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The number of elderly people is constantly increasing in Switzerland. This population is often at higher risk of infections and concomitant decompensation of underlying comorbidities, in particular cardiac or respiratory diseases. Vaccines are some of the most effective preventive measures for limiting morbidity and mortality related to some of those infections, such as influenza or shingles. In order to improve vaccination coverage, it is essential to inform the patients of the benefits of vaccination, and to plan a catch-up vaccination consultation. The goal of this article is to offer a practical guide for the general practitioner detailing vaccines for the elderly recommended in Switzerland.
Le nombre de personnes âgées est en constante augmentation en Suisse. Celles-ci sont souvent plus à risque de présenter des infections et de façon concomitante une décompensation de leurs comorbidités, notamment cardiaques et respiratoires. La vaccination est l'une des mesures préventives efficaces pour limiter la morbimortalité associée à certaines de ces infections, comme la grippe ou le zona. Afin d'améliorer la couverture vaccinale, il est primordial d'informer les patients sur les bénéfices de la vaccination et de prévoir une consultation dédiée à une mise à jour vaccinale. Le but de cet article est d'offrir un guide pratique pour le médecin de famille sur les différents vaccins recommandés chez la personne âgée.
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Clínicos Gerais , Vacinas contra Influenza , Influenza Humana , Idoso , Humanos , Vacinação , Coração , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controleRESUMO
Objectives: To comprehensively analyze the quality of the antibody response between children with Multisystem inflammatory syndrome (MIS-C) and age-matched controls at one month after SARS-CoV-2 exposure, and infected in the same time-period. Methods: Serum from 20 MIS-C children at admission, and 14 control children were analyzed. Antigen specific antibody isotypes and subclasses directed against various antigens of SARS-CoV-2 as well as against human common coronavirus (HCoVs) and commensal or pathogenic microorganisms were assessed by a bead-based multiplexed serological assay and by ELISA. The functionality of these antibodies was also assessed using a plaque reduction neutralization test, a RBD-specific avidity assay, a complement deposition assay and an antibody-dependent neutrophil phagocytosis (ADNP) assay. Results: Children with MIS-C developed a stronger IgA antibody response in comparison to children with uncomplicated COVID-19, while IgG and IgM responses are largely similar in both groups. We found a typical class-switched antibody profile with high level of IgG and IgA titers and a measurable low IgM due to relatively recent SARS-CoV-2 infection (one month). SARS-CoV-2-specific IgG antibodies of MIS-C children had higher functional properties (higher neutralization activity, avidity and complement binding) as compared to children with uncomplicated COVID-19. There was no difference in the response to common endemic coronaviruses between both groups. However, MIS-C children had a moderate increase against mucosal commensal and pathogenic strains, reflecting a potential association between a disruption of the mucosal barrier with the disease. Conclusion: Even if it is still unclear why some children develop a MIS-C, we show here that MIS-C children produce higher titers of IgA antibodies, and IgG antibodies with higher functionality, which could reflect the local gastro-intestinal mucosal inflammation potentially induced by a sustained SARS-CoV-2 gut infection leading to continuous release of SARS-CoV-2 antigens.
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Antígenos de Grupos Sanguíneos , COVID-19 , Doenças do Tecido Conjuntivo , Humanos , Criança , SARS-CoV-2 , Formação de Anticorpos , Anticorpos Antivirais , Imunoglobulina A , Imunoglobulina G , Imunoglobulina MRESUMO
The COVID-19 pandemic has presented a serious challenge to the hepatology community, particularly healthcare professionals and patients. While the rapid development of safe and effective vaccines and treatments has improved the clinical landscape, the emergence of the omicron variant has presented new challenges. Thus, it is timely that the European Association for the Study of the Liver provides a summary of the latest data on the impact of COVID-19 on the liver and issues guidance on the care of patients with chronic liver disease, hepatobiliary cancer, and previous liver transplantation, as the world continues to deal with the consequences of the COVID-19 pandemic.
