Ligand/Receptor-mediated Cell Communication Alteration Causes the Lung Inflammation Microenvironment and the Redistribution of Inter-tissue Immune Cells in COVID-19 Patients (preprint)

How SARS-CoV-2 causes disturbances of the lung microenvironment and systemic immune response remains a mystery. Here, we first analyze detailedly paired single-cell transcriptome data of the lungs, blood and bone marrow of two patients who died of COVID-19. Second, our results demonstrate that SARS-CoV-2 infection significantly increases the cellular communication frequency between AT1/AT2 cells and highly inflammatory myeloid cells, and induces the pulmonary inflammation microenvironment, and drives the disorder of fibroblasts, club and ciliated cells, thereby causing the increase of pulmonary fibrosis and mucus accumulation. Third, our works reveal that the increase of the lung T cell infiltration is mainly recruited by myeloid cells through certain ligands/receptors (ANXA1/FPR1, C5AR1/RPS19 and CCL5/CCR1), rather than AT1/AT2. Fourth, we find that some ligands and receptors such as ANXA1/FPR1, CD74/COPA, CXCLs/CXCRs, ALOX5/ALOX5AP, CCL5/CCR1, are significantly activated and shared among patients’ lungs, blood and bone marrow, implying that dysregulated ligands and receptors may cause the migration, redistribution and the inflammatory storm of immune cells in different tissues. Overall, our study reveals a latent mechanism by which the disorders of ligands and receptors caused by SARS-CoV-2 infection drive cell communication alteration, the pulmonary inflammatory microenvironment and systemic immune responses across tissues in COVID-19 patients.

Relations of Treatments for Cardiometabolic Co-Morbidities with Critical Outcomes and Mortality in Hospitalized Patients with Coronavirus Disease 2019 (COVID-19): A Retrospective Cohort Study (preprint)

Background: Available evidence indicates that COVID-19 patients with preexisting cardiometabolic diseases (CMD) such as diabetes, hypertension, and cardiovascular disease (CVD) are more likely to have poor outcomes. We investigated whether pre-admission treatments for CMD may have impact on clinical outcomes in hospitalized COVID-19 patients.Methods: We conducted a retrospective cohort study of 1,525 COVID-19 patients admitted to two designated hospitals in Wuhan, China from January 21, 2020 to March 14, 2020 when majority of the initial COVID-19 patients were hospitalized. All medical records were reviewed by a panel of physicians to determine history of CMD and medications. The primary endpoint was critical illness comprised of admission to intensive care unit (ICU), mechanical ventilation, and use of extracorporeal membrane oxygenation (ECMO). Confirmed secondary endpoint was all-cause mortality. Multivariable logistic regression and Cox regression were used for analyzing primary and secondary endpoint, respectively.Findings: Of the 1,525 patients with COVID-19, 623 (40.9%) had CMD history. Compared with patients without CMD, those with CMD but without treatment had a 3-fold increased risk of critical illness (OR, 3.13; 95% CI, 1.86-5.20), and a 3-fold greater risk of death (HR, 3.08; 95% CI, 1.91-4.99). Among those with CMD comorbidities, the pre-admission treatment for CMD was associated with significantly lower risk of developing critical illness (OR, 0.28; 95% CI, 0.16-0.47) and death (HR, 0.25; 95% CI, 0.16-0.40). These findings were most salient in older patients (> 65 y). Moreover, in patients with hypertension, those treated with ACEI/ARB did not have higher risk of critical illness or death than those who were on other antihypertensive medications.Interpretation: This large retrospective cohort of COVID-19 patients support the notion that pre-admission management of CMD comorbidities significantly improve clinical outcomes and prognosis of COVID-19, especially among those aged > 65 years.Funding Statement: This work was supported by the Science and Technology Program of Guangzhou (No.201803040012), the National Key Research and Development Program of China (No.2017YFC1307603, No.2016YFC1301305) and the Key Area R&D Program of Guangdong Province (No.2019B020227005).Declaration of Interests: None.Ethics Approval Statement: The study was approved by the institution ethics review board (IRB) of Guangdong Provincial People's Hospital and the two collaborating hospitals. This study used only deidentified retrospective data and written-informed consent was waived during the pandemic.

Detection of 2019 novel coronavirus in semen and testicular biopsy specimen of COVID-19 patients (preprint)

Background: As of March 11, 2020, the COVID-19 outbreak was declared as a pandemic. Expending our understanding of the transmission routes of the viral infection is crucial in controlling the outbreak. It is unclear whether the 2019 novel coronavirus (2019-nCoV) can directly infect the testes or male genital tract and be sexually transmitted from males. Methods: From January 31 to March 14, 2020, 12 patients in recovery and one patient died of COVID-19 were included in this descriptive study. The clinical characteristics, laboratory findings, chest CT scans and outcome data were recorded. To examine whether there is sexual transmission from male, we employed realtime polymerase chain reaction testing (RT-PCR) to detect 2019-nCov in semen or testicular biopsy specimen. Findings: The age range of the 12 patients in recovery was 22-38 years. None of the patients developed severe COVID-19 pneumonia. As of March 14, 2020, ten patients discharged from the hospital while the rest 2 had developed into recovery stage. All of the patients in recovery tested negative for 2019-nCoV RNA in semen samples. Another died patient was 67 years old, who died in March 10, 2020 and tissue sample via testicular biopsy was tested negative for viral RNA. Conclusion: No positive RT-PCR result was found in the semen or testicular biopsy specimen. The results from this study show no evidence of sexual transmission of 2019-nCov from males.