Genetic Susceptibility of ACE2 and TMPRSS2 in Six Common Cancers and Possible Impacts on COVID-19.

PURPOSE: Coronavirus disease 2019 (COVID-19) pandemic has spread worldwide rapidly and patients with cancer have been considered as a vulnerable group for this infection. This study aimed to examine the expressions of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in tumor tissues of six common cancer types. MATERIALS AND METHODS: The expression levels of ACE2 and TMPRSS2 in tumors and control samples were obtained from online databases. Survival prognosis and biological functions of these genes were investigated for each tumor type. RESULTS: There was the overexpression of ACE2 in colon and stomach adenocarcinomas compared to controls, meanwhile colon and prostate adenocarcinomas showed a significantly higher expression of TMPRSS2. Additionally, survival prognosis analysis has demonstrated that upregulation of ACE2 in liver hepatocellular carcinoma was associated with higher overall survival (hazard ratio, 0.65; p=0.016) and disease-free survival (hazard ratio, 0.66; p=0.007), while overexpression of TMPRSS2 was associated with a 26% reduced risk of death in lung adenocarcinoma (p=0.047) but 50% increased risk of death in breast invasive carcinoma (p=0.015). CONCLUSION: There is a need to take extra precautions for COVID-19 in patients with colorectal cancer, stomach cancer, and lung cancer. Further information on other types of cancer at different stages should be investigated.

Comparison of Comorbidities in Relation to Critical Conditions among Coronavirus Disease 2019 Patients: A Network Meta-Analysis.

Severe illness and poor outcome are mainly associated with aging or certain medical comorbidities, especially chronic diseases. However, factors for unfavorable prognosis have not been well described owing to relatively small sample sizes and single-center reports. Therefore, this study aimed to compare the contribution of comorbidities in the development of critical conditions in coronavirus disease 2019 (COVID-19) patients. Pooled estimates of relative risks (RRs) and their 95% confidence intervals (CIs) were calculated by conducting a meta-analysis and network meta-analysis of 18 studies. Chronic obstructive pulmonary disease (COPD) was most strongly associated with the overall critical condition (RR = 4.22, 95% CI = 3.12 - 5.69), followed by cardiovascular disease (CVD) (RR = 3.00, 95% CI = 2.41 - 3.73), malignancy (RR = 2.91, 95% CI = 2.16 - 3.91), cerebrovascular accident (CVA) (RR = 2.86, 95% CI = 1.95 - 4.19), diabetes (RR = 2.10, 95% CI = 2.16 - 3.91), hypertension (RR = 2.02, 95% CI = 1.82 - 2.23), and chronic kidney disease (RR = 2.00, 95% CI = 1.36 - 2.94). The presence of comorbidities except for chronic liver disease and chronic kidney disease significantly increased the risk of severe infection, intensive care unit (ICU) admission, and cardiac injury in the subgroup analysis by types of critical conditions. Preexisting hypertension and diabetes additionally increased the risk of acute respiratory distress syndrome (ARDS). Among comorbidities, COPD had the highest probability of leading to severe COVID-19, ICU admission, and liver injury, while malignancy was most likely to cause ARDS and cardiac injury. In summary, preexisting COPD, CVD, CVA, hypertension, diabetes, and malignancy are more likely to worsen the progression of COVID-19, with severe infection, ICU admission requirement, and cardiac injury development.

Systematic review and meta-analysis of factors associated with re-positive viral RNA after recovery from COVID-19.

