A significant majority of patients who've been hospitalized for Covid-19 still had at least one symptom of the disease six months after they'd recovered from their initial coronavirus infection, according to a first-of-its-kind study—and some long-term symptoms were more common than others.

An overview of recovery clinic models for Covid-19 long-haulers

Study details

For the study, published Friday in The Lancet, researchers reviewed data from the EHRs of 2,469 Covid-19 patients who had been admitted to Jin Yin-Tan Hospital in Wuhan, China. All of the patients were discharged from the hospital between Jan. 7, 2020, and May 29, 2020 after meeting "uniform discharge criteria according to the Chinese clinical guidance for Covid-19 pneumonia diagnosis and treatment issued by the National Health Commission," which included having no fever for three consecutive days, showing improvement in respiratory symptoms, showing "obvious resolution and recovery of acute lesion in lung imaging," and receiving two negative test results for the novel coronavirus at least 24 hours apart, the researchers wrote.

The scientists then conducted in-person evaluations of 1,733 of those patients between June 16, 2020, to Sept. 3, 2020. The researchers did not include patients in the follow-up evaluations who were too sick to appear in person, patients who lived in nursing homes, or patients who had been readmitted to the hospital within the months after their discharge.

The patients who were included in the follow-up evaluations participated in physical exams, lab tests, personal interviews about their health, as well as a six-minute walk test, which is used to measure endurance and aerobic capacity. According to the researchers, about 75% of those participants had required supplemental oxygen while they were in the hospital, but most did not require ventilation or high-flow nasal oxygen.

A total of 390 of the follow-up participants also underwent lung function tests, CT scans of their chest, and ultrasounds. The researchers did not evaluate the participants' cognitive or neurological functions.

Key findings

Among the patients who participated in the follow-up evaluations, 76% reported that they were still experiencing at least one symptom associated with Covid-19 six months after they were discharged from the hospital, including 63% who reported experiencing fatigue or muscle weakness at the time of the evaluations. According to the researchers, fatigue and muscle weakness were the most-reported symptoms among the participants at the six-month follow-up evaluations. In addition, about 25% of the participants reported sleeping difficulties, and 23% said they were experiencing anxiety or depression.

The researchers found that, generally, the participants who had needed "more intensive oxygen support" during their hospitalizations for Covid-19 reported worse symptoms at the six-month follow-ups compared with participants who didn't require as much oxygen support, the New York Times reports. But participants who didn't require supplemental oxygen were experiencing notable symptoms at the six-month follow-ups, as well.

For example, 24% of the participants who did not receive supplemental oxygen while hospitalized for Covid-19 had a below-normal score on their six-minute walk test. In comparison, 29% of people who required intensive oxygen during their hospital stays had below-normal scores on the test.

Among the 390 of participants who completed lung function tests as part of the follow-up exams, those who had the most severe cases of Covid-19 performed the worst. However, the researchers also found that 22% of the participants with the mildest cases (in comparison to the rest of the patients) had reduced oxygen flow between their lungs and bloodstream at the six-month mark—even though those patients could breathe without assistance while they were hospitalized for Covid-19.

What do the findings mean?

Ultimately, study co-author Lixue Huang of the China-Japan Friendship Hospital and Capital Medical University said the study shows it's still not clear how long it takes to completely recover from Covid-19—or whether complete recovery is possible for all patients.

"I am most worried about the unknown future for these patients' recovery," Huang said. "At six months after symptoms onset, a considerable proportion of Covid-19 patients had physical and psychological problems. … We still do not know how long it takes for these patients to recover fully from Covid-19 or whether complete recovery is possible in every case."

According to Michael Peluso, an infectious disease physician at the University of California-San Francisco (UCSF), the study is one of the first "that really describes in some level of detail longer-term outcomes among quite a large group of people." Peluso said, "It documents what people providing clinical care to [novel coronavirus] patients have known for a while now—that a large proportion of people do have long-term health consequences."

Steven Deeks, a professor of medicine at UCSF, said the study shows that long-term Covid-19 symptoms affect "a substantial portion of people, far higher than you would expect in the general population." Further, the study shows "there's no specific pathway" for Covid-19, as there are "multiple different outcomes that occur: mental health stuff and pulmonary stuff and quality-of-life stuff."

However, Lauren Ferrante, a pulmonary and critical care physician at Yale School of Medicine, cautioned the findings may be skewed because the researchers excluded some patients from the follow-up studies. "Some of the sickest patients were excluded, so perhaps some of the outcomes that were reported would be worse if those patients were included," she said.

Peluso also noted that patients treated in Wuhan were treated in the first half of 2020, and they likely didn't receive some of the treatments now recognized for Covid-19 patients, such as remdesivir or dexamethasone. According to Peluso, it's possible that patients who receive those treatments might not have the same persisting symptoms as the patients involved in the study.

Separately, David Putrino, who works with Covid-19 patients at Mount Sinai's Center for Post-Covid Care, said it's important to provide context regarding the types of symptoms so-called "Covid-19 long haulers" can experience.

"Within that 76% there are people who are long haulers, people who have long-term cardiac damage because of [novel coronavirus] infection, people who have long-term lung damage and kidney damage, and so on," Putrino said.

"And then my suspicion would be that a large number of individuals are having pretty mild but reportable symptoms," he added. For instance, according to Putrino, although concerning, persisting symptoms such as shortness of breath and loss of smell aren't as severe as some of the other symptoms seen in Covid-19 long haulers.

"This is not to discount these lived experiences, not to say it's not terrible. It is terrible that at six months post-virus people are still feeling symptoms. That really tells us how serious this thing is, but we also need to make sure we report that many of these are very mild symptoms," Putrino concluded (Belluck, New York Times, 1/8; Cooney, STAT News, 1/8; Loh, Bloomberg, 1/8; Huang et al., The Lancet, 1/8).