Molecular and cellular immune features of aged patients with severe COVID-19 pneumonia

Tartaro, Domenico Lo; Neroni, Anita; Paolini, Annamaria; Borella, Rebecca; Mattioli, Marco; Fidanza, Lucia; Quong, Andrew A.; Petes, Carlene; Awong, Génève; Douglas, Samuel; Lin, Derek; Nieto, Jordan; Gozzi, Licia; Franceschini, Erica; Busani, Stefano; Nasi, Milena; Mattioli, Anna Vittoria; Trenti, Tommaso; Meschiari, Marianna; Guaraldi, Giovanni; Girardis, Massimo; Mussini, Cristina; Gibellini, Lara; Cossarizza, Andrea; Biasi, Sara De

doi:10.1038/s42003-022-03537-z

Cited by 36 publications

(27 citation statements)

References 74 publications

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“…Despite this, it is not possible to confirm if the IL-6 was elevated due to the severity of the disease. The severe group has a higher median age ( p = 0.005), that can contribute to elavated IL-6 31 , 32 .…”

Section: Discussionmentioning

confidence: 99%

Serum biomarkers associated with SARS-CoV-2 severity

Batista

Puga

Silva

et al. 2022

Sci Rep

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Immunity with SARS-CoV-2 infection during the acute phase is not sufficiently well understood to differentiate mild from severe cases and identify prognostic markers. We evaluated the immune response profile using a total of 71 biomarkers in sera from patients with SARS-CoV-2 infection, confirmed by RT-PCR and controls. We correlated biological marker levels with negative control (C) asymptomatic (A), nonhospitalized (mild cases-M), and hospitalized (severe cases-S) groups. Among angiogenesis markers, we identified biomarkers that were more frequently elevated in severe cases when compared to the other groups (C, A, and M). Among cardiovascular diseases, there were biomarkers with differences between the groups, with D-dimer, GDF-15, and sICAM-1 higher in the S group. The levels of the biomarkers Myoglobin and P-Selectin were lower among patients in group M compared to those in groups S and A. Important differences in cytokines and chemokines according to the clinical course were identified. Severe cases presented altered levels when compared to group C. This study helps to characterize biological markers related to angiogenesis, growth factors, heart disease, and cytokine/chemokine production in individuals infected with SARS-CoV-2, offering prognostic signatures and a basis for understanding the biological factors in disease severity.

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Section: Discussionmentioning

confidence: 99%

Serum biomarkers associated with SARS-CoV-2 severity

Batista

Puga

Silva

et al. 2022

Sci Rep

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“…Compared to other respiratory viral infections, the immune response to SARS-CoV-2 is characterized by robust production of proinflammatory cytokines but diminished interferon Type I and III responses [ 7 , 8 ]. Molecular and cellular immune features of 31 patients aged > 70 years with severe COVID-19 pneumonia have suggested that inflammation, coupled with the inability to have a proper anti-viral response, could aggravate disease severity and the worst clinical outcome [ 9 ]. Comparative host transcriptome analysis across distant coronavirus genres showed 23 pathways and 21 Differentially expressed genes (DEGs) across ten immune response-associated pathways were shared by these viruses, and these DEGs could be utilized as specific targets for novel coronavirus treatments [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Longitudinal transcriptional analysis of peripheral blood leukocytes in COVID-19 convalescent donors

et al. 2022

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Background SARS-CoV2 can induce a strong host immune response. Many studies have evaluated antibody response following SARS-CoV2 infections. This study investigated the immune response and T cell receptor diversity in people who had recovered from SARS-CoV2 infection (COVID-19). Methods Using the nCounter platform, we compared transcriptomic profiles of 162 COVID-19 convalescent donors (CCD) and 40 healthy donors (HD). 69 of the 162 CCDs had two or more time points sampled. Results After eliminating the effects of demographic factors, we found extensive differential gene expression up to 241 days into the convalescent period. The differentially expressed genes were involved in several pathways, including virus-host interaction, interleukin and JAK-STAT signaling, T-cell co-stimulation, and immune exhaustion. A subset of 21 CCD samples was found to be highly “perturbed,” characterized by overexpression of PLAU, IL1B, NFKB1, PLEK, LCP2, IRF3, MTOR, IL18BP, RACK1, TGFB1, and others. In addition, one of the clusters, P1 (n = 8) CCD samples, showed enhanced TCR diversity in 7 VJ pairs (TRAV9.1_TCRVA_014.1, TRBV6.8_TCRVB_016.1, TRAV7_TCRVA_008.1, TRGV9_ENST00000444775.1, TRAV18_TCRVA_026.1, TRGV4_ENST00000390345.1, TRAV11_TCRVA_017.1). Multiplexed cytokine analysis revealed anomalies in SCF, SCGF-b, and MCP-1 expression in this subset. Conclusions Persistent alterations in inflammatory pathways and T-cell activation/exhaustion markers for months after active infection may help shed light on the pathophysiology of a prolonged post-viral syndrome observed following recovery from COVID-19 infection. Future studies may inform the ability to identify druggable targets involving these pathways to mitigate the long-term effects of COVID-19 infection. Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04360278 Registered April 24, 2020.

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“…The characterization of the immune response mounted against Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection is crucial to understanding and predicting short- and long-term protection. Both innate and adaptive immunity has been well described during severe cases as well as in recovered patients [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ] and it has been reported that an integrated response can limit COVID-19 disease severity [ 11 ]. Developing SARS-CoV-2 antigen-specific CD4+ and CD8+ T cells besides antibodies is crucial to prevent severe outcomes and protect against reinfections [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Patients Recovering from Severe COVID-19 Develop a Polyfunctional Antigen-Specific CD4+ T Cell Response

Paolini

Borella

Neroni

et al. 2022

IJMS

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Specific T cells are crucial to control SARS-CoV-2 infection, avoid reinfection and confer protection after vaccination. We have studied patients with severe or moderate COVID-19 pneumonia, compared to patients who recovered from a severe or moderate infection that had occurred about 4 months before the analyses. In all these subjects, we assessed the polyfunctionality of virus-specific CD4+ and CD8+ T cells by quantifying cytokine production after in vitro stimulation with different SARS-CoV-2 peptide pools covering different proteins (M, N and S). In particular, we quantified the percentage of CD4+ and CD8+ T cells simultaneously producing interferon-γ, tumor necrosis factor, interleukin (IL)-2, IL-17, granzyme B, and expressing CD107a. Recovered patients who experienced a severe disease display high proportions of antigen-specific CD4+ T cells producing Th1 and Th17 cytokines and are characterized by polyfunctional SARS-CoV-2-specific CD4+ T cells. A similar profile was found in patients experiencing a moderate form of COVID-19 pneumonia. No main differences in polyfunctionality were observed among the CD8+ T cell compartments, even if the proportion of responding cells was higher during the infection. The identification of those functional cell subsets that might influence protection can thus help in better understanding the complexity of immune response to SARS-CoV-2.

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Molecular and cellular immune features of aged patients with severe COVID-19 pneumonia

Cited by 36 publications

References 74 publications

Serum biomarkers associated with SARS-CoV-2 severity

Serum biomarkers associated with SARS-CoV-2 severity

Longitudinal transcriptional analysis of peripheral blood leukocytes in COVID-19 convalescent donors

Patients Recovering from Severe COVID-19 Develop a Polyfunctional Antigen-Specific CD4+ T Cell Response

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