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1.
Front Immunol ; 13: 846753, 2022.
Article in English | MEDLINE | ID: covidwho-1809398

ABSTRACT

Objective: To assess the kinetics of the humoral and cell-mediated responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in rheumatoid arthritis (RA) patients treated with different immunosuppressive therapies. Methods: Following vaccine completed schedule, health care workers (HCWs, n = 49) and RA patients (n = 35) were enrolled at 5 weeks (T1) and 6 months (T6) after the first dose of BNT162b2-mRNA vaccination. Serological response was assessed by quantifying anti-receptor-binding domain (RBD)-specific immunoglobulin G (IgG) and SARS-CoV-2 neutralizing antibodies, while cell-mediated response was assessed by a whole-blood test quantifying the interferon (IFN)-γ response to spike peptides. B-cell phenotype and IFN-γ-specific T-cell responses were evaluated by flow cytometry. Results: After 6 months, anti-RBD antibodies were still detectable in 91.4% of RA patients, although we observed a significant reduction of the titer in patients under Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4)-Ig [median: 16.4 binding antibody units (BAU)/ml, interquartile range (IQR): 11.3-44.3, p < 0.0001] or tumor necrosis factor (TNF)-α inhibitors (median: 26.5 BAU/ml, IQR: 14.9-108.8, p = 0.0034) compared to controls (median: 152.7 BAU/ml, IQR: 89.3-260.3). All peripheral memory B-cell (MBC) subpopulations, in particular, the switched IgG+ MBCs (CD19+CD27+IgD-IgM-IgG+), were significantly reduced in RA subjects under CTLA-4-Ig compared to those in HCWs (p = 0.0012). In RA patients, a significantly reduced anti-RBD IgG titer was observed at T6 vs. T1, mainly in those treated with CTLA-4-Ig (p = 0.002), interleukin (IL)-6 inhibitors (p = 0.015), and disease-modifying antirheumatic drugs (DMARDs) ± corticosteroids (CCSs) (p = 0.015). In contrast, a weak nonsignificant reduction of the T-cell response was reported at T6 vs. T1. T-cell response was found in 65.7% of the RA patients at T6, with lower significant magnitude in patients under CTLA-4-Ig compared to HCWs (p < 0.0001). The SARS-CoV-2 IFN-γ-S-specific T-cell response was mainly detected in the CD4+ T-cell compartment. Conclusions: In this study, in RA patients after 6 months from COVID-19 vaccination, we show the kinetics, waning, and impairment of the humoral and, to a less extent, of the T-cell response. Similarly, a reduction of the specific response was also observed in the controls. Therefore, based on these results, a booster dose of the vaccine is crucial to increase the specific immune response regardless of the immunosuppressive therapy.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , COVID-19 , Abatacept , Antibodies, Viral , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunity , Immunoglobulin G , Kinetics , RNA, Messenger , SARS-CoV-2 , T-Lymphocytes , Vaccination
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-317957

ABSTRACT

In January 2020, the novel Coronavirus Disease-2019 (COVID-19) epidemic spread to Italy. The ensuing high rates of patients with pulmonary disease due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections, overwhelmed the Italian health services. Management of inpatients was based on World Health Organization (WHO) and other public health bodies’ and specialist societies’ clinical, diagnostic and therapeutic protocols developed with very low-quality evidence base at that time. Over time, management guidelines and protocols were progressively modified and adapted based on the evolving first hand clinical management experience, and the evidence, which has slowly accumulated from clinical large cohort studies and clinical trials. As of August 9th, 2020, there have been 250.103 confirmed COVID-19 cases (with 35.203 deaths) reported from Italy. We present chronological evolution of the clinical and scientific evidence-based management guidelines to date, and their influence on the health care workers management of patients with COVID-19 disease.Funding Statement: This research was supported by funds to National Institute for Infectious Diseases ‘Lazzaro Spallanzani’ IRCCS from Line one-Ricerca Corrente ‘Infezioni Emergenti e Riemergenti’ and by Progetto COVID 2020 12371675 both funded by Italian Ministry of Health and from European Commission – Horizon 2020 (EXSCALATE4CoV).Sir Zumla and Prof Ippolito are co-PIs of the Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET – https://www.pandora-id.net/) funded by the European and Developing Countries Clinical Trials Partnership. Sir Zumla is in receipt of a National Institutes of Health Research senior investigator award.Declaration of Interests: EN received grants from Gilead science for educational purpose. Al other authors have no conflicts of interest to declareEthics Approval Statement: The authors stated that Ethical approval was not required.

