RESUMO
BACKGROUND: Tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are the top two killers of infectious disease. We aimed to determine the association of TB coinfection with the inhospital mortality of COVID-19 patients in Indonesia as a TB-endemic country. METHODS: We conducted a retrospective cohort study in a tertiary lung hospital in Indonesia. All TB-coinfected COVID-19 patients who were hospitalized between January 2020 and December 2021 were included in the study. COVID-19 patients without TB were randomly selected for the control group. Clinical characteristics and laboratory results were assessed. Survival analysis was performed to determine the estimated death rate and median survival time (MST). Multivariate Cox regression analysis was conducted to define the association of TB coinfection with the in-hospital mortality of COVID-19. RESULTS: We included 86 (8.3%) TB coinfections among 1034 confirmed COVID-19 patients. TB coinfection patients had younger age, malnutrition, and different symptoms compared to the COVID-19 group. TB-coinfected patients had a lower estimated death rate than the COVID-19 group (6.5 vs. 18.8 per 1000 population). MST in the COVID-19 group was 38 (interquartile range 16-47) days, whereas the same observation time failed to determine the MST in the TB coinfection group. TB coinfection had a crude hazard ratio of mortality 0.37 (95% confidence interval [CI] 0.15-0.94, P = 0. 004). The final model analysis including age, sex, and lymphocyte as confounding factors resulted in an adjusted HR of mortality 0.31 (95% CI 0.1-0.9). CONCLUSION: This study showed TB coinfection was negatively associated with the in-hospital mortality of COVID-19.
Assuntos
COVID-19 , Coinfecção , Mortalidade Hospitalar , Centros de Atenção Terciária , Humanos , COVID-19/mortalidade , COVID-19/complicações , Indonésia/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Coinfecção/mortalidade , Coinfecção/microbiologia , Coinfecção/epidemiologia , Estudos Retrospectivos , Centros de Atenção Terciária/estatística & dados numéricos , Adulto , Idoso , SARS-CoV-2 , Tuberculose/mortalidade , Tuberculose/complicações , Tuberculose/epidemiologiaRESUMO
The current Mycobacterium bovis BCG vaccine provides inconsistent protection against pulmonary infection with Mycobacterium tuberculosis. Immunity induced by subcutaneous immunization with BCG wanes and does not promote early recruitment of T cell to the lungs after M. tuberculosis infection. Delivery of Tuberculosis (TB) vaccines to the lungs may increase and prolong immunity at the primary site of M. tuberculosis infection. Pulmonary immunization with recombinant influenza A viruses (rIAVs) expressing an immune-dominant M. tuberculosis CD4+ T cell epitope (PR8-p25 and X31-p25) stimulates protective immunity against lung TB infection. Here, we investigated the potential use of rIAVs to improve the efficacy of BCG using simultaneous immunization (SIM) and prime-boost strategies. SIM with parenteral BCG and intranasal PR8-p25 resulted in equivalent protection to BCG alone against early, acute and chronic M. tuberculosis infection. Boosting BCG with rIAVs increased the frequency of IFN-γ-secreting specific T cells (p<0.001) and polyfunctional CD4+ T cells (p<0.05) in the lungs compared to the BCG alone, however, this did not result in a significant increase in protection against M. tuberculosis compared to BCG alone. Therefore, sequential pulmonary immunization with these rIAVs after BCG increased M. tuberculosis-specific memory T cell responses in the lung, but not protection against M. tuberculosis infection.
Assuntos
Vacina BCG/imunologia , Vírus da Influenza A/imunologia , Mycobacterium tuberculosis/imunologia , Linfócitos T/imunologia , Tuberculose Pulmonar/prevenção & controle , Animais , Epitopos , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Feminino , Imunização Secundária , Imunogenicidade da Vacina , Pulmão/imunologia , Células T de Memória/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Tuberculose Pulmonar/imunologia , Vacinas Sintéticas/imunologiaRESUMO
The lung is the primary site of infection with the major human pathogen, Mycobacterium tuberculosis. Effective vaccines against M. tuberculosis must stimulate memory T cells to provide early protection in the lung. Recently, tissue-resident memory T cells (TRM) were found to be phenotypically and transcriptional distinct from circulating memory T cells. Here, we identified M. tuberculosis-specific CD4+ T cells induced by recombinant influenza A viruses (rIAV) vaccines expressing M. tuberculosis peptides that persisted in the lung parenchyma with the phenotypic and transcriptional characteristics of TRMs. To determine if these rIAV-induced CD4+ TRM were protective independent of circulating memory T cells, mice previously immunized with the rIAV vaccine were treated with the sphingosine-1-phosphate receptor modulator, FTY720, prior to and during the first 17 days of M. tuberculosis challenge. This markedly reduced circulating T cells, but had no effect on the frequency of M. tuberculosis-specific CD4+ TRMs in the lung parenchyma or their cytokine response to infection. Importantly, mice immunized with the rIAV vaccine were protected against M. tuberculosis infection even when circulating T cells were profoundly depleted by the treatment. Therefore, pulmonary immunization with the rIAV vaccine stimulates lung-resident CD4+ memory T cells that are associated with early protection against tuberculosis infection.