Summary SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE2 1 , and is a major antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days. However, following convalescent plasma therapy we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. In vitro , the Spike escape double mutant bearing ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility but incurred an infectivity defect. The ΔH69/ΔV70 single mutant had two-fold higher infectivity compared to wild type, possibly compensating for the reduced infectivity of D796H. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with evidence of reduced susceptibility to neutralising antibodies.
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The objectives of this research were to analyze data from literature based on studies of battered women to determine (a) the correlation of domestic violence and post-traumatic stress disorder (PTSD), (b) the best treatment strategies for PTSD, and (c) the evidence of PTSD treatment effectiveness with battered women. Findings were (a) symptoms of battered women are consistent with PTSD symptoms; (b) certain populations are at higher risk of developing PTSD symptoms; (c) intensity, duration, and perception of the battering experience is a significant factor in the severity of the PTSD symptoms; (d) demographic variables influence PTSD severity; (e) standardized PTSD assessment is needed by professionals working with women experiencing domestic violence; (f) there is a need for greater public health involvement for prevention, identification, and medical treatment of domestic violence and PTSD; and (g) certain treatment strategies are recommended for PTSD but lack rigorous testing of their efficacy.
This is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.
The A2 strain of human respiratory syncytial virus replicated in the nose and lung of BALB/c mice, with virus growing to higher titers in older animals than in younger animals. Virus was recovered from the nose between days 2 and 7 with peak titers on days 3 and 4, and from the lungs between days 2 and 9, with peak titers on days 4 through 6. Serum antibody developed 2 weeks after infection. Viral antigen was demonstrated in the alveolar cells of the lung by immunofluorescence. Histopathological changes included infiltration by mononuclear cells of the peribronchiolar and perivascular tissue, some interstitial thickening, and formation of multinucleated giant cells. Virus could not be recovered from the respiratory tract of mice inoculated with bovine strains of respiratory syncytial virus. Growth of the A2 strain of human respiratory syncytial virus in different cell lines affected its infectivity for mice. Infection of BALB/c mice with respiratory syncytial virus provides a highly reproducible model for the study of the pathogenesis of and mechanisms of immunity to this virus.
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