Does post COVID-19 characterize new diseases and disabilities?

The clinical definition of symptom sequelae of COVID-19 changed over time. Till March 2021, ongoing symptoms for more than four weeks were classified as post-COVID-19 symptoms (PCS),¹ later, on October 2021, the WHO working group defines post-COVID-19 condition (PCC)² as the ongoing symptoms of COVID-19 or newly developed symptoms noted after twelve weeks of initial SARS-CoV-2 infection and these symptoms persist for a minimum of two months, and no other medical diagnosis can explain these symptoms. Several studies have demonstrated the prevalence of PCS as 22.4%, 51%, and 43%, in Bangladeshi,³ Asian^4, and Global⁴ populations respectively. The prevalence of PCC is still in a dilemma because none of the reported symptoms matches WHO criteria.² A meta-analysis⁴ of symptoms diagnosed PCC as symptoms persistent after 4 weeks of COVID-19, other Epidemiological studies from Bangladesh,³ India,⁵ United Kingdom,⁶ and the United States⁷ diagnosed PCC with symptoms noted after 12 weeks of COVID-19 but not persistent for a minimum of two months duration. So, there is a research gap in the epidemiology of PCC according to WHO criteria. PCC causes relapsing, remittent episodes of symptoms causing episodic disabilities,^4,6 but the interaction between disease and disability induced by PCC is still unclear.

To figure out the real scenario of PCC and to characterize the disease and episodic disabilities induced by PCC, a large-scale population-based household screening of 12,628 retrieved contacts of 12 weeks old COVID-19 cases confirmed by Real-time polymerase chain reaction test (RT-PCR) was conducted between July and December 2021 in Bangladesh. Diagnosis of PCC was performed according to WHO criteria.² The COVID-19 Yorkshire Rehabilitation Scale (C19-YRS)⁸ was used to elucidate the clinical scenario (Supplementary File 1) and the International Classification of Disease (ICD-10) was used to determine the disease induced by PCC. Additionally, to determine the spectrum of disability according to the International Classification of Functioning, Disability, and Health (ICF), 19 indicators under five ICF domains were assessed through the sub-scales of six structured and validated outcome tools (Supplementary File 2).

The study revealed higher PCS 0.19 [95% CI: 0.19–0.20] (N = 2507) compared to PCC 0.04 [95% CI: 0.041–0.048] (N = 563) in Bangladeshi people. Fifteen symptoms were found as PCS in our study, and thirteen of them were diagnosed as PCC according to WHO clinical case definition.² Major clinical symptoms associated with PCC (with ICD-10 code) was fatigue (R53. 83) .221, depression (F32.9) .218, cough (R05. 9) .219, pain (R52) .219, weakness (R53) .217, anxiety (F40) .214, insomnia (G47) .211, dyspnea (R06.0) .208, cognitive problems (R41. 84) .201, dizziness (R42) .172, PTSD (F43) .147, and palpitation (R00.2) .147. The population proportion of these PCC is supplied in Supplementary File 3. These symptoms are also evident in previous studies,3, 4, 5, 6, 7 so the ICD-10 codes of these symptoms can be sub-categorized under PCC, which has been coded as “U-09” by the WHO.⁹

In the ICF lens, functional disability was significant in breathlessness, cough, fatigue, pain, anxiety, depression, and insomnia. People with poor physical health, psychological health, and social participation in WHOQoL- Bref had breathlessness, cough, pain, anxiety, depression, and insomnia. The inter-relationship of Post-COVID-19 Condition (PCC), episodic functional disability, and quality of life is supplied in Supplementary File 4. For detailed investigation, structural equation modeling (SEM) was performed to find out the interaction among ICF domains with PCC (Fig. 1). SEM showed a significant association among the domains of the ICF model, which was not observed in earlier studies. The impairments in body structure and function directly affect the activity limitation and participation restriction for a person having PCC or long COVID. With this consequence, the significant impairments in activity limitations and participation restrictions can affect the person's personal and environmental factor domains in ICF.

Fig. 1.

Structural equation modeling (SEM) of interaction among ICF domains with Post-COVID-19 condition (PCC).

This study presented a hypothetical relationship between disease course and episodic disability in PCC. We have identified 13 diseases having ICD-10 codes which can be categorized as PCC under U-09. Though the study is not conclusive and the result might not be generalized because of low ICC values and Deff in sample size calculation, the clinical implication outweighs the limitations. Future systematic reviews or meta-analyses might consider using the cut-off duration ≥12 weeks Post-COVID and individual symptom duration ≥2 months for defining PCC or long COVID. We also highlight the need for future studies on the disease burden of PCC addressing the existing research gap¹⁰ on its episodic pattern, longitudinal disease course, and outcome of multidisciplinary rehabilitation.

Contributors

S.K.C., K.M.A.H, R.S, I.K.J.: concept, design, definition of intellectual content, analysis of data, interpretation of data, manuscript preparation, manuscript editing, manuscript review, final approval, and guarantor. S.K.C., K.M.A.H, R.S, S.A, I.K.J.: literature search, manuscript editing, manuscript review, data acquisition, data analysis, and final approval.

Data sharing statement

Relevant data is available in the paper, the additional request for data should be addressed to the corresponding author (ikjahid_mb@just.edu.bd).

Declaration of interests

None.