Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 20
Filter
1.
Front Mol Biosci ; 9: 839809, 2022.
Article in English | MEDLINE | ID: covidwho-1817986

ABSTRACT

1H NMR spectra of sera have been used to define the changes induced by vaccination with Pfizer-BioNTech vaccine (2 shots, 21 days apart) in 10 COVID-19-recovered subjects and 10 COVID-19-naïve subjects at different time points, starting from before vaccination, then weekly until 7 days after second injection, and finally 1 month after the second dose. The data show that vaccination does not induce any significant variation in the metabolome, whereas it causes changes at the level of lipoproteins. The effects are different in the COVID-19-recovered subjects with respect to the naïve subjects, suggesting that a previous infection reduces the vaccine modulation of the lipoproteome composition.

2.
J Clin Invest ; 131(12)2021 06 15.
Article in English | MEDLINE | ID: covidwho-1731387

ABSTRACT

The characterization of the adaptive immune response to COVID-19 vaccination in individuals who recovered from SARS-CoV-2 infection may define current and future clinical practice. To determine the effect of the 2-dose BNT162b2 mRNA COVID-19 vaccination schedule in individuals who recovered from COVID-19 (COVID-19-recovered subjects) compared with naive subjects, we evaluated SARS-CoV-2 Spike-specific T and B cell responses, as well as specific IgA, IgG, IgM, and neutralizing antibodies titers in 22 individuals who received the BNT162b2 mRNA COVID-19 vaccine, 11 of whom had a previous history of SARS-CoV-2 infection. Evaluations were performed before vaccination and then weekly until 7 days after second injection. Data obtained clearly showed that one vaccine dose is sufficient to increase both cellular and humoral immune response in COVID-19-recovered subjects without any additional improvement after the second dose. On the contrary, the second dose proved mandatory in naive subjects to further enhance the immune response. These findings were further confirmed at the serological level in a larger cohort of naive (n = 68) and COVID-19-recovered (n = 29) subjects, tested up to 50 days after vaccination. These results question whether a second vaccine injection in COVID-19-recovered subjects is required, and indicate that millions of vaccine doses may be redirected to naive individuals, thus shortening the time to reach herd immunity.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunity, Humoral/drug effects , Immunologic Memory/drug effects , SARS-CoV-2 , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Female , Humans , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/metabolism
3.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327684

ABSTRACT

Background: Waning immunity and the surge of SARS-CoV-2 variants are responsible for breakthrough infections, i.e. infections in fully vaccinated individuals. Although the majority of vaccinated infected subjects reports mild or no symptoms, some others require hospitalization. The clinical and immunological features of vaccinated hospitalized COVID-19 patients are currently unknown. Methods: 29 unvaccinated and 36 vaccinated hospitalized COVID-19 patients were prospectively enrolled and clinical and laboratory data. Immunophenotyping of leukocytes subsets, T and B cell SARS-CoV-2 specific responses were evaluated via flow cytometry. Anti-IFN-α autoantibodies were measured via ELISA. Results: Despite vaccinated patients were older and with more comorbidities, unvaccinated subjects showed higher levels of pro-inflammatory markers, more severe disease and increased mortality rate. Accordingly, they presented significant alterations in the circulating leukocyte composition, typical of severe COVID-19. Vaccinated patients displayed higher levels of anti-Spike IgGs and Spike-specific B cells. Of all participants, survivors showed higher levels of anti-Spike IgGs and S-specific CD4+ T cells than non-survivors. At hospital admission, 6 out of 65 patients (9.2%) displayed high serum concentrations of autoantibodies targeting IFN-α. Remarkably, 3 were unvaccinated and eventually died, while the other 3 were vaccinated and survived. Conclusion: Despite more severe pre-existing clinical conditions, vaccinated patients have good outcome. A rapid activation of anti-SARS-CoV-2-specific immunity is fundamental for the resolution of the infection. Therefore, prior immunization through vaccination provides a significant contribute to prevention of disease worsening and can even overcome the presence of high-risk factors (i.e. older age, comorbidities, anti-IFN-α autoantibodies positivity).

