Abstract

Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients—247 home-isolated and 65 hospitalized—comprising 82% of total cases in Bergen during the first pandemic wave in Norway. At 6 months, 61% (189/312) of all patients had persistent symptoms, which were independently associated with severity of initial illness, increased convalescent antibody titers and pre-existing chronic lung disease. We found that 52% (32/61) of home-isolated young adults, aged 16–30 years, had symptoms at 6 months, including loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61). Our findings that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms highlight the importance of infection control measures, such as vaccination.

Discussion

Our study is novel in assessing long COVID symptoms, not only in hospitalized patients but also in young patients and home-isolated patients with milder disease. A strength is a near-complete, geographically defined cohort of both antibody- and reverse-transcriptase polymerase chain reaction (RT-PCR)-positive patients from the first pandemic wave, including all severities of disease, in an immunologically naive population. The small subgroups are a limitation of this study, and our findings should be confirmed in larger cohorts.

We found that a large proportion of survivors of COVID-19 in our cohort had persistent symptoms 6 months after their initial illness. Although it has previously been reported that patients hospitalized for severe COVID-19 frequently suffer long-term symptoms20,21,22,23, we found that more than half of home-isolated, mildly to moderately ill patients with COVID-19 still suffered symptoms 6 months after infection. It is worrying that non-hospitalized, young people (16–30 years old) suffer potentially severe symptoms, such as concentration and memory problems, dyspnea and fatigue, half a year after infection. Particularly for students, such symptoms might interfere with their learning and study progress.

The high prevalence of persistent fatigue in patients with COVID-19 is striking and appears higher than observed after common infections, such as influenza, Epstein–Barr virus mononucleosis and dengue11,12,13. Data from Norway have previously shown slightly lower chronic fatigue prevalence (11%) in the general population24 than in the present household controls (14%), who were younger and had fewer comorbidities than infected patients but were sampled at the same time. However, this apparent difference might be a coincidence owing to low numbers. Our finding that women had higher prevalence of fatigue concurs with results from an earlier study in the general Norwegian population24. The association between severity of illness and persistent symptoms agrees with data from hospitalized patients with COVID-19 (ref. 20). As the respiratory tract is the main target organ for COVID-19, our finding of an association between underlying chronic lung disease (mostly asthma) and persistent symptoms, including fatigue, is not surprising.

The association between severe initial disease and increased antibody titers at 2 months could be due to higher viral load, which could trigger the immune system more profoundly25. The finding of increased convalescent antibody titers with increasing age could be explained by more severe disease in older people, as age is a known strong risk factor for severe COVID-19. However, by contrast with the immunosenescence observed after influenza infection in the elderly, multivariable analysis indicated that age and severity of illness were independently associated with increased antibody titers. These findings call for enhanced surveillance of COVID-19 mass vaccination programs. Home-isolated patients aged 16–30 years with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms. Considering the millions of young people infected during the ongoing pandemic, our findings are a strong impetus for comprehensive infection control and population-wide mass vaccination.

doi: 10.1038/s41591-021-01433-3

Reprinted for educational purposes and social benefit, not for profit. 

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