Relationship between Disease Severity, Immune Response, and Viral Clearance in Unvaccinated Patients with COVID-19: A Cross-sectional Study

Abstract

Introduction: The clinical manifestations of Coronavirus Disease-2019 (COVID-19) range from asymptomatic cases to severe respiratory failure. It is unclear whether disease severity is determined by an excess viral load or a dysregulated immune response. It is also unclear whether the severe immune response is successful in rapid viral clearance. Aim: To understand the relationship between immune response, viral clearance, and the severity of illness in unvaccinated patients suffering from COVID-19. Materials and Methods: This was a cross-sectional observational study of 65 unvaccinated patients suffering from Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) confirmed COVID-19, conducted at a dedicated COVID-19 centre, Dr. D.Y. Patil Hospital, Pimpri, Pune, Maharashtra, India. from September 2020 to April 2021. The subjects were enrolled between day 10 and day 14 of the onset of symptoms and from two distinct clinical groups. Group A consisted of 34 mild cases, and Group B consisted of 31 severe cases, classified according to the national guidelines issued by the Indian Council of Medical Research (ICMR). The clinical progress of the illness and laboratory test records were carefully reviewed. A repeat throat swab for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) RTPCR, blood levels of COVID-19 specific antibodies Immunoglobin G (IgG) and IgM, C-reactive protein (CRP), and D-dimer levels were measured on day 14 of the illness. The data were analysed using MedCalc and Epi Info software. Chi-square and Fisher’sExact tests were used to assess variables such as viral detection, antibody response, and inflammatory markers. Results: In Group A, 2/34 (5.88%) patients tested RT-PCR negative {Cycle threshold (Ct) value cut-off above 35} compared to 5/31 (16.13%) in Group B (p=0.0829). In Groups A and B, respectively, the mean antibody titers were 35390.47 and 36426.11 (p=0.7469), the mean CRP values were 4.91 (p<0.001) and 31.01 mg/dL, and the mean D-dimer levels were 895 and 2896 ng/mL (p<0.001). Conclusion: Both mild and severe COVID-19 cases had a significant antibody response which, however, did not help in viral clearance. Most patients remained RT-PCR positive on day 14 regardless of the disease severity.