The COVID-19 pandemic has caused an unprecedented global health crisis, infecting millions and resulting in widespread mortality. As of 2024, over 760 million confirmed cases and 6.8 million deaths have been reported globally, with India being one of the most severely affected countries. India alone has recorded over 44 million cases and more than 530,000 deaths. The impact on the healthcare system has been profound, highlighting the need for effective responses not only to manage acute infections but also to address long-term health consequences¹.

Fatigue has emerged as one of the most common and persistent symptoms experienced by individuals recovering from COVID-19, frequently extending for months after the acute phase of infection. Known as "long COVID," this debilitating symptom can severely impair a person’s ability to resume normal daily activities and reduce overall quality of life. Although fatigue in COVID-19 patients is widely acknowledged, the underlying mechanisms remain poorly understood². Growing evidence points to immune dysregulation as a key contributor to this persistent fatigue. Changes in immune cell function, alterations in cytokine profiles, and chronic inflammation are all thought to play a role. Furthermore, autoimmune responses and potential viral persistence in tissues could also be influencing factors. However, comprehensive studies investigating these immunological mechanisms in COVID-19-related fatigue, especially in the Indian context, are still limited and require further exploration^3,4.

This research aims to assess the prevalence and severity of fatigue among COVID-19 patients and investigate the potential immunologic mechanisms contributing to this persistent symptom. Understanding the relationship between immune responses and fatigue could inform targeted therapeutic strategies to alleviate long COVID symptoms, thereby improving the quality of life for millions of individuals affected by the long-term effects of the virus. By addressing this critical gap in knowledge, we hope to contribute valuable insights that will enhance patient care and inform public health policy, especially in resource-limited settings like India.

STUDY DESIGN: This was a prospective cohort study.

SAMPLE SIZE: 200 RTPCR confirmed adult Covid 19 patients attending the department of General Medicine, Gandhi Medical College, Secunderabad, Hyderabad were included in the study.

INCLUSION CRITERIA:

1. RTPCR confirmed covid-19
2. Age >18yrs.

EXCLUSION CRITERIA:

1. Chronic bed ridden
2. Covid-19 positive patients with history of cerebrovascular accident (CVA), chronic kidney disease (CKD), congestive heart failure (CHF), malignancy and psychiatric

METHODOLOGY:

A Total of 200 covid 19 patients admitted in Gandhi Hospital, fulfilling the inclusion criteria and after obtaining written informed consent were taken for study. The demographic and clinical characteristics and severity are noted at the time of admission. 5ml venous blood was withdrawn from patients at the time of admission. The serum sample obtained from the blood sample of patients stored at -20 degree Celsius and later used for the assessment of IL-2 and IL-10 with the help of cytokine ELISA kits purchased from Diaclone SAS, manufactured at 6 Rue Docteur Girod, 25020 Besacon cedex, France. These patients were followed up from the time of admission and after discharge. They were assessed for fatigue and graded according to fatigue assessment scale at the end of 1st month and 3rd months after discharge telephonically by enquiring through questionnaire.

 STATISTICAL ANALYSIS:

All the patient’s data are entered in proforma and recorded in Microsoft excel sheet and analysis of data was done using IBM SPSS version 29 operating on windows 11. All the demographic details of the patients are summarized as frequency, percentage, mean and standard deviation, presented using pie chart and bar graphs. The mean difference between the variables was analysed using two way ANOVA. A p- value <0.05 is statistically significant.

TABLE:1 DISTRIBUTION BASED ON GENDER

The gender distribution in our study showed a higher proportion of males (63.5%) compared to females (36.5%).

TABLE:2 DISTRIBUTION BASED ON AGE

In our study population, the highest number of patients in both males and females fell within the 41-50 year age group

TABLE:3 POST-COVID FATIGUE DISTRIBUTION IN PATIENTS

In our study, out of 200 COVID-19 cases during admission, 122 patients exhibited post-COVID fatigue after one month of follow-up, while 109 patients showed post-COVID fatigue after three months of follow-up following discharge from the hospital.

TABLE:4 GENDER WISE DISTRIBUTION OF POST-COVID FATIGUE IN 1^ST MONTH AND 3^RD MONTH

In our study, 74 males experienced post-COVID fatigue at the end of the first month, and 63 males were affected by the third month follow-up. For females, 48 experienced post-COVID fatigue at the end of the first month, and 46 were affected by the third month follow-up.

TABLE:5 POST-COVID FATIGUE SEVERITY IN MALES

In our study, at the end of the first month follow-up, we observed 51 males with mild, 17 with moderate, and 6 with severe post-COVID fatigue. By the end of the third month follow-up, 40 males had mild, 17 had moderate, and 6 had severe post-COVID fatigue.

