Prevalence and patterns of post-COVID-19 symptoms in recovered patients of Delhi, India: a population-based study

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Osong Public Health Res Perspect. 2024;.j.phrp.2023.0251

Publication date (electronic) : 2024 April 22

doi : https://doi.org/10.24171/j.phrp.2023.0251

Nidhi Bhatnagar¹, Mongjam Meghachandra Singh¹, Hitakshi Sharma¹, Suruchi Mishra^,1, Gurmeet Singh¹, Shivani Rao¹, Amod Borle¹, Tanu Anand², Naresh Kumar³, Binita Goswami⁴, Sarika Singh⁵, Mahima Kapoor⁶, Sumeet Singla⁷, Bembem Khuraijam⁵, Nita Khurana⁵, Urvi Sharma⁸, Suneela Garg⁹

¹Department of Community Medicine, Maulana Azad Medical College, New Delhi, India

²Indian Council of Medical Research, New Delhi, India

³Department of Pulmonary Medicine, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India

⁴Department of Biochemistry, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India

⁵Department of Pathology, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India

⁶Department of Psychiatry, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India

⁷Department of Medicine, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India

⁸Directorate General Health Services, Delhi, India

⁹National Institute of Health and Family Welfare, New Delhi, India

Corresponding author: Suruchi Mishra Department of Community Medicine, Maulana Azad Medical College, 2 Bahadur Shah Zafar Marg, New Delhi 110002, India E-mail: drsuruchimishramamc@gmail.com

Received 2023 September 14; Revised 2024 February 26; Accepted 2024 March 6.

Abstract

Introduction

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first spotted in China in December 2019, led to a global pandemic. This pandemic led to a rapid increase in both cases and deaths, as well as overwhelming healthcare infrastructure [1]. On May 5, 2023, the World Health Organization (WHO) announced the end of COVID-19 as a public health emergency of international concern, with over 768 million cases and more than 6.9 million deaths reported to date [2]. The pandemic spurred numerous epidemiological studies aimed at understanding the transmission of the disease, as well as prevention and control strategies. The variability of the disease—influenced by the circulating viral strains—and a limited understanding of its pathophysiology led to the exploration of multiple treatment options during the peak of the outbreak. The broad clinical spectrum of SARS-CoV-2 further complicated the understanding of the disease due to its potential for multiorgan involvement [3,4].

Acute COVID-19 infection reportedly lasts up to 4 weeks before recovery [5]. However, growing evidence suggested that signs and symptoms of COVID-19 infection persist even after recovery in a substantial proportion of cases. The condition characterized by the persistence of symptoms after the initial infection and recovery from COVID-19 has been termed “long COVID,” “post-COVID-19 syndrome,” and “post-acute COVID-19 syndrome” [5]. No consensus has yet been reached on the characteristics defining this condition. The British Medical Association defines a syndrome as a “set of medical signs and symptoms which are correlated with each other and associated with a particular disease” [6]. More specifically, the UK National Institute of Health and Care Excellence defines post-COVID-19 syndrome as “a cluster of signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks and are not explained by an alternative diagnosis” [5]. Long-term symptoms of COVID-19 can include cardiopulmonary symptoms (a decline in respiratory function, fibrosis, pleural involvement, myocarditis, pericardial effusion, etc.), post-COVID-19 thrombosis, immune-mediated manifestations (arthritis, myositis, pancreatitis, etc.), and other skin, neurological, renal, hematological, endocrine, and systemic manifestations [5,7]. The presence of persistent COVID-19 symptoms has reportedly significantly affected the mental health and emotional well-being of patients [8].

To date, research into post-COVID-19 syndrome has been limited, with particularly scant data on long-term outcomes among recovered patients in emerging economies [8,9].Under this backdrop, we designed a study to evaluate the post-COVID phenomenon or symptomatology in patients who have recovered from COVID-19 in Delhi, India. The aim of this research was to ascertain the prevalence, patterns, and duration of symptoms in these recovered individuals.

