Association of Early Inflammation with Age and Asymptomatic Disease in COVID-19

BACKGROUND: Disease severity in COVID-19 ranges from asymptomatic infection to severe disease and death, especially in older subjects. The risk for severe infection and death has been reported to be 2X in those between 30 and 40 years, 3X in those between 40 and 50 years, and 4X in those between 50 and 65 years, compared to the reference group of 18–29 years. OBJECTIVE: To investigate the early changes in host immune responses that are altered with age and the difference in the early host inflammatory response that dictates a symptomatic versus asymptomatic course of COVID-19. PATIENTS AND METHODS: COVID-19 subjects were identified by screening at the airport upon arrival from a foreign destination to China. Patients were either asymptomatic or had a mild disease when the first oro-pharyngeal (OP) swab samples were collected. Patients were quarantined and blood and throat swabs were collected during the course of the disease, allowing identification of the earliest host response to COVID-19. These patients were followed until their OP sample turned COVID-19 negative. RESULTS: Data were obtained from 126 PCR-confirmed COVID-19 patients. The blood samples were obtained within 48 days of qPCR confirmation of viral infection. Older subjects (>30 years) had significantly elevated levels of anti-inflammatory cytokine IL-10, a significant decrease in the percentage of CD8+ T cells, and expansion in NKT cell fraction. This was associated with significantly elevated viral load and a delayed humoral response in older subjects. Compared to symptomatic subjects, asymptomatic patients had an early increase in pro-inflammatory cytokine IL-2, while a decrease in both T regulatory cells and anti-inflammatory cytokine IL-10. Further, asymptomatic disease was associated with early humoral response and faster viral clearance. CONCLUSION: Early inflammatory response potentially plays a critical role for host-defense in COVID-19. The impaired early inflammatory response was associated with older age while a robust early inflammation was associated with asymptomatic disease.