The Effect of Tuberculosis and HIV on the Epidemiological, Clinical, Virological, and Immunological Trajectory of COVID-19: Protocol for a Prospective Case-Ascertained and Surveillance Study.

Background: The COVID-19 pandemic impacted over 620 million people, including approximately 9 million in Africa, and introduced uncertainties, especially regarding coinfection with tuberculosis (TB) or HIV. TB and HIV, both global epidemics, disproportionately affect low- and middle-income countries. Namibia and Botswana have reported high mortality rates due to TB and HIV, highlighting ongoing challenges. Objective: This paper outlines the protocol for a research study in Botswana and Namibia to address these uncertainties and enhance disease management for COVID-19, TB, and HIV, especially with coinfection. The central hypothesis is that TB or HIV coinfection increases the risk of adverse clinical, immunological, and virological COVID-19 outcomes. Methods: Core-NB is a prospective clinical cohort of patients with COVID-19 identified through facility-based surveillance. The objectives were to (1) characterize the early COVID-19 pandemic in conjunction with TB and HIV in clinical, epidemiological, virological, and immunological terms via a household transmission study; and (2) conduct targeted COVID-19 screening and testing in conjunction with TB and HIV case finding through a primary health care (PHC) facility surveillance study. For objective 1, participants were identified with reverse-transcription polymerase chain reaction (PCR) confirmation of COVID-19 at ministry of health-designated laboratories in each country. For objective 2, PHC attendees were enrolled independent of the reason for attending. Results: Index participants and consenting household contacts received home visits, including an initial enrollment visit on day 1 (the day of COVID-19 diagnosis for the index patient) and 3 follow-up visits taking place within 28 days of enrollment. Additionally, there were telephone follow-ups 3 months after enrollment. Age, sex, race, occupation, income, and educational attainment were recorded using a standardized questionnaire for all participants. Three respiratory specimens were obtained from each participant: (1) nasopharyngeal swab (SARS-CoV-2 RNA extraction and PCR); (2) sputum (GeneXpert Ultra active TB testing); and (3) extra sputum (an additional sputum sample was collected in case the GeneXpert Ultra test was positive to use for culture and drug susceptibility testing). The study was funded in October 2021, with data collection starting in June 2022 and finalized in February 2024. The household component enrolled 66 index patients with COVID-19 and 144 household contacts. In total, 1556 participants were enrolled in the PHC clinic component. The primary outcome data analyses are ongoing and expected to be published in July 2026, with secondary outcomes published in December 2026. Conclusions: This study will strengthen COVID-19, TB, and HIV diagnosis, surveillance, and control through (1) high-resolution surveillance and transmission data to establish guidelines and policies; (2) data to develop further interventions; (3) implementation of new technologies to improve care provision and boost the cooperation of stakeholders; (4) support for the development of skills and expertise in-country; and (5) contribution of evidence to build a regional network of expertise in the COVID-19, TB, and HIV coepidemics.