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1.
Nature ; 584(7820): 274-278, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760003

RESUMO

Colonization by the microbiota causes a marked stimulation of B cells and induction of immunoglobulin, but mammals colonized with many taxa have highly complex and individualized immunoglobulin repertoires1,2. Here we use a simplified model of defined transient exposures to different microbial taxa in germ-free mice3 to deconstruct how the microbiota shapes the B cell pool and its functional responsiveness. We followed the development of the immunoglobulin repertoire in B cell populations, as well as single cells by deep sequencing. Microbial exposures at the intestinal mucosa generated oligoclonal responses that differed from those of germ-free mice, and from the diverse repertoire that was generated after intravenous systemic exposure to microbiota. The IgA repertoire-predominantly to cell-surface antigens-did not expand after dose escalation, whereas increased systemic exposure broadened the IgG repertoire to both microbial cytoplasmic and cell-surface antigens. These microbial exposures induced characteristic immunoglobulin heavy-chain repertoires in B cells, mainly at memory and plasma cell stages. Whereas sequential systemic exposure to different microbial taxa diversified the IgG repertoire and facilitated alternative specific responses, sequential mucosal exposure produced limited overlapping repertoires and the attrition of initial IgA binding specificities. This shows a contrast between a flexible response to systemic exposure with the need to avoid fatal sepsis, and a restricted response to mucosal exposure that reflects the generic nature of host-microbial mutualism in the mucosa.


Assuntos
Linfócitos B/citologia , Linfócitos B/imunologia , Imunidade nas Mucosas/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Simbiose/imunologia , Administração Intravenosa , Administração Oral , Animais , Clostridiales/imunologia , Clostridiales/isolamento & purificação , Escherichia coli/imunologia , Escherichia coli/isolamento & purificação , Feminino , Vida Livre de Germes , Imunoglobulina A/química , Imunoglobulina A/imunologia , Imunoglobulina G/química , Imunoglobulina G/imunologia , Cadeias Pesadas de Imunoglobulinas/imunologia , Memória Imunológica/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plasmócitos/citologia , Plasmócitos/imunologia , Priming de Repetição
2.
J Int Med Res ; 48(8): 300060520933810, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32776805

RESUMO

The sudden outbreak of severe acute respiratory syndrome coronavirus 2 pneumonia posed a significant challenge to medical professionals because treatment of critically ill patients requires the efforts of a multidisciplinary team. To highlight this principle, we examined acute kidney injury (AKI) in IgA-dominant infection-associated glomerulonephritis (GN) and menstrual toxic shock syndrome (mTSS). Both GN and mTSS are rare diseases caused by staphylococcal infection, and renal function is frequently impaired. The resulting AKIs are disparate pathological entities driven by distinct immune mechanisms. We begin by describing the case of a diabetic man with pyopneumothorax following methicillin-resistant Staphylococcus aureus (MRSA). He had endocapillary proliferative GN with in situ IgA-dominant immune-complex formation in the mesangium accompanied by complement C3 deposition in the glomerular capillary wall. By contrast, acute tubular necrosis was observed in a case of mTSS; the patient's immune response was stimulated differently by MRSA enterotoxin and exotoxin resulting in aberrant IgA deposition, complement activation, and insufficient antibody production. As a multidisciplinary communication covering the fields of nephrology, immunology, and pathology, this report may help clinicians to understand these distinct renal lesions and make optimal therapeutic decisions expeditiously.


Assuntos
Lesão Renal Aguda/patologia , Glomerulonefrite por IGA/patologia , Imunoglobulina A/imunologia , Distúrbios Menstruais/patologia , Choque Séptico/patologia , Infecções Estafilocócicas/patologia , Lesão Renal Aguda/microbiologia , Adolescente , Betacoronavirus , Ativação do Complemento/imunologia , Infecções por Coronavirus/patologia , Enterotoxinas/metabolismo , Feminino , Glomerulonefrite por IGA/microbiologia , Humanos , Rim/patologia , Masculino , Distúrbios Menstruais/microbiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Pneumotórax/microbiologia , Pneumotórax/patologia , Choque Séptico/microbiologia
3.
MMW Fortschr Med ; 162(14): 44-46, 2020 08.
Artigo em Alemão | MEDLINE | ID: mdl-32780376

