AIM: The aim of the study is to assess the specific antibody response in SARS-CoV-2 patients with and without comorbidities. MATERIALS AND METHODS: This is a prospective observational study conductedto measure SARS-CoV-2–specific antibodies in COVID-19 infected patients. The study included total 60 patients, 30 with co-morbidities and 30 without co-morbidities. Both inpatient and outpatient patients, with positive COVID-19 RTPCR were included and they were followed up at 21 daysand 4 monthspost infection. The blood samples were collected after obtaining the consent from the study participants. Serum was separated by centrifuging the blood samples and were further subjected to ELISA to detect specific IgG antibodies against N and S proteins of SARSCOV2. Data was entered in MS excel and analysed using SPSS 23.0 version software. RESULTS: In the study out of 60 patients, most patients i.e., 48.3% (29/60) were in age group of 41-59 years; followed by 36.7% (22/60) were in age group of <40 years and 15% (9/60) were in age group of ≥60 years. Mean age of patients was 36.4 ± 6.8 years. It was found that, anti-N IgG levels at 21 days were positive in 78.3% (47/60) and negative in 21.7% (13/60) with increase in seropositivity to 93.3% (56/60) and fall in negative rate to 6.7% (4/60) at 4months. On the other hand, anti-S IgG levels at 21 days were positive in 83.3% (50/60), negative in 16.7% (10/60) with positive rate of 96.7% (58/60) and negative rate of 3.3% (2/60) at 4months. Both the antibody assays, anti-N IgG, and anti-S IgG in successive time periods, demonstrated the significant increaseinseropositivityandmaintainedlongevityofantibodieswithtime.Inthestudy, 5/5 patients with IHD and 3/3 patients with COPD had 100% serologic response to both N and S proteins of SARS-CoV-2 at 21 days and 4 months. But no significant strong correlation can be established between the seropositivity and longevity of antibodies with various comorbidities due to limited sample size. CONCLUSION: It was concluded that most of the patients after contracting SARS-CoV-2 infection mount humoral immune response regardless of their age, gender, severity of disease and their association with various comorbidities. The study demonstrated a sustained seropositivity towards the SARS-CoV2 nucleocapsid and spike proteins for at least 120 days post PCR confirmation of COVID-19 patients