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1.
Allergy ; 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1784579

ABSTRACT

BACKGROUND: Several autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. In this study, we longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID-19. METHODS: We performed highly sensitive indirect immunofluorescence assays to detect antinuclear antibodies (ANA) and antineutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome-wide serological profiling in a multicentric cohort of 175 COVID-19 patients followed up to 1 year after infection, eleven vaccinated individuals, and 41 unexposed controls. RESULTS: Compared with healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID-19 and recovery. However, the paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID-19. Furthermore, patients with severe COVID-19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS-CoV-2-specific antibody titers in COVID-19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen-specific humoral responses. Notably, the qualitative breadth of antibodies cross-reactive with other coronaviruses was comparable in ANA-positive and ANA-negative individuals during acute COVID-19. In autoantibody-positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID-19 and alterations of the B-cell compartment after recovery. CONCLUSION: Highly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS-CoV-2 infection, while the presence of autoantibodies in COVID-19 patients correlated with increased antiviral humoral immune responses and inflammatory immune signatures.

3.
Immunity ; 55(2): 201-209, 2022 02 08.
Article in English | MEDLINE | ID: covidwho-1720107

ABSTRACT

SARS-CoV-2 infections mostly lead to mild or even asymptomatic infections in children, but the reasons for this are not fully understood. More efficient local tissue responses, better thymic function, and cross-reactive immunity have all been proposed to explain this. In rare cases of children and young people, but very rarely in adults, post-infectious hyperinflammatory syndromes can develop and be serious. Here, I will discuss our current understanding of SARS-CoV-2 infections in children and hypothesize that a life history and energy allocation perspective might offer an additional explanation to mild infections, viral dynamics, and the higher incidence of rare multisystem inflammatory syndromes in children and young people.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Host-Pathogen Interactions , SARS-CoV-2/physiology , Adaptive Immunity , Age Factors , COVID-19/complications , COVID-19/diagnosis , COVID-19/etiology , Disease Susceptibility , Energy Metabolism , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Patient Outcome Assessment , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/etiology , Trauma Severity Indices , Virus Replication
4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308828

ABSTRACT

BACKGROUND: Despite SARS-CoV-2 immunizations have started in most countries, children are not currently included in the vaccination programs, thus it remains crucial to define their anti-SARS-CoV-2 immune response in order to minimize the risk for other epidemic waves. This study seeks to provide a description of the virology ad anti-SARS-CoV-2 immunity in children with distinct symptomatology. METHODS: Between March and July 2020, we recruited 15 SARS-CoV-2 asymptomatic (AS) and 51 symptomatic children (SY), stratified according to WHO clinical classification. We measured SARS-CoV-2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swabs samples. To define anti-SARS-CoV-2 antibodies we measured neutralization activity and total IgG load (Diasorin). We also evaluated antigen-specific B and CD8+T-cells, using a labelled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink. RESULTS: Virological profiling showed that AS had lower viral load at diagnosis (p=0.004) and faster virus clearance (p=0.0002) compared to SY. Anti-SARS CoV-2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY showed similar titers of SARS-CoV-2 IgG, levels of neutralizing activity, and frequency of Ag-specific B and CD8+T-cells. Whereas pro-inflammatory plasma protein profile was associated to symptomatology. CONCLUSION: We demonstrated the development of anti-SARS-CoV-2 humoral and cellular response with any regards to symptomatology, suggesting the ability of both SY and AS to contribute towards herd immunity. The virological profiling of AS suggested that they have lower virus load associated with faster virus clearance.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308827

ABSTRACT

As the global COVID-19 pandemic progresses and with the school reopening, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children in order to define possible immunization strategies and reconsider pandemic control measures. We analyzed anti-SARS-CoV-2 antibodies (Ab) and their neutralizing activity (PRNT) in 42 COVID-19-infected children 7 days after symptoms onset. Individuals with specific humoral responses presented faster virus clearance, and lower viral load associated to a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2 specific CD4-CD40L+ T-cells and Spike specific B-cells were associated with the anti-SARS-CoV-2 Ab and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, with PRNT+ patients showing higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work shed lights on cellular and humoral anti-SARS-CoV-2 responses in children which may drive future vaccination trials endpoints and quarantine measures policies.Funding: This work was made possible by support from Bambino Gesù Children’s Hospital ricerca corrente 2020 to NC and ricerca corrente 2019 to PP, by PENTA and by Fondazione Cassa di Risparmio di Padova e Rovigo, Progetti di Ricerca Covid-19 (ADR participant).Conflict of Interest: The authors declare no competing interests.Ethical Approval: Local ethical committee approved the study and written informed consent was obtained from all participants or legal guardians.

