Kinetics of viral load, immunological mediators and characterization 1 of a SARS-CoV-2 isolate in mild COVID-19 patients during acute phase of infection

Anantharaj, A.; Gujjar, S.; Kumar, S.; Jain, N.; Wangchuk, J.; Khan, N. A.; Panwar, A.; Kanakan, A.; A, V.; Vasudevan, J. S.; Das, A.; Pandey, A. K.; Pandey, R.; Medigeshi, G. R.

Over 95% of the COVID-19 cases are mild-to-asymptomatic who contribute to disease transmission whereas most of the severe manifestations of the disease are observed in elderly and in patients with comorbidities and dysregulation of immune response has been implicated in severe clinical outcomes. However, it is unclear whether asymptomatic or mild infections are due to low viral load or lack of inflammation. We have measured the kinetics of SARS-CoV-2 viral load in the respiratory samples and serum markers of inflammation in hospitalized COVID-19 patients with mild symptoms. We observed a bi-phasic pattern of virus load which was eventually cleared in most patients at the time of discharge. Viral load in saliva samples from a subset of patients showed good correlation with nasopharyngeal samples. Serum interferon levels were downregulated during early stages of infection but peaked at later stages correlating with elevated levels of T-cell cytokines and other inflammatory mediators such as IL-6 and TNF-alpha which showed a bi-phasic pattern. The clinical recovery of patients correlated with decrease in viral load and increase in interferons and other cytokines which indicates an effective innate and adaptive immune function in mild infections. We further characterized one of the SARS-CoV-2 isolate by plaque purification and show that infection of lung epithelial cells (Calu-3) with this isolate led to cytopathic effect disrupting epithelial barrier function and tight junctions. Finally we showed that zinc was capable of inhibiting SARS-CoV-2 infection in this model suggesting a beneficial effect of zinc supplementation in COVID-19 infection.