Materials and Methods

Results

The study included 413 participants, all of whom presented with mild disease. The response rate was 91.8% (379 patients) at the first follow-up visit and 89.3% (369 patients) at the second follow-up. Following the per-protocol principle, the collected data were analyzed based on the 369 patients who completed the second follow-up. The mean age of the participants was 42.07 years, with a standard deviation of 14.89 years. We examined the sociodemographic characteristics of the participants, including sex, educational status, smoking history, and alcohol consumption. Approximately half (50.1%) of the participants were male, 97.84% were literate, 92.96% had never smoked, and 9.21% reported a history of alcohol consumption. Most participants (93.5%) were vaccinated, and 26.56% had at least 1 comorbidity (Table 1). The analysis revealed significant associations between post-COVID-19 syndrome and both sex and age (p<0.05).

Table 1.

Sociodemographic profile of recovered COVID-19 patients (n=369)

Nearly half of the participants (47.5%) experienced long COVID symptoms, while 79.7% had post-COVID-19 symptoms (Figure 1). The most common symptoms included joint pain (36%), persistent dry cough (35.7%), anxiety (28.4%), and shortness of breath (27.1%). Other symptoms reported were persistent fatigue (21.6%), persistent headache (20.0%), forgetfulness (19.7%), and limb weakness (18.6%) (Table 2). The longest symptom duration was reported for anxiety, at 132 days (IQR, 97–190 days), followed by fatigue at 127 days (IQR, 97–172 days), body ache at 124 days (IQR, 89–157 days), and joint pain/swelling at 115 days (IQR, 89–180 days). Prolonged symptom duration was also noted for shortness of breath, at 112.5 days (IQR, 88.25–181.50 days); headache, at 109.5 days (IQR, 87–139.50 days); and limb weakness, at 109 days (IQR, 83–148.75 days). Anxiety and persistent dry cough had significantly longer durations in men compared to women (p<0.05). Relative to the unvaccinated subgroup, limb weakness and fever lasted significantly longer in vaccinated participants (p<0.05). Additional symptoms included dry cough, lasting 105.5 days (IQR, 86–146 days), and forgetfulness, lasting 100 days (IQR, 87.5–145 days). Notably, forgetfulness persisted for significantly longer in participants with any comorbidity than in those without comorbid conditions (Table 3).

Figure 1.

Pattern of post-COVID-19 symptoms (n=369).

Table 2.

Distribution of study participants on the basis of prevalence of post-COVID-19 symptoms (n=369)

Table 3.

Duration of post-COVID-19 symptoms in study participants

Biochemical investigations were conducted for study participants at baseline, the first follow-up, and the second follow-up. The Shapiro-Wilk normality test indicated that the data were skewed in the distribution of the biochemical parameters. The analysis revealed no significant differences in the median levels of thyroid-stimulating hormone (TSH), hemoglobin A1c (HbA1c), aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT), alkaline phosphatase (ALP), creatinine, urea, or uric acid between individuals with post-COVID-19 syndrome and those without the syndrome (p>0.05). The median values for all parameters fell within normal ranges (Table 4). New instances of elevated HbA1c were detected in 3.5% of patients at the first follow-up and in 6.9% at the second follow-up. New cases of elevated TSH were observed in 9.2% of patients at the first follow-up and in 6.6% at the second visit. In liver function tests, AST/SGOT levels were raised in 4.2% of participants at the first follow-up and in 3.6% at the second follow-up. ALT/SGPT levels were elevated in 8.4% of participants at the first follow-up and in 4.8% at the second visit. Additionally, ALP levels were found to be elevated in 12.6% of participants at the first and in 7.0% at the second follow-up. For the kidney function test panel, patients were assessed regarding creatinine, urea, and uric acid levels. Creatinine levels were raised in 0.8% of patients at the first follow-up and in 1.1% at the second visit. Elevated urea levels were found in only 2.5% of patients at the first and 1.6% at the second follow-up. Similarly, high uric acid levels impacted just 1.9% of patients at the first follow-up and 1.4% at the second follow-up appointment.

