These findings help define long COVID, guiding providers and patients through the recovery process, Barak Mizrahi, MSc, of KI Research Institute, Kfar Malal, Israel, and colleagues reported.
“To provide efficient continuous treatment and prevent adverse events related to potential long term effects and delayed symptoms of COVID-19, determining the magnitude and severity of this phenomenon and distinguishing it from similar clinical manifestations that occur normally or following infections with other pathogens is essential,” the investigators wrote in The BMJ.
To this end, they conducted a retrospective, nationwide cohort study involving 1,913,234 people who took a polymerase chain reaction test for SARS-CoV-2 between March 1, 2020, and Oct. 1, 2021. They compared a range of long-term outcomes at different intervals post infection, and compared these trends across subgroups sorted by age, sex, and variant. Outcomes ranged broadly, including respiratory disorders, cough, arthralgia, weakness, hair loss, and others.
The investigators compared hazard ratios for each of these outcomes among patients who tested positive versus those who tested negative at three intervals after testing: 30-90 days, 30-180 days, and 180-360 days. Statistically significant differences in the risks of these outcomes between infected versus uninfected groups suggested that COVID was playing a role.
“The health outcomes that represent long COVID showed a significant increase in both early and late phases,” the investigators wrote. These outcomes included anosmia and dysgeusia, cognitive impairment, dyspnea, weakness, and palpitations. In contrast, chest pain, myalgia, arthralgia, cough, and dizziness were associated with patients who were in the early phase, but not the late phase of long COVID.
“Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnea and similar risk for other outcomes compared with unvaccinated infected patients,” the investigators noted.
For the long COVID outcomes, plots of risk differences over time showed that symptoms tended to get milder or resolve within a few months to a year. Patients 41-60 years were most likely to be impacted by long COVID outcomes, and show least improvement at 1 year, compared with other age groups.
“We believe that these findings will shed light on what is ‘long COVID’, support patients and doctors, and facilitate better and more efficient care,” Mr. Mizrahi and coauthor Maytal Bivas-Benita, PhD said in a joint written comment. “Primary care physicians (and patients) will now more clearly understand what are the symptoms that might be related to COVID and for how long they might linger. This would help physicians monitor the patients efficiently, ease their patients’ concerns and navigate a more efficient disease management.”
They suggested that the findings should hold consistent for future variants, although they could not “rule out the possibility of the emergence of new and more severe variants which will be more virulent and cause a more severe illness.”
Dr. Monica Verduzco-Gutierrez
One “major limitation” of the study, according to Monica Verduzco-Gutierrez, MD, a physiatrist and professor and chair of rehabilitation medicine at the University of Texas Health Science Center, San Antonio, is the lack of data for fatigue and dysautonomia, which are “the major presentations” that she sees in her long COVID clinic.
“The authors of the article focus on the primary damage being related to the lungs, though we know this is a systemic disease beyond the respiratory system, with endothelial dysfunction and immune dysregulation,” Dr. Verduzco-Gutierrez, who is also director of COVID recovery at the University of Texas Health Science Center, said in an interview.
Although it was reassuring to see that younger adults with long COVID trended toward improvement, she noted that patients 41-60 years “still had pretty significant symptoms” after 12 months.
“That [age group comprises] probably the majority of my patients that I’m seeing in the long COVID clinic,” Dr. Verduzco-Gutierrez said. “If you look at the whole thing, it looks better, but then when you drill down to that age group where you’re seeing patients, then it’s not.”
Dr. Verduzco-Gutierrez is so busy managing patients with long COVID that new appointments in her clinic are now delayed until May 31, so most patients will remain under the care of their primary care providers. She recommended that these physicians follow guidance from the American Academy of Physical Medicine and Rehabilitation, who offer consensus statements based on clinical characteristics, with separate recommendations for pediatric patients.
Our understanding of long COVID will continue to improve, and with it, available recommendations, she predicted, but further advances will require persistent effort.
“I think no matter what this [study] shows us, more research is needed,” Dr. Verduzco-Gutierrez said. “We can’t just forget about it, just because there is a population of people who get better. What about the ones who don’t?”
The investigators and Dr. Verduzco-Gutierrez disclosed no conflicts of interest.