Reference: JAMA Intern Med. 2023 Jun 1;183(6):554-564
Practice Point: Paxlovid seems to reduce both mortality and the risk of long-COVID in people at high risk.
EBM Pearl: Outcome data from observational studies are generally considered less definitive than data from randomized controlled trials, but observational data have the power to generate new hypotheses that may change the direction of future research.
When reports of “long-haul COVID” first appeared in early 2020, some of us had flashbacks to previously described syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-treatment Lyme disease syndrome. As it turns out, many people who have had COVID are reported to experience long-term symptoms and disability as well as higher rates of liver, kidney, lung, and cardiovascular/metabolic disease that can be both life-threateningly severe and long-lasting.
Recently, investigators performed a retrospective cohort analysis of rates of new-onset health conditions after COVID-19 infection in about 300,000 veterans, comparing those who received nirmatrelvir* within 5 days of symptom onset (37,466) and those who received no treatment. Participants were primarily older men with at least one risk factor for severe short-term outcomes from COVID-19. Most were overweight and had been vaccinated. Researchers attempted to adjust comparisons based on pre-existing illness and demographic features using propensity analyses. Not shockingly, mortality within 30 days was significantly decreased in those who received the medication versus those who didn’t (4.7% vs 13.4%). (Those who passed away were excluded from the analysis of new-onset health condition outcomes.) However, treatment also significantly reduced the incidence of post-COVID complications at 180 days, with an absolute risk reduction of 4.51% (95% CI, 4.01-4.99).
What was most interesting for us, however, was the way the investigators defined “long-COVID”, as any of thirteen distinct conditions newly diagnosed 30 days after the initial COVID infection. The list included not only symptoms like fatigue/malaise, dyspnea and myalgia, but also objective complications such as acute renal injury, pulmonary embolism or dysrhythmia. Results showed that between 30 days and 6 months, the treated group was less likely to have any one of these 13 diagnoses, although the likelihood of new-onset diabetes, liver disease, or cough was not significantly different. The interesting thing for the skeptics amongst us was that the reduction in symptoms such as cognitive changes or dyspnea was almost parallel to a reduction in objective diagnoses such as pulmonary embolism or ischemic heart disease, which we would have considered complications of COVID rather than part of a syndrome.
When most of us think of the patients in our office with “long-COVID” we think dyspnea, fatigue, dysautonomia, and neurocognitive impairment. Many of us may not consider objective complications of COVID like PE and arrhythmia to be in the same category. While we are still a far way from a universally-accepted definition of long-COVID, our quest for that clarity could potentially help us understand other mysterious syndromes such as ME/CFS better…or perhaps differently. While there may be controversy about the way the authors of this study lump symptoms and objective findings together, perhaps what matters most is that nirmatrelvir seems to be effective for preventing both.
*The authors only explicitly state that patients received nirmatrelvir, but after consultation with our pharmacist colleagues, we think it’s safe to assume that participants got nirmatrelvir-ritonavir (Paxlovid).
For more information, see the topic COVID-19 in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Dan Randall, MD, Deputy Editor at DynaMed. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Katharine DeGeorge, MD, MS, Senior Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; Nicole Jensen, MD, Family Physician at WholeHealth Medical; Vincent Lemaitre, PhD, Medical Editor at DynaMed; Elham Razmpoosh, PhD, Postdoctoral fellow at McMaster University; and Sarah Hill, MSc, Medical Writer at DynaMed.