RESUMO

Patients with newly diagnosed COVID-19 (coronavirus disease 2019) develop antibodies against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). To date, few data have been obtained of the prevalence of SARS-CoV-2-antibodies in general population and in asymptomatic outpatients in Germany.From March 26 to June 4 2020, 415 asymptomatic outpatients were tested prospectively in Northrhine-Westfalia (Germany), to detect SARS-CoV-2-IgG-antibodies. In case of a positive result, anti-SARS-CoV-2-IgA was determined additionally.5 of 415 asymptomatic outpatients had positive SARS-CoV-2-IgG-antibodies with a calculated prevalence of 1.2%. Reference range of anti-SARS-CoV-2-IgA and IgG was defined as ratio for negative < 0.8, borderline 0.8-1.1 and > 1.1 positive. The mean concentration of SARS-CoV-2-IgG-antibodies of the positive 5 outpatients was lower than in symptomatic patients with COVID-19 (n = 12) and positive PCR of SARS-CoV-2 (3.04 ± 2.58 versus 8.05 ± 6.70; p = 0.002). 4 of 5 patients had elevated SARS-CoV-2-IgA-antibodies (1.61 ± 0.82). In 408 screening-outpatients with negative anti-SARS-CoV-2-ELISA-IgG (< 0.8), the mean ratio was 0.25 ± 0.13. Two patients were in the borderline range (0.83 and 0.86).The prevalence of 1.2% of SARS-CoV-2-IgG-antibodies and consequently the rate of infection in asymptomatic outpatients in Northrhine-Westfalia (Germany) is low. The impact of virus neutralisation by antibodies and consequently immunization is the challenge of further investigations.


Assuntos
Anticorpos Antivirais/sangue , Infecções Assintomáticas , Infecções por Coronavirus/diagnóstico , Imunoglobulina G/sangue , Pneumonia Viral/diagnóstico , Betacoronavirus , Alemanha , Humanos , Imunoglobulina A/sangue , Pacientes Ambulatoriais , Pandemias , Prevalência
5.
Zhonghua Yi Xue Za Zhi ; 100(30): 2332-2335, 2020 Aug 11.
Artigo em Chinês | MEDLINE | ID: mdl-32791806
6.
Zhonghua Yi Xue Za Zhi ; 100(30): 2372-2377, 2020 Aug 11.
Artigo em Chinês | MEDLINE | ID: mdl-32791814

RESUMO

Objective: To investigate the effects of serum immunoglobulin A/complement factor 3 (IgA/C3) ratio and glomerular C3 staining on clinical prognosis in patients with IgA nephropathy. Methods: From January 1st, 2007 to December 30th, 2016, a total of 519 patients with biopsy-proven IgA nephropathy (IgAN) in West China Hospital were retrospectively reviewed and divided into four groups based on serum IgA/C3 ratio and glomerular C3 staining: group A with IgA/C3 ratio ≥3.046 (median) and glomerular C3 staining ≥2 (n=151), group B with IgA/C3 ratio ≥3.046 and glomerular C3 staining<2 (n=109), group C with IgA/C3 ratio<3.046 and glomerular C3 staining ≥2 (n=119), and group D with IgA/C3 ratio<3.046 and glomerular C3 staining<2 (n=140). Clinical data, pathological characteristics and the primary endpoint [≥ 50% decline in estimated glomerular filtration rate (eGFR) and/or end-stage renal disease (ESRD)]were collected. Clinical prognosis and relevant risk factors were analyzed among the four groups. Results: Totally, 519 patients (298 males, 57.4%) with an average age of (33.6±10.9) years were recruited and followed up for (43.4±21.6) months. The rate of complete remission plus partial remission was 74.2% (112/151), 74.3% (81/109), 72.3% (86/119), 81.4% (114/140) in group A, B, C, D, respectively. Meanwhile, The rate of ESRD was highest in group A (14.6% vs 9.2%, 13.4%, 8.6%). Renal outcome (patients reached the endpoint) was worse in group A and C compared with group B and D (15.2%, 16.0 vs 8.3%, 7.9%). Moreover, 80-month renal survival rate was significantly worse in group A (84.8%) than that in group B and D (91.7% and 92.1%), but no statistical significant difference was found between group A and B (P(AB)=0.085; P(AD)=0.028). There was no significant difference of renal survival rate between group A and C (84.8% vs 84.0%, P=0.896). Multivariate Cox model showed that hypertension (HR=2.753, 95%CI: 1.452-5.217, P=0.002), serum creatinine (HR=1.011, 95%CI: 1.008-1.014, P<0.001), and tubular atrophy/interstitial fibrosis (T1/T2) (HR=6.595, 95%CI: 3.107-13.999, P<0.001) were independent predictors of poor renal survival. Conclusion: Serum IgA/C3 ratio and glomerular C3 staining are predictors of renal clinical prognosis in patients with IgA nephropathy.


