Isolation of a panel of ultra-potent human antibodies neutralizing SARS-CoV-2 and viral variants of concern.

In the absence of virus-targeting small-molecule drugs approved for the treatment and prevention of COVID-19, broadening the repertoire of potent SARS-CoV-2-neutralizing antibodies represents an important area of research in response to the ongoing pandemic. Systematic analysis of such antibodies and their combinations can be particularly instrumental for identification of candidates that may prove resistant to the emerging viral escape variants. Here, we isolated a panel of 23 RBD-specific human monoclonal antibodies from the B cells of convalescent patients. A surprisingly large proportion of such antibodies displayed potent virus-neutralizing activity both in vitro and in vivo. Four of the isolated nAbs can be categorized as ultrapotent with an apparent IC100 below 16 ng/mL. We show that individual nAbs as well as dual combinations thereof retain activity against currently circulating SARS-CoV-2 variants of concern (such as B.1.1.7, B.1.351, B.1.617, and C.37), as well as against other viral variants. When used as a prophylactics or therapeutics, these nAbs could potently suppress viral replication and prevent lung pathology in SARS-CoV-2-infected hamsters. Our data contribute to the rational development of oligoclonal therapeutic nAb cocktails mitigating the risk of SARS-CoV-2 escape.

Impairments of cerebral blood flow microcirculation in rats brought on by cardiac cessation and respiratory arrest.

The impairments of cerebral blood flow microcirculation brought on by cardiac and respiratory arrest were assessed with multi-modal diagnostic facilities, utilising laser speckle contrast imaging, fluorescence spectroscopy and diffuse reflectance spectroscopy. The results of laser speckle contrast imaging show a notable reduction of cerebral blood flow in small and medium size vessels during a few minutes of respiratory arrest, while the same effect was observed in large sinuses and their branches during the circulatory cessation. Concurrently, the redox ratio assessed with fluorescence spectroscopy indicates progressing hypoxia, NADH accumulation and increase of FAD consumption. The results of diffuse reflectance spectra measurements display a more rapid grow of the perfusion of deoxygenated blood in case of circulatory impairment. In addition, consequent histopathological analysis performed by using new tissue staining procedure developed in-house. It shows notably higher reduction of size of the neurons due to their wrinkling within brain tissues influenced by circulation impair. Whereas, the brain tissues altered with the respiratory arrest demonstrate focal perivascular oedema and mild hypoxic changes of neuronal morphology. Thus, the study suggests that consequences of a cessation of cerebral blood flow become more dramatic and dangerous compare to respiratory arrest.

Optical percutaneous needle biopsy of the liver: a pilot animal and clinical study.

This paper presents the results of the experiments which were performed using the optical biopsy system specially developed for in vivo tissue classification during the percutaneous needle biopsy (PNB) of the liver. The proposed system includes an optical probe of small diameter acceptable for use in the PNB of the liver. The results of the feasibility studies and actual tests on laboratory mice with inoculated hepatocellular carcinoma and in clinical conditions on patients with liver tumors are presented and discussed. Monte Carlo simulations were carried out to assess the diagnostic volume and to trace the sensing depth. Fluorescence and diffuse reflectance spectroscopy measurements were used to monitor metabolic and morphological changes in tissues. The tissue oxygen saturation was evaluated using a recently developed approach to neural network fitting of diffuse reflectance spectra. The Support Vector Machine Classification was applied to identify intact liver and tumor tissues. Analysis of the obtained results shows the high sensitivity and specificity of the proposed multimodal method. This approach allows to obtain information before the tissue sample is taken, which makes it possible to significantly reduce the number of false-negative biopsies.