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COVID-19 , Hepatopatias , Transplante de Fígado , Neoplasias , Humanos , Hepatopatias/epidemiologia , Hepatopatias/cirurgia , Pandemias , SARS-CoV-2RESUMO
Emerging SARS-CoV-2 variants raise questions about escape from previous immunity. As the population immunity to SARS-CoV-2 has become more complex due to prior infections with different variants, vaccinations or the combination of both, understanding the antigenic relationship between variants is needed. Here, we have assessed neutralizing capacity of 120 blood specimens from convalescent individuals infected with ancestral SARS-CoV-2, Alpha, Beta, Gamma or Delta, double vaccinated individuals and patients after breakthrough infections with Delta or Omicron-BA.1. Neutralization against seven authentic SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta and Omicron-BA.1) determined by plaque-reduction neutralization assay allowed us to map the antigenic relationship of SARS-CoV-2 variants. Highest neutralization titers were observed against the homologous variant. Antigenic cartography identified Zeta and Omicron-BA.1 as separate antigenic clusters. Substantial immune escape in vaccinated individuals was detected for Omicron-BA.1 but not Zeta. Combined infection/vaccination derived immunity results in less Omicron-BA.1 immune escape. Last, breakthrough infections with Omicron-BA.1 lead to broadly neutralizing sera.
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COVID-19 , SARS-CoV-2 , Anticorpos , COVID-19/prevenção & controle , Humanos , VacinaçãoRESUMO
Objective: To comprehensively evaluate SARS-CoV-2 specific B-cell and antibody responses up to one year after mild COVID-19. Methods: In 31 mildly symptomatic COVID-19 participants SARS-CoV-2-specific plasmablasts and antigen-specific memory B cells were measured by ELISpot. Binding antibodies directed against the proteins spike (S), domain S1, and nucleocapsid (N) were estimated using rIFA, ELISA, and commercially available assays, and avidity measured using thiocyanate washout. Neutralizing antibodies against variants of concern were measured using a surrogate-neutralization test. Results: Plasmablast responses were assessed in all participants who gave sequential samples during the first two weeks after infection; they preceded the rise in antibodies and correlated with antibody titers measured at one month. S1 and N protein-specific IgG memory B-cell responses remained stable during the first year, whereas S1-specific IgA memory B-cell responses declined after 6 months. Antibody titers waned over time, whilst potent affinity maturation was observed for anti-RBD antibodies. Neutralizing antibodies against wild-type (WT) and variants decayed during the first 6 months but titers significantly increased for Alpha, Gamma and Delta between 6 months and one year. Therefore, near-similar titers were observed for WT and Alpha after one year, and only slightly lower antibody levels for the Delta variant compared to WT. Anti-RBD antibody responses correlated with the neutralizing antibody titers at all time points, however the predicted titers were 3-fold lower at one year compared to one month. Conclusion: In mild COVID-19, stable levels of SARS-CoV-2 specific memory B cells and antibodies neutralizing current variants of concern are observed up to one year post infection. Care should be taken when predicting neutralizing titers using commercial assays that measure binding antibodies.
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COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Humanos , Glicoproteína da Espícula de CoronavírusRESUMO
Monocytes are known to play a critical role in dengue pathophysiology. However, which monocyte subset expresses what inflammatory mediator(s) and what transcriptional features distinguish each of the monocyte subset in vivo remain poorly understood. In this study we provide a detailed transcriptional analysis of the three human monocyte subsets in healthy children and in children with dengue febrile illness. Notably, we found that the CD14+ CD16high intermediate monocyte subset from dengue patients highly upregulated key genes involved in mediating inflammation, endothelial dysfunction, vascular permeability, tissue extravasation, and clot prevention compared to healthy children. The CD14+CD16low classical monocytes shared some of these features. These two subsets increased massively in patients with severe dengue. By contrast, the CD14-CD16high nonclassical monocyte subset upregulated key genes involved in vasoconstriction, endothelial barrier stability, and are involved in endothelial patrolling while showing a significant decline from circulation. These findings improve our understanding of monocyte responses in dengue.
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BACKGROUND: SARS-CoV-2 infection triggers different auto-antibodies, including anti-apolipoprotein A-1 IgGs (AAA1), which could be of concern as mediators of persistent symptoms. We determined the kinetics of AAA1 response over after COVID-19 and the impact of AAA1 on the inflammatory response and symptoms persistence. METHODS: All serologies were assessed at one, three, six and twelve months in 193 hospital employees with COVID-19. ROC curve analyses and logistic regression models (LRM) were used to determine the prognostic accuracy of AAA1 and their association with patient-reported COVID-19 symptoms persistence at 12 months. Interferon (IFN)-α and-γ production by AAA1-stimulated human monocyte-derived macrophages (HMDM) was assessed in vitro. RESULTS: AAA1 seropositivity was 93% at one month and declined to 15% at 12 months after COVID-19. Persistent symptoms at 12 months were observed in 45.1% of participants, with a predominance of neurological (28.5%), followed by general (15%) and respiratory symptoms (9.3%). Over time, strength of correlations between AAA1 and anti-SARS-COV2 serologies decreased, but remained significant. From the 3rd month on, AAA1 levels predicted persistent respiratory symptoms (area under the curves 0.72-0.74; p < 0.001), independently of disease severity, age and gender (adjusted odds ratios 4.81-4.94; p = 0.02), while anti-SARS-CoV-2 serologies did not. AAA1 increased IFN-α production by HMDMs (p = 0.03), without affecting the IFN-γ response. CONCLUSION: COVID-19 induces a marked though transient AAA1 response, independently predicting one-year persistence of respiratory symptoms. By increasing IFN-α response, AAA1 may contribute to persistent symptoms. If and how AAA1 levels assessment could be of use for COVID-19 risk stratification remains to be determined.
