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

Abstract

ABSTRACTOver 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- α 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.IMPORTANCEA majority of COVID-19 patients are asymptomatic or exhibit mild symptoms despite high viral loads suggesting a key role for the acute phase innate immune response in limiting the damage and clearing the virus. Therefore, it is important to understand the early phase response to SARS-CoV-2 infection in such patients to devise strategies for clinical management of the disease. Our study shows the kinetics of immune mediators in the serum samples collected from hospitalized COVID-19 patients with mild symptoms. We further characterize a virus isolate from one of these patients and demonstrate its effect on epithelial barrier functions and show that zinc was capable of inhibiting SARS-CoV-2 infection under these conditions. Our results suggest a key role for the innate immune responses in the early phase of infection in mitigating clinical symptoms, clearing the virus and recovery from illness and suggest an antiviral role for zinc in COVID-19 infection.