Study: One half of hospitalized COVID-19 patients experience persistent symptoms after one year

Most symptoms of COVID-19 in hospitalized patients are resolved within 12 months, however, around one half still experience at least one persistent symptom, a study of 1,276 patients from Wuhan, China, published in The Lancet, has found.

Around one in three people still experienced shortness of breath and lung impairments persisted in some patients, especially those who had experienced the most severe illness with COVID-19 (at 12 months, 35.7% patients who underwent additional lung health tests had diffusion impairments – reduced flow of oxygen from the lungs to the bloodstream [87/244]). Overall, COVID-19 survivors were less healthy than people from the wider community who had not been infected with the SARS-CoV-2 virus (matched for age, sex and pre-existing conditions).

Our study is the largest to date to assess the health outcomes of hospitalized COVID-19 survivors after 12 months of becoming ill. While most had made a good recovery, health problems persisted in some patients, especially those who had been critically ill during their hospital stay. Our findings suggest that recovery for some patients will take longer than one year, and this should be taken into account when planning delivery of healthcare services post-pandemic."

Professor Bin Cao, National Center for Respiratory Medicine, China-Japan Friendship Hospital, China

Long-term effects of COVID-19 have been widely reported and are an increasing concern. A previous study (by the same researchers) reporting outcomes from 1,733 hospitalized COVID-19 survivors after six months found that around three-quarters of patients had persistent health problems. The new study includes 1,276 patients from the same cohort to assess their health status after 12 months.

Patients had been discharged from Jin Yin-tan Hospital in Wuhan, China, between 7 January and 29 May 2020. They underwent detailed health checks at six and 12 months (taken from the date they first experienced symptoms of COVID-19) to assess any ongoing symptoms and their health-related quality of life. These included face-to-face questionnaires, physical examinations, lab tests, and a six-minute walking test to gauge patients' endurance levels.

The average (median) age of patients included in the study was 57 years. Patient outcomes were tracked for an average (median) of 185 days (six-month check) and 349 days (12-month check).

Many symptoms resolved over time, regardless of the severity of initial COVID-19 disease. The proportion of patients still experiencing at least one symptom after one year fell from 68% at six months (831/1,227) to 49% at 12 months (620/1,272). This decrease was observed regardless of the severity of COVID-19 the patients had experienced when hospitalized.

Fatigue or muscle weakness was the most commonly reported symptom with around half of patients experiencing this at six months (52%, 636/1,230), falling to one in five patients at one year (20%, 255/1,272). Almost one third of patients reported experiencing shortness of breath at 12 months, which was slightly higher than at six months (30% at 12 months [380/1,271] vs 26% at 6 months [313/1,185]). This was more prevalent in patients who had been the most severely ill and had been on a ventilator during their time in hospital (39%, 37/94), compared to those who had not required oxygen treatment (25%, 79/317).

At the six-month check, 349 study participants underwent a lung function test and 244 of those patients completed the same test at 12 months. The proportion of patients experiencing diffusion impairment did not improve from six months to 12 months and this was seen across all groups regardless of how ill they had been when hospitalized (Scale 3, no supplemental oxygen required during hospitalization: 21% at 6 months [12/57], 23% at 12 months [13/56]; Scale 4, required supplemental oxygen: 26% at 6 months [32/124], 31% at 12 months [36/117]; Scale 5-6, required ventilation during hospitalization: 57% at 6 months [39/69], 54% at 12 months [38/70]).

Also at the six-month check, 353 study participants given a chest CT scan. Around one half of them showed lung abnormalities on their scan and were offered a repeat scan at 12 months (52.7%, 186/353). Of the 118 patients who completed the scan at 12 months, the proportion of patients with abnormalities decreased substantially across all groups but was still high, particularly in the most critically ill group (Scale 3: 39% [11/28]; Scale 4: 40% [21/52]; Scale 5-6: 87% [33/38]).