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COVID-19 , Anticorpos Antivirais , Antivirais , Apolipoproteína A-I , Autoanticorpos , Humanos , SARS-CoV-2RESUMO
IMPORTANCE: The SARS-CoV-2 variant B.1.1.529 (Omicron) escapes neutralizing antibodies elicited after COVID-19 vaccination, while T-cell responses might be better conserved. It is crucial to assess how a third vaccination modifies these responses, particularly for immunocompromised patients with readily impaired antibody responses. OBJECTIVE: To determine T-cell responses to the Omicron spike protein in anti-CD20-treated patients with multiple sclerosis (MS) before and after a third messenger RNA COVID-19 vaccination. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study conducted from March 2021 to November 2021 at the University Hospital Geneva, adults with MS receiving anti-CD20 treatment (ocrelizumab) were identified by their treating neurologists and enrolled in the study. A total of 20 patients received their third dose of messenger RNA COVID-19 vaccine and were included in this analysis. INTERVENTIONS: Blood sampling before and 1 month after the third vaccine dose. MAIN OUTCOMES AND MEASURES: Quantification of CD4 and CD8 (cytotoxic) T cells specific for the SARS-CoV-2 spike proteins of the vaccine strain as well as the Delta and Omicron variants, comparing frequencies before and after the third vaccine dose. RESULTS: Of 20 included patients, 11 (55%) were male, and the median (IQR) age was 45.8 (37.8-53.3) years. Spike-specific CD4 and CD8 T-cell memory against all variants were maintained in 9 to 12 patients 6 months after their second vaccination, albeit at lower median frequencies against the Delta and Omicron variants compared with the vaccine strain (CD8 T cells: Delta, 83.0%; 95% CI, 73.6-114.5; Omicron, 78.9%; 95% CI, 59.4-100.0; CD4 T cells: Delta, 72.2%; 95% CI, 67.4-90.5; Omicron, 62.5%; 95% CI, 51.0-89.0). A third dose enhanced the number of responders to all variants (11 to 15 patients) and significantly increased CD8 T-cell responses, but the frequencies of Omicron-specific CD8 T cells remained 71.1% (95% CI, 41.6-96.2) of the responses specific to the vaccine strain. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with MS treated with ocrelizumab, there were robust T-cell responses recognizing spike proteins from the Delta and Omicron variants, suggesting that COVID-19 vaccination in patients taking B-cell-depleting drugs may protect them against serious complications from COVID-19 infection. T-cell response rates increased after the third dose, demonstrating the importance of a booster dose for this population.
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COVID-19 , Esclerose Múltipla , Adulto , Anticorpos Monoclonais Humanizados , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Estudos Prospectivos , RNA Mensageiro , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/uso terapêuticoRESUMO
During this global health crisis, COVID-19 unfortunately did not spare pregnant women, who are at greater risk of becoming infected, developing severe forms and having obstetric complications. In this article we will talk about the risks associated with COVID-19 during pregnancy and in particular the existing data on the drugs to be administered in the event of illness and how to avoid infection and its complications through vaccination.
Durant cette crise sanitaire mondiale, le Covid-19 n'a malheureusement pas épargné les femmes enceintes. Celles-ci sont plus à risque d'être infectées, de développer des formes sévères et d'avoir des complications obstétricales. Dans cet article, nous allons parler des risques liés au Covid-19 durant la grossesse et notamment des données existantes sur les médicaments à administrer en cas de maladie et comment éviter l'infection et ses complications grâce à la vaccination.
