The aim of this Series paper is to review the interactions between COVID-19 and tuberculosis, including the population-level impact of COVID-19 on tuberculosis outcomes, the clinical presentation and diagnosis of tuberculosis–COVID-19 co-infection, the patient-level impact of COVID-19 on the management and prognosis of tuberculosis, and interventional strategies that could be used to mitigate the devastating effects of COVID-19 on the global burden of tuberculosis, including lessons learned from responses to the COVID-19 pandemic. We emphasise the ways in which tuberculosis care and management have been neglected compared with COVID-19, and how low SARS-CoV-2 vaccine coverage in tuberculosis-endemic countries, despite the high rates of infection and emergence of new variants, will continue to fuel the global tuberculosis pandemic. Priorities for the rapid restoration of tuberculosis care and prevention—and progress towards End TB Strategy targets—in the era of COVID-19 are presented
Few comprehensive studies document the prevalence of tuberculosis in patients with COVID-19. Tuberculosis prevalence (past, current, or past and current) is estimated to vary by between about 2% and 8% in hospitalised COVID-19 cohorts from tuberculosis-endemic countries; for example, an analysis of surveillance data from South Africa found that among 3217 individuals hospitalised with COVID-19, 5·5% had current tuberculosis and 4·0% had previous tuberculosis (data from the South African NICD). In a population Cohort study of about 3·5 million patients from the Western Cape province of South Africa (22 308 of whom were diagnosed with COVID-19), about 10% of those with COVID-19 had a diagnosis of previous tuberculosis or current active tuberculosis, with about 2% having concurrent active tuberculosis and COVID-19 in an inpatient setting.In another study of 219 265 individuals who were hospitalised with COVID-19, 5·0% of those aged 20–39 years had concurrent active tuberculosis although this is probably an underestimate given the scarcity of comprehensive testing for tuberculosis and because of other reasons, such as lack of clinical suspicion. In a limited (minimally invasive tissue sampling) post-mortem biopsy study undertaken in Johannesburg, South Africa (n=150), microbiologically proven tuberculosis was detected in 3% of COVID-19-positive biopsies and 13% of COVID-19-negative biopsies.For comparative purposes, the prevalence of tuberculosis in the same general population, including those with subclinical or undiagnosed tuberculosis in the community, is about 0·5–1%
Lessons learned from COVID-19
The COVID-19 pandemic has taught the world that epidemics can only be controlled by several interventions, some personal (eg, masking and vaccinations) and others societal (eg, social protection and lockdowns). The Swiss cheese respiratory pandemic defence model created by Mackay outlines the multiple layers of these personal and shared responsibilities that are needed to prevent the spread of SARS-CoV-2. The model has several layers of Swiss cheese to illustrate the fact that a single layer of protection will not be enough to stop COVID-19. Because of the holes in each slice, the coronavirus will always get through; therefore, multiple layers of protection are needed to halt the pandemic. We need a similar, comprehensive approach for tuberculosis, captured in the tuberculosis Swiss cheese model, with three broad levels: societal, personal, and person-centric health-care systems interventions. By addressing the multiple layers, including improving the glacial pace of tuberculosis research, correcting suboptimal and deficient research funding, and treating tuberculosis as the global emergency that it is, we could end tuberculosis
COVID-19 has set tuberculosis control efforts back by about a decade. This setback will probably translate into long-term increases in tuberculosis-related deaths and structural lung disease. With low rates of SARS-CoV-2 vaccination in tuberculosis-endemic countries and the emergence of new variants, this trend is likely to continue. New strategies involving triage tools and innovative active case-finding interventions require urgent implementation to reverse these alarming trends. We have provided several examples of the successful use of such interventions in different parts of the world. A more cohesive global approach is now urgently required.
Active tuberculosis and COVID-19 screening should be combined in tuberculosis-endemic settings. False-negative results might occur with both tuberculosis and COVID-19 testing, and better diagnostics, independent of samples obtained from the respiratory tract, are needed for both diseases. The inability to distinguish between acute tuberculosis disease and COVID-19 has implications for strategies of IPC in tuberculosis-endemic settings, including the provision of N95 (or equivalent) respirators to HCWs. Individuals with active tuberculosis and COVID-19 should be monitored more closely with a lower threshold for referral and intervention.
The vicious cycle of poverty and death is exacerbated by the twin epidemics of tuberculosis and COVID-19 (with HIV making up a triad of infectious disease epidemics in some settings, and a non-communicable disease epidemic expanding in tandem).In some settings, disruption of HIV diagnosis and treatment programmes might fuel the tuberculosis pandemic. It is therefore crucial to support and revitalise both tuberculosis and HIV programmes. That airborne and aerosol-based spread is the dominant form of SARS-CoV-2 and M tuberculosis transmission has important implications for interrupting the spread of both diseases and for protecting HCWs. COVID-19 will exacerbate the situation in endemic settings, in which there is already an appreciable burden of pulmonary disability and lung damage caused by tuberculosis. Addressing the mortality and morbidity associated with tuberculosis and COVID-19 will require global unity, political will—addressing global inequalities and power monopolies—improved funding for vaccine development, and enhanced support for preventive and interventional strategies for both diseases.
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