Insights into the lung microenvironment after severe COVID-19

The SARS-CoV-2 is the betacoronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Severe COVID-19 affects approximately 10-15% of patients and results in prolonged morbidity and mortality. Little is known about the immunophenotypic changes of the lung parenchyma driven by the viral infection in patients who die of severe COVID-19. Ultrasound-guided lung biopsies (LB) were collected (IRB approval#1561/21) within few hours from death in 15 severe COVID-19 patients between November 2020 and January 2021, in two patients who underwent lung transplantation after COVID-19 and in one patient who had surgery for bacterial superinfection during COVID-19 disease. All samples underwent histologic and immunohistochemistry evaluation and molecular profiling using the nCounter Host Response and Coronavirus Panel plus. As controls, lungs from end-stage usual interstitial pneumonia (UIP;n=9) and from lobectomy for lung cancer (Norm;n=5) were used. Eleven lungs (61%) were positive for SARS-CoV-2 RNA. Signs of diffuse alveolar damage (DAD) were observed in 6 patients (30%). COVID-19 lungs showed a marked macrophage infiltration with M2 polarization compared with controls. Globally, COVID-19 lungs showed distinct molecular profiles from UIP or Norm lungs. Specifically, a marked upregulation of interferon-genes that was directly correlated with SARS-CoV-2 genes was seen in COVID-19 lungs. COVID-19-specific genes signatures (Log2FC >1.5;adj p<0.05) obtained using VENN diagram showed impairment of the STAT3-pathway accompanied by the upregulation of the NFkB signaling. Results herein provide new insights into lung alterations induced by severe COVID-19 and suggest novel potential targets for therapeutic intervention.

Surely you are joking, Mr Docking!

In the wake of recent COVID-19 pandemics scientists around the world rushed to deliver numerous CADD (Computer-Aided Drug Discovery) methods and tools that could be reliably used to discover novel drug candidates against the SARS-CoV-2 virus. With that, there emerged a trend of a significant democratization of CADD that contributed to the rapid development of various COVID-19 drug candidates currently undergoing different stages of validation. On the other hand, this democratization also inadvertently led to the surge rapidly performed molecular docking studies to nominate multiple scores of novel drug candidates supported by computational arguments only. Albeit driven by best intentions, most of such studies also did not follow best practices in the field that require experience and expertise learned through multiple rigorously designed benchmarking studies and rigorous experimental validation. In this Viewpoint we reflect on recent disbalance between small number of rigorous and comprehensive studies and the proliferation of purely computational studies enabled by the ease of docking software availability. We further elaborate on the hyped oversale of CADD methods' ability to rapidly yield viable drug candidates and reiterate the critical importance of rigor and adherence to the best practices of CADD in view of recent emergence of AI and Big Data in the field.

Scoliosis: online exercises versus telerehabilitation A feasibility trial

BACKGROUND: During the interruption of the non-urgent healthcare services in Italy due to the SARS-Cov-2 pandemic, telemedicine proved to be an effective alternative, in that it supported exercise delivery in individuals with adolescent idiopathic scoliosis (AIS). Recent scientific evidence demonstrates its feasibility and patient satisfaction. During the lockdown period, the Department of Pediatric Orthopedics at the Istituto di Cura Citta di Pavia supported subjects affected by AIS in two manners: online with the physical therapist (TR) and by using pre-recorded videos (VE). The aim of the present exploratory trial was to evaluate the practice of telerehabilitation in order to employ it in case of new lockdown measures. METHODS: Adherence, perceived enjoyment during the exercise performance and degree of satisfaction with technology were assessed on 18 subjects with AIS, divided into two groups according to the type of exercise administration (seven patients in TR;11 patients in VE). RESULTS: The VE group shows a more noticeable adherence than the TR group. Nonetheless, the perceived enjoyment is more significant in the TR subjects than in the VE ones. The level of satisfaction with technology is positive in both groups under study, without remarkable differences. CONCLUSIONS: The exercise administered at a distance has been positively perceived by all the subjects, though on different levels according to the type of technology employed. Results speak in favor of the use of technology as a means to therapeutic exercise delivery in individuals with AIS. Nevertheless, it is not clear which of the two types it is better to suggest. Biopsychologically speaking, the individual choice is likely to be the most workable solution.