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Active or latent tuberculosis increases susceptibility to COVID-19 and disease severity

Liu, Y.; Bi, L.; Chen, Y.; Wang, Y.; Fleming, J.; Yu, Y.; Gu, Y.; Liu, C.; Fan, L.; Wang, X.; Cheng, M.

2020-03-16 infectious diseases
10.1101/2020.03.10.20033795 medRxiv
Show abstract

ImportanceRisk factors associated with COVID-19, the viral pneumonia originating in Wuhan, China, in Dec 2019, require clarification so that medical resources can be prioritized for those at highest risk of severe COVID-19 complications. Infection with M. tuberculosis (MTB), the pathogen that causes TB and latently infects [~]25% of the global population, may be a risk factor for SARS-CoV-2 infection and severe COVID-19 pneumonia. ObjectiveTo determine if latent or active TB increase susceptibility to SARS-COV-19 infection and disease severity, and lead to more rapid development of COVID-19 pneumonia. DesignAn observational case-control study of 36 confirmed COVID-19 cases from Shenyang, China, conducted in Feb 2020. Final date of follow-up: Feb 29, 2020. Cases were grouped according to COVID-19 pneumonia severity (mild/moderate, severe/critical), and MTB infection status compared. Comparisons were made with MTB infection data from another case-control study on bacterial/viral pneumonia at Shenyang Chest Hospital. SettingMulti-center study involving three primary care hospitals in Shenyang, China. Participants86 suspected COVID-19 cases from participating primary-care hospitals in Shenyang. All 36 SARS-CoV-2 +ve cases (based on RT-PCR assay) were included. Disease severity was assessed using the Diagnostic and Treatment Guidelines of the National Health Commission of China (v6). Mean age, 47 years (range: 25-79), gender ratio, 1:1. ExposuresConfirmed COVID-19 pneumonia. Interferon-gamma Release Assays (IGRA) were performed using peripheral blood to determine MTB infection. Main Outcome and MeasuresEpidemiological, demographic, clinical, radiological, and laboratory data were collected. Comparison of MTB infection status between patients with mild/moderate and severe/critical COVID-19 pneumonia. ResultsMean age of 36 COVID-19 patients: 47 (range: 25-79); M/F: 18/18; Wuhan/Hubei connection: 42%. Mild/moderate cases: 27 (75%); severe/critical: 9 (25%). MTB infection (IGRA+ve): 13 cases (36.11%), including 7 of 9 severe/critical cases. MTB infection rate: higher in COVID-19 (36.11%) than bacterial pneumonia (20%; p=0.0047) and viral pneumonia patients (16.13%; p=0.024). MTB infection more common than other co-morbidities (36.11% vs diabetes: 25%; hypertension: 22.2%; coronary heart disease: 8.33%; COPD: 5.56%). MTB co-infection linked with disease severity (severe/critical 78% vs mild/moderate cases 22%; p=0.0049), and rate of disease progression: infection to development of symptoms (MTB+SARS-CoV-2: 6.5{+/-}4.2 days vs SARS-COV-2: 8.9{+/-}5.2 days; p=0.073); from symptom development to diagnosed as severe (MTB+SARS-CoV-2: 3.4{+/-}2.0 days vs SARS-COV-2: 7.5{+/-}0.5 days; p=0.075). Conclusions and RelevanceMTB infection likely increases susceptibility to SARS-CoV-2, and increases COVID-19 severity, but this requires validation in a larger study. MTB infection status of COVID-19 patients should be checked routinely at hospital admission. Key PointsO_ST_ABSQuestionC_ST_ABSIs latent or active tuberculosis (TB) a risk factor for SARS-CoV-19 infection and progression to severe COVID-19 pneumonia? FindingsIn this observational case-control study of 36 COVID-19 cases from Shenyang, China, we found tuberculosis history (both of active TB and latent TB) to be an important risk factor for SARS-CoV-2 infection. Patients with active or latent TB were more susceptible to SARS-CoV-2, and COVID-19 symptom development and progression were more rapid and severe. MeaningTuberculosis status should be assessed carefully at patient admission and management and therapeutic strategies adjusted accordingly to prevent rapid development of severe COVID-19 complications.

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