorial analysis of SARS-CoV-2 and circulating human coronavirus (HCoV) antibody responses. Utilizing empirical tailored cut-offs and computational approaches based on training and validation cohorts comprising pre-pandemic (N=825) and SARS-CoV-2 infected plasma donors (N=389), we defined several analysis strategies that allow a highly accurate definition of SARS-CoV-2 seroconversion and prediction of neutralization activity. Intriguingly, HCoV reactivity was significantly higher in SARS-CoV-2 negative donors. Amongst SARS-CoV-2 infected individuals, elevated SARS-CoV-2 responses were linked to higher HCoV activity suggesting that pre-existing HCoV immunity may confer protection against SARS-CoV-2 acquisition and promote development of SARS-CoV-2 specific antibody responses. Deciphering interdependencies between SARS-CoV-2 and HCoV immunity should be enforced as understanding their impact on infection may allow soliciting cross-protective activities for broader coronavirus prevention.

ASSESSING THE POTENTIAL IMPACT OF TRANSMISSION DURING PROLONGED VIRAL SHEDDING ON THE EFFECT OF LOCKDOWN RELAXATION ON COVID-19 (preprint)

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.