Background: The novel coronavirus has a high mortality rate (over 1% for patients older than 50 years). This can only be partially ascribed to other comorbidities. A possible explanation is a factor that assures a prompt response to SARS-CoV-2 in younger people, independent from the novelty of the virus itself. A factor is believed to stimulate the immune system and provide immunity against more antigens. The only external stimulation received by healthy people is vaccination (eg, the diphtheria, tetanus, and pertussis [DTP] vaccine). One hypothesis is that vaccination helps develop specific immunity but generates sprouting immunity against antigens in transit. The underlying immunological phenomena are the “bystander effect” and “trained immunity.” The developed immunity gives protection for years until it naturally fades out. After the fifth decade of life, the immune system is almost incompetent when a viral infection occurs, and thus, at this stage, the novel coronavirus can enter the body and cause acute respiratory distress syndrome. Objective: The initial aim is to demonstrate that blood monocytes and natural killer cells show overpowering hyperactivity, while CD4+ and CD8+ T cells experience impediments to their defensive functions in patients with severe SARS-CoV-2 infection. The secondary objectives are to correlate clinical data and vaccination history with laboratory immune patterns in order to identify protective factors. Subsequently, we are also interested in characterizing the phenotypes and state of the degree of activation of peripheral blood mononuclear cells, including monocytes, natural killer cells, and CD4+ and CD8+ T cells, in healthy subjects vaccinated with the Pfizer vaccine. Methods: Data will be collected using the following 3 approaches: (1) an experimental analysis to study the innate immune response and to identify genetic profiles; (2) an epidemiological analysis to identify the patients’ vaccination history; and (3) a clinical analysis to detect the immunological profile. Results: The protocol was approved by the Ethics Committee on April 16, 2020, and the study started on April 27, 2020. As of February 2021, enrollment has been completed. Immunological analysis is ongoing, and we expect to complete this analysis by December 2022

Immune-mediated mechanisms in patients tested positive for SARS-CoV-2: Protocol for a multianalysis study

Ietto, Giuseppe
Primo
;
Mortara, Lorenzo
Secondo
;
Dalla Gasperina, Daniela;Iovino, Domenico;Azzi, Lorenzo;Baj, Andreina;Ageno, Walter;Genoni, Angelo Paolo;Acquati, Francesco;Gallazzi, Matteo;Spina, Giorgia;Coco, Grace;Noonan, Douglas;Vigezzi, Andrea;Monti, Elisa;Iori, Valentina;Masci, Federica;Franchi, Caterina;Di Saverio, Salomone
Penultimo
;
Carcano, Giulio
Ultimo
2022

Abstract

Background: The novel coronavirus has a high mortality rate (over 1% for patients older than 50 years). This can only be partially ascribed to other comorbidities. A possible explanation is a factor that assures a prompt response to SARS-CoV-2 in younger people, independent from the novelty of the virus itself. A factor is believed to stimulate the immune system and provide immunity against more antigens. The only external stimulation received by healthy people is vaccination (eg, the diphtheria, tetanus, and pertussis [DTP] vaccine). One hypothesis is that vaccination helps develop specific immunity but generates sprouting immunity against antigens in transit. The underlying immunological phenomena are the “bystander effect” and “trained immunity.” The developed immunity gives protection for years until it naturally fades out. After the fifth decade of life, the immune system is almost incompetent when a viral infection occurs, and thus, at this stage, the novel coronavirus can enter the body and cause acute respiratory distress syndrome. Objective: The initial aim is to demonstrate that blood monocytes and natural killer cells show overpowering hyperactivity, while CD4+ and CD8+ T cells experience impediments to their defensive functions in patients with severe SARS-CoV-2 infection. The secondary objectives are to correlate clinical data and vaccination history with laboratory immune patterns in order to identify protective factors. Subsequently, we are also interested in characterizing the phenotypes and state of the degree of activation of peripheral blood mononuclear cells, including monocytes, natural killer cells, and CD4+ and CD8+ T cells, in healthy subjects vaccinated with the Pfizer vaccine. Methods: Data will be collected using the following 3 approaches: (1) an experimental analysis to study the innate immune response and to identify genetic profiles; (2) an epidemiological analysis to identify the patients’ vaccination history; and (3) a clinical analysis to detect the immunological profile. Results: The protocol was approved by the Ethics Committee on April 16, 2020, and the study started on April 27, 2020. As of February 2021, enrollment has been completed. Immunological analysis is ongoing, and we expect to complete this analysis by December 2022
Antigen; Blood; COVID-19; Epidemiology; Genetics; Immune response; Immune system; Immunity; Immunology; Immunomodulation; Infectious disease; Mechanism; Monocyte; Natural killer cell; Phenotype; Protection; SARS-CoV-2; Severe acute respiratory syndrome; Vaccine; White blood cell
Ietto, Giuseppe; Mortara, Lorenzo; Dalla Gasperina, Daniela; Iovino, Domenico; Azzi, Lorenzo; Baj, Andreina; Ageno, Walter; Genoni, Angelo Paolo; Acquati, Francesco; Gallazzi, Matteo; Spina, Giorgia; Coco, Grace; Pierin, Federica; Noonan, Douglas; Vigezzi, Andrea; Monti, Elisa; Iori, Valentina; Masci, Federica; Franchi, Caterina; Di Saverio, Salomone; Carcano, Giulio
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11383/2115324
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