Assuntos
Glomerulonefrite por IGA , Adulto , China , Complemento C3/análise , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Imunoglobulina A , Masculino , Prognóstico , Estudos Retrospectivos , Coloração e Rotulagem , Adulto Jovem
7.
Nat Commun ; 11(1): 4198, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826914

RESUMO

COVID-19 caused by SARS-CoV-2 has become a global pandemic requiring the development of interventions for the prevention or treatment to curtail mortality and morbidity. No vaccine to boost mucosal immunity, or as a therapeutic, has yet been developed to SARS-CoV-2. In this study, we discover and characterize a cross-reactive human IgA monoclonal antibody, MAb362. MAb362 binds to both SARS-CoV and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding, by overlapping the ACE2 structural binding epitope. Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2. When converted to secretory IgA, MAb326 also neutralizes authentic SARS-CoV-2 virus while the IgG isotype shows no neutralization. Our results suggest that SARS-CoV-2 specific IgA antibodies, such as MAb362, may provide effective immunity against SARS-CoV-2 by inducing mucosal immunity within the respiratory system, a potentially critical feature of an effective vaccine.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Betacoronavirus/imunologia , Imunoglobulina A/imunologia , Peptidil Dipeptidase A/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Animais , Anticorpos Monoclonais/metabolismo , Anticorpos Neutralizantes/metabolismo , Chlorocebus aethiops , Reações Cruzadas , Epitopos , Células HEK293 , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina A Secretora/imunologia , Imunoglobulina A Secretora/metabolismo , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Modelos Moleculares , Mutação , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Vírus da SARS/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Células Vero
8.
Analyst ; 145(16): 5638-5646, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32638712

RESUMO

An evaluation of a rapid portable gold-nanotechnology measuring SARS-CoV-2 IgM, IgA and IgG antibody concentrations against spike 1 (S1), spike 2 (S) and nucleocapsid (N) was conducted using serum samples from 74 patients tested for SARS-CoV-2 RNA on admission to hospital, and 47 historical control patients from March 2019. 59 patients were RNA(+) and 15 were RNA(-). A serum (±) classification was derived for all three antigens and a quantitative serological profile was obtained. Serum(+) was identified in 30% (95% CI 11-48) of initially RNA(-) patients, in 36% (95% CI 17-54) of RNA(+) patients before 10 days, 77% (95% CI 67-87) between 10 and 20 days and 95% (95% CI 86-100) after 21 days. The patient-level diagnostic accuracy relative to RNA(±) after 10 days displayed 88% sensitivity (95% CI 75-95) and 75% specificity (95% CI 22-99), although specificity compared with historical controls was 100% (95%CI 91-100). This study provides robust support for further evaluation and validation of this novel technology in a clinical setting and highlights challenges inherent in assessment of serological tests for an emerging disease such as COVID-19.


Assuntos
Anticorpos Antivirais/análise , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Testes Sorológicos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , Técnicas de Laboratório Clínico , Estudos de Coortes , Infecções por Coronavirus/sangue , Reações Falso-Negativas , Feminino , Ouro/química , Humanos , Imunoglobulina A/análise , Imunoglobulina A/imunologia , Imunoglobulina G/análise , Imunoglobulina G/imunologia , Imunoglobulina M/análise , Imunoglobulina M/imunologia , Masculino , Nanopartículas Metálicas/química , Pessoa de Meia-Idade , Proteínas do Nucleocapsídeo/imunologia , Pandemias , Pneumonia Viral/sangue , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto Jovem
9.
J Clin Virol ; 129: 104529, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32659710

RESUMO

BACKGROUND: COVID-19 pandemic has spread worldwide since December 2019. Serological tests for SARS-CoV-2 antibody testing are needed for detection of current or past infections. A wide range of commercial tests is available. However, most of them need to be validated. STUDY DESIGN: The aim was to compare a commercial IgG and IgA ELISA (Euroimmun) with three lateral flow immunoassays (LFI): Hangzhou Alltest Biotech, Wuhan UNscience Biotechnology and Guangzhou Wondfo Biotech. Specificity was calculated with 62 available serum samples from 2018/19. The study included 152 sera from patients of which 109 were RT-PCR positive. Sensitivities for ELISA anti SARS-CoV-2 IgG and IgA were 81.5 % and 93.1 % and specificities 100 % and 80.6 %, respectively. LFI showed variable performances, overall results being better for Guangzhou Wondfo Biotech. CONCLUSIONS: Commercial serological tests are useful for detection of antibodies in patients with COVID-19. ELISA presented better results than LFI. The results allowed to incorporate the most sensitive LFI to the daily workflow, combining with ELISA. Careful validation is encouraged before clinical laboratories start using these tests.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Imunoensaio/métodos , Pneumonia Viral/diagnóstico , Testes Sorológicos/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Sensibilidade e Especificidade , Adulto Jovem
11.
Medicine (Baltimore) ; 99(28): e20911, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664086

RESUMO

BACKGROUND: Allergic rhinitis (AR) is a common allergic disorder worldwide. Western medicine is not optimistic about the therapeutic effect of this disease. However, moxibustion can enhance vital energy or immunity through a great number of clinical trials. Thus, the aim of this systematic review and meta-analysis is to systematically evaluate the effectiveness and safety of indirect moxibustion for treating AR. METHODS: We will conduct a comprehensive literature search in Medline, PubMed, Web of Science, Embase, the Cochrane Library, China National Knowledge Infrastructure Database, WanFang Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database from inception to August 2020 without any language restriction. In addition, we will retrieve the unpublished studies and the references of initially included literature manually. Reviewers will identify studies, extract data, and assess the quality independently. The outcomes of interest include: total effective rate, total nasal symptom score, total non-nasal symptom score, rhinitis quality of life questionnaire, visual analog scale, laboratory indicators (i.e., serum levels of IgE, IgA, or IgG), and adverse events. Randomized clinical trials will be collected, methodological quality will be evaluated using the Cochrane risk-of-bias assessment tool, and the level of evidence will be rated using the Grading of Recommendations, Assessment, Development and Evaluation approach. Meta-analysis will be performed using RevMan 5.3.0 software. The heterogeneity test will be conducted between the studies, and P < .1 and I > 50% are the thresholds for the tests. We will utilize the fixed effects model or the random effects model according to the size of heterogeneity. RESULTS: Because the review is ongoing, no results can be reported. CONCLUSIONS: The results of this review will provide reliable evidence for effectiveness and safety of indirect moxibustion for treating AR. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. This systematic review and meta-analysis will be disseminated online and on paper to help guide clinicians. PROSPERO REGISTRATION NUMBER: CRD42019140944.


Assuntos
Imunidade/efeitos dos fármacos , Moxibustão/métodos , Rinite Alérgica/terapia , China/epidemiologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Moxibustão/efeitos adversos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Rinite Alérgica/epidemiologia , Rinite Alérgica/psicologia , Segurança , Resultado do Tratamento , Escala Visual Analógica
12.
Rev Assoc Med Bras (1992) ; 66(6): 752-756, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32696881

RESUMO

OBJECTIVE To study the profile of associated autoimmune diseases in a series of patients with systemic lupus erythematosus (SLE) and see if such associations are linked to IgA deficiency. METHODS Two hundred eighty-one patients with SLE were studied for Ig A levels by nephelometry. Levels equal to or under 0.05g/dL were considered as IgA deficiency. Epidemiological and clinical data, including the presence of associated autoimmune diseases, were extracted from the patient's charts. RESULTS Ig A deficiency was found in 6% of the patients. In 30.2% of SLE patients, there was at least one more autoimmune disease; Hashimoto thyroiditis and Sjögren's syndrome were the most common. No association between the occurrence of associated autoimmune disease with IgA deficiency was found. CONCLUSIONS There is a high prevalence of autoimmune diseases associated with SLE. IgA deficiency does not affect the presence of these associations.


Assuntos
Doenças Autoimunes , Deficiência de IgA , Lúpus Eritematoso Sistêmico , Síndrome de Sjogren , Humanos , Imunoglobulina A
13.
Emerg Microbes Infect ; 9(1): 1692-1694, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32654611

RESUMO

Three hundred and ninety-seven primary- and secondary-care physicians were tested for the presence of IgG (and IgA) antibodies against SARS-coronavirus-2 with a commercially available ELISA. In 19 of 20 individuals with PCR-proven infection and only mild to moderate symptoms not requiring hospitalization positive IgG levels occurred within two to three weeks. Among the remaining 377 persons without clear-cut evidence of infection, unequivocally positive IgG antibodies were found in only one, showing a surprisingly low prevalence (0.3%, 95% CI: 0.01-1.5) in physicians with likely contacts with infected patients in a region highly affected by the pandemic (Tyrol, Austria).


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Médicos de Atenção Primária , Atenção Secundária à Saúde
14.
Rev Esp Salud Publica ; 942020 Jul 09.
Artigo em Espanhol | MEDLINE | ID: mdl-32643708

RESUMO

The SARS-CoV-2 pandemic has had a major impact on birth care and lactation. The lack of knowledge regarding the transmission mechanisms and the potential risks for the mother and the newborn, even when the vertical transmission of the virus has not been demonstrated, has led to the abandonment of practices such as skin-to-skin and the early initiation of breastfeeding (BF), which offer great benefits for maternal and child health. Taking into account the available scientific evidence and the protective effect of BF, the World Health Organization (WHO), and other organisms recommend, in cases of suspected or confirmed SARS-CoV-2 infection of the mother, maintaining mother-child contact and BF, adopting preventive measure procedures to minimize the risk of contagion. These measures include hand hygiene, before and after contact with the newborn and the use of a mask. If a temporary separation of mother and child is required, it is recommended to feed the newborn with expressed breast milk. The presence of IgA antibodies against SARS-CoV-2 has been confirmed in the milk of infected women, so BF could reduce the clinical impact of the disease in the infant, if it becomes infected.


Assuntos
Infecções por Coronavirus/prevenção & controle , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Leite Humano/virologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Anticorpos Antivirais/análise , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Feminino , Higiene das Mãos , Humanos , Imunoglobulina A/análise , Lactente , Recém-Nascido , Máscaras , Leite Humano/imunologia , Pneumonia Viral/epidemiologia , Espanha , Organização Mundial da Saúde
15.
Emerg Microbes Infect ; 9(1): 1467-1469, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32552365

RESUMO

A maternal woman was positive for SARS-CoV-2 tested in throat swabs but negative tested in other body fluids, and she had IgG and IgA detected in breast milk. Her infant negative for SARS-CoV-2 at birth had elevated IgG in serum but quickly decayed. These findings suggest that breastfeeding might have the potential benefit to the neonates.


Assuntos
Anticorpos Antivirais/análise , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Leite Humano/imunologia , Pneumonia Viral/imunologia , Complicações Infecciosas na Gravidez/virologia , Adulto , Anticorpos Antivirais/imunologia , China , Feminino , Humanos , Imunoglobulina A/análise , Imunoglobulina G/análise , Recém-Nascido , Leite Humano/virologia , Pandemias , Gravidez , Complicações Infecciosas na Gravidez/imunologia
16.
Cochrane Database Syst Rev ; 6: CD013652, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32584464

RESUMO

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and resulting COVID-19 pandemic present important diagnostic challenges. Several diagnostic strategies are available to identify current infection, rule out infection, identify people in need of care escalation, or to test for past infection and immune response. Serology tests to detect the presence of antibodies to SARS-CoV-2 aim to identify previous SARS-CoV-2 infection, and may help to confirm the presence of current infection. OBJECTIVES: To assess the diagnostic accuracy of antibody tests to determine if a person presenting in the community or in primary or secondary care has SARS-CoV-2 infection, or has previously had SARS-CoV-2 infection, and the accuracy of antibody tests for use in seroprevalence surveys. SEARCH METHODS: We undertook electronic searches in the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. We conducted searches for this review iteration up to 27 April 2020. SELECTION CRITERIA: We included test accuracy studies of any design that evaluated antibody tests (including enzyme-linked immunosorbent assays, chemiluminescence immunoassays, and lateral flow assays) in people suspected of current or previous SARS-CoV-2 infection, or where tests were used to screen for infection. We also included studies of people either known to have, or not to have SARS-CoV-2 infection. We included all reference standards to define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction tests (RT-PCR) and clinical diagnostic criteria). DATA COLLECTION AND ANALYSIS: We assessed possible bias and applicability of the studies using the QUADAS-2 tool. We extracted 2x2 contingency table data and present sensitivity and specificity for each antibody (or combination of antibodies) using paired forest plots. We pooled data using random-effects logistic regression where appropriate, stratifying by time since post-symptom onset. We tabulated available data by test manufacturer. We have presented uncertainty in estimates of sensitivity and specificity using 95% confidence intervals (CIs). MAIN RESULTS: We included 57 publications reporting on a total of 54 study cohorts with 15,976 samples, of which 8526 were from cases of SARS-CoV-2 infection. Studies were conducted in Asia (n = 38), Europe (n = 15), and the USA and China (n = 1). We identified data from 25 commercial tests and numerous in-house assays, a small fraction of the 279 antibody assays listed by the Foundation for Innovative Diagnostics. More than half (n = 28) of the studies included were only available as preprints. We had concerns about risk of bias and applicability. Common issues were use of multi-group designs (n = 29), inclusion of only COVID-19 cases (n = 19), lack of blinding of the index test (n = 49) and reference standard (n = 29), differential verification (n = 22), and the lack of clarity about participant numbers, characteristics and study exclusions (n = 47). Most studies (n = 44) only included people hospitalised due to suspected or confirmed COVID-19 infection. There were no studies exclusively in asymptomatic participants. Two-thirds of the studies (n = 33) defined COVID-19 cases based on RT-PCR results alone, ignoring the potential for false-negative RT-PCR results. We observed evidence of selective publication of study findings through omission of the identity of tests (n = 5). We observed substantial heterogeneity in sensitivities of IgA, IgM and IgG antibodies, or combinations thereof, for results aggregated across different time periods post-symptom onset (range 0% to 100% for all target antibodies). We thus based the main results of the review on the 38 studies that stratified results by time since symptom onset. The numbers of individuals contributing data within each study each week are small and are usually not based on tracking the same groups of patients over time. Pooled results for IgG, IgM, IgA, total antibodies and IgG/IgM all showed low sensitivity during the first week since onset of symptoms (all less than 30.1%), rising in the second week and reaching their highest values in the third week. The combination of IgG/IgM had a sensitivity of 30.1% (95% CI 21.4 to 40.7) for 1 to 7 days, 72.2% (95% CI 63.5 to 79.5) for 8 to 14 days, 91.4% (95% CI 87.0 to 94.4) for 15 to 21 days. Estimates of accuracy beyond three weeks are based on smaller sample sizes and fewer studies. For 21 to 35 days, pooled sensitivities for IgG/IgM were 96.0% (95% CI 90.6 to 98.3). There are insufficient studies to estimate sensitivity of tests beyond 35 days post-symptom onset. Summary specificities (provided in 35 studies) exceeded 98% for all target antibodies with confidence intervals no more than 2 percentage points wide. False-positive results were more common where COVID-19 had been suspected and ruled out, but numbers were small and the difference was within the range expected by chance. Assuming a prevalence of 50%, a value considered possible in healthcare workers who have suffered respiratory symptoms, we would anticipate that 43 (28 to 65) would be missed and 7 (3 to 14) would be falsely positive in 1000 people undergoing IgG/IgM testing at days 15 to 21 post-symptom onset. At a prevalence of 20%, a likely value in surveys in high-risk settings, 17 (11 to 26) would be missed per 1000 people tested and 10 (5 to 22) would be falsely positive. At a lower prevalence of 5%, a likely value in national surveys, 4 (3 to 7) would be missed per 1000 tested, and 12 (6 to 27) would be falsely positive. Analyses showed small differences in sensitivity between assay type, but methodological concerns and sparse data prevent comparisons between test brands. AUTHORS' CONCLUSIONS: The sensitivity of antibody tests is too low in the first week since symptom onset to have a primary role for the diagnosis of COVID-19, but they may still have a role complementing other testing in individuals presenting later, when RT-PCR tests are negative, or are not done. Antibody tests are likely to have a useful role for detecting previous SARS-CoV-2 infection if used 15 or more days after the onset of symptoms. However, the duration of antibody rises is currently unknown, and we found very little data beyond 35 days post-symptom onset. We are therefore uncertain about the utility of these tests for seroprevalence surveys for public health management purposes. Concerns about high risk of bias and applicability make it likely that the accuracy of tests when used in clinical care will be lower than reported in the included studies. Sensitivity has mainly been evaluated in hospitalised patients, so it is unclear whether the tests are able to detect lower antibody levels likely seen with milder and asymptomatic COVID-19 disease. The design, execution and reporting of studies of the accuracy of COVID-19 tests requires considerable improvement. Studies must report data on sensitivity disaggregated by time since onset of symptoms. COVID-19-positive cases who are RT-PCR-negative should be included as well as those confirmed RT-PCR, in accordance with the World Health Organization (WHO) and China National Health Commission of the People's Republic of China (CDC) case definitions. We were only able to obtain data from a small proportion of available tests, and action is needed to ensure that all results of test evaluations are available in the public domain to prevent selective reporting. This is a fast-moving field and we plan ongoing updates of this living systematic review.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Especificidade de Anticorpos , Infecções por Coronavirus/epidemiologia , Reações Falso-Negativas , Reações Falso-Positivas , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pandemias , Pneumonia Viral/epidemiologia , Padrões de Referência , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Reação em Cadeia da Polimerase Via Transcriptase Reversa/estatística & dados numéricos , Viés de Seleção , Sensibilidade e Especificidade , Testes Sorológicos/métodos , Testes Sorológicos/normas
17.
Infection ; 48(4): 631-634, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32524515

RESUMO

There have been concerns about high rates of thus far undiagnosed SARS-CoV-2 infections in the health-care system. The COVID-19 Contact (CoCo) Study follows 217 frontline health-care professionals at a university hospital with weekly SARS-CoV-2-specific serology (IgA/IgG). Study participants estimated their personal likelihood of having had a SARS-CoV-2 infection with a mean of 21% [median 15%, interquartile range (IQR) 5-30%]. In contrast, anti-SARS-CoV-2 IgG prevalence was about 1-2% at baseline. Regular anti-SARS-CoV-2 IgG testing of health-care professionals may aid in directing resources for protective measures and care of COVID-19 patients in the long run.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Coronavirus/imunologia , Pessoal de Saúde , Pneumonia Viral/imunologia , Adolescente , Adulto , Idoso , Betacoronavirus , Infecções por Coronavirus/diagnóstico , Feminino , Alemanha , Hospitais Universitários , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Prevalência , Estudos Soroepidemiológicos , Testes Sorológicos , Adulto Jovem
18.
Clin Microbiol Infect ; 26(8): 1082-1087, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32473953

RESUMO

OBJECTIVES: To evaluate the diagnostic performance of seven rapid IgG/IgM tests and the Euroimmun IgA/IgG ELISA for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in COVID-19 patients. METHODS: Specificity was evaluated in 103 samples collected before January 2020. Sensitivity and time to seropositivity was evaluated in 167 samples from 94 patients with COVID-19 confirmed with RT-PCR on nasopharyngeal swab. RESULTS: Specificity (confidence interval) of lateral flow assays (LFAs) was ≥91.3% (84.0-95.5) for IgM, ≥90.3% (82.9-94.8) for IgG, and ≥85.4% (77.2-91.1) for the combination IgM OR IgG. Specificity of the ELISA was 96.1% (90.1-98.8) for IgG and only 73.8% (64.5-81.4) for IgA. Sensitivity 14-25 days after the onset of symptoms was between ≥92.1% (78.5-98.0) and 100% (95.7-100) for IgG LFA compared to 89.5% (75.3-96.4) for IgG ELISA. Positivity of IgM OR IgG for LFA resulted in a decrease in specificity compared to IgG alone without a gain in diagnostic performance, except for VivaDiag. The results for IgM varied significantly between the LFAs with an average overall agreement of only 70% compared to 89% for IgG. The average dynamic trend to seropositivity for IgM was not shorter than for IgG. At the time of hospital admission the sensitivity of LFA was <60%. CONCLUSIONS: Sensitivity for the detection of IgG antibodies 14-25 days after the onset of symptoms was ≥92.1% for all seven LFAs compared to 89.5% for the IgG ELISA. The results for IgM varied significantly, and including IgM antibodies in addition to IgG for the interpretation of LFAs did not improve the diagnostic performance.


Assuntos
Anticorpos Antivirais/análise , Antígenos Virais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/imunologia , Testes Diagnósticos de Rotina , Feminino , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Sensibilidade e Especificidade , Fatores de Tempo , Adulto Jovem
19.
J Clin Virol ; 129: 104468, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32485620

RESUMO

As the Coronavirus 2019 (COVID-19) pandemic evolves, the development of immunoassays to help determine exposure and potentially predict immunity has become a pressing priority. In this report we present the performance of the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for semi-quantitative detection of IgA and IgG antibodies in serum and plasma samples using recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Specimens from patients, with and without COVID-19 infection, were tested at the University of Chicago Clinical Microbiology and Immunology Laboratory. Of 86 samples from SARS-CoV-2 PCR-negative patients, including 28 samples positive for common human coronavirus strains, 76 tested negative and 10 tested positive for IgA (88.4% agreement, 95% CI: 79.9-93.6) while 84 tested negative and 2 tested positive for IgG (97.7% agreement, 95% CI: 91.9-99.6). Of 82 samples from SARS-CoV-2 PCR-positive patients, 14 tested negative and 68 tested positive for IgA (82.9% agreement, 95% CI: 73.4-89.5) while 27 tested negative and 55 tested positive for IgG (67.1% agreement, 95% CI: 56.3-76.3). Of samples collected ≥4 days after positive PCR, 38 of 42 (90.5% agreement, 95% CI: 77.9-96.2) were positive for IgA, and 42 of 42 (100% agreement, 95% CI: 91.6-100) were positive for IgG, respectively. The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay demonstrated good sensitivity for detection of IgA and excellent sensitivity for detection of IgG antibodies from samples collected ≥4 days, after COVID-19 diagnosis by PCR. This assay demonstrated good specificity for IgA and excellent specificity for IgG and demonstrated only borderline cross reaction in 2 of the 28 samples from patients with common human coronaviruses infection, types NL63 and OC43.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Pneumonia Viral/diagnóstico , Chicago , Humanos , Pandemias , Sensibilidade e Especificidade , Testes Sorológicos/métodos
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