ABSTRACT
Emerging variants of concern (VOCs) drive the SARS-CoV-2 pandemic. We assessed VOC B.1.1.7, now prevalent in several countries, and VOC B.1.351, representing the greatest threat to populations with immunity to the early SARS-CoV-2 progenitors. B.1.1.7 showed a clear fitness advantage over the progenitor variant (wt-S614G) in ferrets and two mouse models, where the substitutions in the spike glycoprotein were major drivers for fitness advantage. In the "superspreader" hamster model, B.1.1.7 and wt-S614G had comparable fitness, whereas B.1.351 was outcompeted. The VOCs had similar replication kinetics as compared to wt-S614G in human airway epithelial cultures. Our study highlights the importance of using multiple models for complete fitness characterization of VOCs and demonstrates adaptation of B.1.1.7 towards increased upper respiratory tract replication and enhanced transmission in vivo. Summary sentenceB.1.1.7 VOC outcompetes progenitor SARS-CoV-2 in upper respiratory tract replication competition in vivo.
ABSTRACT
BackgroundViral shedding patterns and its correlation with the immune responses of mildly symptomatic COVID-19 patients are still poorly characterized. MethodsWe enrolled the first five COVID-19 patients quarantined in our institution; none received immunomodulatory treatment. We monitored shedding of viral RNA and infectious virus by RT-PCR and cell culture from the upper respiratory tract, and characterized the kinetics of systemic innate and adaptive immune responses. ResultsDespite mild clinical disease, high viral loads and shedding of infectious virus were observed from the respiratory tract, with isolation of infectious virus and prolonged positivity by PCR up to day 7 and 19 post onset of symptoms, respectively. Robust innate responses characterized by an increase in activated CD14+CD16+ monocytes and cytokine responses were observed as early as 2 days after symptoms onset. Cellular and humoral SARS-CoV-2 specific adaptive responses were detectable in all patients. ConclusionInfectious virus shedding was limited to the first week of symptom onset in mild cases. A strong innate response, characterized by the mobilization of activated monocytes during the first days of infection, as well as SARS-CoV-2 specific antibodies were detectable, even in patients with mild disease. SummaryWe describe viral and immune profiles of the first five SARS-CoV-2 patients in our institution, showing high viral loads and infectious viral shedding in early acute disease. Mild patients mount an innate response sufficient for viral control and specific immunity.
