Long COVID in low-income and middle-income countries: the hidden public health crisis.

The COVID-19 pandemic exposed crucial fault lines in society both within and between different societies. Over the past 3 years, inequity has been highlighted in several areas including research capacity, surveillance, and availability of COVID-19 therapeutics and vaccines. These disparities are particularly pronounced when comparing high-income countries (HICs) and low-income and middle-income countries (LMICs). Wide disparities also exist between countries with respect to research and coordinated national responses towards the long-term effects of COVID-19, often referred to as long COVID or post-COVID-19 condition. Post-COVID-19 condition is defined by WHO as a complex, multi-system condition with symptoms persisting in individuals at least 3 months after the resolution of the acute SARS-CoV-2 infection, when no alternative diagnosis can be provided.1Soriano JB Murthy S Marshall JC Relan P Diaz JV A clinical case definition of post-COVID-19 condition by a Delphi consensus.Lancet Infect Dis. 2022; 22: e102-e107Summary Full Text Full Text PDF PubMed Scopus (554) Google Scholar Although the prevalence of long COVID is unknown, studies have suggested that between 10% and 45% of those infected experience long COVID, indicating that at least 65 million people suffer from symptoms that impair their functional and cognitive capacity.2Davis HE McCorkell L Vogel JM Topol EJ Long COVID: major findings, mechanisms and recommendations.Nat Rev Microbiol. 2023; 21: 133-146Crossref PubMed Scopus (329) Google Scholar, 3O'Mahoney LL Routen A Gillies C et al.The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: a systematic review and meta-analysis.EClinicalMedicine. 2022; 55101762PubMed Google Scholar However, there is a paucity of studies examining patient cohorts from LMICs.4Michelen M Manoharan L Elkheir N et al.Characterising long COVID: a living systematic review.BMJ Glob Health. 2021; 6e005427Crossref PubMed Scopus (328) Google Scholar Understanding the burden of long COVID in LMICs will help policy makers establish adequate access to services to ensure patients regain an improved quality of life. Few studies have characterised the long COVID burden in LMICs; however, the International Severe Acute Respiratory and Emerging Infection Consortium characterisation protocol is one of the exceptions. Of the 14 112 enrolled patients who recovered from acute COVID-19 from 20 countries on four continents, 5565 (39·4%) patients were enrolled in nine LMICs.5Sigfrid L Cevik M Jesudason E et al.What is the recovery rate and risk of long-term consequences following a diagnosis of COVID-19? A harmonised, global longitudinal observational study protocol.BMJ Open. 2021; 11e043887Crossref PubMed Scopus (30) Google Scholar Findings from this study have not yet been published. A South African longitudinal cohort study reported that 39% of 3700 participants had persistent symptoms at 6 months after COVID-19 infection.6Jassat W Mudara C Vika C et al.A cohort study of post-COVID-19 condition across the Beta, Delta, and Omicron waves in South Africa: 6-month follow-up of hospitalized and nonhospitalized participants.Int J Infect Dis. 2023; 128: 102-111Summary Full Text Full Text PDF PubMed Scopus (8) Google Scholar Incomplete characterisation of COVID-19 within LMICs might hide a high burden of long COVID, yet largely unquantified. Many LMICs might not have sufficient research or surveillance infrastructure to accurately report the magnitude and effect of the problem. Conducting long COVID research in LMICs is challenging due to inadequate referral systems and the restricted capacity for patient recall and follow-up. Furthermore, the detection of acute COVID-19 might be underestimated in LMICs, particularly in most African nations due to insufficient testing and under-reporting for SARS-CoV-2.7Bradshaw D Dorrington R Moultrie T Groenewald P Moultrie H Underestimated COVID-19 mortality in WHO African region.Lancet Glob Health. 2022; 10e1559Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar LMICs might not have adequate capacity for multidisciplinary rehabilitation services to treat people with long COVID, which requires a comprehensive range of inpatient and outpatient services and complex continuing care, which is restricted by the shortage and urban distribution of rehabilitation professionals.8Sivan M Rayner C Delaney B Fresh evidence of the scale and scope of long covid.BMJ. 2021; 373: n853Crossref PubMed Scopus (35) Google Scholar In HICs, many patients experience barriers to navigating the health-care system to receive adequate care for long COVID despite primary care services being equipped to manage most people with long COVID and the existence, in some countries such as the UK, of specialist long COVID clinics supported by community-based interdisciplinary services to manage more complex patients.9Greenhalgh T Sivan M Delaney B Evans R Milne R Long COVID-an update for primary care.BMJ. 2022; 378e072117Google Scholar People with long COVID in LMICs currently receive fragmented care if any care at all, due to constrained health systems, under-resourced primary care services, and many competing priorities due to the considerable burdens of non-communicable and chronic infectious diseases. Chronic disability resulting from long COVID could place an additional burden on these already overstretched health-care resources, exacerbating health inequalities and adversely affecting economies. Furthermore, even within countries, the most deprived individuals who have higher rates of comorbidities, restricted access to health care, and difficulties in returning to full-time work, are most