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COVID-19 , Vacinas contra Influenza , Preparações Farmacêuticas , Complicações Infecciosas na Gravidez , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , SARS-CoV-2RESUMO
Emerging variants of concern (VOCs) are driving the COVID-19 pandemic1,2. Experimental assessments of replication and transmission of major VOCs and progenitors are needed to understand the mechanisms of replication and transmission of VOCs3. Here we show that the spike protein (S) from Alpha (also known as B.1.1.7) and Beta (B.1.351) VOCs had a greater affinity towards the human angiotensin-converting enzyme 2 (ACE2) receptor than that of the progenitor variant S(D614G) in vitro. Progenitor variant virus expressing S(D614G) (wt-S614G) and the Alpha variant showed similar replication kinetics in human nasal airway epithelial cultures, whereas the Beta variant was outcompeted by both. In vivo, competition experiments showed a clear fitness advantage of Alpha over wt-S614G in ferrets and two mouse models-the substitutions in S were major drivers of the fitness advantage. In hamsters, which support high viral replication levels, Alpha and wt-S614G showed similar fitness. By contrast, Beta was outcompeted by Alpha and wt-S614G in hamsters and in mice expressing human ACE2. Our study highlights the importance of using multiple models to characterize fitness of VOCs and demonstrates that Alpha is adapted for replication in the upper respiratory tract and shows enhanced transmission in vivo in restrictive models, whereas Beta does not overcome Alpha or wt-S614G in naive animals.
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COVID-19/transmissão , COVID-19/virologia , Mutação , SARS-CoV-2/classificação , SARS-CoV-2/fisiologia , Replicação Viral , Substituição de Aminoácidos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Animais de Laboratório/virologia , COVID-19/veterinária , Cricetinae , Modelos Animais de Doenças , Células Epiteliais/virologia , Feminino , Furões/virologia , Humanos , Masculino , Mesocricetus/virologia , Camundongos , Camundongos Transgênicos , SARS-CoV-2/genética , SARS-CoV-2/crescimento & desenvolvimento , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Virulência/genéticaRESUMO
BACKGROUND: Patients treated with anti-CD20 therapy are particularly at risk of developing severe coronavirus disease 2019 (COVID-19); however, little is known regarding COVID-19 vaccine effectiveness in this population. METHODS: This prospective observational cohort study assesses humoral and T-cell responses after vaccination with 2 doses of mRNA-based COVID-19 vaccines in patients treated with rituximab for rheumatic diseases or ocrelizumab for multiple sclerosis (nâ =â 37), compared to immunocompetent individuals (nâ =â 22). RESULTS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies were detectable in only 69.4% of patients and at levels that were significantly lower compared to controls who all seroconverted. In contrast to antibodies, Spike (S)-specific CD4â T cells were equally detected in immunocompetent and anti-CD20 treated patients (85-90%) and mostly of a Th1 phenotype. Response rates of S-specific CD8â T cells were higher in ocrelizumab (96.2%) and rituximab-treated patients (81.8%) as compared to controls (66.7%). S-specific CD4â and CD8â T cells were polyfunctional but expressed more effector molecules in patients than in controls. During follow-up, 3 MS patients without SARS-CoV-2-specific antibody response had a mild breakthrough infection. One of them had no detectable S-specific T cells after vaccination. CONCLUSIONS: Our study suggests that patients on anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines, despite impaired humoral responses. This could play an important role in the reduction of complications of severe COVID-19.
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Tratamento Farmacológico da COVID-19 , COVID-19 , Vacinas Virais , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Estudos Prospectivos , RNA Mensageiro , Rituximab , SARS-CoV-2 , VacinaçãoRESUMO
The use of immune checkpoint inhibitors (ICI) has substantially increased the overall survival of cancer patients and has revolutionized the therapeutic situation in oncology. However, not all patients and cancer types respond to ICI, or become resistant over time. Combining ICIs with therapeutic cancer vaccines is a promising option as vaccination may help to overcome resistance to immunotherapies while immunotherapies may increase immune responses to the particular cancer vaccine by reinvigorating exhausted T cells. Thus, it would be possible to reprogram a response with appropriate vaccines, using a particular cancer antigen and a corresponding ICI. Target populations include currently untreatable cancer patients or those who receive treatment regimens with high risk of serious side effects. In addition, with the increased use of ICI in clinical practice, questions arise regarding safety and efficacy of administration of conventional vaccines, such as influenza or COVID-19 vaccines, during active ICI treatment. This review discusses the main principles of prophylactic and therapeutic cancer vaccines, the potential impact on combining therapeutic cancer vaccines with ICI, and briefly summarizes the current knowledge of safety and effectiveness of influenza and COVID-19 vaccines in ICI-treated patients.
