Eight of 10 COVID-19 patients had lingering symptoms or signs 14 or more days after acute infection, a systematic review and meta-analysis showed.
More than 50 symptoms tied to SARS-CoV-2 infection persisted, most commonly fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), dyspnea (24%), and anosmia (24%) were identified, according to Sonia Villapol, PhD, of Houston Methodist Research Institute in Texas, and colleagues. The findings were reported in a medRxiv preprint and have not undergone peer review.
"We estimated that a total 80% of the patients infected with SARS-CoV-2 developed one or more long-term symptoms," Villapol said. "Preventive measures, rehabilitation techniques, and clinical management strategies designed to address prevalent long-term effects of COVID-19 are urgently needed," she told MedPage Today.
To date, there's no established diagnosis for the slow, persistent condition that people with lasting effects of COVID-19 experience; terms like "long COVID," "long haulers," and "post-acute COVID-19" have been used, Villapol and colleagues noted. In their review, they referred to lingering symptoms and signs as "long-term effects of COVID-19."
Last year, a widely-cited CDC survey showed 35% of COVID-19 patients had not returned to usual health 2 to 3 weeks after testing positive, but those were mild, outpatient cases. Early in 2021, a study in the Lancet showed that 6 months after illness onset, 76% of hospitalized COVID-19 patients in Wuhan, China, reported at least one symptom that persisted, mostly fatigue or muscle weakness.
In their meta-analysis, Villapol and colleagues included 47,910 people with a confirmed COVID-19 diagnosis in 15 studies that had evaluated symptoms, signs, or laboratory parameters 2 weeks or more week post-viral infection. Each study had a minimum of 100 patients. Nine studies were from Great Britain or Europe, three were from the U.S.
Six studies focused only people hospitalized for COVID-19; the others included mild, moderate, and severe cases. Patients ranged from ages 17 to 87 years, and follow-up time ranged from 14 to 110 days.
Fatigue was the most common symptom of both long and acute COVID-19, Villapol and colleagues noted: "It is present even after 100 days of the first symptom of acute COVID-19."
During follow-up, 34% of patients had an abnormal chest x-ray or CT. Elevated markers also were seen, including D-dimer (20%), NT-proBNP (11%), C-reactive protein (8%), serum ferritin (8%), procalcitonin (4%), and IL-6 (3%).
Other lingering symptoms were pulmonary (cough, chest discomfort, reduced pulmonary diffusing capacity, sleep apnea, pulmonary fibrosis), cardiovascular (arrhythmias, myocarditis), or neurologic or psychiatric (memory loss, depression, anxiety, sleep disorders).
All meta-analyses showed medium to high heterogeneity. "Future studies need to stratify by sex, age, previous comorbidities, severity of COVID-19 (ranging from asymptomatic to severe), and duration of each symptom," the researchers wrote. From the clinical perspective, multi-disciplinary teams with whole-patient perspectives are needed to address long COVID-19 care, they added.
Limitations include possible selection or reporting bias, small sample sizes for some outcomes, and variation in how outcomes and markers were defined. "Another limitation is that, given that COVID-19 is a new disease, it is not possible to determine how long these effects will last," Villapol and colleagues said.
"To determine whether these long-term effects either complicate previous diseases or are a continuation of COVID-19, there is a need for prospective cohort studies." they added. Measures like blood markers of genetic, inflammatory, immune, and metabolic function need to be standardized to compare studies, and open questions should be included.
Disclosures
The research was supported by the National Institute for Neurological Disorders and Stroke and the Houston Methodist Research Institute.
Villapol disclosed no relevant relationships with industry. A co-author is an employee of Novartis.
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