4.
J Clin Invest ; 132(6)2022 03 15.
Article in English | MEDLINE | ID: covidwho-1685792

ABSTRACT

BACKGROUNDImmunization against SARS-CoV-2, the causative agent of COVID-19, occurs via natural infection or vaccination. However, it is currently unknown how long infection- or vaccination-induced immunological memory will last.METHODSWe performed a longitudinal evaluation of immunological memory to SARS-CoV-2 up to 1 year after infection and following mRNA vaccination in naive individuals and individuals recovered from COVID-19 infection.RESULTSWe found that memory cells are still detectable 8 months after vaccination, while antibody levels decline significantly, especially in naive individuals. We also found that a booster injection is efficacious in reactivating immunological memory to spike protein in naive individuals, whereas it was ineffective in previously SARS-CoV-2-infected individuals. Finally, we observed a similar kinetics of decay of humoral and cellular immunity to SARS-CoV-2 up to 1 year following natural infection in a cohort of unvaccinated individuals.CONCLUSIONShort-term persistence of humoral immunity, together with the reduced neutralization capacity versus the currently prevailing SARS-CoV-2 variants, may account for reinfections and breakthrough infections. Long-lived memory B and CD4+ T cells may protect from severe disease development. In naive individuals, a booster dose restored optimal anti-spike immunity, whereas the needs for vaccinated individuals who have recovered from COVID-19 have yet to be defined.FUNDINGThis study was supported by funds to the Department of Experimental and Clinical Medicine, University of Florence (Project Excellence Departments 2018-2022), the University of Florence (project RICTD2122), the Italian Ministry of Health (COVID-2020-12371849), and the region of Tuscany (TagSARS CoV 2).


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , CD4-Positive T-Lymphocytes , COVID-19/prevention & control , Humans , Immunity, Humoral , Spike Glycoprotein, Coronavirus , Vaccination
5.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1678999

ABSTRACT

Although accumulating data have investigated the effect of SARS-CoV-2 mutations on antibody neutralizing activity, less is known about T cell immunity. In this work, we found that the ancestral (Wuhan strain) Spike protein can efficaciously reactivate CD4+ T cell memory in subjects with previous Alpha variant infection. This finding has practical implications, as in many countries only one vaccine dose is currently administered to individuals with previous COVID-19, independently of which SARS-CoV-2 variant was responsible of the infection. We also found that only a minority of Spike-specific CD4+ T cells targets regions mutated in Alpha, Beta and Delta variants, both after natural infection and vaccination. Finally, we found that the vast majority of Spike-specific CD4+ T cell memory response induced by natural infection or mRNA vaccination is conserved also against Omicron variant. This is of importance, as this newly emerged strain is responsible for a sudden rise in COVID-19 cases worldwide due to its increased transmissibility and ability to evade antibody neutralization. Collectively, these observations suggest that most of the memory CD4+ T cell response is conserved against SARS-CoV-2 variants of concern, providing an efficacious line of defense that can protect from the development of severe forms of COVID-19.

6.
Eur J Immunol ; 52(2): 352-355, 2022 02.
Article in English | MEDLINE | ID: covidwho-1530141

ABSTRACT

A late presenter AIDS patient with severe T cell depletion presented non-severe COVID-19 symptoms, with prolonged viral shedding. Our case report supports the hypothesis that an effective T cell response may be dispensable for the control of COVID-19 progression to severe forms, while it may be necessary for SARS-CoV-2 clearance.


Subject(s)
Acquired Immunodeficiency Syndrome/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Acquired Immunodeficiency Syndrome/blood , Adult , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , COVID-19/blood , Female , Humans , SARS-CoV-2/metabolism
7.
Semin Immunol ; 55: 101508, 2021 06.
Article in English | MEDLINE | ID: covidwho-1482974

ABSTRACT

One and half year following the occurrence of COVID-19 pandemic, significant efforts from laboratories all over the world generated a huge amount of data describing the prototypical features of immunity in the course of SARS-CoV-2 infection. In this Review, we rationalize and organize the main observations, trying to define a "core" signature of immunity in COVID-19. We identified six hallmarks describing the main alterations occurring in the early infection phase and in the course of the disease, which predispose to severe illness. The six hallmarks are dysregulated type I IFN activity, hyperinflammation, lymphopenia, lymphocyte impairment, dysregulated myeloid response, and heterogeneous adaptive immunity to SARS-CoV-2. Dysregulation and exhaustion came out as the trait d'union, connecting abnormalities affecting both innate and adaptive immunity, humoral and cellular responses.


