Antihistamines Could Help Some Long Covid Patients, New Research Suggests

In a new case report this week, medical professionals in California say that at least two of their patients have experienced substantial and rapid relief from their long covid symptoms with the help of over-the-counter antihistamines. Importantly, the findings are only anecdotal at this point, but they may point to new avenues of research for understanding and treating this complex condition.

The report, published Monday in the Journal for Nurse Practitioners, concerns two middle-aged women believed to have caught covid-19 during the first year of the pandemic. Both were generally healthy and regularly exercised prior to their illness, and both developed a variety of lingering symptoms following their initial bout of sickness. These chronic symptoms included fatigue, cognitive impairment (often known as brain fog), and an inability to tolerate exercise, while one patient even appeared to develop “covid toes”—the discoloration and pain along a person’s toes and fingers that have been seen in some patients post-covid.

Despite seeking medical care, neither patient’s symptoms improved much over the next several months. Both had a history of allergies and sometimes used antihistamines to treat them, though.

In one case, six months after her initial symptoms began, the woman (who had a history of allergies triggered by dairy) ate a piece of cheese, which led her to take an over-the-counter antihistamine medication. Soon after, she experienced “considerable relief of fatigue and improved ability to concentrate,” which then returned over the next three days when she stopped taking the medication. In the second case, the woman switched to a different antihistamine medication than usual 13 months into her long covid, after which she experienced the same pattern of almost immediate relief. Both women have since continued to routinely take antihistamines, and both have reported a near-full recovery of their symptoms, even allowing them to exercise regularly again.

There have been reports among long covid patient groups on social media about the possible benefits of antihistamines. These cases were even brought to the attention of these researchers, primarily from the University of California, Irvine, through members of Survivor Corps, a long covid advocacy group hosted on Facebook. But near as they can tell, these are the first case reports in the literature to document the potential of antihistamines for patients with long covid, also known as postacute sequelae of SARS-CoV-2, or PASC.

“The clinical presentations described here are consistent with other research on PASC and offer anecdotal evidence for treatment of PASC symptoms with a highly accessible over-the-counter histamine antagonist,” the authors wrote.

As the authors note, there is clear evidence that a dysfunctional immune system can contribute to covid symptoms, including aspects of our immunity that could be regulated through antihistamines. So there may be a plausible mechanism for their success here. But there are some very important considerations to be noted as well.

For one, neither woman tested positive for an active case of covid-19, though they did experience common acute symptoms such as fever, cough, and body aches (in one case, the woman’s illness reportedly began in January 2020, when PCR testing was severely limited). Nor did either patient test positive for antibodies for the coronavirus at a later date. These negative results do not mean that they didn’t contract covid-19. Neither PCR nor antibody tests are 100% accurate and people’s antibody levels can wane over time, while some never develop a robust antibody response to infection. But it could hold some importance for comparing the potential of these treatments for those with antibodies and those without.

Another factor is that long covid is suspected to have more than one root cause. So even if antihistamines can benefit some patients, they may not do much of anything for others. In any case, the authors say that more research is needed to test out the promise of these drugs for long covid. And they also advise that if patients want to explore these treatments right now, they should ideally work together with their medical providers to do so.

“Most patients tell us that providers have not recommended anything that has helped. If patients wish to try OTC antihistamines, I urge them to do so under medical supervision. And because providers may not know about new potential treatments, I would encourage patients to be active in their care and consider taking research and case reports like ours to appointments with providers so they can help create a regimen that will work,” said study author Melissa Pinto, an associate professor of nursing at UCI, in a statement. “The next steps for this research into antihistamine treatment are to conduct broad-based trials in order to evaluate efficacy and to develop dosage schedules for clinical practice guidelines.”