Development of Long COVID: New Symptoms and Risk Factors Identified

Development of long COVID correlated independently with 62 different symptoms across multiple organ systems as well as several sociodemographic and clinical risk factors, according to study findings published in Nature Medicine.

Researchers conducted a population-based, retrospective, matched-cohort study in the United Kingdom from January 31, 2020 and April 15, 2021 to improve understanding of risk factors associated with long COVID development. They collected data on nonhospitalized patients who experienced symptoms consistent with long COVID at least 3 months after onset of acute COVID-19 infection from the Clinical Practice Research Datalink (CPRD) Aurum.

During this study period, 486,149 nonhospitalized adults had confirmed COVID-19 infection, while 8,030,224 people did not have records of confirmed or suspected COVID-19 infection.

After 3 months, 62 symptoms significantly correlated with COVID-19 infection, especially the following:

• anosmia (adjusted hazard ratio [aHR], 6.49; 95% CI, 5.02-8.39),
• hair loss (aHR, 3.99; 95% CI, 3.63-4.39),
• Sneezing (aHR, 2.77; 95% CI, 1.40-5.50)
• problems ejaculating (aHR, 2.63; 95% CI, 1.61-4.28),
• decreased libido (aHR, 2.36; 95% CI, 1.61-3.47),
• shortness of breath at rest (aHR, 2.20; 95% CI, 1.57-3.08), and
• fatigue (aHR, 1.92; 95% CI, 1.81-2.03).

Of the 486,149 nonhospitalized adults with confirmed COVID-19, 384,137 had a minimum of 12 weeks of follow-up, and 20,864 (5.4%) reported at least 1 long COVID symptom.

The researchers performed propensity-score matching, selecting 1,944,580 people of the 8,030,224 people without recorded COVID-19 infection. Only 1,501,689 participants in this cohort had a minimum of 12-weeks of follow-up, and 65,293 (4.3%) reported at least 1 long COVID symptom.

The researchers observed several risk factors for developing long COVID, including:

• female sex (aHR, 1.52; 95% CI, 1.48-1.56),
• lower socioeconomic status (aHR, 1.11; 95% CI, 1.07-1.16),
• smoking or smoking history (aHR, 1.12; 95% CI, 1.08-1.15 and aHR, 1.08; 95% CI, 1.05-1.11, respectively), and
• obesity (aHR, 1.10; 95% CI, 1.07-1.14).

They also observed various comorbidities as risk factors for long COVID, including, but not limited to:

• chronic obstructive pulmonary disorder (aHR, 1.55; 95% CI, 1.47-1.64),
• benign prostatic hyperplasia (aHR, 1.39; 95% CI, 1.28-1.52), and
• fibromyalgia (aHR, 1.37; 95% CI, 1.28-1.47)

Long COVID occurred more frequently among people of minority ethnicities and along a gradient of decreasing age with people between the ages of 18 and 30 demonstrating increased risk of developing long COVID.

“Infection with [COVID-19] is independently associated with the reporting of 62 symptoms spanning multiple organ systems 12 weeks or longer after infection,” the researchers stated. “A wide range of both sociodemographic and clinical factors are independently associated with development of persistent symptoms.”

Study limitations included potential misclassification bias, lack of true representation of long COVID burden based solely on coded health care data secondary to decreased encounters with primary care providers during the pandemic, potential underreporting by patients, and the inability of the researchers to investigate all aspects of long COVID, particularly impact on daily functioning.