6.
Acta Paediatr ; 111(2): 354-362, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1528356

ABSTRACT

AIM: Our aim was to describe the outcomes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. METHODS: This national, population-based, longitudinal, multicentre study used Swedish data that were prospectively collected between 1 December 2020 and 31 May 2021. All patients met the World Health Organization criteria for MIS-C. The outcomes 2 and 8 weeks after diagnosis are presented, and follow-up protocols are suggested. RESULTS: We identified 152 cases, and 133 (87%) participated. When followed up 2 weeks after MIS-C was diagnosed, 43% of the 119 patients had abnormal results, including complete blood cell counts, platelet counts, albumin levels, electrocardiograms and echocardiograms. After 8 weeks, 36% of 89 had an abnormal patient history, but clinical findings were uncommon. Echocardiogram results were abnormal in 5% of 67, and the most common complaint was fatigue. Older children and those who received intensive care were more likely to report symptoms and have abnormal cardiac results. CONCLUSION: More than a third (36%) of the patients had persistent symptoms 8 weeks after MIS-C, and 5% had abnormal echocardiograms. Older age and higher levels of initial care appeared to be risk factors. Structured follow-up visits are important after MIS-C.


Subject(s)
COVID-19 , Adolescent , Aged , COVID-19/complications , Child , Critical Care , Echocardiography , Humans , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
7.
Pediatr Allergy Immunol ; 32(8): 1833-1842, 2021 11.
Article in English | MEDLINE | ID: covidwho-1282025

ABSTRACT

BACKGROUND: Although SARS-CoV-2 immunizations have started in most countries, children are not currently included in the vaccination programs; thus, it remains crucial to define their anti-SARS-CoV-2 immune response in order to minimize the risk for other epidemic waves. This study sought to provide a description of the virology ad anti-SARS-CoV-2 immunity in children with distinct symptomatology. METHODS: Between March and July 2020, we recruited 15 SARS-CoV-2 asymptomatic (AS) and 51 symptomatic (SY) children, stratified according to WHO clinical classification. We measured SARS-CoV-2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swab samples. To define anti-SARS-CoV-2 antibodies, we measured neutralization activity and total IgG load (DiaSorin). We also evaluated antigen-specific B and CD8+T cells, using a labeled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink. RESULTS: Virological profiling showed that AS patients had lower viral load at diagnosis (p = .004) and faster virus clearance (p = .0002) compared with SY patients. Anti-SARS-CoV-2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY patients showed similar titers of SARS-CoV-2 IgG, levels of neutralizing activity, and frequency of Ag-specific B and CD8+ T cells, whereas pro-inflammatory plasma protein profile was found to be associated with symptomatology. CONCLUSION: We demonstrated the development of anti-SARS-CoV-2 humoral and cellular response with any regard to symptomatology, suggesting the ability of both SY and AS patients to contribute toward herd immunity. The virological profiling of AS patients suggested that they have lower virus load associated with faster virus clearance.


Subject(s)
COVID-19 , Antibodies, Viral/blood , B-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Child , Humans , Immunoglobulin G/blood , SARS-CoV-2 , Serologic Tests
8.
J Exp Med ; 218(6)2021 06 07.
Article in English | MEDLINE | ID: covidwho-1203555

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) emerged in April 2020 in communities with high COVID-19 rates. This new condition is heterogenous but resembles Kawasaki disease (KD), a well-known but poorly understood and clinically heterogenous pediatric inflammatory condition for which weak associations have been found with a myriad of viral illnesses. Epidemiological data clearly indicate that SARS-CoV-2 is the trigger for MIS-C, which typically occurs about 1 mo after infection. These findings support the hypothesis of viral triggers for the various forms of classic KD. We further suggest that rare inborn errors of immunity (IEIs) altering the immune response to SARS-CoV-2 may underlie the pathogenesis of MIS-C in some children. The discovery of monogenic IEIs underlying MIS-C would shed light on its pathogenesis, paving the way for a new genetic approach to classic KD, revisited as a heterogeneous collection of IEIs to viruses.


