Long COVID in India: Clinical patterns, challenges and implications for infectious diseases specialists

India’s COVID-19 burden has transitioned from acute pandemic management to long-term sequelae care. Among these, long COVID, also known as post-COVID condition or post-acute sequelae of COVID-19, has emerged as a clinically heterogeneous and operationally challenging entity. For infectious diseases specialists, long COVID raises important questions around pathophysiology, surveillance, reinfection and continuity of care in a population with high exposure density and comorbidity burden.

Case definition and diagnostic framework

Per the World Health Organization definition, long COVID is a condition characterized by persistence of symptoms beyond three months of the acute phase of COVID-19, lasting at least two months and not explained by an alternative diagnosis. (1) This definition is particularly relevant in India, where overlap with endemic infections (e.g., tuberculosis and dengue), nutritional deficiencies and chronic noncommunicable diseases complicates attribution. Importantly, long COVID may follow mild or asymptomatic infection and is not restricted to hospitalized cases. (2)

Epidemiology and relevance to India

Global estimates suggest that 10% to 30% of individuals infected with SARS-CoV-2 develop persistent symptoms. (3) Extrapolated to India’s scale of infection, this implies a substantial and ongoing clinical burden. Recurrent infections, circulation of immune-evasive variants and uneven vaccine uptake in early waves may further amplify risk. Indian cohort data remain limited, but available hospital-based studies indicate persistence of fatigue, dyspnea, weakness, myalgia, ageusia, neurocognitive symptoms and psychological morbidity after discharge from hospital. (4,5)

Clinical phenotypes

Long COVID is best understood as a syndrome with multiple overlapping phenotypes rather than a single disease entity:

Fatigue and post-exertional malaise

Debilitating fatigue and post-exertional malaise are the most frequently reported features, characterized by symptom exacerbation following physical activity. (6) This phenotype has implications for rehabilitation strategies, as indiscriminate graded exercise may exacerbate symptoms in a subset of patients.

Respiratory sequelae

Persistent dyspnea, reduced diffusion capacity and exercise intolerance may follow even moderate disease, reflecting residual parenchymal changes, microvascular injury, airway hyperreactivity or dysfunctional breathing patterns. (7)

Neurocognitive and neurological manifestations

Patients commonly report “brain fog,” memory impairment, sleep disturbance, headache, anosmia and dysautonomia-like symptoms. Neuroinflammatory mechanisms, endothelial dysfunction and autonomic imbalance have been proposed. (8)

Cardiovascular and autonomic involvement

Palpitations, orthostatic intolerance, inappropriate sinus tachycardia and chest pain are increasingly recognized, sometimes resembling postural orthostatic tachycardia syndrome.  (9)

Psychological and psychiatric sequelae

Anxiety, depression and post-traumatic stress disorder may coexist with somatic complaints, particularly after severe illness or intensive care unit admission. (10) These should be evaluated as integral components rather than secondary considerations.

Pathophysiological considerations

Multiple, potentially overlapping mechanisms have been proposed, including viral persistence or antigenic remnants, immune dysregulation, autoantibody formation, endothelial dysfunction, microthrombosis and reactivation of latent viruses. (11) For infectious diseases specialists, these hypotheses reinforce the importance of longitudinal follow-up and careful interpretation of inflammatory and immune markers, while avoiding over-investigation in clinically stable patients.

Diagnostic and management challenges in India

From a clinical standpoint, long COVID in India presents several challenges:

• Fragmented care pathways: This leads to patients cycling between specialties due to lack of coordinated oversight.
• Resource constraints: This limits access to advanced imaging, pulmonary function testing and autonomic studies.
• Overlapping endemic diseases: This necessitates vigilant exclusion of alternative diagnoses, such as TB, anemia, thyroid disorders and uncontrolled diabetes.

A pragmatic approach emphasizes structured clinical assessment, judicious investigations guided by red-flag symptoms and early referral to multidisciplinary care when available. (12)

Implications for infectious diseases specialists

ID physicians are uniquely positioned to lead long COVID care in the following ways:

• Establishing post-COVID follow-up pathways within infectious diseases or general medicine clinics
• Educating patients and colleagues that persistent symptoms do not imply ongoing infectivity but may reflect post-infectious sequelae
• Collaborating with pulmonology, cardiology, neurology, rehabilitation and mental health services
• Contributing to surveillance and research efforts to generate India-specific data on risk factors, reinfection and outcomes

Conclusion

Long COVID represents the chronic phase of the COVID-19 pandemic and is likely to remain a significant clinical entity in India. For infectious diseases specialists, it demands a shift from outbreak-oriented care to longitudinal, patient-centered management. Developing standardized follow-up protocols, integrating multidisciplinary care and generating robust Indian data will be essential to address this emerging burden effectively.

References

1. Soriano JB, Murthy S, Marshall JC, et al. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022;22(4):e102-e-107. DOI: 1016/S1473-3099(21)00703-9.
2. Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601-15. DOI: 1038/s41591-021-01283-z.
3. Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: A cohort study. Lancet. 2023;401(10393):e21-e33. DOI: 10.1016/S0140-6736(23)00810-3.
4. Tomar BS, Singh M, Nathiya D, et al. Prevalence of symptoms in patients discharged from COVID are facility of NIMS hospital: Is RT-PCR negativity truly reflecting recovery? A single-centre observational study. Int J Gen Med. 2021;14:1069-78. DOI: 10.2147/IJGM.S295499.
5. Kulkarni MV, Nayse VJ, Bansod CM. Persistent symptoms and functional health status among Covid-19 patients after discharge from a Covid hospital. J Family Med Prim Care. 2023;12(10):2496-500. DOI: 4103/jfmpc.jfmpc_663_23.
6. Twomey R, DeMars J, Franklin K, et al. Chronic fatigue and post-exertional malaise in people living with long COVID: An observational study. Phys Ther. 2022;102(4):pzac005. DOI: 10.1093/ptj/pzac005.
7. Kersten J, Wolf A, Hoyo L, et al. Symptom burden correlates to impairment of diffusion capacity and exercise intolerance in long COVID patients. Sci Rep. 2022;12:8801. DOI: 10.1038/s41598-022-12839-5.
8. Stefanou MI, Palaiodimou L, Bakola E, et al. Neurological manifestations of long-COVID syndrome: A narrative review. Ther Adv Chronic Dis. 2022;13:20406223221076890. DOI: 10.1177/20406223221076890.
9. Bisaccia G, Ricci F, Recce V, et al. Post-acute sequelae of COVID-19 and cardiovascular autonomic dysfunction: What do we know? J Cardiovasc Dev Dis. 2021;8(11):156. DOI: 10.3390/jcdd8110156.
10. Schou TM, Joca S, Wegener G, et al. Psychiatric and neuropsychiatric sequelae of COVID-19 – A systematic review. Brain Behav Immun. 2021;97:328-48. DOI: 1016/j.bbi.2021.07.018.
11. Davis HE, McCorkell L, Vogel JM, et al. Long COVID: Major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023;21(3):133-46. DOI: 10.1038/s41579-022-00846-2.
12. Kumar G, Bhalla A, Mukherjee A, et al. Post COVID sequelae among COVID-19 survivors: Insights from the Indian National Clinical Registry for COVID-19. BMJ Glob Health. 2023;8(10):e012245. DOI: 10.1136/bmjgh-2023-012245.