likely to experience the most severe effects of long COVID.10de Leeuw E Yashadhana A Hitch D Long COVID: sustained and multiplied disadvantage.Med J Aust. 2022; 216: 222-224Crossref PubMed Scopus (6) Google Scholar LMICs also have lower coverage of adequate social protection measures, such as social support grants or social relief of distress grants, to mitigate the ongoing negative effects of the pandemic. There is currently no widely agreed-upon treatment for long COVID in clinical practice. Studies have pointed to potential biological pathways that could be targeted with repurposed medicines and novel therapeutics to address specific symptoms or long COVID phenotypes. A scoping review in 2022 revealed that of 59 registered trials on long COVID therapeutics, only 15 enrolled patients from LMICs,11Ceban F Leber A Jawad MY et al.Registered clinical trials investigating treatment of long COVID: a scoping review and recommendations for research.Infect Dis. 2022; 54: 467-477Crossref PubMed Scopus (26) Google Scholar limiting the ability to explore the effectiveness and generalisability of potential therapeutics in a wide range of settings and different populations. These countries do not have access to novel COVID-19 therapeutics12Usher AD The global COVID-19 treatment divide.Lancet. 2022; 399: 779-782Summary Full Text Full Text PDF PubMed Scopus (19) Google Scholar and will also face challenges in accessing candidate long COVID treatments. With out-of-pocket health expenditure between 30 and 40% in LMICs,13WHOGlobal spending on health: a world in transition.https://apps.who.int/iris/bitstream/handle/10665/330357/WHO-HIS-HGF-HF-WorkingPaper-19.4-eng.pdf?ua=1Date: 2019Date accessed: May 16, 2023Google Scholar even if novel therapies are available and accessible, they might not be affordable. Despite some data showing that COVID-19 vaccination reduces the risk of reporting long COVID symptoms,14Byambasuren O Stehlik P Clark J Alcorn K Glasziou P Effect of covid-19 vaccination on long covid: systematic review.BMJ Med. 2023; 2e000385Crossref PubMed Google Scholar inequity in access to vaccines and lower vaccination coverage in LMICs15United Nations Development ProgrammeGlobal dashboard for vaccine equity.https://data.undp.org/vaccine-equity/Date: 2023Date accessed: June 8, 2023Google Scholar reduces the potential for protection against developing long COVID in these settings. As the world shifts its focus from addressing the immediate pandemic crisis and large-scale COVID-19 vaccine distribution towards strengthening preparedness for future threats, it is crucial that we utilise this opportunity to better understand the long-term implications of multi-system viral infections. The long-term burden of disease from what we initially thought was an acute viral illness was not fully anticipated and planned for. There is a need to facilitate additional research from LMICs to understand and define the characteristics of long COVID in this context. Extending the follow-up periods of COVID-19 patients for up to 2 to 3 years will provide better insight into the effect of COVID-19 on wellbeing, mental health, and activities of daily living and employment. Moreover, it is essential that pandemic preparedness efforts concentrate on enhancing research capacity and establishing robust surveillance systems across numerous LMICs that can document the full spectrum of pandemic disease burdens. Support is necessary for LMICs to set up multidisciplinary rehabilitation services. These services should at the least be established in major centres. These centres are crucial for identifying optimal care pathways and provision of well structured and personalised programmes of rehabilitation to address the care needs of people with long COVID. It is imperative that new therapeutics proven to be effective in preventing and treating long COVID be made readily available at affordable costs in LMICs. Furthermore, research on the underlying mechanisms of long COVID and therapeutics should include participants from LMICs. In addition, long COVID care programmes should incorporate patient perspectives and understand their lived experiences, leveraging innovative methods for disseminating information and supporting patients and communities, empowering, and actively involving them in their care. It is crucial for professional societies and government agencies in LMICs to develop evidenced-based clinical practice guidelines and implement workforce training programmes for clinicians, especially in primary care settings where long COVID is often misdiagnosed. By recognising patients presenting with long COVID more effectively, more comprehensive support can be provided. This support should encompass physical, cognitive, social, and occupational aspects to fully aid in the patient's recovery. As we learn from the COVID-19 pandemic and better prepare for emerging threats, it is crucial to further investigate post-infection syndromes. These investigations will contribute to future pandemic preparedness and ensure that LMICs are not once again marginalised in these efforts. CC reports grants from US Centers for Disease Control and Prevention, Sanofi Pasteur, Wellcome Trust, Bill and Melinda Gates Foundation, and PATH outside of the submitted work. LFR reports grants and personal fees from Merck and Pfizer and personal fees from GSK outside of the submitted work. DM is principal investigator of the StopCOVID observational cohort study and co-leads the Post COVID-Core Outcome Set project. JC reports grants from Wellcome Trust, Philippine Council for Health Research and Development, Pfizer, and Zuellig Pharma outside of the submitted work. WJ, FB, MH, ME, CAA-M, and BC declare no competing interests.