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Hair loss, reduced sex drive, and erectile dysfunction have joined a list of better-known symptoms linked to long COVID in patients who were not hospitalized, according to findings of a large study.
Anuradhaa Subramanian, PhD, with the Institute of Applied Health Research at the University of Birmingham in the United Kingdom, led the research published online on July 25 in Nature Medicine.
The team analyzed 486,149 adult electronic health records from patients with confirmed COVID in the U.K., compared to 1.9 million people with no prior history of COVID, from January 2020 to April 2021. Researchers matched both groups closely in terms of demographic, social, and clinical traits.
The team identified 62 symptoms, including the well-known indicators of long COVID, such as fatigue, loss of sense of smell, shortness of breath, and brain fog, but also hair loss, sexual dysfunction, chest pain, fever, loss of control of bowel movements, and limb swelling.
“These differences in symptoms reported between the infected and uninfected groups remained even after we accounted for age, sex, ethnic group, socioeconomic status, body mass index, smoking status, the presence of more than 80 health conditions, and past reporting of the same symptom,” Subramanian and co-researcher Shamil Haroon, PhD, wrote in a summary of their research in The Conversation.
They point out that only 20 of the symptoms they found are included in the World Health Organization’s clinical case definition for long COVID.
They also found that people more likely to have persistent symptoms 3 months after COVID infection were also more likely to be young, female, smokers, to belong to certain minority ethnic groups, and to have lower socioeconomic status. They were also more likely to be obese and have a wide range of health conditions.
Haroon, an associate clinical professor at the University of Birmingham, says that one reason it appeared that younger people were more likely to get symptoms of long COVID may be that older adults with COVID were more likely to be hospitalized and weren’t included in this study.
“Since we only considered non-hospitalized adults, the older adults we included in our study may have been relatively healthier and thus had a lower symptom burden,” he says.
Subramania notes that older patients were more likely to report lasting COVID-related symptoms in the study, but when researchers accounted for a wide range of other conditions that patients had before infection (which generally more commonly happen in older adults), they found younger age as a risk factor for long-term COVID-related symptoms.
In the study period, most patients were unvaccinated, and results came before the widespread Delta and Omicron variants.
More than half (56.6%) of the patients infected with the virus that causes COVID had been diagnosed in 2020, and 43.4% in 2021. Less than 5% (4.5%) of the patients infected with the virus and 4.7% of the patients with no recorded evidence of a COVID infection had received at least a single dose of a COVID vaccine before the study started.
Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, CA, and editor-in-chief of Medscape (WebMD’s sister site for medical professionals), says more studies need to be done to see whether results would be different with vaccination status and evolving variants.
But he notes that this study has several strengths: “The hair loss, libido loss, and ejaculation difficulty are all new symptoms,” and the study – large and carefully controlled – shows these issues were among those more likely to occur.
A loss of sense of smell – which is not a new observation – was still the most likely risk shown in the study, followed by hair loss, sneezing, ejaculation difficulty, and reduced sex drive; followed by shortness of breath, fatigue, chest pain associated with breathing difficulties, hoarseness, and fever.
Three Main Clusters of Symptoms
Given the wide range of symptoms, long COVID likely represents a group of conditions, the authors wrote.
They found three main clusters. The largest, with roughly 80% of people with long COVID in the study, faced a broad spectrum of symptoms, ranging from fatigue, to headache, to pain. The second largest group, (15%) mostly had symptoms having to do with mental health and thinking skills, including depression, anxiety, brain fog, and insomnia. The smallest group (5%) had mainly respiratory symptoms such as shortness of breath, coughing, and wheezing.
Putting symptoms in clusters will be important to start understanding what leads to long COVID, says Farha Ikramuddin, MD, a physiatrist and rehabilitation specialist at the University of Minnesota Medical School in Minneapolis.
She says though the symptoms listed in this paper are new in published research, she has certainly been seeing them over time in her long COVID clinic. (The researchers also used only coded health care data, so they were limited in what symptoms they could discover, she notes.)
Ikramuddin says a strength of the paper is its large size, but she also cautioned that it’s difficult to determine whether members of the comparison group truly had no COVID infection when the information is taken from their medical records. Often, people test at home or assume they have COVID and don’t test, she says, and therefore the information wouldn’t be recorded.
Evaluating non-hospitalized patients is also important, she says, as much of the research on long COVID has come from hospitalized patients, so little has been known about the symptoms of those with milder infections.
“Patients who have been hospitalized and have long COVID look very different from the patients who were not hospitalized,” Ikramuddin says.
One clear message from the paper, she says, is that listening and asking extensive questions about symptoms are important with patients who have had COVID.
“Counseling has also become very important for our patients in the pandemic,” she says.
It will also be important to do studies on returning to work for patients with long COVID to see how many are able to return and at what capacity, Ikramuddin says.
Nature Medicine: “Symptoms and risk factors for long COVID in non-hospitalized adults.”