Subject(s)
COVID-19/etiology , Mucocutaneous Lymph Node Syndrome/genetics , Mucocutaneous Lymph Node Syndrome/virology , SARS-CoV-2/pathogenicity , Systemic Inflammatory Response Syndrome/etiology , Biomarkers/blood , COVID-19/epidemiology , COVID-19/immunology , Child , Cytokines/blood , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Inflammation/etiology , Inflammation/genetics , Inflammation/immunology , Inflammation Mediators/blood , Lymphohistiocytosis, Hemophagocytic/genetics , Lymphohistiocytosis, Hemophagocytic/virology , Models, Biological , Mucocutaneous Lymph Node Syndrome/epidemiology , Pandemics , SARS-CoV-2/immunology , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/immunology
10.
Cell Rep ; 34(11): 108852, 2021 03 16.
Article in English | MEDLINE | ID: covidwho-1135278

ABSTRACT

As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Adaptive Immunity/immunology , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , COVID-19/virology , Child , Humans , Immunity, Humoral/immunology , Proteome/immunology , SARS-CoV-2/immunology , Signal Transduction/immunology , Viral Load/immunology
11.
Nat Med ; 27(1): 28-33, 2021 01.
Article in English | MEDLINE | ID: covidwho-1028101

ABSTRACT

COVID-19, caused by SARS-CoV-2 infection, is mild to moderate in the majority of previously healthy individuals, but can cause life-threatening disease or persistent debilitating symptoms in some cases. The most important determinant of disease severity is age, with individuals over 65 years having the greatest risk of requiring intensive care, and men are more susceptible than women. In contrast to other respiratory viral infections, young children seem to be less severely affected. It is now clear that mild to severe acute infection is not the only outcome of COVID-19, and long-lasting symptoms are also possible. In contrast to severe acute COVID-19, such 'long COVID' is seemingly more likely in women than in men. Also, postinfectious hyperinflammatory disease has been described as an additional outcome after SARS-CoV-2 infection. Here I discuss our current understanding of the immunological determinants of COVID-19 disease presentation and severity and relate this to known immune-system differences between young and old people and between men and women, and other factors associated with different disease presentations and severity.


Subject(s)
COVID-19/immunology , COVID-19/physiopathology , SARS-CoV-2/physiology , Adaptive Immunity , Adult , Age Factors , Aged , COVID-19/complications , COVID-19/epidemiology , COVID-19/etiology , Child , Female , Humans , Immunity, Innate , Immunologic Deficiency Syndromes/chemically induced , Immunologic Deficiency Syndromes/immunology , Immunologic Deficiency Syndromes/virology , Male , SARS-CoV-2/immunology , Severity of Illness Index , Sex Factors , Systemic Inflammatory Response Syndrome/etiology , Virus Internalization
12.
Cell ; 183(4): 968-981.e7, 2020 11 12.
Article in English | MEDLINE | ID: covidwho-746088

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.


Subject(s)
Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Systemic Inflammatory Response Syndrome/pathology , Autoantibodies/blood , Betacoronavirus/isolation & purification , COVID-19 , Child , Child, Preschool , Coronavirus Infections/complications , Coronavirus Infections/virology , Cytokines/metabolism , Female , Humans , Immunity, Humoral , Infant , Male , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/immunology , Mucocutaneous Lymph Node Syndrome/pathology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Principal Component Analysis , Proteome/analysis , SARS-CoV-2 , Severity of Illness Index , Systemic Inflammatory Response Syndrome/etiology , Systemic Inflammatory Response Syndrome/immunology , T-Lymphocyte Subsets/cytology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism
14.
Cell Rep Med ; 1(5): 100078, 2020 08 25.
Article in English | MEDLINE | ID: covidwho-694586

ABSTRACT

Severe disease of SARS-CoV-2 is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5-7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Given that every patient is captured at different stages of infection, longitudinal monitoring of the immune response is critical and systems-level analyses are required to capture cellular interactions. Here, we report on a systems-level blood immunomonitoring study of 37 adult patients diagnosed with COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFNγ-eosinophil axis activated before lung hyperinflammation and changes in cell-cell co-regulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.


Subject(s)
COVID-19/immunology , Adaptive Immunity , Adult , Basophils/metabolism , COVID-19/blood , Cell Communication , Convalescence , Eosinophils/metabolism , Female , Humans , Inflammation , Interferon-gamma/blood , Interleukin-6/blood , Longitudinal Studies , Male , SARS-CoV-2 , Severity of Illness Index
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