Subject(s)
COVID-19 , Adaptive Immunity , Humans , Pandemics , SARS-CoV-2
8.
Journal of Clinical Investigation ; 131(12):1-7, 2021.
Article in English | ProQuest Central | ID: covidwho-1334628

ABSTRACT

The characterization of the adaptive immune response to COVID-19 vaccination in individuals who recovered from SARS-CoV-2 infection may define current and future clinical practice. To determine the effect of the 2-dose BNT162b2 mRNA COVID-19 vaccination schedule in individuals who recovered from COVID-19 (COVID-19-recovered subjects) compared with naive subjects, we evaluated SARS-CoV-2 Spike-specific T and B cell responses, as well as specific IgA, IgG, IgM, and neutralizing antibodies titers in 22 individuals who received the BNT162b2 mRNA COVID-19 vaccine, 11 of whom had a previous history of SARS-CoV-2 infection. Evaluations were performed before vaccination and then weekly until 7 days after second injection. Data obtained clearly showed that one vaccine dose is sufficient to increase both cellular and humoral immune response in COVID-19-recovered subjects without any additional improvement after the second dose. On the contrary, the second dose proved mandatory in naive subjects to further enhance the immune response. These findings were further confirmed at the serological level in a larger cohort of naive (n = 68) and COVID-19-recovered (n = 29) subjects, tested up to 50 days after vaccination. These results question whether a second vaccine injection in COVID-19-recovered subjects is required, and indicate that millions of vaccine doses may be redirected to naive individuals, thus shortening the time to reach herd immunity.

11.
Clin Transl Immunology ; 10(5): e1281, 2021.
Article in English | MEDLINE | ID: covidwho-1222609

ABSTRACT

OBJECTIVE: Although the adaptive immune response to SARS-CoV-2 has been characterised in the acute and early convalescent phase of the disease, few studies explore whether natural infection elicits long-lasting immunological memory in recovered individuals. In this work, we aimed to assess the maintenance of immunological memory to SARS-CoV-2. METHODS: We evaluated the long-term virus-specific cellular and humoral immune response in the members of an Italian Serie A football team, who experienced a cluster of COVID-19 in March 2020, which was strictly evaluated in the following months. RESULTS: Our results highlight a heterogeneous magnitude of immunological memory at 5 months after infection. Indeed, 20% of the subjects displayed a weak cellular and humoral memory to SARS-CoV-2, suggesting that they may be at higher risk of reinfection. In addition, a history of symptomatic COVID-19 was associated with higher levels of SARS-CoV-2-reactive CD4+ T cells and specific antibody levels than in asymptomatic individuals. CONCLUSION: Collectively, these data demonstrate that immunity to SARS-CoV-2 is maintained five months postinfection even if the magnitude of response is heterogeneous among individuals. This finding suggests that some COVID-19-recovered subjects may benefit from vaccination.

12.
PLoS Pathog ; 17(2): e1009243, 2021 02.
Article in English | MEDLINE | ID: covidwho-1058312

ABSTRACT

The current pandemic emergence of novel coronavirus disease (COVID-19) poses a relevant threat to global health. SARS-CoV-2 infection is characterized by a wide range of clinical manifestations, ranging from absence of symptoms to severe forms that need intensive care treatment. Here, plasma-EDTA samples of 30 patients compared with age- and sex-matched controls were analyzed via untargeted nuclear magnetic resonance (NMR)-based metabolomics and lipidomics. With the same approach, the effect of tocilizumab administration was evaluated in a subset of patients. Despite the heterogeneity of the clinical symptoms, COVID-19 patients are characterized by common plasma metabolomic and lipidomic signatures (91.7% and 87.5% accuracy, respectively, when compared to controls). Tocilizumab treatment resulted in at least partial reversion of the metabolic alterations due to SARS-CoV-2 infection. In conclusion, NMR-based metabolomic and lipidomic profiling provides novel insights into the pathophysiological mechanism of human response to SARS-CoV-2 infection and to monitor treatment outcomes.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19/drug therapy , Lipidomics , Lipids/blood , SARS-CoV-2/metabolism , COVID-19/blood , COVID-19/epidemiology , Female , Humans , Male , Nuclear Magnetic Resonance, Biomolecular
13.
Mucosal Immunol ; 14(2): 305-316, 2021 03.
Article in English | MEDLINE | ID: covidwho-947522

ABSTRACT

The novel coronavirus SARS-CoV-2 enters into the human body mainly through the ACE2 + TMPRSS2+ nasal epithelial cells. The initial host response to this pathogen occurs in a peculiar immune microenvironment that, starting from the Nasopharynx-Associated Lymphoid Tissue (NALT) system, is the product of a long evolutionary process that is aimed to first recognize exogenous airborne agents. In the present work, we want to critically review the latest molecular and cellular findings on the mucosal response to SARS-CoV-2 in the nasal cavity and in NALT, and to analyze its impact in the subsequent course of COVID-19. Finally, we want to explore the possibility that the regulation of the systemic inflammatory network against the virus can be modulated starting from the initial phases of the nasal and nasopharyngeal response and this may have several clinical and epidemiological implications starting from a mucosal vaccine development.


