The results, published March 1 in the British Journal of Clinical Pharmacology, were based on a large clinical review of medical database reports that described the effects of paracetamol (acetaminophen), nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen, and opioid analgesics such a morphine and codeine on the body’s immune system. “Our review shows some of the common pain and fever medications may work with the immune system to fight infection, whereas others work against it and increase the risk of contracting or responding badly to infectious diseases,” says the lead author, Christina Abdel-Shaheed, PhD, with the faculty of medicine and health at Sydney’s School of Public Health. In key findings highlighted by the research team, aspirin was found to be an affordable and accessible therapeutic option for tuberculosis, a serious bacterial infection that attacks that lungs. As suggested in other research, this therapeutic effect may apply to COVID-19 as well. An article published in October 2021 in the BMJ journal Heart stated that aspirin improved clinical outcomes for those who contracted coronavirus, and a study published in Clinical Epidemiology and Global Health the same year suggested that the use of aspirin was significantly associated with a reduced risk of mortality among patients with COVID-19. When looking at antipyretics (fever-reducing drugs) as a group, however, these medications (which include acetaminophen, ibuprofen, and aspirin) can reduce the desirable immune response when taken for post-vaccination relief. “Taking paracetamol or ibuprofen before or immediately after vaccination — for example for COVID-19 — to try to prevent mild fever or headache is not recommended, because this could reduce the body’s desirable immune response to the vaccine,” says Dr. Abdel-Shaheed. “For chicken pox, use of ibuprofen is not recommended as it might increase the risk of secondary bacterial skin infections.” The study authors also highlighted that the anti-inflammatory medicine indomethacin (used to treat mild to moderate acute pain and relieve symptoms of arthritis or gout) may reduce viral replication in COVID-19, but large-scale human trials are needed. Justin Beardsley, MBChB, PhD, an infectious disease specialist at Westmead Hospital and a researcher with the Sydney Institute for Infectious Diseases who coauthored the study, points to one of the most important discoveries, that morphine taken for pain may suppress key cells of the immune system and heighten the risk of infection, especially after cancer surgery. More studies are needed in this area of research to provide insights into how common drugs might be repurposed to treat infectious diseases, says Andrew McLaughlin, PhD, the dean of the Sydney Pharmacy School and part of the research team. “With the urgent need for new treatments for COVID-19 and the declining efficacy of some antimicrobial agents due to resistance, now more than ever we need medicines which can maintain or enhance the efficacy of anti-infective drug treatments,” he says. Julie Parsonnet, MD, an infectious-disease doctor at Stanford University in California who was not involved in the study, stresses that much of the research so far is contradictory, and we cannot be certain of the effect these medications will have on our immune systems in relation to infectious diseases. For instance, while some research has suggested aspirin and indomethacin may help prevent death related to COVID-19, other data indicated they had no effect at all. “In the absence of clinical trials, it is hard to know the truth,” says Dr. Parsonnet. “The research suggests that we might need to do more focused human research on this subject.”