Long Covid: a global health issue - a prospective, cohort study set in four continents

Abstract

Introduction: A proportion of people develop Long Covid after acute COVID-19, but with most studies concentrated in high-income countries (HICs), the global burden is largely unknown. Our study aims to characterise long-term COVID-19 sequelae in populations globally and compare the prevalence of reported symptoms in HICs and low-income and middle-income countries (LMICs).

Methods: A prospective, observational study in 17 countries in Africa, Asia, Europe and South America, including adults with confirmed COVID-19 assessed at 2 to <6 and 6 to <12 months post-hospital discharge. A standardised case report form developed by International Severe Acute Respiratory and emerging Infection Consortium's Global COVID-19 Follow-up working group evaluated the frequency of fever, persistent symptoms, breathlessness (MRC dyspnoea scale), fatigue and impact on daily activities.

Results: Of 11 860 participants (median age: 52 (IQR: 41-62) years; 52.1% females), 56.5% were from HICs and 43.5% were from LMICs. The proportion identified with Long Covid was significantly higher in HICs vs LMICs at both assessment time points (69.0% vs 45.3%, p<0.001; 69.7% vs 42.4%, p<0.001). Participants in HICs were more likely to report not feeling fully recovered (54.3% vs 18.0%, p<0.001; 56.8% vs 40.1%, p<0.001), fatigue (42.9% vs 27.9%, p<0.001; 41.6% vs 27.9%, p<0.001), new/persistent fever (19.6% vs 2.1%, p<0.001; 20.3% vs 2.0%, p<0.001) and have a higher prevalence of anxiety/depression and impact on usual activities compared with participants in LMICs at 2 to <6 and 6 to <12 months post-COVID-19 hospital discharge, respectively.

Conclusion: Our data show that Long Covid affects populations globally, manifesting similar symptomatology and impact on functioning in both HIC and LMICs. The prevalence was higher in HICs versus LMICs. Although we identified a lower prevalence, the impact of Long Covid may be greater in LMICs if there is a lack of support systems available in HICs. Further research into the aetiology of Long Covid and the burden in LMICs is critical to implement effective, accessible treatment and support strategies to improve COVID-19 outcomes for all.

Keywords: COVID-19; Cohort study; Epidemiology; Global Health; Public Health.

Figure 1. Geographical distribution of participating sites. The map shows the distribution of the participating sites in Brazil, Colombia, France, The Gambia, Gibraltar, India, Israel, Italy, Norway, Malaysia, Portugal, Russian Federation, South Africa, Spain, Sudan, Ukraine, and the UK, and their country income classification. HIC, high-income country; LMIC, low-income and middle-income country.

Figure 2. Post-COVID-19 sequelae post-hospital discharge in HICs compared with LMICs. The figures present the differences in post-COVID-19 manifestations among participants in lower-to-middle-income settings (blue dots) compared with those in high-income settings (orange dots). The grey shading illustrates the level of significance, dark grey=p< 0.01, medium grey=p<0.05, white=non-significant differences. EQ5D5L, EuroQol 5-Dimension 5-level; HICs, high-income countries; LMIC, lower-income and middle-income countries.

Figure 3. Breathlessness before and after SARS-CoV-2 infection by setting. The graph shows the level of breathlessness before and after developing COVID-19 measured using the Medical Research Council (MRC) dyspnoea scale. 0=no breathlessness; 1=mild breathlessness, 2=breathlessness, 3=moderate breathlessness; 4=severe breathlessness. HIC, high-income country; LMIC, lower-income and middle-income country.

Figure 4. Risk factors for long -term COVID-19 sequelae The graphs present risk factors for experiencing Long Covid (4a), fatigue (4b) and reduced functioning and quality of life (QoL) (4c), respectively, at 2 -to- < 6 months post-COVID-19 hospital discharge. HIC: high-income country; LMIC: lower-income and middle-income country.