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1.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328786

ABSTRACT

Aging is a major risk factor for developing severe COVID-19, but few detailed data are available concerning immunological changes after infection in aged individuals. Here we describe main immune characteristics in 31 patients with severe SARS-CoV-2 infection who were >70 years old, compared to 33 subjects <60 years of age. Differences in plasma levels of 62 cytokines, landscape of peripheral blood mononuclear cells, T cell repertoire, transcriptome of central memory CD4 + T cells, specific antibodies are reported along with features of lung macrophages. Elderly subjects have higher levels of pro-inflammatory cytokines, more circulating plasmablasts, reduced plasmatic level of anti-S and anti-RBD IgG3 antibodies, lower proportions of central memory CD4 + T cells, more immature monocytes and CD56 + pro-inflammatory monocytes, lower percentages of circulating follicular helper T cells (cTfh), antigen-specific cTfh cells with a less activated transcriptomic profile, lung resident activated macrophages that promote collagen deposition and fibrosis. Our study underlines the importance of inflammation in the response to SARS-CoV-2 and suggests that inflammaging, coupled with the inability to mount a proper anti-viral response, could exacerbate disease severity and the worst clinical outcome in old patients.

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-306885

ABSTRACT

In 14 pregnant women who had asymptomatic or paucisymptomatic SARS-CoV-2 infection, we performed a detailed 38-parameter analysis of peripheral blood mononuclear cells by mass cytometry, studied the expression of T-cell master regular genes, investigated cell proliferation and cytokine production, and measured plasma levels of 62 cytokines. No patient showed lymphopenia or gross alterations of white blood cells. Unsupervised analyses revealed that most immune parameters were similar in patients and uninfected controls, apart from an increase in low density neutrophils in SARS-CoV-2 positive women. Also, patients did not show altered plasma levels of interleukin-6 or other main inflammatory molecules, but displayed significant increases of anti-inflammatory cytokines such as IL-1RA, IL-10 and IL-19, and decreased levels of IL-17, PD-L1 and D-dimer. The endogenous control of inflammation, as evidenced by plasma levels of soluble molecules, could be a strategy used during pregnancy to avoid virus-induced damages and maintain a normal immune response.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-306884

ABSTRACT

We have deeply investigated T cell compartment, plasma cytokines and cells producing cytokines in patients affected by Covid-19. At admission, patients were lymphopenic;in all of them SARS-CoV-2 was detected in a nasopharyngeal swab specimen by real-time RT-PCR, and pneumonia was subsequently confirmed by X-rays.Detailed 18-parameter flow cytometry was performed in 21 patients and 13 controls. Coupling polychromatic cytometry with unsupervised data analysis, we found that patients show an increased amount of CD4+ T lymphocytes that were activated, exhausted, stem memory or Treg. Similar results concerning activation and exhaustion were found in the CD8+ T cell compartment, within which the differences were even greater.Measuring plasma level of 31 cytokines linked to inflammation revealed that Covid-19 showed a dramatic increase of several molecules, such as TH1 and TH2 cytokines, chemokines, galectins, pro- and anti-inflammatory mediators, confirming the importance of a massive immune activation causing the cytokine storm. Then, intracellular staining detecting the simultaneous production of different cytokines after a para-physiologic stimulus given by anti-CD3/CD28 mAbs revealed not only a high capacity to produce a variety of molecules, including TNF-a, IFN-g and IL-2, but also a significant skewing of CD4+ T cells towards the TH17 phenotype.A therapeutic approach now exists based on the administration of drugs that block IL-6 pathway, and is now consistently improving the course of the disease. IL-17 is crucial in recruiting and activating neutrophils, cells that can migrate to the lung and are heavily involved in the pathogenesis of Covid-19. We show here that a significant skewing of activated T cells towards TH17 functional phenotype exists in Covid-19 patients. Thus, we suggest that blocking IL-17 pathway by already available biological drugs that are used to treat different pathologies could be a novel, additional strategy to improve the health of patients infected by SARS-CoV-2.

6.
Nat Commun ; 12(1): 4677, 2021 07 29.
Article in English | MEDLINE | ID: covidwho-1387356

ABSTRACT

SARS-CoV-2 infection can affect all human beings, including pregnant women. Thus, understanding the immunological changes induced by the virus during pregnancy is nowadays of pivotal importance. Here, using peripheral blood from 14 pregnant women with asymptomatic or mild SARS-CoV-2 infection, we investigate cell proliferation and cytokine production, measure plasma levels of 62 cytokines, and perform a 38-parameter mass cytometry analysis. Our results show an increase in low density neutrophils but no lymphopenia or gross alterations of white blood cells, which display normal levels of differentiation, activation or exhaustion markers and show well preserved functionality. Meanwhile, the plasma levels of anti-inflammatory cytokines such as interleukin (IL)-1RA, IL-10 and IL-19 are increased, those of IL-17, PD-L1 and D-dimer are decreased, but IL-6 and other inflammatory molecules remain unchanged. Our profiling of antiviral immune responses may thus help develop therapeutic strategies to avoid virus-induced damages during pregnancy.


Subject(s)
COVID-19/immunology , Cytokines/blood , Inflammation/immunology , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/immunology , Adolescent , Adult , Asymptomatic Infections , Biomarkers/blood , COVID-19/blood , COVID-19/virology , Case-Control Studies , Cross-Sectional Studies , Cytokines/immunology , Female , Humans , Inflammation/blood , Inflammation/prevention & control , Inflammation/virology , Middle Aged , Pregnancy , Pregnancy Complications, Infectious/blood , SARS-CoV-2/isolation & purification , Young Adult
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