SARS-CoV-2 variants show temperature-dependent enhancedpolymerase activity in the upper respiratory tract and high transmissibility

With the convergent global emergence of SARS-CoV-2 variants of concern (VOC), a precise comparison study of viral fitness and transmission characteristics is necessary for the prediction of dominant VOCs and the development of suitable countermeasures. While airway temperature plays important roles in the fitness and transmissibility of respiratory tract viruses, it has not been well studied with SARS-CoV-2. Here we demonstrate that natural temperature differences between the upper (33{degrees}C) and lower (37{degrees}C) respiratory tract have profound effects on SARS-CoV-2 replication and transmission. Specifically, SARS-COV-2 variants containing the P323L or P323L/G671S mutation in the NSP12 RNA-dependent RNA polymerase (RdRp) exhibited enhanced RdRp enzymatic activity at 33{degrees}C compared to 37{degrees}C and high transmissibility in ferrets. MicroScale Thermophoresis demonstrated that the NSP12 P323L or P323L/G671S mutation stabilized the NSP12-NSP7-NSP8 complex interaction. Furthermore, reverse genetics-derived SARS-CoV-2 variants containing the NSP12 P323L or P323L/G671S mutation displayed enhanced replication at 33{degrees}C, and high transmission in ferrets. This suggests that the evolutionarily forced NSP12 P323L and P323L/G671S mutations of recent SARS-CoV-2 VOC strains are associated with increases of the RdRp complex stability and enzymatic activity, promoting the high transmissibility.

Hyperintense Acute Reperfusion Marker on FLAIR in Patient with Possible Contrast-Induced Encephalopathy Following Cerebral Angiography

Contrast-induced encephalopathy (CIE) is a rare complication of angiography and endovascular intervention following administration of iodinated intravenous contrast agents. Neuroimaging findings of CIE usually show cerebral edema, leptomeningeal enhancement, and parenchymal signal abnormality on fluid-attenuated inverse recovery (FLAIR). Hyperintense acute reperfusion marker (HARM) generally implies an enhancement of the subarachnoid cerebrospinal fluid space on brain FLAIR imaging in cases of acute ischemic stroke or hyperperfusion syndrome. We report a case of possible CIE following cerebral angiography, accompanied by HARM sign.