Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19

Abstract

Background

Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues.

Methods and findings

We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score–matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan–Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control.

Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms.

Conclusions

Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.

Abstract

Maxime Taquet and colleagues investigate the incidence, co-occurrence and evolution of long-COVID features in more than a quarter of a million people.

Author summary

Why was this study done?

• Long-COVID has been described in recent studies. But we do not know the risk of developing features of this condition and how it is affected by factors such as age, sex, or severity of infection.

• We do not know if the risk of having features of long-COVID is more likely after Coronavirus Disease 2019 (COVID-19) than after influenza.

• We do not know about the extent to which different features of long-COVID co-occur.

What did the researchers do and find?

• This research used data from electronic health records of 273,618 patients diagnosed with COVID-19 and estimated the risk of having long-COVID features in the 6 months after a diagnosis of COVID-19. It compared the risk of long-COVID features in different groups within the population and also compared the risk to that after influenza.

• The research found that over 1 in 3 patients had one or more features of long-COVID recorded between 3 and 6 months after a diagnosis of COVID-19. This was significantly higher than after influenza.

• For 2 in 5 of the patients who had long-COVID features in the 3- to 6-month period, they had no record of any such feature in the previous 3 months.

• The risk of long-COVID features was higher in patients who had more severe COVID-19 illness, and slightly higher among females and young adults. White and non-white patients were equally affected.

What do these findings mean?

• Knowing the risk of long-COVID features helps in planning the relevant healthcare service provision.

• The fact that the risk is higher after COVID-19 than after influenza suggests that their origin might, in part, directly involve infection with SARS-CoV-2 and is not just a general consequence of viral infection. This might help in developing effective treatments against long-COVID.

• The findings in the subgroups, and the fact that the majority of patients who have features of long-COVID in the 3- to 6-month period already had symptoms in the first 3 months, may help in identifying those at greatest risk.