How South Africa’s National Institute for Communicable Diseases Filled a Research Gap on Long COVID
South Africa’s National Institute for Communicable Diseases (NICD) conducted a large-scale research project on the long-term effects of the SARS CoV-2 infection to better characterize the risk factors and prevalence in South Africa of what has become known as post COVID-19 condition (PCC) or ‘long COVID’. The research filled a knowledge gap on the continent and for low- and middle-income countries. The study was recognized by the IANPHI General Assembly as a key public health achievement for NICD.
NICD's internationally applauded research team working on long COVID. From left to right: Tracy Arendse, Waasila Jassat, Molebogeng Moyo, Lucille Blumberg, Natalie Mayet, Caroline Vika, Tasmeeya Moola, Manana Sibanda
Photo credit: NICD
While there is a growing understanding about acute COVID-19 and the associated risk factors for severity and mortality, there is a gap in knowledge on the long-term complications of COVID-19 internationally, in low- and middle-income countries, and in African countries. According to the World Health Organization (WHO), long COVID is defined as a condition that occurs in individuals with a history of probable or confirmed SARS CoV-2 infection, usually three months from the onset of symptomatic COVID-19 that last for at least two months and cannot be explained by an alternative diagnosis. Much like the emerging symptoms of COVID-19, the common symptoms of long COVID include fatigue, shortness of breath, cognitive dysfunction, and possibly others that can have an impact on everyday functioning. Symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. During long COVID, it is possible that symptoms fluctuate or relapse over time.
To better characterize the risk factors and prevalence of long COVID in the country, South Africa’s national public health institute and member of IANPHI – the National Institute for Communicable Diseases – launched a research project in October 2020, developed as part of a multi-country study coordinated by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC), an international research initiative based in Oxford, England. It involved a collaboration between 60 countries to analyze pooled data and provide a better understanding of long COVID from a global aspect.
PCC was not yet a recognized priority for the country, as we were overwhelmed with the response to acute infections, and strengthening our laboratory testing and clinical guidelines and services was a priority. However, we had strong support and encouragement from our National Department of Health for the study.
Facing a constrained resource environment at NICD, the research team led by Dr. Waasila Jassat, was able to obtain funding from the Bill & Melinda Gates Foundation (BMGF) for the initial set-up of the study. After successfully demonstrating the importance of the study, the team obtained additional funding from BMGF to continue the follow-up study for a further year.
One of the notable successes of the project was how quickly the research team was able to secure funding, receive ethical approval, establish the partnership with ISARIC, and develop data collection tools and databases, which happened all within two months, during the initial waves of the COVID-19 pandemic. The project team consisted of only four data collectors for the first four months, before expanding to ten full time research assistants once additional funding was obtained.
Dr. Jassat and her team started data collection in January 2021. The project successfully enrolled over 2,500 participants with planned three-, six- and 12-month follow-ups. The study was expanded to include an additional cohort of participants infected during the first and fourth waves, so that the effect of different variants on long COVID could be studied. The study was also expanded to include a non-hospitalized cohort so that the research team could compare the prevalence of and risk factors for long COVID amongst hospitalized and non-hospitalized patients with SARS-CoV-2.
While starting a study during a pandemic is challenging, we benefited from the strong sense of collaboration and partnership that had developed in that time, with local and international organizations, people working with a common purpose, willing to share knowledge, ideas and resources to support each other.
The initial findings following completion of three-month assessments amongst hospitalized participants were published in the Lancet in September 2022. This national study found a high prevalence of persistent symptoms at three months after hospital discharge following SARS-CoV-2 infection in two-thirds of participants, with effects on daily living, functioning, and occupation in South Africa. These findings can inform public health measures, including identifying individuals at increased risk of developing PCC, and providing patient support and information.
Most participants in the cohort (66.7%) reported persistent symptoms three months after hospital discharge and a significant impact of PCC on their daily lives. In the Lancet, Dr. Jassat and her co-authors wrote that “the large burden of PCC symptoms identified in this study emphasized the need for a national health strategy. This should include the development of clinical guidelines and training of health-care workers for identifying, assessing, and caring for patients affected by PCC; establishment of multidisciplinary health services; and provision of information and support to people who have PCC.”
