Long-Term Existence of SARS-CoV-2 in COVID-19 Patients:Host Immunity,Viral Virulence,and Transmissibility

COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms(PIS).However,we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS.This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients.Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected.The median age of the studied cohort was59.83±12.94 years.All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to112 days PIS.Peripheral lymphocytes counts were normal.The ratios of interferon gamma(IFN-c)-secreting cells to total CD4^(+)and CD8^(+)cells were normal as 24.68%±9.60%and 66.41%±14.87%respectively.However,the number of IFNc-secreting NK cells diminished(58.03%±11.78%).All patients presented detectable IgG,which positively correlated with mild neutralizing activity(Mean value neutralisation antibodies titers=157.2,P=0.05).No SARS-CoV-2 virus was isolated in Vero E6 cells inoculated with nasopharyngeal swab samples from all patients 50 days PIS,and the cytopathic effect was lacking.But one sample was positive for SARS-CoV-2 nucleic acid test in cell supernatants after two passages.Genome sequencing revealed that only three synonymous variants were identified in spike protein coding regions.In conclusion,decreased IFN-c production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence.Further,low viral load and weak viral pathogenicity were observed in COVID-19 patients with long-term SARSCoV-2 infection.