Subject(s)
COVID-19/immunology , Nasopharynx/virology , SARS-CoV-2/physiology , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/pathology , COVID-19/transmission , COVID-19 Vaccines/immunology , Humans , Immune Evasion , Lymphoid Tissue/immunology , Nasopharynx/immunology , Serine Endopeptidases/metabolism , Virus Internalization
14.
Immunol Lett ; 228: 122-128, 2020 12.
Article in English | MEDLINE | ID: covidwho-909223

ABSTRACT

As of October 2020 management of Coronavirus disease 2019 (COVID-19) is based on supportive care and off-label or compassionate-use therapies. On March 2020 tocilizumab - an anti-IL-6 receptor monoclonal antibody - was suggested as immunomodulatory treatment in severe COVID-19 because hyperinflammatory syndrome occurs in many patients similarly to the cytokine release syndrome that develops after CAR-T cell therapy. In our retrospective observational study, 20 severe COVID-19 patients requiring intensive care were treated with tocilizumab in addition to standard-of-care therapy (SOC) and compared with 13 COVID-19 patients receiving only SOC. Clinical respiratory status, inflammatory markers and vascular radiologic score improved after one week from tocilizumab administration. On the contrary, these parameters were stable or worsened in patients receiving only SOC. Despite major study limitations, improvement of alveolar-arterial oxygen gradient as well as vascular radiologic score after one week may account for improved pulmonary vascular perfusion and could explain the more rapid recovery of COVID-19 patients receiving tocilizumab compared to controls.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Respiration/drug effects , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/pathology , Combined Modality Therapy , Critical Care , Female , Humans , Male , Middle Aged , Receptors, Interleukin-6/antagonists & inhibitors , Retrospective Studies , SARS-CoV-2 , Time Factors , Treatment Outcome
15.
Eur J Immunol ; 50(12): 2013-2024, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-880266

ABSTRACT

The characterization of cell-mediated and humoral adaptive immune responses to SARS-CoV-2 is fundamental to understand COVID-19 progression and the development of immunological memory to the virus. In this study, we detected T-cells reactive to SARS-CoV-2 proteins M, S, and N, as well as serum virus-specific IgM, IgA, IgG, in nearly all SARS-CoV-2 infected individuals, but not in healthy donors. Virus-reactive T cells exhibited signs of in vivo activation, as suggested by the surface expression of immune-checkpoint molecules PD1 and TIGIT. Of note, we detected antigen-specific adaptive immune response both in asymptomatic and symptomatic SARS-CoV-2 infected subjects. More importantly, symptomatic patients displayed a significantly higher magnitude of both cell-mediated and humoral adaptive immune response to the virus, as compared to asymptomatic individuals. These findings suggest that an uncontrolled adaptive immune response contribute to the development of the life-threatening inflammatory phase of the disease. Finally, this study might open the way to develop effective vaccination strategies.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Carrier State/immunology , Immunity, Humoral , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Adult , Carrier State/virology , Female , Humans , Programmed Cell Death 1 Receptor/immunology , Receptors, Immunologic/immunology , Viral Proteins/immunology
17.
Immunology ; 161(4): 345-353, 2020 12.
Article in English | MEDLINE | ID: covidwho-738708

ABSTRACT

SARS-CoV-2 is responsible for a new infectious disease (COVID-19) in which individuals can either remain asymptomatic or progress from mild to severe clinical conditions including acute respiratory distress syndrome and multiple organ failure. The immune mechanisms that potentially orchestrate the pathology in SARS-CoV-2 infection are complex and only partially understood. There is still paucity of data on the features of myeloid cells involved in this viral infection. For this reason, we investigated the different activation status profiles and the subset distribution of myeloid cells and their correlation with disease progression in 40 COVID-19 patients at different stages of disease. COVID-19 patients showed a decrease in the absolute number of plasmacytoid and myeloid dendritic cells, different subset distribution of monocytes and different activation patterns of both monocytes and neutrophils, coupled to a significant reduction of HLA-DR monocyte levels. We found that some of these alterations are typical of all COVID-19 patients, while some others vary at different stages of the disease and correlate with biochemical parameters of inflammation. Collectively, these data suggest that not only the lymphoid, but also the myeloid compartment, is severely affected by SARS-CoV-2 infection.


Subject(s)
COVID-19/immunology , Dendritic Cells/immunology , Myeloid Cells/immunology , Adult , Aged , COVID-19/pathology , Dendritic Cells/pathology , Female , Flow Cytometry , Humans , Intensive Care Units , Male , Myeloid Cells/pathology
18.
Leukemia ; 35(4): 1121-1133, 2021 04.
Article in English | MEDLINE | ID: covidwho-725732

ABSTRACT

Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus high-flow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.