TABLE:6 POST-COVID FATIGUE SEVERITY IN FEMALES

In our study, at the end of the first month follow-up, we observed 28 females with mild, 14 with moderate, and 6 with severe post-COVID fatigue. By the end of the third month follow-up, 30 females had mild, 10 had moderate, and 6 had severe post-COVID fatigue.

TABLE:7 GENDER WISE DISTRIBUTION OF POST-COVID FATIGUE IN PATIENTS WITH OXYGEN/NIV/MV/RA REQUIRED DURING THE ADMISSION PERIOD

In our study population requiring different modes of oxygen support, the largest group was on oxygen inhalation, followed by non-invasive ventilation, and then mechanical ventilation. Among the patients who required oxygen support, we observed the highest incidence of fatigue.

TABLE:8 AGE-WISE DISTRIBUTION OF OXYGEN REQUIREMENTS IN POST-COVID FATIGUE IN MALE PATIENTS

In our study, the highest number of male patients requiring oxygen inhalation for post-COVID fatigue were in the 41-50 year age group, while those requiring non-invasive ventilation were primarily in the 31-40 year age group, and mechanical ventilation was most commonly needed by patients in the 41-50 year age group.

TABLE:9 AGE-WISE DISTRIBUTION OF OXYGEN REQUIREMENTS IN FEMALE PATIENTS WITH POST-COVID FATIGUE.

In our study, the highest number of female patients requiring oxygen inhalation for post-COVID fatigue were in the 41-50 year age group, while those needing non-invasive ventilation were primarily in the 51-60 year age group, and mechanical ventilation was most commonly required by patients in the 31-40 year age group.

TABLE:10 AN ASSOCIATION BETWEEN POST-COVID FATIGUE SEVERITY AND MEAN INFLAMMATORY MARKERS

In our study, the mean levels of inflammatory markers (IL-10 and IL-2) were highest in severe cases of fatigue, followed by moderate and mild cases, respectively.

TABLE 11: Two way ANOVA

1. R Squared = .159 (Adjusted R Squared = .153)

This prospective cohort study included 200 COVID-19 patients at Gandhi Hospital, Secunderabad, Telangana, over 18 months, examining post-COVID fatigue and its correlation with disease severity and inflammatory markers.

Among the study population, males comprised 63.5% (127), and females 36.5% (73). Fatigue assessments at one and three months post-discharge showed 122 patients (61%) experiencing fatigue at one month, reducing to 109 patients (54.5%) by three months. Gender analysis revealed fatigue prevalence among males was 60% (74) at one month and 58% (63) at three months, while among females, it was 40% (48) and 42% (46) respectively. The 41–50 age group accounted for the highest patient count (70), with males (44) showing maximum representation. Fatigue severity correlated positively with disease severity, as patients requiring mechanical ventilation during their hospital stay experienced the most severe fatigue, followed by those on non-invasive ventilation. Patients on oxygen inhalation experienced moderate fatigue, while those without supplemental oxygen showed minimal or no fatigue. Longer hospital stays were also strongly associated with increased fatigue severity.

Inflammatory markers IL-2 and IL-10 were significant predictors of fatigue. Mean IL-2 levels were 17.59 (SD 13.36), with males having a mean of 17.363 (SD 12.366) and females having a mean of 17.98 (SD 15.024). Mean IL-10 levels were 49.57 (SD 51.34), with males at 46.58 (SD 39.589) and females at 54.77 (SD 67.084). Severe fatigue was observed more frequently in patients with higher inflammatory marker levels. Age-wise distribution of fatigue severity showed that males aged 41–50 had the highest incidence of mild and severe fatigue, while moderate fatigue peaked in the 31–40 group. Among females, the 31–40 group had the highest mild fatigue cases at one month, shifting to the 41–50 group by three months. These findings are consistent with previous studies; Townsend et al. and Sohaib Khatib et al. also reported higher post-COVID fatigue in females^5,6. Renuka Sarap et al. observed persistent fatigue at two weeks post-discharge (mean score 3.8), which reduced significantly after one year (mean score 1.05)⁷. Similar results with other studies are observed⁸.This study underscores the prolonged impact of COVID-19, particularly in severe cases and those with elevated inflammatory markers, highlighting the need for long-term patient support.

Post-COVID fatigue is a significant concern for patients recovering from COVID-19, impacting their daily functioning and quality of life. Evaluating inflammatory markers during admission not only helps in assessing the severity of the disease but also provides insight into the likelihood of developing fatigue after recovery. Our study found a positive correlation between inflammatory markers, age, and the severity of post-COVID fatigue. Early assessment of fatigue is crucial for timely intervention and effective management of symptoms. Using a fatigue assessment scale to grade severity allows for more tailored rehabilitation strategies. Since females are more prone to post-COVID fatigue, they should be given targeted counseling and support to help them manage recovery and improve their overall well-being.

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