4.
Int J Infect Dis ; 113 Suppl 1: S82-S87, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1575296

ABSTRACT

OBJECTIVES: The interaction of COVID-19 and tuberculosis (TB) are still poor characterized. Here we evaluated the immune response specific for Micobacterium tuberculosis (Mtb) and SARS-CoV-2 using a whole-blood-based assay-platform in COVID-19 patients either with TB or latent TB infection (LTBI). METHODS: We evaluated IFN-γ level in plasma from whole-blood stimulated with Mtb antigens in the Quantiferon-Plus format or with peptides derived from SARS-CoV-2 spike protein, Wuhan-Hu-1 isolate (CD4-S). RESULTS: We consecutively enrolled 63 COVID-19, 10 TB-COVID-19 and 11 LTBI-COVID-19 patients. IFN-γ response to Mtb-antigens was significantly associated to TB status and therefore it was higher in TB-COVID-19 and LTBI-COVID-19 patients compared to COVID-19 patients (p ≤ 0.0007). Positive responses against CD4-S were found in 35/63 COVID-19 patients, 7/11 LTBI-COVID-19 and only 2/10 TB-COVID-19 patients. Interestingly, the responders in the TB-COVID-19 group were less compared to COVID-19 and LTBI-COVID-19 groups (p = 0.037 and 0.044, respectively). Moreover, TB-COVID-19 patients showed the lowest quantitative IFN-γ response to CD4-S compared to COVID-19-patients (p = 0.0336) and LTBI-COVID-19 patients (p = 0.0178). CONCLUSIONS: Our data demonstrate that COVID-19 patients either TB or LTBI have a low ability to build an immune response to SARS-CoV-2 while retaining the ability to respond to Mtb-specific antigens.


Subject(s)
COVID-19 , Coinfection , Tuberculosis , Antigens, Bacterial/immunology , Antigens, Viral/immunology , COVID-19/immunology , Humans , Interferon-gamma/immunology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Tuberculosis/immunology
5.
Front Immunol ; 12: 740249, 2021.
Article in English | MEDLINE | ID: covidwho-1448730