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BACKGROUND: SARS-CoV-2 infection leads to high viral loads in the upper respiratory tract that may be determinant in virus dissemination. The extent of intranasal antiviral response in relation to symptoms is unknown. Understanding how local innate responses control virus is key in the development of therapeutic approaches. METHODS: SARS-CoV-2-infected patients were enrolled in an observational study conducted at the Geneva University Hospitals, Switzerland, investigating virological and immunological characteristics. Nasal wash and serum specimens from a subset of patients were collected to measure viral load, IgA specific for the S1 domain of the spike protein, and a cytokine panel at different time points after infection; cytokine levels were analyzed in relation to symptoms. RESULTS: Samples from 13 SARS-CoV-2-infected patients and six controls were analyzed. We found an increase in CXCL10 and IL-6, whose levels remained elevated for up to 3 weeks after symptom onset. SARS-CoV-2 infection also induced CCL2 and GM-CSF, suggesting local recruitment and activation of myeloid cells. Local cytokine levels correlated with viral load but not with serum cytokine levels, nor with specific symptoms, including anosmia. Some patients had S1-specific IgA in the nasal cavity while almost none had IgG. CONCLUSION: The nasal epithelium is an active site of cytokine response against SARS-CoV-2 that can last more than 2 weeks; in this mild COVID-19 cohort, anosmia was not associated with increases in any locally produced cytokines.
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COVID-19/imunologia , Citocinas/biossíntese , Inflamação/etiologia , Mucosa Nasal/imunologia , SARS-CoV-2 , Carga Viral , Adulto , Idoso , Anticorpos Antivirais , COVID-19/virologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2/imunologiaRESUMO
SARS-CoV-2 infection in children is less severe than it is in adults. We perform a longitudinal analysis of the early innate responses in children and adults with mild infection within household clusters. Children display fewer symptoms than adults do, despite similar initial viral load, and mount a robust anti-viral immune signature typical of the SARS-CoV-2 infection and characterized by early interferon gene responses; increases in cytokines, such as CXCL10 and GM-CSF; and changes in blood cell numbers. When compared with adults, the antiviral response resolves faster (within a week of symptoms), monocytes and dendritic cells are more transiently activated, and genes associated with B cell activation appear earlier in children. Nonetheless, these differences do not have major effects on the quality of SARS-CoV-2-specific antibody responses. Our findings reveal that better early control of inflammation as observed in children may be key for rapidly controlling infection and limiting the disease course.
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Anticorpos Antivirais/imunologia , COVID-19/genética , COVID-19/imunologia , Citocinas/metabolismo , Imunidade Inata , SARS-CoV-2/imunologia , Transcriptoma , Imunidade Adaptativa , Adolescente , Adulto , Linfócitos B/metabolismo , COVID-19/virologia , Quimiocina CXCL10/metabolismo , Criança , Pré-Escolar , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Lactente , Inflamação/virologia , Interferons/metabolismo , Estudos Longitudinais , Pessoa de Meia-Idade , Monócitos/metabolismo , Análise de Sequência de RNA , Carga Viral , Adulto JovemRESUMO
T cells are important in tumour immunity but a better understanding is needed of the differentiation of antigen-specific T cells in human cancer1,2. Here we studied CD8 T cells in patients with human papillomavirus (HPV)-positive head and neck cancer and identified several epitopes derived from HPV E2, E5 and E6 proteins that allowed us to analyse virus-specific CD8 T cells using major histocompatibility complex (MHC) class I tetramers. HPV-specific CD8 T cells expressed PD-1 and were detectable in the tumour at levels that ranged from 0.1% to 10% of tumour-infiltrating CD8 T lymphocytes (TILs) for a given epitope. Single-cell RNA-sequencing analyses of tetramer-sorted HPV-specific PD-1+ CD8 TILs revealed three transcriptionally distinct subsets. One subset expressed TCF7 and other genes associated with PD-1+ stem-like CD8 T cells that are critical for maintaining T cell responses in conditions of antigen persistence. The second subset expressed more effector molecules, representing a transitory cell population, and the third subset was characterized by a terminally differentiated gene signature. T cell receptor clonotypes were shared between the three subsets and pseudotime analysis suggested a hypothetical differentiation trajectory from stem-like to transitory to terminally differentiated cells. More notably, HPV-specific PD-1+TCF-1+ stem-like TILs proliferated and differentiated into more effector-like cells after in vitro stimulation with the cognate HPV peptide, whereas the more terminally differentiated cells did not proliferate. The presence of functional HPV-specific PD-1+TCF-1+CD45RO+ stem-like CD8 T cells with proliferative capacity shows that the cellular machinery to respond to PD-1 blockade exists in HPV-positive head and neck cancer, supporting the further investigation of PD-1 targeted therapies in this malignancy. Furthermore, HPV therapeutic vaccination efforts have focused on E6 and E7 proteins; our results suggest that E2 and E5 should also be considered for inclusion as vaccine antigens to elicit tumour-reactive CD8 T cell responses of maximal breadth.