The findings of the six-month assessments have just been published on Europe PMC and published as a preprint on MedRXiv. The analysis included 3,700 hospitalized and non-hospitalized participants, infected during the periods that Beta, Delta, and Omicron BA.1 variants dominated in South Africa. The analysis revealed a prevalence of PCC among South African participants at six months of 46.7% in hospitalized participants and 18.5% in non-hospitalized participants. With over 90% of South Africans having evidence of prior SARS-CoV-2 infection as evidenced by SARS-CoV-2 sero-surveys, it is likely that many people could be affected by PCC. Encouragingly, the research showed a decreasing prevalence of persistent symptoms and impact on quality of life over time.
With the changing nature of the COVID-19 pandemic and the emergence of new viral variants in the context of greater population immunity, the study showed a difference in PCC by circulating SARS-CoV-2 variants of concern, with decreased risk of persistent symptoms at six months among participants infected during the Omicron wave compared to the Beta wave. While some studies have suggested that individuals who have received a COVID-19 vaccination have reduced risk of developing PCC or experience improvement in symptoms, in the study, participants who were vaccinated had no difference in persistent symptoms compared to those who were unvaccinated.
Other risk factors for PCC in the study included older age, female sex, non-black race, the presence of a comorbidity, greater number of acute COVID-19 symptoms, hospitalization, and COVID-19 severity.
Caring for Long COVID Patients in Low- and Middle-Income Countries
As the research team began to understand the characteristics and evolution of PCC better, the priority of low- and middle-income countries remains to ensure that they have health services to cater for people with ongoing debilitating symptoms. These findings have serious implications for resource-constrained healthcare systems that have limited post-acute care services and where physical, cognitive, and mental health disabilities often go under-recognized. LMICs also do not generally have adequate social safety nets, and the impact of chronic symptoms on the workforce and on families’ livelihoods remain a concern.
The research findings already informed public health measures to address long COVID, including identifying those who are at risk of developing long COVID, providing patient support and messaging, developing clinical pathways and guidelines for the care of these patients, and for informing other aspects of health service planning.
Findings were presented locally to government, research, and industry audiences, and on the international stage to WHO, ISARIC, the Africa Centres for Disease Control and Prevention, and the Institution of Occupational Safety and Health, the world’s chartered body for safety and health professionals. The data also contributed to the ISARIC International Cohort on long COVID, further expanding on the international understanding of long COVID and its disease process.
The study also provided scientific evidence that supported the government’s decision to include long COVID as an important area of focus of the national COVID-19 clinical working group, to update national COVID-19 clinical guidelines to include long COVID, and to implement training of healthcare workers on long COVID.
Our approach to research has always been one of producing data for action, not simply for publications in high impact journals, but to inform public awareness and government action. What we are most proud of though, is that we have from the beginning been focused on improving the lives of people living with PCC, individuals who struggle with debilitating persistent symptoms, who feel alone, and who are confronted with health services that do not recognize or attend to their concerns adequately.
In addition, the project helped raise an increased amount of awareness on long COVID and its effects. In collaboration with the NICD Communications team, the team was able to develop online resources for community members and published the testimonials of long COVID sufferers to bring an important aspect to this complex pandemic.
Dr. Waasila Jassat and her team are continuing to conduct the PCC study and will be completing the last 12-month assessment by January 2023, at which they hope to publish the one-year follow-up findings that will analyze PCC in hospitalized and non-hospitalized cohorts, infected across each wave dominated by the D614G mutation, Beta, Delta, and Omicron variants. They hope to collaborate on further publications of pooled global data with ISARIC. In doing so, they will continue to raise awareness through the media and by sharing study findings with government to strengthen our country’s response to PCC.
Ultimately the credit should go to the amazing study team who worked tirelessly to get the study up and running, because they believed so strongly in the importance of what we were doing.
Publications mentioning NICD’s long COVID research
- A Cohort Study Post COVID-19 across the Beta, Delta and Omicron waves in South Africa: 6-month follow up of hospitalised participants (MedRXiv)
- A Cohort Study Post COVID-19 across the Beta, Delta and Omicron waves in South Africa: 6-month follow up of hospitalised participants (Europe PMC)
- Post-COVID-19 condition 3 months after hospitalisation with SARS-CoV-2 in South Africa: a prospective cohort study (The Lancet)
- Long COVID in South Africa: Findings from a Longitudinal Cohort of Patients at one month after Hospitalization with SARS-CoV-2, using an ISARIC Multi-Country Protocol (NICD journal)
- Long-COVID: An evolving problem with an extensive impact (South African Medical Journal)
Press articles mentioning NICD’s long COVID research
- How will long Covid play out over the coming years? Eight experts weigh in (The Guardian)
- PCC: Post Covid-19 condition a huge burden for SA (Health E News)
NICD's patient support materials and interviews