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Multiple Sclerosis Journal ; 28(3 Supplement):623-624, 2022.
Article in English | EMBASE | ID: covidwho-2138875


Introduction: Anti-SARS-CoV2 vaccination induces specific Tand B-cell responses in healthy subjects (HS). In MS patients treated with anti-CD20 drugs, the antibody response is reduced or absent, whereas specific T-cell responses are maintained. It is not known whether and how vaccination affects innate responses mediated by natural killer (NK) cells in HS and in MS patients treated with anti-CD20 drugs. Objective(s): To evaluate whether and how NK cells contribute to the immune response following anti-SARS-CoV2 vaccination in HS and in ocrelizumab-treated MS patients Aims: The aims of this work were: 1) to evaluate the effects of anti-SARS CoV2 vaccination on the phenotype of NK cells from HS and from ocrelizumab-treated MS patients and 2) to evaluate how peptides from the SARS-CoV2 spike protein affect NK cell responses before and after anti-SARS-CoV2 vaccination. Method(s): We enrolled 21 MS patients treated with ocrelizumab and 20 HS. Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood and stored under liquid nitrogen. Thawed PBMCs were cultured overnight in presence/absence of SARS-CoV2 peptides or peptides from the cytomegalovirus (CMV), with/without activating cytokines. Phenotype of NK cells through a 13-marker flow cytometry panel and intracellular production of IFN-gamma were evaluated after culture. Result(s): Findings: 1) Vaccination increased the proportion of CD56dim NK cells in HS and MS patients. CD56posCD16neg NK cells, more abundant in MS patients before vaccination, decreased thereafter. Lower pre-vaccination activation capability of NK cells from MS patients compared to HS in response to stimulus with cytokines was reverted by vaccination. 2) Before vaccination, peptides from the SARS-CoV2 protein downregulated the production of IFN- gamma from NK cells of HS, but not ocrelizumabtreated MS patients, who had significantly lower baseline IFN-gamma NK cells 3) After vaccination, peptides from the SARS-CoV2 protein did not affect the production of IFN- gamma from NK cells of HS. Conclusion(s): The results of this work demonstrate anti-SARSCoV2 vaccination increases the proportion of effector CD56dim NK cells in HS and ocrelizumab-treated patients. Spike peptides inhibit the function of NK cells from HS before, but not after vaccination. Such phenomenon may contribute to the pathogenicity of SARS-CoV2 in unvaccinated subjects.

Pediatric Rheumatology ; 20(SUPPL 1), 2022.
Article in English | EMBASE | ID: covidwho-1677513


Introduction: COVID-19 severe pneumonia has been associated to systemic inflammation and elevation of blood parameters and reminiscent of cytokine storm syndrome. Stimulation of PBMC from patients with severe COVID-19 have shown a high secretion of IL-1β, a pivotal cytokine driving inflammatory phenotypes, which maturation and secretion is regulated by NLRP3 inflammasome. Steroidal anti-inflammatory therapies have shown efficacy in reducing mortality in critically ill patients, however the mechanisms by which SARS-CoV2 virus triggers such an extensive inflammation remain unexplained. Objectives: The overall objective of this study was to investigate if SARS-CoV2 drives inflammation in COVID-19 patients through NLRP3 inflammasome activation and IL-1β secretion. Methods: Samples from SARS-CoV2 infected patients, were collected at day 0 and at 3 and 7 following treatment with anakinra. Fresh monocytes, purified through adherence, were cultured for 3, 6, 18 h in the presence or absence of LPS (100 ng/ml) and MCC950 (10μM). Release of IL-1β, IL-1Ra, IL-6, TNF-α, IL-18 was quantified by ELISA kit. Relative gene expression analysis of ORF3a gene was performed by RT-qPCR. THP-1 cells were transfected with a plasmid containing ORF3a sequence by nucleofection. NLRP3 inflammasome and ASC speck formation were detected by confocal microscopy and/or by FACS analysis. Results: In the present study we show that circulating monocytes from COVID-19 patients display ASC specks, index of NLRP3 activation, and spontaneously secrete IL-1β in vitro. This spontaneous activation reverts following patient's treatment with the IL-1 receptor antagonist anakinra. Transfection of a monocytic cell line with cDNA coding for the ORF3a SARS-CoV2 protein, resulted in NLRP3- dependent ASC speck formation. The involvement of ORF3a in inflammasome activation was further supported by the detection by RT-PCR of ORF3a in monocytes from COVID-19 patients. Conclusion: In summary, these results provide a mechanistic explanation for the strong inflammatory manifestations associated to COVID-19 and further evidence that NLRP3 and IL-1β targeting could represent an effective strategy in this disease.

Italian Journal of Medicine ; 15(1):67-70, 2021.
Article in English | Web of Science | ID: covidwho-1178480


Since the novel coronavirus disease 2019 (COVID-19) has been declared a pandemic, the possibility of recurrence of the disease after recovery has become a debated issue. We report a case of an 84-years-old male patient who was admitted to our hospital for dyspnea and fever. Lab and clinical workout showed that he had COVID-19. After a full recovery of symptoms and a double negative nasopharyngeal swab of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) by realtime polymerase chain reaction assay, he was discharged from the hospital. One month later, he developed dyspnea and fever again with lung involvement. Surprisingly, the nasopharyngeal swab of SARS-CoV-2 was positive. Since he denied contacts with confirmed or suspected cases of COVID-19, he probably experienced a reactivation of a persistent infection. The failed eradication of the virus could depend on both virus' escape mechanisms and dysfunctional immune response. Further studies are needed to confirm the hypothesis of viral reactivation and identify signs of an incomplete clearance.