COVID-19 risk – or also opportunity?

In 2015, the WHO set a goal to eliminate tuberculosis by 2035. Already, the milestones by 2020 – including a 35% reduction in mortality and 0% catastrophic costs for families affected by the disease – could only be half achieved by 2019, at best. With the onset of the corona pandemic, the goal has become even more distant. But the resulting new general attention to infectious diseases also holds opportunities for the fight against TB.

SARS-CoV-2 caused 170 million new cases and 3.5 million deaths worldwide in the past year and a half. In comparison, tuberculosis (TB) accounted for 10 million new cases and 1.4 million deaths in 2019. These are thus probably the two most relevant, or at least the two deadliest, infectious diseases at present, as Dr. Ralf Otto-Knapp, specialist in internal medicine, pneumology and infectiology, Medical Care Center at Helios Klinikum Emil von Behring, Berlin (D), reminded us by way of introduction. While TB mortality is concentrated in central and southern Africa, and thus in the poorer regions of the world, coronavirus also affects more resource-rich regions such as Western Europe and North America.

In contrast to coronavirus, mortality from tuberculosis is largely evenly distributed across all age groups, with a focus found at most in male patients between the ages of 15 and 34. However, in resource-poor regions, these are often the people who are responsible for providing for a family of several people.

Resources shared in pandemic times

In times of pandemic, resources in care must be shared. With the onset of the corona pandemic, this was primarily at the expense of tuberculosis care structures: on the provider side, diagnostics for SARS-CoV-2 were used, staff were withdrawn, and funding was cut. All of this made case finding for tuberculosis difficult. This was particularly evident in the high-incidence countries of India, Indonesia, the Philippines and South Africa. For patients, this resulted in more difficult visits to the doctor due to lockdowns and other restrictions, treatments should take place at home – what this means for infection control has not yet been clarified. Economic consequences should also not go unmentioned, which in turn mostly affect the poorer population.

A survey by the German Central Committee to Combat Tuberculosis (DZK) showed that about a quarter of all German health offices surveyed experienced limitations in environmental testing, in tuberculosis counseling, and also in diagnostics and care. This mainly concerns active case finding, which accounts for about 12% of TB cases in Germany. There are no data from Germany on passive case finding, but an Italian study from the National Institute for Infectious Diseases in Rome saw 43% fewer cases in the 2019 vs. 2020 comparison and, most importantly, a patient-side diagnostic delay of 75 days (2020) vs. 30 days (2019). “That’s 45 more days that others can become infected and that can also make for more severe cases, which was shown radiologically by the Timika score in this study,” Dr. Otto-Knapp said.

Overall, case numbers in Germany were already down in 2019, and a further decline is expected in 2020. The reasons given by the Robert Koch Institute for this include lower (labor) migration from high-prevalence countries, but also underdiagnosis and underreporting.

Age at COVID-19 more significant than TB disease

Regarding COVID-19 mortality in TB patients, there are mainly studies from high prevalence countries, the largest data collection to date is from South Africa with over 15,000 patients in the public health system. There, a hazard ratio (aHR, 95% CI 1.81-4.04) of 2.7 was seen for mortality during TB disease and 1.51 (95% CI 1.18-1.93) after disease. The Philippines showed a similar picture (HR 2.17 during TB disease). “Of course, these are both health care systems that are difficult to compare with conditions in Central Europe,” the expert noted.

There is little data from low-incidence countries to date. A Global Tuberculosis Network (GTN) analysis showed in 26 centers-mainly in low-incidence countries (including Belgium, France, Russia, Spain, Switzerland, Italy)-that mortality was nevertheless significantly higher than average at 10.6%, but the cohort was relatively small (n=69) and heterogeneous. The authors discuss mainly age as a relevant risk factor, which appeared more significant than tuberculosis per se in this study [1].

The prospect of more solid data in the near future is especially promising with regard to the Indian subcontinent, as this is where more than a quarter of all tuberculosis cases occur annually and India is also considered a COVID-19 hotspot. “There is certainly a large number of co-infected patients to be expected here.”

Vaccinate TB patients against COVID-19?

What might be the reasons behind the presumed more severe COVID-19 courses in tuberculosis patients? Immunological causes are discussed: a common dysregulation in the immune response, especially in the polyfunctional profiles of CD4 cells. This could create a dual risk in co-infections, which provides for a worse COVID-19 course and results in TB progression.

There are no study data yet on TB and COVID-19 vaccination. An expert panel has published the following recommendations on the DZK website:

• Contraindications to vaccination are not known.
• However, if you have acute symptoms or side effects from TB therapy, you should consider postponing the vaccination date.
• There is currently no prioritization for TB patients, so the individual decision is left to the treating physicians to decide whether to prioritize their TB patients.

Another question that is currently the subject of intense debate in the international literature is whether tuberculosis vaccination (BCG) can help against severe courses of coronavirus infection. Epidemiological and retrospective studies suggest efficacy in this regard, especially since heterologous protective effects against other viral and, in some cases, bacterial infections are known. However, the efficacy of BCG vaccination against coronavirus is by no means proven, Dr. Otto-Knapp clarified. On the contra side, he added, there are already plenty of well-performing COVID-19 vaccines and many more in development, while BCG vaccine is in short supply worldwide and further shortages could contribute to infant mortality.

Dr. Otto-Knapp therefore emphasized in summary that it is imperative that priorities for TB worldwide be raised again. “The resources that have gone into fighting the coronavirus pandemic were certainly necessary, but now we need to see that no major damage is done by other diseases.” And even though the care of TB patients is more difficult internationally at the moment, the opportunities presented by the coronavirus pandemic should definitely be seized: International research structures have emerged that can also be used for TB research, there is increased political attention to infectious diseases, and there is increased attention in the general population to infection control, such as wearing masks and coughing hygiene. He also said there are definitely synergies in diagnostics and care that should be exploited.

Take-Home Messages

• The coronavirus pandemic ensures delayed diagnosis and thus further spread and advanced disease of TB that is more difficult to treat.
• Increased risk for COVID-19 mortality is hypothesized for TB disease, and possibly for progression of latent TB infection. However, the data base for this assumption is relatively weak and mainly from high-prevalence countries.
• In the case of sequelae due to TB, the risk due to the sequelae must be considered.
• Important: the consistent continuation of TB therapy at all levels of care.

Source: Presentation “COVID-19 and Tuberculosis – Risks and Opportunities” at the session “Tuberculosis and Other Mycobacteria – New Recommendations and Developments”. 61st Congress of the German Society for Pneumology and Respiratory Medicine e.V., 4.6.2021.

Congress: DGP 2021 digital

Literature:

1. Motta I, et al: Tuberculosis, COVID-19 and migrants: preliminary analysis of deaths occurring in 69 patients from two cohorts. Pulmonology 2020; 26 (4): 233-240; doi: 10.1016/j.pulmoe.2020.05.002.

InFo PNEUMOLOGY & ALLERGOLOGY 2021; 3(3): 24-25 (published 9/16-21, ahead of print).