Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly transmittable pathogen that is responsible for the pandemic of acute respiratory disease, termed Coronavirus Disease 2019 (COVID-19). This pathogen has a huge impact on public health, and international efforts are underway to decipher the underlying immune responses orchestrating the interplay between protection and inflammation. However, key gaps remain, which can have implications on prognosis and therapeutic strategies against COVID-19. In a prospective observational cohort study of 81 patients, we measured plasma samples for levels of cytokines and chemokines and found that levels of pro-inflammatory IL-6, IP-10, IL-12, and IL-18 correlated with disease severity. IL-6 has also been identified as a key cytokine in the inflammatory cascade in other studies. This suggests that immunomodulators may be beneficial as an adjunct or alternative to antivirals. Consequentially, a small-scale trial with COX-2 inhibitors was performed, with promising reduction of IL-6 in high-risk COVID-19 pneumonia patients more than 50 years of age. Treatment was also not associated with an increase in adverse outcomes. Its potential for therapeutic use as an immune modulator warrant further evaluation in a large randomized controlled trial.