BackgroundCOVID-19 is an infectious disease currently spreading worldwide. The COVID-19 virus requires angiotensin-converting enzyme 2, an enzyme that plays a vital role in regulating the apelinergic system for entry into target cells. The underlying diseases of hypertension, diabetes mellitus, and obesity are risk factors for the severity of COVID-19 infection. This study aimed to compare the serum levels of apelin and nitric oxide in hospitalized COVID-19 patients and non-COVID-19 subjects with and without the mentioned risk factors.MethodsSerum samples were taken from 69 COVID-19 patients and 71-matched non-COVID-19 participants enrolled in the Kerman coronary artery disease risk factors cohort study. Study participants were divided into eight groups of control (healthy), hypertension, diabetes mellitus, obesity, COVID-19, COVID-19 + hypertension, COVID-19 + diabetes mellitus, and COVID-19 + obesity (n = 15–20 in each group). Serum apelin and nitrite were measured by the enzyme-linked immunosorbent assay and colorimetric methods, respectively.ResultsHypertensive and obese patients had lower serum apelin compared to the control group. In addition, apelin content was lower in the COVID-19 and COVID-19 + diabetes mellitus groups compared to the non-COVID-19 counterpart groups. Serum apelin levels were positively associated with arterial O2sat. and negatively with the severity of lung involvement. Nitric oxide metabolites were significantly lower in the COVID-19, COVID-19 + diabetes mellitus, and COVID-19 + obesity groups.ConclusionsThe lower apelin and nitric oxide levels in patients with hypertension and obesity or their reduction due to infection with COVID-19 or concomitant COVID-19 + diabetes mellitus may make them vulnerable to experiencing severe diseases.