COVID-19 Increases Chronic Fatigue Risk

In a study published in the Journal of Infection and Public Health, researchers conducted a retrospective cohort study on 3,227,281 pairs of patients with and without COVID-19 from a larger dataset of over 115 million patients to investigate the associations between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and chronic fatigue syndrome (CFS) risk, especially in the presence of comorbidities.

Cox proportional hazard models showed that patients with prior SARS-CoV-2 infections had a higher risk of developing CFS (HR = 1.59). The highest risk groups were adults over 65, Asians (HR = 1.75), females, and those with comorbidities such as diabetes, obesity, hypertension, and hyperlipidemia. The omicron variation was associated with somewhat higher CFS risk (HR = 1.40) than previous SARS-CoV-2 strains (alpha HR = 1.33, delta HR = 1.40). Risk levels for Omicron were similar to Delta, despite Omicron often causing milder acute illness.

Furthermore, contrary to prior research, this study discovered that non-hospitalized patients had a higher risk of acquiring CFS (HR = 1.64) than hospitalized patients (HR = 1.22), refuting the notion that more severe initial infections enhance long-term fatigue risk.

Background
The coronavirus disease 2019 (COVID-19) pandemic remains one of the most devastating in human history, infecting about 700 million people and killing over 7 million in just four years. While social distancing measures and vaccination programs have significantly reduced illness transmission and severity, many COVID-19 survivors describe persisting or unique symptoms that cause debilitation for months or years after the first infection.

Alarmingly, these disorders, collectively known as “long COVID,” are thought to affect up to 78% of survivors, leaving them with chronic chest discomfort, lung ailments, muscular aches, and chronic fatigue syndrome (CFS). Although studies have been conducted to determine the link between SARS-CoV-2 infection and CFS risk, none have examined the impact of confounders, such as comorbidities and other medical problems.

A growing body of research supports a positive feedback loop between long-term COVID and other chronic illnesses, with the former increasing the risk and severity of the latter. Furthermore, long COVID is a multi-organ illness, emphasizing the importance of large-scale cohort studies exploring the links between CFS and long COVID risk factors.

About the Study

The current study employs a large cohort (COVID-19 cases; n = 3,227,281 pairings) spanning a range of infection severity, age, gender, race/ethnicity, vaccination status, and comorbidities to determine the risk connections between prior COVID-19 infections and CFS risk. Between January 2020 and December 2023, study data were gathered from the TriNetX database in the United States (US), a collaborative network that contains electronic health records for over 115 million people. Participants were chosen by first identifying CFS patients in the database (n = 3,227,281) and then using 1:1 propensity score matching (PSM) to match them with CFS-free patients (non-COVID-19 controls).

Demographics, infection and comorbidity diagnoses, continuing drugs, treatments, and laboratory test results were all considered relevant data. The study looked at age, gender, COVID-19 vaccination status and illness severity, hypertensive diseases, race, ischemic heart diseases, hyperlipidemia, cerebrovascular diseases, chronic renal disease, chronic obstructive pulmonary disease, and depression. Patients were further separated into subcohorts based on the wave (alpha, delta, or omicron) of their first SARS-CoV-2 infection. Interest led to medically proven CFS diagnoses.

Standardized Mean Differences (SMD) were used to compare variables between COVID-19 and non-COVID-19 participants, whereas Kaplan-Meier analysis computed CFS incidence rates and univariate Cox proportional hazard models computed hazard ratios (HRs; CFS risk) in case and control cohorts.

Conclusions
The current study examines a cohort of over 6 million individuals to determine the risk connections between COVID-19, its comorbidities, and eventual CFS risk. The results confirmed earlier studies by establishing a greater CFS risk (HR = 1.59) in COVID-19 patients compared to COVID-19-free counterparts. Unlike previous studies, this study highlighted the significant influence of race, with Asian patients having the highest CFS risk (HR = 1.75), as well as the importance of comorbidities, with chronic obstructive pulmonary disease (COPD) contributing to increased risk (HR = 1.43), in addition to the known comorbidities of obesity, diabetes, and hypertension.

The results on hospitalization severity were unexpected, as non-hospitalized patients had a significantly higher risk of developing CFS (HR = 1.64) than those hospitalized on the same day (HR = 1.22), implying that prompt medical care during acute infection may reduce long-term fatigue risk.

Together, these data provide a complete assessment of the CFS risk landscape, allowing doctors to better understand the needs of COVID-19 patients and potentially improve their quality of life.

For more information: Risk of chronic fatigue syndrome after COVID-19: A retrospective cohort study of 3227281 patients, In Journal of Infection and Public Health, https://doi.org/10.1016/j.jiph.2024.102559