© The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.BACKGROUND Although the detection of viral particles by reverse transcription polymerase chain reaction (RT-PCR) is the gold standard diagnostic test for coronavirus disease 2019 (COVID-19), the false-negative results constitute a big challenge. AIM To examine a group of patients diagnosed and treated as possible COVID-19 pneumonia whose multiple nasopharyngeal swab samples were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR but then serological immunoglobulin M/immunoglobulin G (IgM/IgG) antibody against SARS-CoV-2 were detected by rapid antibody test. METHODS Eighty possible COVID-19 patients who had at least two negative consecutive COVID-19 RT-PCR test and were subjected to serological rapid antibody test were evaluated in this study. RESULTS The specific serological total IgM/IgG antibody against SARS-CoV-2 was detected in twenty-two patients. The mean age of this patient group was 63.2± 13.1-years-old with a male/female ratio of 11/11. Cough was the most common symptom (90.9%). The most common presenting chest computed tomography findings were bilateral ground glass opacities (77.2%) and alveolar consolidations (50.1%). The mean duration of time from appearance of first symptoms to hospital admission, to hospital admission, to treatment duration and to serological positivity were 8.6 d, 11.2 d, 7.9 d, and 24 d, respectively. Compared with reference laboratory values, serologically positive patients have shown increased levels of acute phase reactants, such as C-reactive protein, ferritin, and procalcitonin and higher inflammatory markers, such as erythrocyte sedimentation rate, lactate dehydrogenase enzyme, and fibrin end-products, such as D-dimer. A left shift on white blood cell differential was observed with increased neutrophil counts and decreased lymphocytes. CONCLUSION Our study demonstrated the feasibility of a COVID-19 diagnosis based on rapid antibody test in the cases of patients whose RT-PCR samples were negative. Detection of antibodies against SARS-CoV-2 with rapid antibody test should be included in the diagnostic algorithm in patients with possible COVID-19 pneumonia.