At the 12-month check, 1,252 of the patients reported their work status before and after being discharged from hospital. Around half of the patients had retired before COVID-19 (53%, 658/1,252), reflecting the older age of the study group (median age of 57 years). Of the patients who had been employed full or part-time before falling ill, the majority had returned to their original job (88%, 422/479) and most had returned to their pre-COVID-19 level of work (76%, 321/422) within 12 months. Among those who did not return to their original work, 32% cited decreased physical function (18/57), 25% were unwilling to do their previous role (14/57), and 18% were unemployed (10/57).

Compared with men, women were 1.4 times more likely to report fatigue or muscle weakness, twice as likely to report anxiety or depression, and almost three times as likely to have lung diffusion impairment after 12 months. People who had been treated with corticosteroids during the acute phase of their illness with COVID-19 were 1.5 times as likely to experience fatigue or muscle weakness after 12 months, compared to those who had not been treated with corticosteroids during their illness. The authors say these findings will be important to follow up in future research to better understand why COVID-19 symptoms persist in some people.

When compared with people of the same age, sex and pre-existing health problems who had not had COVID-19, hospitalized survivors were more likely to experience pain or discomfort at 12 months (29% COVID-19 survivors [337/1,164] vs 5% wider community [53/1,164]). They were also more likely to experience mobility problems (9% [103/1,164] vs 4% [41/1,164]). All of the symptoms recorded in the study questionnaire were more prevalent in people who had had COVID-19, compared with people from the wider community who had not had COVID-19.

Lixue Huang, one of the study authors, from Capital Medical University and China-Japan Friendship Hospital, China, said: "We did not have baseline data for the study participants from before they fell ill with COVID-19. However, the health status of matched people from the community who have never had COVID-19 gives us a useful comparison and can help us to understand the impact of the disease on survivors' quality of life." [1]

Mental health is an important consideration in the recovery of COVID-19 patients. Slightly more patients experienced anxiety or depression at one year than at six months (23% at 6 months [274/1,187] vs 26% at 12 months [331/1,271]) and the proportion was much greater in COVID-19 survivors than in matched people from the wider community (26% [300/1,164] vs 5% [59/1,164]).

Xiaoying Gu, one of the study's authors, from Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, China, said: "We do not yet fully understand why psychiatric symptoms are slightly more common at one year than at six months in COVID-19 survivors. These could be caused by a biological process linked to the virus infection itself, or the body's immune response to it. Or they could be linked to reduced social contact, loneliness, incomplete recovery of physical health or loss of employment associated with illness. Large, long-term studies of COVID-19 survivors are needed so that we can better understand the long term physical and mental health consequences of COVID-19." [1]

The authors note their study was focused on a single hospital and so patient outcomes may not be generalizable to other settings. Additionally, the study included only a small number of patients who had been admitted to intensive care (94/1,276) and findings relating to the most critically ill patients should be interpreted with caution.

A Lancet editorial published at the same time says: "As the COVID-19 pandemic continues, the need to understand and respond to long COVID is increasingly pressing. Symptoms such as persistent fatigue, breathlessness, brain fog, and depression could debilitate many millions of people globally. Yet very little is known about the condition… With no proven treatments or even rehabilitation guidance, long COVID affects people's ability to resume normal life and their capacity to work. The effect on society, from the increased health-care burden and economic and productivity losses, is substantial. Long COVID is a modern medical challenge of the first order."

It continues: "The scientific and medical communities must collaborate to explore the mechanism and pathogenesis of long COVID, estimate the global and regional disease burdens, better delineate who is most at risk, understand how vaccines might affect the condition, and find effective treatments via randomized controlled trials. At the same time, health-care providers must acknowledge and validate the toll of the persistent symptoms of long COVID on patients, and health systems need to be prepared to meet individualized, patient-oriented goals, with an appropriately trained workforce involving physical, cognitive, social, and occupational elements. Answering these research questions while providing compassionate and multidisciplinary care will require the full breadth of scientific and medical ingenuity. It is a challenge to which the whole health community must rise."