Development and characterization of anti-SARS-CoV-2 intravenous immunoglobulin from COVID-19 convalescent plasma.

Background: The authors describe the developmental process of intravenous anti-COVID-19 hyperimmune immunoglobulin from anti-SARS-CoV-2 neutralizing antibody-containing plasma. Furthermore, the authors investigated its safety and protective activity in animal models. Materials & methods: The manufacturing process included standard ethanol fractionation, chromatographic purification steps and virus removal or inactivation. Results: The authors produced pure and safe immunoglobulin for intravenous administration, with 98.1 ± 6.5 mg/ml protein content, of which 97.6 ± 0.7% was IgG. The concentration factor of SARS-CoV-2 neutralizing antibodies was 9.4 ± 1.4-times. Safety studies in animals showed no signs of acute/chronic toxicity or allergenic or thrombogenic properties. Intravenous anti-COVID-19 hyperimmune immunoglobulin protected immunosuppressed hamsters against SARS-Cov-2. Conclusion: The obtained results can allow the start of clinical trials to study the safety and efficacy in healthy adults.

An intravenous immunoglobulin with a high concentration of SARS-CoV-2-neutralizing antibodies was prepared from COVID-19 convalescent plasma, which could be utilized as a passive immunization tool in regard to COVID-19 treatment. The manufacturing process employed conforms to commonly held business standards within the intravenous immunoglobulin industry and includes plasma ethanol fractionation following chromatographic purification and special virus removal or inactivation steps. The results of the preclinical in vitro and in vivo experiments demonstrate that the immunoglobulin produced in this study is pure and safe enough to be considered for intravenous applications. The SARS-CoV-2 neutralizing antibody concentration was found to have increased 9.4 ± 1.4-times compared with human plasma. The anti-COVID-19 hyperimmune immunoglobulin showed no signs of toxicity and did not cause any blood clot formations when administered to rabbits. Furthermore, the anti-COVID-19 hyperimmune immunoglobulin was demonstrated to protect immunosuppressed hamsters against SARS-CoV-2.

Increased local switch costs in mild cognitive impairment.

Task switching performance was assessed in a group of healthy young, healthy old, and MCI-diagnosed participants. Highly significant RT-related local switch costs were found in the MCI group. This contrasts the typical finding that in normal aging local switch costs show no age-related deficit. Local switch costs deficits may be a diagnostic tool in differentiating normal and pathological cognitive aging.

Study of Alzheimer family case reveals hemochromotosis-associated HFE mutation.

We report a family case of type II early-onset Alzheimer's disease (AD) inherited over three generations. None of the patients in the family had mutations in the genes believed to be the major risk factors for AD, such as APP, presenilin 1 or 2. Targeted exome sequencing of 249 genes that were previously reported to be associated with AD revealed a rare mutation in hemochromatosis (HFE) gene known to be associated with hemochromotosis. Compared to previous studies, we show that HFE mutation can possess the risk of AD in transferrin-, APOE- and APP-normal patients.