Science
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An urgent global quest for effective therapies to prevent and treat coronavirus disease 2019 (COVID-19) is ongoing. We previously described REGN-COV2, a cocktail of two potent neutralizing antibodies (REGN10987 and REGN10933) that targets nonoverlapping epitopes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. ⋯ Similarly, administration in hamsters limits weight loss and decreases lung titers and evidence of pneumonia in the lungs. Our results provide evidence of the therapeutic potential of this antibody cocktail.
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Neurodegeneration in Alzheimer's disease (AD) is closely associated with the accumulation of pathologic tau aggregates in the form of neurofibrillary tangles. We found that a p. Asp395Gly mutation in VCP (valosin-containing protein) was associated with dementia characterized neuropathologically by neuronal vacuoles and neurofibrillary tangles. ⋯ Asp395Gly VCP mice was knocked in, as compared with injected wild-type mice. These findings suggest that p. Asp395Gly VCP is an autosomal-dominant genetic mutation associated with neurofibrillary degeneration in part owing to reduced tau disaggregation, raising the possibility that VCP may represent a therapeutic target for the treatment of AD.
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The future trajectory of the coronavirus disease 2019 (COVID-19) pandemic hinges on the dynamics of adaptive immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, salient features of the immune response elicited by natural infection or vaccination are still uncertain. We use simple epidemiological models to explore estimates for the magnitude and timing of future COVID-19 cases, given different assumptions regarding the protective efficacy and duration of the adaptive immune response to SARS-CoV-2, as well as its interaction with vaccines and nonpharmaceutical interventions. We find that variations in the immune response to primary SARS-CoV-2 infections and a potential vaccine can lead to markedly different immune landscapes and burdens of critically severe cases, ranging from sustained epidemics to near elimination. Our findings illustrate likely complexities in future COVID-19 dynamics and highlight the importance of immunological characterization beyond the measurement of active infections for adequately projecting the immune landscape generated by SARS-CoV-2 infections.