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Role of latent tuberculosis infections in reduced COVID-19 mortality: Evidence from an instrumental variable method analysis.

ABSTRACT: Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, there has been significant interest in the potential protective effect of the Bacillus Calmette-Guerin (BCG) vaccine against COVID-19 mortality. This effect has been attributed to innate immune responses induced by BCG vaccination. However, these studies ignore an important fact: according to World Health Organization estimates, about a quarter of the world's population may have latent tuberculosis infection (LTBI), a condition in which there is no evidence of clinically active tuberculosis but persistent immune responses are stimulated by Mycobacterium tuberculosis antigens. Thus, both LTBI and BCG induce lifelong immunity and may provide immunological protection against COVID-19. In this study, the relationship between LTBI and reduced COVID-19 mortality was analyzed using the instrumental variable method. The results showed with robust statistical support that LTBI was also associated with reduced COVID-19 mortality.

SUBMITTER: Takahashi H

PROVIDER: S-EPMC7448767 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Role of latent tuberculosis infections in reduced COVID-19 mortality: Evidence from an instrumental variable method analysis.

Takahashi Harutaka H

Medical hypotheses 20200826

Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, there has been significant interest in the potential protective effect of the Bacillus Calmette-Guerin (BCG) vaccine against COVID-19 mortality. This effect has been attributed to innate immune responses induced by BCG vaccination. However, these studies ignore an important fact: according to World Health Organization estimates, about a quarter of the world's population may have latent tuberculosis infection (LTBI), a condit ...[more]

PMID: 33254521

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Project description:ImportanceChoosing between competing treatment options is difficult for patients and clinicians when results from randomized and observational studies are discordant. Observational real-world studies yield more generalizable evidence for decision making than randomized clinical trials, but unmeasured confounding, especially in time-to-event analyses, can limit validity.ObjectivesTo compare long-term survival after carotid endarterectomy (CEA) and carotid artery stenting (CAS) in real-world practice using a novel instrumental variable method designed for time-to-event outcomes, and to compare the results with traditional risk-adjustment models used in observational research for survival analyses.Design, setting, and participantsA multicenter cohort study was performed. The Vascular Quality Initiative, an observational quality improvement registry, was used to compare long-term mortality after CEA vs CAS. The study included 86 017 patients who underwent CEA (n = 73 312) or CAS (n = 12 705) between January 1, 2003, and December 31, 2016. Patients were followed up for long-term mortality assessment by linking the registry data to Medicare claims. Medicare claims data were available through September 31, 2015.ExposureProcedure type (CEA vs CAS).Main outcomes and measuresThe hazard ratios (HRs) of all-cause mortality using unadjusted, adjusted, propensity-matched, and instrumental variable methods were examined. The instrumental variable was the proportion of CEA among the total carotid procedures (endarterectomy and stenting) performed at each hospital in the 12 months before each patient's index operation and therefore varies over the study period.ResultsParticipants who underwent CEA had a mean (SD) age of 70.3 (9.4) years compared with 69.1 (10.4) years for CAS, and most were men (44 191 [60.4%] for CEA and 8117 [63.9%] for CAS). The observed 5-year mortality was 12.8% (95% CI, 12.5%-13.2%) for CEA and 17.0% (95% CI, 16.0%-18.1%) for CAS. The unadjusted HR of mortality for CEA vs CAS was 0.67 (95% CI, 0.64-0.71), and Cox-adjusted and propensity-matched HRs were similar (0.69; 95% CI, 0.65-0.74 and 0.71; 95% CI, 0.65-0.77, respectively). These findings are comparable with published observational studies of CEA vs CAS. However, the association between CEA and mortality was more modest when estimated by instrumental variable analysis (HR, 0.83; 95% CI, 0.70-0.98), a finding similar to data reported in randomized clinical trials.Conclusions and relevanceThe study found a survival advantage associated with CEA over CAS in unadjusted and Cox-adjusted analyses. However, this finding was more modest when using an instrumental variable method designed for time-to-event outcomes for risk adjustment. The instrumental variable-based results were more similar to findings from randomized clinical trials, suggesting this method may provide less biased estimates of time-dependent outcomes in observational analyses.

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Role of latent tuberculosis infections in reduced COVID-19 mortality: Evidence from an instrumental variable method analysis.

Publications

Role of latent tuberculosis infections in reduced COVID-19 mortality: Evidence from an instrumental variable method analysis.

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