Long Term Implications in Surgical Re-assisting (L.I.S.A. study) During Covid-19 Outbreak: A Retrospective Observational Study on a Rural Population. (preprint)

Background: The spread of the COVID-19 is having a worldwide impact on surgicaltreatment. Our aim was to investigate the impact of the pandemic in a rural hospital in a lowdensely populated area.MethodsWe investigated the volume and type of surgical operations during the pandemic(March 2020 - February 2021) versus pre-pandemic period (March 2019 - February 2020) aswell as during the first and second pandemic waves compared to the pre-pandemic period.We compared the volume and timing of emergency appendectomy and cholecystectomyduring the pandemic versus pre-pandemic period, the volume, timing and stages of electivegastric and colorectal resections for cancer during the pandemic versus the pre-pandemicperiod.ResultsIn the prepandemic versus pandemic period, 42 versus 24 appendectomies and 174versus 126 cholecystectomies (urgent and elective) were performed. Patients operated onbefore as opposed to during the pandemic were older (58 vs. 52 years old, p=0.006),including for cholecystectomy (73 vs. 66 years old, p=0.01) and appendectomy (43 vs. 30years old, p = 0.04).The logistic regression analysis with regard to cholecystectomy and appendectomy performedin emergency showed that male sex and age were both associated to gangrenous typehistology, both in pandemic and prepandemic period. Finally, we found a reduction in cancerstage I and IIA in pandemic versus prepandemic period, with no increase in the moreadvanced stages.Conclusionsthe reduction in services imposed by governments during the first months oftotal lock down did not justify the whole decrease in surgical interventions in the year of thepandemic. Data suggest that greater "non-operative management" for cases of appendicitisand acute cholecystitis does not lead to an increase in cases operated over time, nor to anincrease in the "gangrenous" pattern, which seems to depend on age advanced and malepopulation.

Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike (preprint)

There are as yet no licenced therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric Spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2 (ACE2), initiating conformational changes that drive membrane fusion. We find that monoclonal antibody CR3022 binds the RBD tightly, neutralising SARS-CoV-2 and report the crystal structure at 2.4 A of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilising, CR3022 epitope is inaccessible in the prefusion Spike, suggesting that CR3022 binding would facilitate conversion to the fusion-incompetent post-fusion state. Cryo-EM analysis confirms that incubation of Spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope may be useful therapeutically, possibly in synergy with an antibody blocking receptor attachment.Funding: This work was supported by a grant from the CAMS-Oxford Institute to D.I.S. E.E.F and J.Ren are supported by the Wellcome Trust (101122/Z/13/Z), Y.Z. by Cancer Research UK (C375/A17721) and D.I.S. and E.E.F. by the UK Medical Research Council (MR/N00065X/1). J.H. is supported by a grant from the EPA Cephalosporin Fund. PPUK is funded by the Rosalind Franklin Institute EPSRC Grant no. EP/S025243/1. The National Institute for Health Research Biomedical Research Centre Funding Scheme supports G.R.S. together with the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (grant number: 2018-I2M-2-002), which also supports D.I.S. G.R.S. is also supported as a Wellcome Trust Senior Investigator (grant 095541/A/11/Z). T.M. is supported by Cancer Research UK grants C20724/A14414 and C20724/A26752 to Christian Siebold. This is a contribution from the UK Instruct-ERIC Centre. The Wellcome Centre for Human Genetics is supported by the Wellcome Trust (grant 090532/Z/09/Z). Virus used for the neutralisation assays was a gift from Julian Druce, Doherty Centre, Melbourne, Australia. Conflict of Interest: The authors declare no competing interests.

Development and Validation of a New Risk Score for Infection From Coronavirus (SARS-COV-2) [Ri.S.I.Co], That We Learned on the Field Treating Coronavirus Disease (COVID-19) Patients (preprint)

Background: The pandemic of Coronavirus Disease 2019 asked to change the organization of entire hospitals to try to prevent them to become epidemiological clusters. The actually adopted diagnostic tools are lacking of sensibility or specificity. The aim of the study is to create an easy-to-get risk score (Ri.S.I.Co., RIsk Score for Infection from new COronavirus), developed on the field, to stratify patients admitted to the hospital according to their risk of Covid-19 infection.Methods: This prospective study included all patients who were consecutively admitted in the “suspected COVID-19 department” of the Bufalini Hospital, Cesena (Italy). All clinical, radiological and laboratory predictors were included in a multivariable logistic regression model to create a risk model. A simplified model was internally ed externally validated. Two score thresholds for stratifying the probability of COVID-19 infection were introduced.Results: From 11th March to 5th April 2020, 200 patients were consecutively admitted. A Ri.S.I.Co lower than 2 had an higher sensibility than SARS-Cov-2 nucleic acid detection  (96,2% vs 65,4%, p<0,001). The presence of ground glass pattern at lung-CT scan had a lower sensibility than a Ri.S.I.Co lower than 2 (88,5% vs 96,2%, p<0,001) and a lower specificity than a Ri.S.I.Co higher than 6 (75,0% vs 96,9%, p<0,001). Conclusions: We believe that the Ri.S.I.Co could allow to stratify admitted patients according to their risk, avoiding hospitals becoming themselves the main Covid-19 carriers. Furthermore, it could guide clinicians in starting therapies early in severe-onset cases with a high probability of COVID-19, before molecular SARS-CoV-2 infection is confirmed.Strengths and limitations of this study:Ri.S.I.Co., (RIsk Score for Infection from new COronavirus) is an easy-to-get risk-score developed on the field, to stratify patients admitted to the hospital according to their risk of Covid-19 infection.We believe that the Ri.S.I.Co could allow to stratify admitted patients according to their risk, before molecular SARS-CoV-2 infection is confirmed, avoiding hospitals becoming themselves the main Covid-19 carriers.Ri.S.I.Co had an higher sensibility than SARS-Cov-2 nucleic acid detection and an higher sensibility and specificity of the presence of ground glass pattern at lung-CT scan.Ri.S.I.Co was developed and validated on hospitalized patients, further studies would be necessary to understand if it is generalizable to non-hospitalized patients or on the population of other countries with different mean age, different prevalence of comorbidities and different health policies.