Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.
It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their differing antibody response profiles. Here, we performed a pilot study of four serological assays to assess the amounts of anti-SARS-CoV-2 antibodies in serum samples obtained from 491 healthy individuals prior to the SARS-CoV-2 pandemic, 51 individuals hospitalized with COVID-19, 209 suspected cases of COVID-19 with mild symptoms, and 200 healthy blood donors. We used two ELISA assays that recognized the full-length nucleoprotein (N) or trimeric spike (S) protein ectodomain of SARS-CoV2. In addition, we developed the S-Flow assay that recognized the S protein expressed at the cell surface using flow cytometry, and the Luciferase Immunoprecipitation System (LIPS) assay that recognized diverse SARS-CoV-2 antigens including the S1 domain and the C-terminal domain of N by immunoprecipitation. We obtained similar results with the four serological assays. Differences in sensitivity were attributed to the technique and the antigen used. High anti-SARS-CoV-2 antibody titers were associated with neutralization activity, which was assessed using infectious SARS-CoV-2 or lentiviral-S pseudotype virus. In hospitalized patients with COVID-19, seroconversion and virus neutralization occurred between 5 and 14 days after symptom onset, confirming previous studies. Seropositivity was detected in 32% of mildly-symptomatic individuals within 15 days of symptom onset and in 3% of healthy blood donors. The four antibody assays we used enabled a broad evaluation of SARS-CoV-2 seroprevalence and antibody profiling in different subpopulations within one region.
Hemovigilance is an important tool not only to analyze blood transfusion incidents, but also to measure the effects of new processes or corrective actions at a national level.
Most cases of hepatitis E viral (HEV) infection in developed countries are autochthonous. Nevertheless, the reported seroprevalence of HEV varies greatly depending on the geographical area and the performance of the immunoassay used. We used validated assays to determine the prevalence of anti-HEV immunoglobulin G (IgG) and IgM among 10,569 French blood donors living in mainland France and three overseas areas. Epidemiological information was collected using a specific questionnaire. We found an overall IgG seroprevalence of 22.4% (8%-86.4%) depending on the geographical area (P < 0.001). The presence of anti-HEV IgG was associated with increasing age (P < 0.001) and eating pork meat (P 5 0.03), pork liver sausages (P < 0.001), game meat (P < 0.01), offal (P < 0.001), and oysters (P 5 0.02). Conversely, drinking bottled water was associated with a lower rate of anti-HEV IgG (P 5 0.02). Overall IgM seroprevalence was 1% (0%-4.6%). The frequency of anti-HEV IgM was higher in donors living in a high anti-HEV IgG seroprevalence area (1.9% versus 0.7%, P < 0.001) and in those eating pork liver sausage (1.4% versus 0.7%, P < 0.01), pât e (1% versus 0.4, P 5 0.04), and wild boar (1.3% versus 0.7%, P < 0.01). Conclusion: HEV is endemic in France and hyperendemic in some areas; eating habits alone cannot totally explain the exposure to HEV, and contaminated water could contribute to the epidemiology of HEV infection in France. (HEPATOLOGY 2016;63:1145-1154 H epatitis E virus (HEV) is a single-stranded, positive sense RNA virus that is a member of the Hepeviridae family.(1) Four major genotypes of human HEV are recognized. HEV genotypes 1 and 2 have been found only in humans and are prevalent in developing countries. They are responsible for both sporadic cases and large outbreaks linked to drinking contaminated water. HEV genotypes 3 and 4 are anthropozoonotic and prevalent in developed countries. These HEV genotypes have been detected in a wide range of domestic and wild animals, which are believed to play a major role in the human epidemiology of the virus. (2) HEV genotypes 1 and 2 mainly affect young adults, mostly men, aged 15-30. Almost half of all cases become jaundiced, and pregnant women during the third trimester and patients with underlying chronic liver disease are most at risk of a severe form of hepatitis E.(3) HEV genotypes 3 and 4 mainly affect older men. Most infections are asymptomatic, but patients suffering from chronic liver disease are at risk of developing acute liver failure.(3) Immunosuppressed individuals infected with genotype 3 or 4 may develop a chronic infection that can rapidly progress to cirrhosis. (4) Autochthonous infections are frequently reported in developed countries, particularly in western Europe. (5) The virus can be transmitted by contaminated food, (3) mainly undercooked pig meat, (6) although other modes of contamination have been described. They are often occupational, such as direct exposure to animals or to slaughterhouse meat. The risk of HEV transmission through blood pro...
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