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. 2023 Dec 21:14:1292486.
doi: 10.3389/fimmu.2023.1292486. eCollection 2023.

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

Annabelle Cottam  1 , Ismaila L Manneh  2 , Awa Gindeh  2 , Abdou K Sillah  2 , Ousainou Cham  2 , Joseph Mendy  2 , Amadou Barry  2 , Edward G Coker  2 , Georgetta K Daffeh  2 , Simon Badjie  2 , Salieu Barry  2 , Olumuyiwa Owolabi  2 , Jill Winter  3 , Gerhard Walzl  4 , Jayne S Sutherland  2
Affiliations

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

Annabelle Cottam et al. Front Immunol. .

Abstract

Background: Tuberculosis (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).

Methods: Serum 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.

Results: Strikingly, 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).

Conclusions: Our 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.

Keywords: COVID-19; cytokines; inflammatory profiles; respiratory disease; tuberculosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
(A) Baseline serum cytokine concentrations in TB and ORD patients. Scatter plots illustrate the distribution of serum concentrations (pg/mL) of G-CSF, IL-1ra, IP-10 and PDGF-BB in the TB (n=68) and ORD (n=93) cohorts. Median concentrations are depicted as solid lines. Comparisons were performed using Mann-Whitney tests. (B) Serum cytokine concentrations in TB patients with (PCR+) and without (PCR-) concurrent COVID-19. Scatter plots illustrate the distribution of serum IL-8, IL-13, TNF-α and IP-10 concentrations (pg/mL) within PCR- (n=24; green) and PCR+ (n=5; pink) TB cohorts. Medians are represented by solid lines. Comparisons were performed using Mann-Whitney tests.
Figure 2
Figure 2
Serum cytokine concentrations in TB patients with (Sero+) and without (Sero-) prior SARS-CoV-2 infection. Scatter plots represent the distribution of serum cytokine concentrations (G-CSF, IL-1β, IL-4, IL-7, IL-8, IL-13, IP-10, TNF-α) (pg/mL) within SARS-CoV-2 Sero+ (n=39; orange) and Sero- (n=24; green) TB patient cohorts. Medians are displayed as solid lines. Comparisons were performed using Mann-Whitney tests.
Figure 3
Figure 3
Serum cytokine levels in ORD patients with (Sero+) and without (Sero-) prior SARS-CoV-2 infection. Scatter plots represent the distribution of serum cytokine concentrations (IFN-γ, IL-1β, IL-7 and TNF-α) (pg/mL) within SARS-CoV-2 Sero+ (n=60; light blue) and Sero- (n=25; dark blue) ORD patient cohorts. Medians are represented by solid lines. Comparisons were performed using Mann-Whitney tests.
Figure 4
Figure 4
Serum IL-1ra levels in TB patients with (Sero+) and without (Sero-) prior SARS-CoV-2 infection throughout TB treatment. Longitudinal scatter plots illustrate the distribution of serum IL-1ra concentration (pg/mL) within SARS-CoV-2 Sero- (n=24; green) and Sero+ (n=39; orange) TB patient cohorts. Medians are represented by lines. (** p<0.001 *** p<0.0001). A Kruskal-Wallis test was used to analyze trends in cytokine distributions, with Dunn’s multiple comparisons to test for differences between timepoints.
Figure 5
Figure 5
Serum cytokine concentrations in TB patients with (Sero+) and without (Sero-) prior SARS-CoV-2 infection throughout TB treatment. Scatter plots show the distribution of cytokine concentrations (G-CSF, IL-1β, IL-4, IL-7, IL-8, IL-13, IP-10, TNF-α and Basic FGF) (pg/mL) in SARS-CoV-2 Sero- (n=24; green) vs Sero+ (n=39; orange) TB patients at months (M) 0, 2 and 6 of TB treatment. Comparisons were performed using Mann-Whitney tests.
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References

    1. World Health Organization . Global Tuberculosis Report 2022 (2022). Available at: https://www.who.int/teams/global-tuberculosis-programme/tb-reports/globa... (Accessed May 15 2023).
    1. Cilloni L, Fu H, Vesga JF, Dowdy D, Pretorius C, Ahmedov S, et al. . The potential impact of the COVID-19 pandemic on the tuberculosis epidemic a modelling analysis. EClinicalMedicine (2020) 28:100603. doi: 10.1016/j.eclinm.2020.100603 - DOI - PMC - PubMed
    1. Sia JK, Rengarajan J. Immunology of mycobacterium tuberculosis infections. Microbiol Spectr (2019) 7:10–128. doi: 10.1128/microbiolspec.GPP3-0022-2018 - DOI - PMC - PubMed
    1. Ernst JD. The immunological life cycle of tuberculosis. Nat Rev Immunol (2012) 12:581–91. doi: 10.1038/nri3259 - DOI - PubMed
    1. Liu QY, Han F, Pan LP, Jia HY, Li Q, Zhang ZD. Inflammation responses in patients with pulmonary tuberculosis in an intensive care unit. Exp Ther Med (2018) 15:2719–26. doi: 10.3892/etm.2018.5775 - DOI - PMC - PubMed

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