ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy Orthopaedic Guidelines for the COVID-19 Post-Outbreak Period: Experience from Wuhan, People's Republic of China

As the outbreak of coronavirus disease 2019 (COVID-19) progresses, prognostic markers for early identification of high-risk individuals are an urgent medical need Italy has one of the highest numbers of SARS-CoV-2-related deaths and one of the highest mortality rates Worldwide, a more severe course of COVID-19 is associated with older age, comorbidities, and male sex Hence, we searched for possible genetic components of COVID-19 severity among Italians by looking at expression levels and variants in ACE2 and TMPRSS2 genes, crucial for viral infection Exome and SNP-array data from a large Italian cohort were used to compare the rare-variants burden and polymorphisms frequency with Europeans and East Asians Moreover, we looked into gene expression databases to check for sex-unbalanced expression While we found no significant evidence that ACE2 is associated with disease severity/sex bias, TMPRSS2 levels and genetic variants proved to be possible candidate disease modulators, prompting for rapid experimental validations on large patient cohorts Currently, the coronavirus disease 2019 (COVID-19) crisis has rapidly spread worldwide As the earliest outbreak area of the pandemic, Wuhan, People's Republic of China, is gradually recovering to its normal state under the effective control of government authorities Outpatient services in major hospitals are now being restored An accumulation of asymptomatic infections is a potential risk for medical personnel, especially when there is crowding in hospitals As the biggest center for orthopaedic patients in Wuhan, our orthopaedic outpatient department admits >300 patients per day Optimal guidelines on how to handle this huge number of patients during the post-outbreak stage of the COVID-19 pandemic, particularly with regard to potential asymptomatic infection, are urgently needed for orthopaedic surgeons We have developed and proposed applicable guidelines to fill this knowledge gap, including the necessary protective strategies for medical personnel in orthopaedic outpatient and inpatient wards as well as during surgery We also have provided mental health recommendations for health-care workers To the best of our knowledge, these guidelines are the first of their kind for orthopaedic surgeons who are slowly reestablishing medical activity following the pandemic