Table 4.

Association between biochemical parameters and post-COVID-19 syndrome

A peripheral blood smear was conducted for patients at baseline, the first follow-up, and the second follow-up. Transformed lymphocytes and activated monocytes were observed in 1.1% of the participants at the first follow-up and 0.8% at the second appointment. An abnormal absolute neutrophil count was detected in the peripheral smears of 16.5% of patients at the first follow-up and 11.7% at the second. In turn, an abnormal absolute eosinophil count was noted in 7.9% of participants at the first follow-up and in 4.6% at the second. Electrocardiogram (ECG) results were abnormal in 2.2% of the participants at the first follow-up, with diagnoses including blocks (37.5%), bradycardia (25%), low voltage complexes (12.5%), Q waves (12.5%), and arrhythmias (12.5%). No ECG abnormalities were reported at the second follow-up visit. At the first follow-up, 4.06% of participants presented with abnormal chest X-ray findings, which were identified in the parenchymal (66.67%), pleural (26.67%), and mediastinal (6.66%) regions. At the second follow-up, 2.16% had abnormal findings, with involvement of the parenchymal (62.5%), pleural (12.5%), and mediastinal (25%) regions (Figure 2).

Figure 2.

No. of participants with electrocardiogram (ECG) and chest X-ray abnormalities (n=369).

Discussion

Our study clarifies the potential long-term symptoms experienced by patients diagnosed with COVID-19. To our knowledge, this is one of the first community-based prospective cohort studies to evaluate post-COVID-19 syndrome in India. Within our participant cohort, the prevalence of post-COVID-19 syndrome was alarmingly high, with nearly two-thirds reporting 1 or more post-COVID symptoms. This finding aligns with research by Huang et al. [12] in China in 2020, where approximately two-thirds (68%) of participants reported at least 1 post-COVID-19 symptom. In contrast, a prospective cohort study by Selvakumar et al. [13] in 2023 in Norway found that nearly half (48.5%) of participants experienced post-COVID-19 syndrome, a lower rate than our findings. This discrepancy may be attributed to differences in the age profiles of the participants, which ranged from 12 to 25 years in the Norwegian study, as well as the prevalence of the B.1.1.7 (Alpha) variant of SARS-CoV-2 in that region in 2020. In contrast, our study coincided with the predominance of the Omicron variant of SARS-CoV-2. Another investigation by Naik et al. [10] in 2021 examined the clinical features and risk factors associated with post-COVID-19 signs and symptoms in a Northern Indian population. There, only 9.9% of participants reported symptoms 12 weeks following COVID-19 infection. The difference in findings might stem from the larger sample size of the latter study and the dominance of the SARS-CoV-2 Delta variant during their research period. Additional studies conducted around the world with similar objectives have reported a higher prevalence of post-COVID-19 syndrome (Table 1) [14,15].

In the present study, 25.2% of participants were diagnosed with 1 or more comorbidities at baseline, a figure that was 26.56% at the second follow-up visit. This finding is consistent with a study by Menges et al. [16] in 2021, which found that 34% of participants reported at least 1 chronic comorbidity at baseline. Our study indicated that 12.1% of participants had hypertension and 9.7% had diabetes mellitus. By comparison, a study by Cioboata et al. [17] in 2022 reported 36% of participants as exhibiting hypertension and 14.52% as having diabetes. The discrepancy may be attributable to the Alpha strain of COVID-19, which was present during the period of the latter study. We found no statistically significant relationship between the incidence of post-COVID-19 syndrome and the presence of any comorbidity. A 2023 study by Falsetti et al. [18] analyzed 3 years of data to assess whether the burden of comorbidities correlates with COVID-19 outcomes. Their nationwide analysis suggested that the development of post-COVID-19 symptoms was associated with a higher burden of comorbidities (p<0.0001). However, differences in sample size and study period, as well as the involvement of a different COVID-19 strain, could explain the variations in these findings. In our study, 93.5% of participants had received 2 doses of a COVID-19 vaccine at the time of baseline data collection. This aligns with national data from India, which indicated a vaccination coverage of 90% in 2022–2023 [19]. We observed no significant difference in post-COVID-19 symptoms between the vaccinated and unvaccinated cohorts (Table 1).