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Alphapapillomavirus/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/virologia , Linfócitos do Interstício Tumoral/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Células-Tronco/citologia , Alphapapillomavirus/isolamento & purificação , Linfócitos T CD8-Positivos/classificação , Linfócitos T CD8-Positivos/metabolismo , Vacinas Anticâncer/imunologia , Diferenciação Celular , Proliferação de Células , Proteínas de Ligação a DNA/imunologia , Humanos , Linfócitos do Interstício Tumoral/classificação , Linfócitos do Interstício Tumoral/citologia , Linfócitos do Interstício Tumoral/metabolismo , Proteínas Oncogênicas Virais/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/imunologia , RNA-Seq , Receptores de Antígenos de Linfócitos T/imunologia , Análise de Célula Única , Células-Tronco/imunologia , Fator 1 de Transcrição de Linfócitos T/metabolismo , Linfócitos T/imunologia , Transcrição GênicaRESUMO
BACKGROUND: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights into the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. We aimed at determining (a) the association between anti-SARS-CoV-2 and anti-apoA-1 humoral response and (b) the degree of linear homology between SARS-CoV-2, apoA-1 and Toll-like receptor 2 (TLR2) epitopes. DESIGN: Bioinformatics modelling coupled with mimic peptides engineering and competition experiments were used to assess epitopes sequence homologies. Anti-SARS-CoV-2 and anti-apoA-1 IgG as well as cytokines were assessed by immunoassays on a case-control (n = 101), an intensive care unit (ICU; n = 126) and a general population cohort (n = 663) with available samples in the pre and post-pandemic period. RESULTS: Using bioinformatics modelling, linear sequence homologies between apoA-1, TLR2 and Spike epitopes were identified but without experimental evidence of cross-reactivity. Overall, anti-apoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (P < .0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-day kinetics, reaching 82% for anti-apoA-1 seropositivity. In the general population, SARS-CoV-2-exposed individuals displayed higher anti-apoA-1 IgG seropositivity rates than nonexposed ones (34% vs 16.8%; P = .004). CONCLUSION: COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.
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Anticorpos Antivirais/imunologia , Apolipoproteína A-I/imunologia , Autoanticorpos/imunologia , COVID-19/imunologia , Citocinas/imunologia , Imunidade Humoral/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína A-I/química , Biologia Computacional , Epitopos/química , Feminino , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Peptídeos , SARS-CoV-2 , Homologia de Sequência de Aminoácidos , Glicoproteína da Espícula de Coronavírus/química , Receptor 2 Toll-Like/química , Receptor 2 Toll-Like/imunologia , Adulto JovemRESUMO
PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) vaccination is considered one of the most promising and socioeconomically sustainable strategy to help control the pandemic and several vaccines are currently being distributed in nationwide mass immunization campaigns. Very limited data are available on benefits and risks of COVID-19 vaccination in immunocompromised patients and in particular in solid organ or hematopoietic stem cell transplant recipients as they were excluded from phase III trials. This review summarizes current knowledge, international guidelines and controversies regarding COVID-19 vaccination in these vulnerable populations. RECENT FINDINGS: Various COVID-19 vaccine platforms showed good efficacy in phase III trials in the immunocompetent and there are data arising on the safety and immunogenicity of these vaccines in the immunocompromised population. SUMMARY: Transplant recipients could benefit significantly from COVID-19 vaccination, both through active immunization provided they elicit protective vaccine responses, and probably through cocooning by immunization of caregivers and healthcare personnel and thus reducing the risk of SARS-coronavirus-2 exposure. Although awaiting more data on the safety and efficacy of COVID-19 vaccines to inform potential adaptations of vaccine regimens, we strongly recommend prioritizing COVID-19 vaccination of solid and hematopoietic stem cell transplant recipients to decrease COVID-19-related morbidity and mortality.