ABSTRACT

Objective: To assess in rheumatoid arthritis (RA) patients, treated with different immunosuppressive therapies, the induction of SARS-CoV-2-specific immune response after vaccination in terms of anti-region-binding-domain (RBD)-antibody- and T-cell-specific responses against spike, and the vaccine safety in terms of clinical impact on disease activity. Methods: Health care workers (HCWs) and RA patients, having completed the BNT162b2-mRNA vaccination in the last 2 weeks, were enrolled. Serological response was evaluated by quantifying anti-RBD antibodies, while the cell-mediated response was evaluated by a whole-blood test quantifying the interferon (IFN)-γ-response to spike peptides. FACS analysis was performed to identify the cells responding to spike stimulation. RA disease activity was evaluated by clinical examination through the DAS28crp, and local and/or systemic clinical adverse events were registered. In RA patients, the ongoing therapeutic regimen was modified during the vaccination period according to the American College of Rheumatology indications. Results: We prospectively enrolled 167 HCWs and 35 RA patients. Anti-RBD-antibodies were detected in almost all patients (34/35, 97%), although the titer was significantly reduced in patients under CTLA-4-inhibitors (median: 465 BAU/mL, IQR: 103-1189, p<0.001) or IL-6-inhibitors (median: 492 BAU/mL, IQR: 161-1007, p<0.001) compared to HCWs (median: 2351 BAU/mL, IQR: 1389-3748). T-cell-specific response scored positive in most of RA patients [24/35, (69%)] with significantly lower IFN-γ levels in patients under biological therapy such as IL-6-inhibitors (median: 33.2 pg/mL, IQR: 6.1-73.9, p<0.001), CTLA-4-inhibitors (median: 10.9 pg/mL, IQR: 3.7-36.7, p<0.001), and TNF-α-inhibitors (median: 89.6 pg/mL, IQR: 17.8-224, p=0.002) compared to HCWs (median: 343 pg/mL, IQR: 188-756). A significant correlation between the anti-RBD-antibody titer and spike-IFN-γ-specific T-cell response was found in RA patients (rho=0.432, p=0.009). IFN-γ T-cell response was mediated by CD4+ and CD8+ T cells. Finally, no significant increase in disease activity was found in RA patients following vaccination. Conclusion: This study showed for the first time that antibody-specific and whole-blood spike-specific T-cell responses induced by the COVID-19 mRNA-vaccine were present in the majority of RA patients, who underwent a strategy of temporary suspension of immunosuppressive treatment during vaccine administration. However, the magnitude of specific responses was dependent on the immunosuppressive therapy administered. In RA patients, BNT162b2 vaccine was safe and disease activity remained stable.


Subject(s)
Antibodies, Viral/immunology , Arthritis, Rheumatoid/therapy , COVID-19 Vaccines/immunology , Immunotherapy/adverse effects , T-Lymphocytes/immunology , Aged , Arthritis, Rheumatoid/immunology , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/immunology , COVID-19/prevention & control , Female , Humans , Interferon-gamma/immunology , Lymphocyte Count , Male , Middle Aged , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/cytology , Vaccines, Synthetic/immunology
6.
Int J Infect Dis ; 107: 247-250, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1300800

ABSTRACT

Prolonged B-cell depletion due to anti-CD20 monoclonal antibody (mAbs) therapy impairs the adaptive immune response, causing severe manifestations during COronaVIrus Disease-2019 (COVID-19). The cases of two patients under anti-CD20 therapy who experienced prolonged and severe COVID-19 successfully treated with mAbs against Severe Acute Respiratory Syndrome-CoV-2 spike proteins are reported.


Subject(s)
Antibodies, Monoclonal/therapeutic use , B-Lymphocytes/immunology , COVID-19/complications , Lymphocyte Depletion/adverse effects , SARS-CoV-2 , Antigens, CD20/immunology , COVID-19/drug therapy , Female , Humans , Male , Middle Aged , Severity of Illness Index
9.
Euro Surveill ; 25(30)2020 07.
Article in English | MEDLINE | ID: covidwho-690936

ABSTRACT

We report a case of Legionella pneumonia in a dishwasher of a restaurant in Rome, Italy, just after the end of the lockdown that was in place to control the SARS-CoV-2 epidemic. The case highlights the importance of strict monitoring of water and air systems immediately before reopening business or public sector buildings, and the need to consider Legionella infections among the differential diagnosis of respiratory infections after lockdown due to the ongoing COVID-19 pandemic.


Subject(s)
Antigens, Bacterial/urine , Legionella pneumophila/isolation & purification , Legionella/isolation & purification , Legionnaires' Disease/diagnosis , Levofloxacin/therapeutic use , Pneumonia/diagnosis , Administration, Intravenous , Adult , Anti-Infective Agents, Urinary/therapeutic use , Cough/etiology , Fever/etiology , Headache/etiology , Humans , Legionnaires' Disease/drug therapy , Legionnaires' Disease/urine , Male , Pneumonia/drug therapy , Pneumonia/urine , Treatment Outcome
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