Subject(s)
COVID-19/drug therapy , COVID-19/virology , Compassionate Use Trials , Janus Kinase 1/antagonists & inhibitors , Janus Kinase 2/antagonists & inhibitors , Janus Kinase Inhibitors/therapeutic use , SARS-CoV-2/drug effects , Aged , Aged, 80 and over , Biomarkers , COVID-19/diagnosis , COVID-19/metabolism , Combined Modality Therapy , Comorbidity , Female , Humans , Janus Kinase Inhibitors/pharmacology , Male , Middle Aged , Nitriles , Prospective Studies , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Pyrimidines , Severity of Illness Index , Treatment Outcome , Viral Load
19.
J Allergy Clin Immunol Pract ; 8(8): 2575-2581.e2, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-611996

ABSTRACT

BACKGROUND: The early identification of patients at risk of clinical deterioration is of interest considering the timeline of COVID-19 after the onset of symptoms. OBJECTIVE: The aim of our study was to evaluate the usefulness of testing serum IL-6 and other serological and clinical biomarkers, to predict a short-term negative clinical course of patients with noncritical COVID-19. METHODS: A total of 208 patients with noncritical COVID-19 pneumonia at admission were consecutively enrolled. Clinical and laboratory findings obtained on admission were analyzed by using survival analysis and stepwise logistic regression for variable selection. Three-day worsening as outcome in a logistic model to generate a prognostic score was used. RESULTS: Clinical worsening occurred in 63 patients (16 = died; 39 = transferred to intensive care unit; 8 worsening of respiratory failure). Forty-five of them worsened within 3 days after admission. The risk of clinical worsening was progressively enhanced along with increasing quartiles of IL-6 levels. Multivariate analysis showed that IL-6 (P = .005), C-reactive protein (CRP) (P = .003), and SaO2/FiO2 (P = .014) were the best predictors for clinical deterioration in the first 3 days after admission. The combined score yielded an area under the curve = 0.88 (95% confidence interval: 0.83-0.93). A nomogram predicting the probability of 3-day worsening was generated. The score also showed good performance for 7-day and 14- or 21-day worsening and in predicting death occurring during all the follow-up. CONCLUSIONS: Combining IL-6, CRP, and SaO2/FiO2 in a score may help clinicians to identify on admission those patients with COVID-19 who are at high risk for a further 3-day clinical deterioration.


Subject(s)
Clinical Deterioration , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Interleukin-6/blood , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Adult , Aged , Aged, 80 and over , Betacoronavirus , Biomarkers , C-Reactive Protein/analysis , COVID-19 , Comorbidity , Coronavirus Infections/blood , Coronavirus Infections/mortality , Female , Humans , Kaplan-Meier Estimate , Length of Stay , Male , Middle Aged , Oxygen/blood , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/mortality , ROC Curve , Retrospective Studies , SARS-CoV-2 , Time Factors , Young Adult
20.
J Clin Invest ; 130(9): 4694-4703, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-401302

ABSTRACT

BACKGROUNDCoronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral immune response is crucial to achieve pathogen clearance; however, in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options.METHODSWe performed a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes.RESULTSPatients with COVID-19 showed decreased numbers of circulating T, B, and NK cells and exhibited a skewing of CD8+ T cells toward a terminally differentiated/senescent phenotype. In agreement, CD4+ T and CD8+ T, but also NK cells, displayed reduced antiviral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in patients with COVID-19, particularly in those who required intensive care. The latter group of patients also showed increased serum IL-6 levels that inversely correlated to the frequency of granzyme A-expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells.CONCLUSIONThe association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms.FUNDINGThis study was supported by funds from the Department of Experimental and Clinical Medicine of University of Florence (the ex-60% fund and the "Excellence Departments 2018-2022 Project") derived from Ministero dell'Istruzione, dell'Università e della Ricerca (Italy).


Subject(s)
Betacoronavirus , Coronavirus Infections/immunology , Cytotoxicity, Immunologic , Interleukin-6/immunology , Pneumonia, Viral/immunology , Adult , Aged , Aged, 80 and over , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/epidemiology , Critical Care , Cytokines/blood , Cytokines/immunology , Female , Granzymes/blood , Granzymes/immunology , Humans , Interleukin-6/blood , Killer Cells, Natural/immunology , Male , Middle Aged , Models, Immunological , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/epidemiology , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL