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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-316115

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic started over one year ago and produced almost 3.5 million deaths worldwide. We have been recently overwhelmed by a wide literature on how the immune system recognizes Severe Acute Respiratory Syndrome Coronavirus 2 and contributes to COVID-19 pathogenesis. Although originally considered a respiratory viral disease, COVID-19 is recognized as a far more complex, multi-organ-, immuno-mediated-, and mostly heterogeneous disorder. Though efficient innate and adaptive immunity may control infection, when the patient fails to mount an adequate immune response, a high innate-induced inflammation can lead to different clinical outcomes through heterogeneous compensatory mechanisms. The variability of viral load and persistence, the genetic alterations of virus-driven receptors/signaling pathways and the plasticity of innate and adaptive responses may all account for the extreme heterogeneity of pathogenesis and clinical patterns. As recently done for some inflammatory disorders as asthma, rhinosinusitis with polyposis and atopic dermatitis, herein we suggest to define different endo-types and the related phenotypes along COVID-19. Patients should be stratified for evolving symptoms and tightly monitored for surrogate biomarkers of innate and adaptive immunity. This would allow to preventively identify each endo-type (and its related phenotype) and to treat patients precisely with agents targeting pathogenic mechanisms.

2.
Allergy ; 77(4): 1114-1128, 2022 04.
Article in English | MEDLINE | ID: covidwho-1440721

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic started in March 2020 and caused over 5 million confirmed deaths worldwide as far August 2021. We have been recently overwhelmed by a wide literature on how the immune system recognizes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and contributes to COVID-19 pathogenesis. Although originally considered a respiratory viral disease, COVID-19 is now recognized as a far more complex, multi-organ-, immuno-mediated-, and mostly heterogeneous disorder. Though efficient innate and adaptive immunity may control infection, when the patient fails to mount an adequate immune response at the start, or in advanced disease, a high innate-induced inflammation can lead to different clinical outcomes through heterogeneous compensatory mechanisms. The variability of viral load and persistence, the genetic alterations of virus-driven receptors/signaling pathways and the plasticity of innate and adaptive responses may all account for the extreme heterogeneity of pathogenesis and clinical patterns. As recently applied to some inflammatory disorders as asthma, rhinosinusitis with polyposis, and atopic dermatitis, herein we suggest defining different endo-types and the related phenotypes along COVID-19. Patients should be stratified for evolving symptoms and tightly monitored for surrogate biomarkers of innate and adaptive immunity. This would allow to preventively identify each endo-type (and its related phenotype) and to treat patients precisely with agents targeting pathogenic mechanisms.


Subject(s)
COVID-19 , Adaptive Immunity , Humans , Immunity, Innate , Pandemics , SARS-CoV-2
3.
Front Immunol ; 12: 728513, 2021.
Article in English | MEDLINE | ID: covidwho-1394762

ABSTRACT

VITT is a rare, life-threatening syndrome characterized by thrombotic symptoms in combination with thrombocytopenia, which may occur in individuals receiving the first administration of adenoviral non replicating vectors (AVV) anti Covid19 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) is characterized by high levels of serum IgG that bind PF4/polyanion complexes, thus triggering platelet activation. Therefore, identification of the fine pathophysiological mechanism by which vaccine components trigger platelet activation is mandatory. Herein, we propose a multistep mechanism involving both the AVV and the neo-synthetized Spike protein. The former can: i) spread rapidly into blood stream, ii), promote the early production of high levels of IL-6, iii) interact with erythrocytes, platelets, mast cells and endothelia, iv) favor the presence of extracellular DNA at the site of injection, v) activate platelets and mast cells to release PF4 and heparin. Moreover, AVV infection of mast cells may trigger aberrant inflammatory and immune responses in people affected by the mast cell activation syndrome (MCAS). The pre-existence of natural antibodies binding PF4/heparin complexes may amplify platelet activation and thrombotic events. Finally, neosynthesized Covid 19 Spike protein interacting with its ACE2 receptor on endothelia, platelets and leucocyte may trigger further thrombotic events unleashing the WITT syndrome.


Subject(s)
Antibodies/adverse effects , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Purpura, Thrombocytopenic, Idiopathic/physiopathology , Adenoviridae/genetics , Animals , Blood Platelets/immunology , Blood Platelets/pathology , COVID-19 Vaccines/immunology , Disease Models, Animal , Genetic Vectors , Humans , Mice , Platelet Activation/immunology , Platelet Factor 4 , Rabbits
4.
Biomedicines ; 9(9)2021 Sep 04.
Article in English | MEDLINE | ID: covidwho-1390533

ABSTRACT

The Coronavirus disease 2019 (COVID-19) pandemic has represented an unprecedented challenge for humankind from health, economic, and social viewpoints. In February 2020, Italy was the first western country to be deeply hit by the pandemic and suffered the highest case/fatality rate among western countries. Brand new anti-COVID-19 vaccines have been developed and made available in <1-year from the viral sequence publication. Patients with compromised immune systems, such as autoimmune-autoinflammatory disorders (AIAIDs), primary (PIDs) and secondary (SIDs) immunodeficiencies, have received careful attention for a long time regarding their capacity to safely respond to traditional vaccines. The Italian Immunological Societies, therefore, have promptly faced the issues of safety, immunogenicity, and efficacy/effectiveness of the innovative COVID-19 vaccines, as well as priority to vaccine access, in patients with AIADs, PIDs, and SIDs, by organizing an ad-hoc Task Force. Patients with AIADs, PIDs, and SIDs: (1) Do not present contraindications to COVID-19 vaccines if a mRNA vaccine is used and administered in a stabilized disease phase without active infection. (2) Should usually not discontinue immunosuppressive therapy, which may be modulated depending on the patient's clinical condition. (3) When eligible, should have a priority access to vaccination. In fact, immunizing these patients may have relevant social/health consequences, since these patients, if infected, may develop chronic infection, which prolongs viral spread and facilitates the emergence of viral variants.

6.
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
7.
J Allergy Clin Immunol ; 146(1): 18-22, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-197498

ABSTRACT

The novel coronavirus disease 2019 has rapidly increased in pandemic scale since it first appeared in Wuhan, China, in December 2019. In these troubled days the scientific community is asking for rapid replies to prevent and combat the emergency. It is generally accepted that only achieving a better understanding of the interactions between the virus and the host immune response and of the pathogenesis of infection is crucial to identify valid therapeutic tools to control virus entry, replication, and spread as well as to impair its lethal effects. On the basis of recent research progress of severe acute respiratory syndrome coronavirus 2 and the results on previous coronaviruses, in this contribution we underscore some of the main unsolved problems, mostly focusing on pathogenetic aspects and host immunity to the virus. On this basis, we also touch important aspects regarding the immune response in asymptomatic subjects, the immune evasion of severe acute respiratory syndrome coronavirus 2 in severe patients, and differences in disease severity by age and sex.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Immune Evasion/immunology , Pneumonia, Viral/immunology , Adolescent , Adult , Age Factors , Aged , COVID-19 , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2 , Sex Factors , Young Adult
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