Background: The world is under serious threat with the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). However, there is no effective drug for the treatment of COVID-19. Based on analyses of available data, we deduced that the excessive prostaglandins E2 (PGE2) accumulation mediated by cyclooxygenase-2 (COX-2) was the key pathological basis of COVID-19. Methods: The urine PGE2 levels were measured by mass spectrometry. An experimental study about Celebrex to treat COVID-19 was conducted based on routine treatment. A total of 44 confirmed COVID-19 patients were enrolled (Experimental group n=37, Control group n=7). Patients in experimental group were given Celebrex once or twice a day (0.2 g/time) for 7-14 days. The dosage or duration was modified for individuals. Clinical outcomes of Celebrex adjuvant therapy were evaluated by vital signs, laboratory tests, and computed tomography upon the discontinuance of Celebrex. Results: We found that the concentrations of PGE2 in urine samples of COVID-19 patients were significantly higher than that of healthy individuals (mean value is 170 ng/ml vs 18.8 ng/ml, p<0.01) and positively correlated with the progression of COVID-19. Among the experimental group (ordinary n=29, severe n=7, critical n=1), 25 cases were treated with full dose and 11 cases with half dose of Celebrex, and 1 case with Ibuprofen. The remission rate were 100%, 82% and 57% in full dose, half dose and control group respectively. Celebrex significantly reduced the PGE2 levels and promoted recovery of ordinary or severe COVID-19. Conclusion: Our study suggests that Celebrex adjuvant treatment may be helpful for the therapy of COVID-19.