“Despite the evidence that fever can serve a protective function, old habits die hard, ” so wrote Blumenthal in 1997. Old habits about fever are indeed hard to shake, and this may be particularly so in a pandemic, where history’s lessons and hard-earned knowledge from epidemiology, evidence-based medicine, and good scientific hygiene seem to be in short supply.

Recently, Reuters published an article entitled “False claim: Avoid medications to lower fever if sick with COVID-19” (link here)

The Reuters piece begins by highlighting social media posts that “claim that taking medication to lower fever, such as paracetamol (Tylenol) and ibuprofen (Advil), should be avoided when sick with the new coronavirus.” The author of the Reuters fact check article writes: “This claim is false. Health authorities around the world have recommended the use of fever-lowering over-the-counter medicines to cope with COVID-19 symptoms.” The article then refers to information from the WHO, European Union healthcare regulator, UK NHS, and the CDC, Mayo clinic and others – all recommending some form of over the counter medication to treat fever during COVID-19.

Here, the Reuters author makes an argument based on an appeal to authority. It does not cite any actual evidence to support it’s contention that avoiding medications to lower fever is a false claim. Let’s review the evidence.

As we have described in previous posts, fever is an evolutionarily-conserved host defense against infection with a wide phylogenetic distribution. For background see here, here, here, and here.

As to the question of treating fever, Eyers et al. (2010) performed a meta-analysis of   animal studies. They examined the effects of antipyretic medications like ibuprofen or tylenol in non-human animals with influenza. Full text available here:  JRSocMed2010:103:403–411.DOI10.1258/jrsm.2010.090441

From Eyers et al. 2010 Effect on Mortality of Antipyretics

Eyers et al. found an increased risk of death in experimental animals when antipyretics are given. The above meta-analysis focused on influenza infection – A or B – depending on the individual study.  It suffers from the limitation that the experimental animals were not people and ranged from chicks to mice of different ages.

What about the human data? In a large-scale randomized controlled trial, there was no survival benefit when critically ill patients receive acetaminophen. There was no benefit to critically ill patients when given ibuprofen in another randomized trial.  One randomized controlled trial is occasionally cited in support of the idea that cooling critically ill patients with fever; Shortgen et al. showed increased survival in those who were cooled cooling at 14 days. Very importantly, however, as the authors wrote: “the difference in mortality was no longer significant at ICU or hospital discharge.” A more recent metaanalysis (Young 2019) showed no survival benefit to aggressive measures to reduce temperature in infected patients, even in the sickest subgroups:

From Young 2019: Fever control in critically ill adults. An individual patient data meta-analysis of randomised controlled trials

What lessons can we draw from this? As Paul Young suggested last year, less is more in the active management of elevated body temperature of ICU patients; for those with infection, it is better to be hot than cold.

The best evidence from animal or human studies tells us that treating fever does not help those with infection survive better.

Exactly what we should or should not do for those with COVID-19 remains an open question. Patients reaching for the acetaminophen or ibuprofen bottle should be aware that it is unlikely to help them. When a medical intervention is ineffective, it probably should be avoided, because all we are left with are harms. (For an overview of evidence based medicine, check out the great website the NNT.com and pay close attention to the concepts of number needed to treat and the number needed to harm).  To declare “false claim” to those advocating for caution about acetaminophen and ibuprofen is unsubstantiated and not consistent with the best evidence on the topic.

Read also: The Evolution and Adaptive Value of Fever

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Joe Alcock

Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine