Objectives Impairment of type I interferon (IFN‐I) immunity has been reported in critically ill COVID‐19 patients. This defect can be explained in a subset of patients by the presence of circulating autoantibodies (auto‐Abs) against IFN‐I. We set out to improve the detection and the quantification of IFN‐I auto‐Abs in a cohort of critically ill COVID‐19 patients, in order to better evaluate the prevalence of these Abs as the pandemic progresses, and how they correlate with the clinical course of the disease. Methods The concentration of anti ‐ IFN‐α 2 Abs was determined in the serum of 84 critically ill COVID‐19 patients who were admitted to ICU in Hospices Civils de Lyon , France, using a commercially available kit (Thermo Fisher, Catalog #BMS217). Results A total of 21 of 84 (25%) critically ill COVID‐19 patients had circulating anti‐IFN‐α 2 Abs above cut‐off (> 34 ng mL −1 ). Among them, 15 of 21 had Abs with neutralising activity against IFN‐α 2 , that is 15 of 84 (18%) critically ill patients. In addition, we noticed an impairment of the IFN‐I response in the majority of patients with neutralising anti‐IFN‐α 2 Abs. There was no significant difference in the clinical characteristics or outcome of with or without neutralising anti‐IFN‐α 2 auto‐Abs. We detected anti‐IFN‐α 2 auto‐Abs in COVID‐19 patients' sera throughout their ICU stay. Finally, we also found auto‐Abs against multiple subtypes of IFN‐I including IFN‐ω. Conclusions We reported that 18% of critically ill COVID‐19 patients were positive for IFN‐I auto‐Abs, whereas all mild COVID‐19 patients were negative, confirming that the presence of these antibodies is associated with a higher risk of developing a critical COVID‐19 form.

Background The association between SARS-CoV-2 commercial serological assays and virus neutralization test (VNT) has been poorly explored in mild patients with COVID-19. Methods 439 serum specimens were longitudinally collected from 76 healthcare workers with RT-PCR-confirmed COVID-19. The clinical sensitivity (determined weekly) of nine commercial serological assays were evaluated. Clinical specificity was assessed using 69 pre-pandemic sera. Correlation, agreement and concordance with the VNT were also assessed on a subset of 170 samples. Area under the ROC curve (AUC) was estimated at 2 neutralizing antibody titers. Results The Wantai Total Ab assay targeting the receptor binding domain (RBD) within the S protein presented the best sensitivity at different times during the course of disease. The clinical specificity was greater than 95% for all tests except for the Euroimmun IgA assay. The overall agreement with the presence of neutralizing antibodies ranged from 62.2% (95%CI; 56.0-68.1) for bioMérieux IgM to 91.2% (87.0-94.2) for Siemens. The lowest negative percent agreement (NPA) was found with the Wantai Total Ab assay (NPA 33% (21.1-48.3)). The NPA for other total Ab or IgG assays targeting the S or the RBD was 80.7% (66.7-89.7), 90.3 (78.1-96.1) and 96.8% (86.8-99.3) for Siemens, bioMérieux IgG and DiaSorin, respectively. None of commercial assays have sufficient performance to detect a neutralizing titer of 80 (AUC<0.76). Conclusions Although some assays show a better agreement with VNT than others, the present findings emphasize that commercialized serological tests including those targeting the RBD cannot substitute a VNT for the assessment of functional antibody response.

O perfil antigênico de 45 herpesvírus (44 de bovinos, sendo seis amostras de referência de BHV-1 e 15 prováveis BHV-1; três amostras de referência de BHV-5 e 20 prováveis BHV-5) e uma amostra de herpesvírus bubalino (BuHV) foi examinado com um painel de anticorpos monoclonais (Acms) produzidos contra antígenos de herpesvírus bovinos. Para os exames, foi utilizada a prova de imunoperoxidase (IPX) sobre cultivos de células infectadas, tendo os Acms como anticorpos primários. A determinação dos padrões de reatividade das amostras de vírus frente aos Acms permitiu a diferenciação entre os tipos 1 e 5. Todas as amostras isoladas de casos de encefalite apresentaram perfil de BHV-5. Quatro amostras de BHV-5 isoladas de áreas geograficamente distintas apresentaram perfís de reatividade diferenciados em relação às demais amostras do tipo 5. Duas amostras de vírus com perfil antigênico de BHV-5 foram isoladas de sêmen de animais infectados. Estes resultados comprovam a utilidade da caracterização antigênica com este painel de Acms na tipagem de amostras de BHV-1 e BHV-5.

Objective: To characterize the phenotype of a large population of Italian patients with adult onset ($ 40 years) diabetes who were attending outpatient clinics and who were screened for glutamic acid decarboxylase 65 autoantibodies (GADA), protein tyrosine phosphatase IA-2 (IA-2A) and IA2b/phogrin (IA-2bA). Design and methods: This was a cross-sectional study comprising a total of 881 patients, aged # 70 years, diagnosed with type 2 diabetes after the age of 40 years, and consecutively recruited in five clinics located in different geographic areas of Italy (Milan, Florence, Rome, Naples and Catania). Their mean disease duration was 8.1 (6.9; S.D.) years. GADA, IA-2A and IA-2bA were measured with radiobinding assays with in vitro translated S-methionine-labelled glutamic acid decarboxylase 65 (GAD65) or IA-2 or IA-2b. Anthropometric and clinical data were collected and compared amongst patients with or without autoantibodies. Results: Sixty-three (7.1%) patients had one or more autoantibodies, 58 (6.6%) had GADA, 22 (2.5%) had IA-2A, six (0.7%) had IA-2bA and 19 (2.15%) had two or more autoantibodies. IA-2A or IA-2bA, in the absence of GADA, were found in only five patients. Autoantibody-positive patients were more often female (63.5 vs 36.5%; P , 0.009), had higher glycated haemoglobin (Hb A1c) (P , 0.001), lower body mass index (BMI; P , 0.0005) and waist/hip ratio (WHR; P , 0.01); female gender being the main contributor to BMI and WHR. We did not observe any differences in age at diagnosis or duration of disease with respect to the presence or absence of islet autoantibodies. The proportion of patients on insulin therapy was higher in patients with two or more antibodies, compared with those with one antibody only, and no antibodies (P for trend , 0.001), and among patients with GADA, in those with higher antibody titre (73.9% in those with . 10 units vs 42.0% in those with # 10 units; P , 0.007). Conclusions: Patients with adult onset diabetes characterized by autoimmunity to b-cells showed a clinical phenotype with anthropometric features that differed from those classically observed in patients with type 2 diabetes. The number and titre of autoantibodies, which reflect the severity of autoimmunity and b-cell impairment, amplified this difference. The usefulness of autoantibody screening in adult-onset diabetes is further emphasized by these findings. European Journal of Endocrinology 154 441-447

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