In the present study, we found no significant differences in liver function or kidney function parameters between the groups of patients with and without post-COVID-19 syndrome. The reported values were comparable between the groups. This is consistent with the findings of Alfadda et al. [20] in 2022, who investigated clinical and biochemical parameters in individuals 6 months post-recovery from COVID-19. Furthermore, we observed a decrease in lymphocyte count from baseline to the second follow-up in our study. Gameil et al. [21] in 2021 reported similar findings when assessing long-term biochemical residue after COVID-19 recovery. Additionally, we noted a decline in monocyte counts in participants at follow-up, which aligns with the findings of Ruenjaiman et al. [22] in their study on the response of innate immune cells after recovery from SARS-CoV-2 infection. At the 3-month follow-up, 4.06% of our participants presented with abnormal chest X-ray findings. This is notably lower than the 50.4% reported by Fogante et al. [23], who observed chest X-ray abnormalities in participants at the same follow-up interval. The discrepancy between these findings may be attributed to differences in methodology; specifically, Fogante et al. [23] focused on hospitalized patients, which could account for the higher rate of abnormalities. In our cohort, only 2.2% of participants exhibited ECG changes at the first follow-up, with no ECG changes observed at the second follow-up. Ovrebotten et al. [24] conducted a study assessing changes in cardiac structure and function 3 to 12 months after hospitalization for COVID-19 and found that, regardless of the severity of the initial illness and persistent dyspnea, cardiac structure and function remained unchanged.

A major strength of our study is the confirmation that all participants tested positive for SARS-CoV-2 via RT-PCR testing, thus minimizing the potential for misclassification. The data collection form employed in our study adhered to the standard format established by the WHO and underwent rigorous pretesting. The field staff responsible for conducting the interviews were well-trained and possessed a strong understanding of COVID-19. Although the sampling technique was robust in minimizing bias, its generalizability to larger populations may be limited by the small sample size.

On that note, our study has several limitations. First, the absence of baseline clinical profiles for the participants prior to COVID-19 infection represents a major drawback. Second, since participants self-reported their symptoms experienced after COVID-19, a potential exists for recall bias. Third, we were unable to determine whether the post-COVID-19 symptoms were attributable to COVID-19 vaccination, reinfection, or post-COVID-19 syndrome. Furthermore, while it would have been possible to include a variety of factors—such as data from the acute phase—in data collection from the patients’ medical histories, we limited the scope to the after-effects of COVID-19 infection to keep the study manageable. Finally, although we presume that the Omicron variant was predominant during the study period, we lack definitive evidence to confirm this.

Conclusion

In our study, the most common post-COVID-19 symptoms were joint pain, dry cough, anxiety, and shortness of breath. The most frequently reported comorbidities were obesity, hypertension, and diabetes. The longest median duration of symptoms was observed for loss of appetite, followed by anxiety and shortness of breath. Both sex and age were significantly associated with the presence of post-COVID-19 syndrome. Participants with any comorbidity in conjunction with post-COVID-19 syndrome exhibited a significantly longer duration of forgetfulness than participants without comorbid conditions. Additionally, we noted a general trend of significant improvement in ECG and chest X-ray findings at subsequent follow-ups.

The study findings suggest that clinical symptoms persist in participants for up to 6 months, with multi-system involvement observed during the post-COVID-19 period. Consequently, this necessitates long-term, regular follow-up appointments. As the post-COVID-19 sequelae are not well-defined, it is crucial to continue researching the long-term effects of COVID-19 to better understand how to treat and prevent post-COVID-19 syndrome. In conclusion, our study supports the use of a comprehensive healthcare approach to holistic patient management.

HIGHLIGHTS

Supplementary Material

Supplementary data are available at https://doi.org/10.24171/j.phrp.2023.0251.

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