Potential Similarities in Sex Difference in Key Genes and Their Expression, Network, EQTL and Pathways between COVID-19 and Chronic Kidney Disease Based on Mouse Model.

COVID-19 and chronic kidney disease (CKD) share similarity in sex bias and key genes in the disease pathway of sex difference. We investigated the sex difference of molecular pathways of four key players of these two diseases using an existing large set of whole genome expression profiles from the kidneys of female and male mouse models. Our data show that there is little to no correlation at the whole genome expression level between female and male mice among these four genes. There are considerable sex differences among genes in upstream regulation, Ace2 complex interaction, and downstream pathways. Snap25 and Plcb4 may play important roles in the regulation of the expression level of Adam17, Tmprss2, and Cd146 in females. In males, Adh4 is a candidate gene for the regulation of Adam17, while Asl, Auts2, and Rabger1 are candidates for Tmprss2. Within the Ace2 complex, Cd146 directly influences the expression level of Adam17 and Ace2 in the female, while in the male Adam potentially has a stronger influence on Ace2 than that of Tmprss2. Among the top 100 most related genes, only one or two genes from four key genes and 11 from the control B-Actin were found to be the same between sexes. Among the top 10 sets of genes in the downstream pathway of Ace2, only two sets are the same between the sexes. We concluded that these known key genes and novel genes in CKD may play significant roles in the sex difference in the CKD and COVID-19 disease pathways.

Heterotopic lung transplant: a feasible approach to compensate for organ shortages.

Lung transplants are still limited by the shortage of suitable donor lungs, especially during the coronavirus disease 2019 pandemic. A heterotopic lung transplant (HLTx), as a flexible surgical procedure, can maximize the potential of donor lungs in an emergency, but its widespread use is hindered by difficulties in anastomosis and paucity of outcome data. We performed a retrospective review of 4 patients, each of whom received an HLTxs over 1 year, including 1 left-to-right single HLTx, 2 right-to-left single HLTxs and 1 lobar HLTx (right upper lobe-to-left). The median recipient age was 58.5 years (46-68); 3 patients were male. The postoperative hospital stay was 33 days (30-42). One recipient lived for 10 years and died of bronchiolitis obliterans syndrome; the others were alive with no major morbidity at 12 to 31 months after the operation with a 1-year survival of 100%. The follow-up chest images showed that transplanted lungs could be inflated well and adapted morphologically to fill the thoracic cavity in the short and long term. This study demonstrates that an HLTx is a feasible alternative to a conventional lung transplant in emergency cases and could be considered in selected patients at advanced medical centres.

First lung transplant in Wuhan for a critical and elderly COVID-19 patient.

INTRODUCTION: We report the case of a 65-year-old Coronavirus disease 2019 (COVID-19) patient with pneumonia and subsequent end-stage pulmonary failure who required 63 days of mechanical ventilation (MV) and 62 days of extracorporeal membrane oxygenation (ECMO). METHODS: On Day 45, a comprehensive interdisciplinary discussion on the best course of treatment resulted in the general consensus that his lungs would not recover. As such, he was evaluated and listed for a lung transplant. RESULTS: We performed a bilateral lung transplant, and the patient was weaned off ECMO and MV postoperatively. This is the first report of lung transplants in patients with COVID-19 in Wuhan. CONCLUSIONS: We suggest that a lung transplantation may be a viable treatment for patients with end-stage pulmonary failure secondary to COVID-19 in selected situations.

COVID-19 vaccine: Call for employees in international transportation industries and international travelers as the first priority in global distribution.

While countries are in a hurry to obtain SARS-CoV-2 vaccine, we are concerned with the availability of vaccine and whether a vaccine will be available to all in need. We predicted three possible scenarios for vaccine distributions and urge an international united action on the worldwide equitable access. In case the international community does not reach a consensus on how to distribute the vaccine to achieve worldwide equitable access, we call for a distribution plan that includes the employees in international transportation industries and international travelers to halt the disease transmission and promote the recovery of the global economy.

Lung transplantation as therapeutic option in acute respiratory distress syndrome for coronavirus disease 2019-related pulmonary fibrosis.

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS: LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.

High incidence of stroke in COVID-19 patients.

A retrospective analysis of 11 COVID-19 patients complicated with stroke was performed. It was found that the incidence of stroke in patients with COVID-19 was significantly higher than the average level of the general population (P=0.003), and the D-dimer levels of 11 stroke patients were significantly higher than other patients (P=0.004). The significant increase of D-dimer can be used as an early warning indicator of cerebral infarction. It is critical to have a response plan for treating acute stroke in COVID-19 patients.

Novel insight from the first lung transplant of a COVID-19 patient.

BACKGROUND: To reveal detailed histopathological changes, virus distributions, immunologic properties and multi-omic features caused by SARS-CoV-2 in the explanted lungs from the world's first successful lung transplantation of a COVID-19 patient. MATERIALS AND METHODS: A total of 36 samples were collected from the lungs. Histopathological features and virus distribution were observed by optical microscope and transmission electron microscope (TEM). Immune cells were detected by flow cytometry and immunohistochemistry. Transcriptome and proteome approaches were used to investigate main biological processes involved in COVID-19-associated pulmonary fibrosis. RESULTS: The histopathological changes of the lung tissues were characterized by extensive pulmonary interstitial fibrosis and haemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3+ CD4- T cells, neutrophils, NK cells, γ/δ T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL-1ß and IL-6 were in the area of mild fibrosis. Multi-omics analyses revealed a total of 126 out of 20,356 significant different transcription and 114 out of 8,493 protein expression in lung samples with mild and severe fibrosis, most of which were related to fibrosis and inflammation. CONCLUSIONS: Our results provide novel insight that the significant neutrophil/ CD3+ CD4- T cell/ macrophage activation leads to cytokine storm and severe fibrosis in the lungs of COVID-19 patient and may contribute to a better understanding of COVID-19 pathogenesis.