Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19(1,2), host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases(3-7). They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.Peer reviewe

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Prevalence and death rate of COVID-19 in systemic autoimmune diseases in the first three pandemic waves. Relationship to disease subgroups and ongoing therapies

none84noAutoimmune systemic diseases (ASD) represent a predisposing condition to COVID-19. Our prospective, observational multicenter telephone survey study aimed to investigate the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients.Ferri, Clodoveo; Raimondo, Vincenzo; Gragnani, Laura; Giuggioli, Dilia; Dagna, Lorenzo; Tavoni, Antonio; Ursini, Francesco; L'Andolina, Massimo; Caso, Francesco; Ruscitti, Piero; Caminiti, Maurizio; Foti, Rosario; Riccieri, Valeria; Guiducci, Serena; Pellegrini, Roberta; Zanatta, Elisabetta; Varcasia, Giuseppe; Olivo, Domenico; Gigliotti, Pietro; Cuomo, Giovanna; Murdaca, Giuseppe; Cecchetti, Riccardo; De Angelis, Rossella; Romeo, Nicoletta; Ingegnoli, Francesca; Cozzi, Franco; Codullo, Veronica; Cavazzana, Ilaria; Colaci, Michele; Abignano, Giuseppina; De Santis, Maria; Lubrano, Ennio; Fusaro, Enrico; Spinella, Amelia; Lumetti, Federica; De Luca, Giacomo; Bellando-Randone, Silvia; Visalli, Elisa; Bosco, Ylenia Dal; Amato, Giorgio; Giannini, Daiana; Bilia, Silvia; Masini, Francesco; Pellegrino, Greta; Pigatto, Erika; Generali, Elena; Mariano, Giuseppa Pagano; Pettiti, Giorgio; Zanframundo, Giovanni; Brittelli, Raffaele; Aiello, Vincenzo; Caminiti, Rodolfo; Scorpiniti, Daniela; Ferrari, Tommaso; Campochiaro, Corrado; Brusi, Veronica; Fredi, Micaela; Moschetti, Liala; Cacciapaglia, Fabio; Paparo, Sabrina Rosaria; Ragusa, Francesca; Mazzi, Valeria; Elia, Giusy; Ferrari, Silvia Martina; Di Cola, Ilenia; Vadacca, Marta; Lorusso, Sebastiano; Monti, Monica; Lorini, Serena; Aprile, Maria Letizia; Tasso, Marco; Miccoli, Mario; Bosello, Silvia; D'Angelo, Salvatore; Doria, Andrea; Franceschini, Franco; Meliconi, Riccardo; Matucci-Cerinic, Marco; Iannone, Florenzo; Giacomelli, Roberto; Salvarani, Carlo; Zignego, Anna Linda; Fallahi, Poupak; Antonelli, AlessandroFerri, Clodoveo; Raimondo, Vincenzo; Gragnani, Laura; Giuggioli, Dilia; Dagna, Lorenzo; Tavoni, Antonio; Ursini, Francesco; L'Andolina, Massimo; Caso, Francesco; Ruscitti, Piero; Caminiti, Maurizio; Foti, Rosario; Riccieri, Valeria; Guiducci, Serena; Pellegrini, Roberta; Zanatta, Elisabetta; Varcasia, Giuseppe; Olivo, Domenico; Gigliotti, Pietro; Cuomo, Giovanna; Murdaca, Giuseppe; Cecchetti, Riccardo; De Angelis, Rossella; Romeo, Nicoletta; Ingegnoli, Francesca; Cozzi, Franco; Codullo, Veronica; Cavazzana, Ilaria; Colaci, Michele; Abignano, Giuseppina; De Santis, Maria; Lubrano, Ennio; Fusaro, Enrico; Spinella, Amelia; Lumetti, Federica; De Luca, Giacomo; Bellando-Randone, Silvia; Visalli, Elisa; Bosco, Ylenia Dal; Amato, Giorgio; Giannini, Daiana; Bilia, Silvia; Masini, Francesco; Pellegrino, Greta; Pigatto, Erika; Generali, Elena; Mariano, Giuseppa Pagano; Pettiti, Giorgio; Zanframundo, Giovanni; Brittelli, Raffaele; Aiello, Vincenzo; Caminiti, Rodolfo; Scorpiniti, Daniela; Ferrari, Tommaso; Campochiaro, Corrado; Brusi, Veronica; Fredi, Micaela; Moschetti, Liala; Cacciapaglia, Fabio; Paparo, Sabrina Rosaria; Ragusa, Francesca; Mazzi, Valeria; Elia, Giusy; Ferrari, Silvia Martina; Di Cola, Ilenia; Vadacca, Marta; Lorusso, Sebastiano; Monti, Monica; Lorini, Serena; Aprile, Maria Letizia; Tasso, Marco; Miccoli, Mario; Bosello, Silvia; D'Angelo, Salvatore; Doria, Andrea; Franceschini, Franco; Meliconi, Riccardo; Matucci-Cerinic, Marco; Iannone, Florenzo; Giacomelli, Roberto; Salvarani, Carlo; Zignego, Anna Linda; Fallahi, Poupak; Antonelli, Alessandr