Previous studies reported the positive viral RNA among coronavirus disease-2019 (COVID-19) recovered patients. This study aimed to summarize the current evidence of factors associated with the risk of disease recurrence. PubMed and Embase were searched until September 2020 to identify studies assessing characteristics of recurrence and nonrecurrence subjects after discharge. Random-effect meta-analysis was used to pool estimates of odds ratio (OR) or weighted mean difference (WMD) and their 95% confidence intervals (CIs) across studies. Meta-analysis data were available for age, sex, hospital duration, disease severity, seven comorbidities, five symptoms, five indexes of blood routine, nine indexes of blood biochemistry, four treatment therapies, two antibodies, and history of high-risk contact. Among them, hospital duration of recurrence cases was significantly shorter than nonrecurrence subjects (WMD, -1.55 days; 95% CI, -2.66 to -0.45). Fatigue, positive Immunoglobulin M (IgM), and positive IgG were associated with an increased risk of recurrence cases, with ORs and 95% CIs of 4.06 (1.14-14.4), 2.95 (1.15-7.61), and 3.45 (1.58-7.54), respectively. In contrast, the odds of recurrence cases were observed to significantly lower in subjects with elevated lactate dehydrogenase and C-reactive protein, low lymphocyte count, steroid and arbidol use, with ORs (95% CIs) of 1.08 (0.27-4.37), 0.49 (0.27-0.97), 0.64 (0.42-0.97), 0.48 (0.25-0.96), and 0.48 (0.25-0.92), respectively. This study provided up-to-date evidence of several clinical and epidemiological characteristics in the association with COVID-19 recurrence cases. Further in-depth analyses for the causal effect of factors on re-positive viral RNA are needed for the management of discharged patients with COVID-19.

Ambient air pollution, meteorology, and COVID-19 infection in Korea.

The outbreak of novel pneumonia coronavirus disease has become a public health concern worldwide. Here, for the first time, the association between Korean meteorological factors and air pollutants and the COVID-19 infection was investigated. Data of air pollutants, meteorological factors, and daily COVID-19 confirmed cases of seven metropolitan cities and nine provinces were obtained from 3 February 2020 to 5 May 2020 during the first wave of pandemic across Korea. We applied the generalized additive model to investigate the temporal relationship. There was a significantly nonlinear association between daily temperature and COVID-19 confirmed cases. Each 1°C increase in temperature was associated with 9% (lag 0-14; OR = 1.09; 95% CI = 1.03-1.15) increase of COVID-19 confirmed cases when the temperature was below 8°C. A 0.01 ppm increase in NO2 (lag 0-7, lag 0.14, and lag 0-21) was significantly associated with increases of COVID-19 confirmed cases, with ORs (95% CIs) of 1.13 (1.02-1.25), 1.19 (1.09-1.30), and 1.30 (1.19-1.41), respectively. A 0.1 ppm increase in CO (lag 0-21) was associated with the increase in COVID-19 confirmed cases (OR = 1.10, 95% CI = 1.04-1.16). There was a positive association between per 0.001 ppm of SO2 concentration (lag 0, lag 0-7, and lag 0-14) and COVID-19 confirmed cases, with ORs (95% CIs) of 1.13 (1.04-1.22), 1.20 (1.11-1.31), and 1.15 (1.07-1.25), respectively. There were significantly temporal associations between temperature, NO2 , CO, and SO2 concentrations and daily COVID-19 confirmed cases in Korea.

Treatment Options for Severe Acute Respiratory Syndrome, Middle East Respiratory Syndrome, and Coronavirus Disease 2019: a Review of Clinical Evidence.

Coronaviruses have caused serious Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Coronavirus Disease 2019 (COVID-19) outbreaks, and only remdesivir has been recently indicated for the treatment of COVID-19. In the line of therapeutic options for SARS and MERS, this study aims to summarize the current clinical evidence of treatment options for COVID-19. In general, the combination of antibiotics, ribavirin, and corticosteroids was considered as a standard treatment for patients with SARS. The addition of this conventional treatment with lopinavir/ritonavir, interferon, and convalescent plasma showed potential clinical improvement. For patients with MERS, ribavirin, lopinavir/ritonavir, interferon, and convalescent plasma were continuously recommended. However, a high-dose of corticosteroid was suggested for severe cases only. The use of lopinavir/ritonavir and convalescent plasma was commonly reported. There was limited evidence for the effect of corticosteroids, other antiviral drugs like ribavirin, and favipiravir. Monoclonal antibody of tocilizumab and antimalarial agents of chloroquine and hydroxychloroquine were also introduced. Among antibiotics for infection therapy, azithromycin was suggested. In conclusion, this study showed the up-to-date evidence of treatment options for COVID-19 that is helpful for the therapy selection and the development of further guidelines and recommendations. Updates of on-going clinical trials and observational studies may confirm the current findings.

Characteristics of COVID-19 Recurrence: A Systematic Review and Meta-Analysis.

