Characterization of the immune impairment of patients with tuberculosis and COVID-19 coinfection

Fard, Saeid Najafi; Aiello, Alessandra; Navarra, Assunta; Cuzzi, Gilda; Vanini, Valentina; Migliori, Giovanni Battista; Gualano, Gina; Cerva, Carlotta; Grifoni, Alba; Sette, Alessandro; Vaia, Francesco; Palmieri, Fabrizio; Goletti, Delia

doi:10.1016/j.ijid.2023.03.021

Cited by 19 publications

(20 citation statements)

References 28 publications

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“…These results support a previous finding that COVID-co-infected patients had reduced Mtb -specific T-cells, as IL-13, TNF-α and IP-10 are produced by Th1/Th2 cells in TB ( 19 , 25 ). Consistently, a recent study found lower Th1- and Th2-associated cytokines, including IP-10, in co-infected patients compared to TB-only patients ( 26 ); however, a concomitant rise in innate inflammation was reported, which we did not see. Differences in baseline inflammation and pathogen genetics may explain this discrepancy, as their participants were mostly from a non-endemic setting.…”

Section: Discussionsupporting

confidence: 89%

The impact of prior SARS-CoV-2 infection on host inflammatory cytokine profiles in patients with TB or other respiratory diseases

Cottam,

Manneh,

Gindeh

et al. 2023

Front. Immunol.

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BackgroundTuberculosis (TB) and COVID-19 are the two leading causes of infectious disease mortality worldwide, and their overlap is likely frequent and inevitable. Previous research has shown increased mortality in TB/COVID-coinfected individuals, and emerging evidence suggests that COVID-19 may increase susceptibility to TB. However, the immunological mechanisms underlying these interactions remain unclear. In this study, we aimed to elucidate the impact of prior or concurrent COVID-19 infection on immune profiles of TB patients and those with other respiratory diseases (ORD).MethodsSerum and nasopharyngeal samples were collected from 161 Gambian adolescents and adults with either TB or an ORD. Concurrent COVID-19 infection was determined by PCR, while prior COVID-19 was defined by antibody seropositivity. Multiplex cytokine immunoassays were used to quantify 27 cytokines and chemokines in patient serum samples at baseline, and throughout treatment in TB patients.ResultsStrikingly, TB and ORD patients with prior COVID-19 infection were found to have significantly reduced expression of several cytokines, including IL-1β, TNF-α and IL-7, compared to those without (p<0.035). Moreover, at month-six of anti-TB treatment, seropositive patients had lower serum Basic FGF (p=0.0115), IL-1β (p=0.0326) and IL-8 (p=0.0021) than seronegative. TB patients with acute COVID-19 coinfection had lower levels of IL-8, IL-13, TNF-α and IP-10 than TB-only patients, though these trends did not reach significance (p>0.035).ConclusionsOur findings demonstrate that COVID-19 infection alters the subsequent response to TB and ORDs, potentially contributing to pathogenesis. Further work is necessary to determine whether COVID-19 infection accelerates TB disease progression, though our results experimentally support this hypothesis.

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Section: Discussionsupporting

confidence: 89%

The impact of prior SARS-CoV-2 infection on host inflammatory cytokine profiles in patients with TB or other respiratory diseases

Cottam,

Manneh,

Gindeh

et al. 2023

Front. Immunol.

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“…A study by Najafi-Fard et al. ( 49 ) looked at 119 study participants and compared the plasma immune profile of the 14 TB/COVID-19 co-infected cohort, to the COVID-19 only patients, TB only patients, or 20 healthy controls using a 27-plex multiplex assay. They found that levels of circulating TNF had the strongest association with TB/COVID-19 co-infection compared with COVID-19.…”

Section: Resultsmentioning

confidence: 99%

Immune interaction between SARS-CoV-2 and Mycobacterium tuberculosis

Booysen,

Wilkinson,

Sheerin

et al. 2023

Front. Immunol.

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SARS-CoV-2 and Mycobacterium tuberculosis (Mtb) are major infectious causes of death, with meta-analyses and population-based studies finding increased mortality in co-infected patients simultaneously diagnosed with COVID-19 and tuberculosis (TB). There is a need to understand the immune interaction between SARS-CoV-2 and Mtb which impacts poor outcomes for those co-infected. We performed a PubMed and preprint search using keywords [SARS-CoV-2] AND [tuberculosis] AND [Immune response], including publications after January 2020, excluding reviews or opinions. Abstracts were evaluated by authors for inclusion of data specifically investigating the innate and/or acquired immune responses to SARS-CoV-2 and Mtb in humans and animal models, immunopathological responses in co-infection and both trials and investigations of potential protection against SARS-CoV-2 by Bacille Calmette Guérin (BCG). Of the 248 articles identified, 39 were included. Incidence of co-infection is discussed, considering in areas with a high burden of TB, where reported co-infection is likely underestimated. We evaluated evidence of the clinical association between COVID-19 and TB, discuss differences and similarities in immune responses in humans and in murine studies, and the implications of co-infection. SARS-CoV-2 and Mtb have both been shown to modulate immune responses, particularly of monocytes, macrophages, neutrophils, and T cells. Co-infection may result in impaired immunity to SARS-CoV-2, with an exacerbated inflammatory response, while T cell responses to Mtb may be modulated by SARS-CoV-2. Furthermore, there has been no proven potential COVID-19 clinical benefit of BCG despite numerous large-scale clinical trials.

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“…Conversely, most patients who died were in the group in which the COVID-19 diagnosis was before/during TB treatment, underscoring that concomitant TB and COVID-19 is associated with greater severity and worse outcomes and faster median time to death ( figure 2 ). We have already shown that TB and COVID-19 co-infection may be associated with more severe clinical conditions than either disease alone [ 9 , 10 , 12 ] and with a T-cell impairment to in vitro response to severe acute respiratory syndrome coronavirus 2 [ 17 , 18 ]. B oulle et al .…”

Section: Discussionmentioning

confidence: 99%

Long-term outcomes of the global tuberculosis and COVID-19 co-infection cohort

Casco,

Jorge,

Palmero

et al. 2023

Eur Respir J

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BackgroundLongitudinal cohort data of patients with tuberculosis (TB) and COVID-19 are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19.MethodsWe collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk regression models, and the log rank test was used to compare survival and mortality attributed to TB, COVID-19 or both.ResultsOverall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19versusthose dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (Hazard Ratio-HR 1.05, 95% confidence interval-CI 1.03–1.07), HIV infection (HR 2.29, CI 1.02–5.16), and invasive ventilation (HR 4.28, CI 2.34–7.83). For COVID-19 mortality the adjusted risks were: higher age (HR 1.03, CI 1.02–1.04), male sex (HR 2.21, CI 1.24–3.91), oxygen requirement (HR 7.93, CI 3.44–18.26), and invasive ventilation (HR 2.19, CI1.36–3.53).ConclusionsIn our global cohort, death was the outcome in more than 10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes.

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Characterization of the immune impairment of patients with tuberculosis and COVID-19 coinfection

Cited by 19 publications

References 28 publications

The impact of prior SARS-CoV-2 infection on host inflammatory cytokine profiles in patients with TB or other respiratory diseases

The impact of prior SARS-CoV-2 infection on host inflammatory cytokine profiles in patients with TB or other respiratory diseases

Immune interaction between SARS-CoV-2 and Mycobacterium tuberculosis

Long-term outcomes of the global tuberculosis and COVID-19 co-infection cohort

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