ABSTRACT
SARS-CoV-2 enters the respiratory tract where it infects the alveoli epithelial lining. However, patients have sequelae that extend well beyond the alveoli into the pulmonary vasculature and perhaps beyond to brain and other organs. Because of the dynamic events within blood vessels, histology fails to report on platelet and neutrophil dynamics. Because of the rapid non-transcriptional behaviour of these cells neither single-cell RNAseq nor proteomics report robustly on their critical behaviours. We used intravital-microscopy in level-3 containment to examine the pathogenesis of SARS-CoV-2 within three organs in mice expressing human-ACE-2 ubiquitously (CAG-AC-70) or on epithelium (K18-promoter). Using a neon-green-SARS-CoV-2, we observed both epithelium and endothelium infected in AC70 mice but only the epithelium in K18 mice. There was increased neutrophils in the microcirculation but not in the alveoli of the AC70 lungs. Platelets formed large aggregates in the pulmonary capillaries. Despite only neurons being infected within the brain, profound neutrophil adhesion forming the nidus of large platelet aggregates were observed in the brain microcirculation with many non-perfused microvessels. Neutrophils were seen breaching the brain endothelial layer associated with a significant disruption of the blood-brain-barrier. Despite ubiquitous ACE-2 expression, CAG-AC-70 mice had very small increases in blood cytokine, no increase in thrombin, no infected circulating cells and no liver involvement suggesting limited systemic effects. In summary, our imaging of SARS-CoV-2-infected mice gave direct evidence that there is a significant perturbation locally in the lung and brain microcirculation induced by local viral infection leading to increased inflammation and thrombosis in these organs.
ABSTRACT
PURPOSE: Coronavirus disease 2019 (COVID-19) has affected many parts of daily life and healthcare, including cancer screening and diagnosis. The purpose of this study was to determine whether there was an upshift in the colorectal cancer stage at diagnosis due to delays related to the COVID-19 outbreak. METHODS: From January to June of each year from 2017 to 2020, a total of 3,229 patients who were first diagnosed with colorectal cancer were retrospectively reviewed. Those enrolled from 2017 to 2019 were classified as the 'pre-COVID' group, and those enrolled in 2020 were classified as the 'COVID' group. The primary outcome was the rate of stage IV disease at the time of diagnosis. RESULTS: There was no statistically significant difference in the proportion of stage IV patients between the pre-COVID and COVID groups (P = 0.19). The median preoperative carcinoembryonic antigen level in the COVID group was higher than in the pre-COVID group in all stages (all P < 0.05). In stage I, II patients who underwent radical surgery, the lymphatic invasion was more presented in COVID patients (P = 0.009). CONCLUSION: We did not find significant stage upshifting in colorectal cancer during the COVID-19 outbreak. However, there were more initially unresectable stage IV colorectal cancer patients with a low conversion rate to resectable status, and more patients had factors related to poor prognosis. These results may become more apparent over time, so it is vital not to neglect cancer screening to not delay the diagnosis during the COVID-19 epidemic.
ABSTRACT
BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread around the globe, and it is important to determine the risk factors of death in the general population. Our study aimed to determine the risk factors of death and severe illness requiring supplemental oxygen therapy based on the demographic and clinical characteristics of COVID-19 patients in Korea. METHODS: In this study, we used data provided by the Korea Disease Control and Prevention Agency (KDCA) and analyzed a total of 5,068 patients with COVID-19, excluding 19 pregnant women and 544 individuals with missing data. We performed logistic regression analysis to determine the impact of early symptoms on survival and severe disease. Logistic regression models included sex, age, number of comorbidities, symptoms on admission, blood pressure, heart rate, and body temperature as explanatory variables, and death and oxygen therapy as outcome variables. RESULTS: Logistic regression analyses revealed that the male sex, older age (≥ 60 years), higher number of comorbidities, presence of symptoms on admission, heart rate ≥ 120 bpm, and body temperature ≥ 37.5°C presented with higher risk of in-hospital death and oxygen therapy requirement. Conversely, rhinorrhea and headache were associated with a low risk of death and oxygen therapy requirement. The findings showed that cough, sputum, and fever were the most common symptoms on admission, while 25.3% of patients with COVID-19 were asymptomatic. CONCLUSION: COVID-19 patients with high-risk early symptoms on admission, such as dyspnea and altered mental status, and those without low-risk symptoms of rhinorrhea and headache should be included in priority treatment groups.