Background: Previous studies reported the recurrence of coronavirus disease 2019 (COVID-19) among discharge patients. This study aimed to examine the characteristic of COVID-19 recurrence cases by performing a systematic review and meta-analysis. Methods: A systematic search was performed in PubMed and Embase and gray literature up to September 19, 2020. A random-effects model was applied to obtain the pooled prevalence of disease recurrence among recovered patients and the prevalence of subjects underlying comorbidity among recurrence cases. The other characteristics were calculated based on the summary data of individual studies. Results: A total of 41 studies were included in the final analysis, we have described the epidemiological characteristics of COVID-19 recurrence cases. Of 3,644 patients recovering from COVID-19 and being discharged, an estimate of 15% (95% CI, 12% to 19%) patients was re-positive with SARS-CoV-2 during the follow-up. This proportion was 14% (95% CI, 11% to 17%) for China and 31% (95% CI, 26% to 37%) for Korea. Among recurrence cases, it was estimated 39% (95% CI, 31% to 48%) subjects underlying at least one comorbidity. The estimates for times from disease onset to admission, from admission to discharge, and from discharge to RNA positive conversion were 4.8, 16.4, and 10.4 days, respectively. Conclusion: This study summarized up-to-date evidence from case reports, case series, and observational studies for the characteristic of COVID-19 recurrence cases after discharge. It is recommended to pay attention to follow-up patients after discharge, even if they have been in discharge quarantine.

Short-term exposure to ambient air pollution in association with COVID-19 of two clusters in South Korea.

OBJECTIVES: This study aimed to examine the association between six air pollutants and COVID-19 infection in two main clusters, which accounted for 83% of total confirmed cases in Korea. METHODS: We collected the data on daily confirmed cases between February 24, 2020 and September 12, 2020. Data on six air pollutants (PM2.5 , PM10 , O3 , NO2 , CO and SO2 ) and four meteorological factors (temperature, wind speed, humidity and air pressure) were obtained on seven days prior to the research period. The generalised additive model and the distributed lag nonlinear model were applied to generate the relative risks (RRs) and 95% confidence intervals (CIs) for the associations. Pooled estimates for clusters were obtained by applying a random-effects model. RESULTS: We found that NO2 concentration was positively associated with daily confirmed cases in both Seoul-Gyeonggi and Daegu-Gyeongbuk clusters, with RRs (95% CIs) of 1.22 (1.03-1.44) and 1.66 (1.25-2.19), respectively. However, SO2 concentration was observed to be associated with daily confirmed cases in the Seoul-Gyeonggi cluster only (RR = 1.30, 95% CI = 1.10-1.54), whereas PM2.5 and CO concentrations were observed to be associated with daily confirmed cases in the Daegu-Gyeongbuk cluster only (RR = 1.14, 95% CI = 1.02-1.27 and RR = 1.30, 95% CI = 1.15-1.48, respectively). CONCLUSIONS: Our data found that NO2 concentration was positively associated with daily confirmed cases in both clusters, whereas the effect of PM2.5 , CO and SO2 on COVID-19 infection in two clusters was different.

Treatment Options for Severe Acute Respiratory Syndrome, Middle East Respiratory Syndrome, and Coronavirus Disease 2019: a Review of Clinical Evidence

Coronaviruses have caused serious Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Coronavirus Disease 2019 (COVID-19) outbreaks, and only remdesivir has been recently indicated for the treatment of COVID-19. In the line of therapeutic options for SARS and MERS, this study aims to summarize the current clinical evidence of treatment options for COVID-19. In general, the combination of antibiotics, ribavirin, and corticosteroids was considered as a standard treatment for patients with SARS. The addition of this conventional treatment with lopinavir/ritonavir, interferon, and convalescent plasma showed potential clinical improvement. For patients with MERS, ribavirin, lopinavir/ritonavir, interferon, and convalescent plasma were continuously recommended. However, a high-dose of corticosteroid was suggested for severe cases only. The use of lopinavir/ritonavir and convalescent plasma was commonly reported. There was limited evidence for the effect of corticosteroids, other antiviral drugs like ribavirin, and favipiravir. Monoclonal antibody of tocilizumab and antimalarial agents of chloroquine and hydroxychloroquine were also introduced. Among antibiotics for infection therapy, azithromycin was suggested. In conclusion, this study showed the up-to-date evidence of treatment options for COVID-19 that is helpful for the therapy selection and the development of further guidelines and recommendations. Updates of on-going clinical trials and observational studies may confirm the current findings.