Sinergismo tra l'olio essenziale di Mentha suaveolens ed i farmaci antimicrobici

L’olio essenziale di Mentha suaveolens possiede proprietà antimicotiche e antivirali, in particolare nei confronti del fungo opportunista Candida albicans e del virus Herpes simplex, che possono essere sfruttate in sinergia con i comuni farmaci convenzionali

Comparison of different photoresist buffer layers in SPR sensors based on D-shaped POF and gold film

A comparative analysis of two optical fiber sensing platforms is presented. The sensors are based on surface plasmon resonance (SPR) in a D-shaped plastic optical fiber (POF) with a photoresist buffer layer between the exposed POF core and the thin gold film. We show how the sensor's performances change when the photoresist layer changes. The photoresist layers proposed in this analysis are SU-8 3005 and S1813. The experimental results are congruent with the numerical studies and it is instrumental for chemical and bio-chemical applications. Usually, the photoresist layer is required in order to increase the performance of the SPR-POF sensor

Periosteum-derived micro-grafts for tissue regeneration of human maxillary bone

The bone regeneration is one of the most important challenges for regenerative medicine. In maxillo-facial area, bone resorption of the alveolar crest occurs after tooth extraction and leads to several risks for rehabilitation treatments, including dental implants procedures. Goal of our study was to demonstrate the efficacy of an innovative clinical protocol of bone tissue engineering called Rigenera protocol, aimed to create and optimize bio-complexes constituted by collagen biomaterial and human autologous periosteum-derived micro-grafts. We assessed the capacity of these bio-complexes to prevent the bone resorption in the alveolar crest with respect to simple collagen performing histological evaluations of neo-formed osseous tissue. We demonstrated that autologous bio-complexes significantly reduced the bone resorption of both horizontal and vertical dimension of alveolar crest when compared to collagen alone. We also showed that these bio-complexes accelerate the ossification process triggering the formation of new osseous tissue after 45 days from treatment and increasing the calcified matrix after 60 days and until to 120 days with respect to collagen alone. Taken together, these data showed the efficacy of bio-complexes composed by periosteum-derived micro-grafts and collagen in the alveolar ridge preservation through a reduction of bone resorption and an enhancement of new osseous tissue formation

Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study

Background Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19.Methods This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed.Findings Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H2O (33\u201352), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H2O [25\u201343]; p<0\ub70001). 17 (6%) of 297 patients with COVID-19-associated ARDS had compliances greater than the 95th percentile of the classical ARDS cohort. Total lung weight did not differ between the two cohorts. CT pulmonary angiograms (obtained in 23 [8%] patients with COVID-19-related ARDS) showed that 15 (94%) of 16 patients with D-dimer concentrations greater than the median had bilateral areas of hypoperfusion, consistent with thromboembolic disease. Patients with D-dimer concentrations equal to or less than the median had ventilatory ratios lower than those of patients with D-dimer concentrations greater than the median (1\ub766 [1\ub732\u20131\ub795] vs 1\ub790 [1\ub750\u20132\ub733]; p=0\ub70001). Patients with static compliance equal to or less than the median and D-dimer concentrations greater than the median had markedly increased 28-day mortality compared with other patient subgroups (40 [56%] of 71 with high D-dimers and low compliance vs 18 [27%] of 67 with low D-dimers and high compliance, 13 [22%] of 60 with low D-dimers and low compliance, and 22 [35%] of 63 with high D-dimers and high compliance, all p=0\ub70001).Interpretation Patients with COVID-19-associated ARDS have a form of injury that, in many aspects, is similar to that of those with ARDS unrelated to COVID-19. Notably, patients with COVID-19-related ARDS who have a reduction in respiratory system compliance together with increased D-dimer concentrations have high mortality rate