Absence of detectable SARS-CoV-2 replication in ex vivo cultured cornea and cornea-derived epithelial cells.

PURPOSE: To study the possibility of SARS-CoV-2 to infect human corneal cells and tissues under standard corneal culture conditions using explants of COVID-19 donors and primary cornea-derived epithelial cells. METHODS: Cornea isolated from deceased COVID-19 donors was cultured for 4 weeks, and SARS-CoV-2 replication was monitored by qRT-PCR. Furthermore, primary corneal epithelial cells from healthy donors were cultured ex vivo and infected with SARS-CoV-2 and human cytomegalovirus (HCMV) as a control. Infection status was assessed by western blotting and reporter gene expression using green fluorescent protein-expressing viral strains. ACE2 and TMPRSS2 receptor expression levels in cornea and epithelial cells were assessed by qRT-PCR. RESULTS: We did not detect SARS-CoV-2 replication in 10 corneas isolated from deceased COVID-19 patients and cultured for 4 weeks, indicating absence of infection under natural conditions. Furthermore, high-titer SARS-CoV-2 infection of ex vivo cultured cornea-derived epithelial cells did not result in productive virus replication. In contrast, the same cells were highly permissive for HCMV. This phenotype could potentially be explained by low ACE2 and TMPRSS2 transcriptional activity in cornea and cornea-derived epithelial cells. CONCLUSIONS: Our data suggest that cornea and limbal epithelial cells are refractory to productive SARS-CoV-2 infection. This could be due to the absence of robust receptor expression levels necessary for viral entry. This study adds further evidence to support the very low possibility of transmission of SARS-CoV-2 from an infected corneal transplant donor to a recipient in corneal organ cultures.

Evaluation of a medical education policy with compulsory rural service in China.

Background: Since 2010, China has implemented a national programme to train general practitioners for rural areas. The programme enrolled medical students with a rural background who signed a contract for 6 years' compulsory rural service after graduation. China is transitioning its national COVID-19 strategies in view of the features of coronavirus Omicron variant, the vaccination coverage, and the need for socioeconomic development. Strengthening primary health care, especially the health workforce in rural areas, should be an important consideration during the policy transition. This study aims to evaluate the implementation process of enrolling medical students in the programme, their willingness to work in the rural settings and their actual job choice after graduation. Methods: The study chose four medical universities in central and western China. A total of 2,041 medical graduates who have signed a contract for compulsory rural service and 1,576 medical graduates enrolled "as usual" (no compulsory rural service) were recruited in five campaigns-every June from 2015 to 2019. A survey was conducted 1 week before their graduation ceremony. Results: The top three reasons for choosing this programme were: a recommendation of a family member or teacher, a guaranteed job after graduation and the waiver of the tuition fee. 23.0-29.7% of the study participants were not familiar with the policy details. 39.1% of the medical students signed a contract with a county other than that of their hometown. Medical graduates on the compulsory rural service programme had very low willingness (1.9%) to work in rural areas but 86.1% of them actually worked at township health centers. In contrast, the willingness to work at township health centers was 0.2% for the comparison group (medical graduates without the contract), and their actual job choice at township health centers was 0%. Conclusions: Although the well-trained medical graduates on the compulsory rural service programme have low willingness to work in the township health centers, 86.1% of them choose to do so following their contract. This programme will strengthen the primary health workforce to deal with the increasing disease burden as China is transitioning its national COVID-19 strategies.

CD8+ Tregs kill pathogenic cells to avert autoimmunity.

Mouse Ly49+CD8+ regulatory T cells (Tregs) can subdue autoreactive CD4+ T cells to suppress autoimmunity. Recently, Li et al. demonstrated that killer-cell immunoglobulin-like receptor (KIR)+CD8+ T cells are the human equivalent of Ly49+CD8+ regulatory T cells and kill pathogenic CD4+ T cells, which can be increased in certain human autoimmune diseases and viral infections.

Hypertension as a sequela in patients of SARS-CoV-2 infection.

