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What proportion of individuals experienced common long COVID symptom clusters?

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Mariecus CM Jarvis-Mays, PharmD, MEd

In an effort to better understand and diagnose long COVID, researchers of a new study published October 10, 2022, in JAMA looked at the proportion of individuals who experienced common self-reported long COVID symptom clusters 3 months after initial symptomatic SARS-CoV-2 infection in 2020 and 2021.

Approximately 6.2% of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of 3 long COVID symptoms clusters after adjusting for health status before SARS-CoV-2 infection. A total of 51.0% had persistent fatigue with bodily pain or mood swings; 60.4% had ongoing respiratory problems, and 35.4% had cognitive problems.

The estimated mean duration of long COVID was 9 months among hospitalized individuals and 4 months among non-hospitalized individuals and occurred in 27.5% and 5.7% of individuals, respectively. Of those admitted to ICUs, 43.1% experienced long COVID. An estimated 15.1% of individuals meeting long COVID criteria continued to experience symptoms 12 months after initial infection. Researchers also noted that symptom clusters were more common in women than men.

Trial design and overview

The three common clusters studied were persistent fatigue with bodily pain or mood swings; cognitive problems (forgetfulness or difficulty concentrating, commonly referred to as brain fog); and ongoing respiratory problems (shortness of breath and persistent cough as the main symptom).

The main outcome was proportion of individuals with at least 1 of the 3 self-reported long COVID symptom clusters 3 months after SARS-CoV-2 infection and 12 months after COVID-19 illness. Estimates were separated for hospitalized and non-hospitalized individuals, those aged older or younger than 20 years, and males and females. Secondary outcomes included duration and relative severity of long COVID symptom clusters.

In this observational analysis, the research team used data from 56 distinct sources. A pooling of 44 published studies, 10 collaborating cohort studies, and 2 electronic medical record databases were used to evaluate 1.2 million individuals from 22 countries with symptomatic SARS-CoV-2 infection between March of 2020 and January of 2022. Data ranged from full account of SARS-CoV-2 infection to volunteer reporting via an app and medical insurance claims.

Potential impact

Thus far, most surveillance of COVID-19 has concentrated on the number of infections, hospital admissions, and deaths. This study, however, focused on the proportion of patients with long COVID and the duration of symptoms. Quantifying long COVID can help policy makers provide adequate access to recovery services, aid in the return to workplace or school, and help restore mental health and social life.

WHO released a clinical case definition for long COVID, or post-COVID-19, in October of 2021, which necessitates a 3-month duration after SARS-CoV-2 infection and exclusion of alternative causes. Eighty-four long-term symptoms have been identified, but the most common are fatigue, cognitive problems, and respiratory problems.

According to the research findings, long COVID by sex is distinct from severe acute SARS-CoV-2 infection. Females tend to experience less severe disease with viral infection and mount higher antibody response. X-linked chromosomes are thought to influence susceptibility to viral infection and autoimmune diseases, which long COVID is thought to be. An estimated 63.2% of individuals with long COVID are female with a statistically significant difference of 5.1% between sexes.

Age also showed statistically significant differences in estimated long COVID risk. There was a 2.0% difference for males aged 20 years and older and those younger than 20 years old. In females, there was a 7.2% difference between the two age groups.

Researchers noted that the amount and quality of data used in the analysis varied per source. Very few studies included asymptomatic individuals and some studies lacked information regarding prior health status, thus necessitating exclusion of those individuals and a correction factor, respectively.

Additionally, the WHO case definition requiring a duration of 3 months was used. Durations as low as 3 weeks have been suggested as no competent virus has been replicated beyond 3 weeks of infection. Data did not cover the Omicron variant wave as the analysis only accounted for symptomatic SARS-CoV-2 infection through the end of 2021.

Generalizability is limited as it was assumed that long COVID follows a similar course in all countries and duration estimates for long COVID were based on data from only high-income countries. Additionally, new symptoms and events have been reported to occur more frequently since the study first commenced as there have been data reporting lags. Some common reports include cardiovascular complications, thromboembolic events, and kidney, liver, gastrointestinal, endocrine, and skin disorders. There are 84 different long COVID symptoms and all could not be evaluated.

These estimates do not reflect the full burden and range of long COVID as a result, researchers noted. Geographical, economic, and symptomology differences could become clearer with additional research and future findings. ■



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