BACKGROUND: COVID-19 is a respiratory infectious disease caused by SARS-CoV-2, and cardiovascular damage is commonly observed in affected patients. We sought to investigate the effect of SARS-CoV-2 infection on cardiac injury and hypertension during the current coronavirus pandemic. STUDY DESIGN AND METHODS: The clinical data of 366 hospitalized COVID-19-confirmed patients were analyzed. The clinical signs and laboratory findings were extracted from electronic medical records. Two independent, experienced clinicians reviewed and analyzed the data. RESULTS: Cardiac injury was found in 11.19% (30/268) of enrolled patients. 93.33% (28/30) of cardiac injury cases were in the severe group. The laboratory findings indicated that white blood cells, neutrophils, procalcitonin, C-reactive protein, lactate, and lactic dehydrogenase were positively associated with cardiac injury marker. Compared with healthy controls, the 190 patients without prior hypertension have higher AngⅡ level, of which 16 (8.42%) patients had a rise in blood pressure to the diagnostic criteria of hypertension during hospitalization, with a significantly increased level of the cTnI, procalcitonin, angiotensin-II (AngⅡ) than those normal blood pressure ones. Multivariate analysis indicated that elevated age, cTnI, the history of hypertension, and diabetes were independent predictors for illness severity. The predictive model, based on the four parameters and gender, has a good ability to identify the clinical severity of COVID-19 in hospitalized patients (area under the curve: 0.932, sensitivity: 98.67%, specificity: 75.68%). CONCLUSION: Hypertension, sometimes accompanied by elevated cTnI, may occur in COVID-19 patients and become a sequela. Enhancing Ang II signaling, driven by SARS-CoV-2 infection, might play an important role in the renin-angiotensin system, and consequently lead to the development of hypertension in COVID-19.

Clinical characteristics, risk factors, and cardiac manifestations of cancer patients with COVID-19.

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features, which may be deteriorated in patients with cancer. However, cardiac outcomes of cancer patients with COVID-19 have not been closely examined. We retrospectively assessed 1,244 patients with COVID-19 from February 1 to August 31, 2020 (140 cancer and 1,104 noncancer patients). Demographic and clinical data were obtained and compared between cancer and noncancer groups. Including the cardiac biomarkers, we also analyzed laboratory findings between these two groups. Risk factors for in-hospital mortality were identified by multivariable Cox regression models. For cancer group, 56% were in severe and critical status with more diabetes and immune deficiency, whereas the proportion was 10% for noncancer group. Patients with cancer had increased levels of leukocyte, neutrophil count, and blood urea nitrogen (BUN) (all P < 0.01), whereas lymphocyte count was significantly lower (P < 0.001). The most common solid tumor types were gastrointestinal cancer (26%), lung cancer (21%), and breast and reproductive cancer (both 19%). There is a rising for cardiac biomarkers, including pro-B-type natriuretic peptide (Pro-BNP), sensitive troponin I (cTnI), myoglobin (MYO), creatine kinase-MB (CK-MB), as well as D-Dimer in COVID-19 cancer population, especially in deceased subjects with cancer. The 30-day in-hospital mortality in cancer group was dramatically raised than that in noncancer group (12.9% vs. 4.0%, P < 0.01). In multivariable Cox regression models, fever, disease severity status, and underlying diseases were risk factors for mortality. COVID-19 patients with cancer relate to deteriorating conditions and poor cardiac outcomes accompanied by a high in-hospital mortality, which warrants more aggressive treatment.NEW & NOTEWORTHY Our study indicates that the 30-day mortality is higher in COVID-19 patients with cancer; more COVID-19 patients with cancer are in severe and critical status; age, respiratory rate, neutrophil count, AST, BUN, MYO, Pro-BNP, disease severity status, underlying diseases, and fever are risk factors for in-hospital mortality among COVID-19 cancer cases; COVID-19 patients with cancer display severely impaired myocardium, damaged heart function, and imbalanced homeostasis of coagulation; what is more, those with both cancer and CVD have more significantly increased Pro-BNP and D-Dimer level.

The Scientific Foundation of Chinese Herbal Medicine against COVID-19.

The recent coronavirus disease 2019 (COVID-19) pandemic outbreak has caused a serious global health emergency. Supporting evidence shows that COVID-19 shares a genomic similarity with other coronaviruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and that the pathogenesis and treatment strategies that were applied 17 years ago in combating SARS-CoV and other viral infections could be taken as references in today's antiviral battle. According to the clinical pathological features of COVID-19 patients, patients can suffer from five steps of progression, starting with severe viral infection and suppression of the immune system and eventually progressing to cytokine storm, multi-organ damage, and lung fibrosis, which is the cause of mortality. Therefore, early prevention of disease progression is important. However, no specific effective drugs and vaccination are currently available, and the World Health Organization is urging the development of novel prevention and treatment strategies. Traditional Chinese medicine could be used as an alternative treatment option or in combination with Western medicine to treat COVID-19, due to its basis on historical experience and holistic pharmacological action. Here, we summarize the potential uses and therapeutic mechanisms of Chinese herbal formulas (CHFs) from the reported literature, along with patent drugs that have been recommended by institutions at the national and provincial levels in China, in order to verify their scientific foundations for treating COVID-19. In perspective, more basic and clinical studies with multiple high-tech and translational technologies are suggested to further confirm the therapeutic efficacies of CHFs.