Asymptomatic patients and asymptomatic phases of Coronavirus Disease 2019 (COVID-19): a population-based surveillance study.

In this population-based study, we identified 307 confirmed COVID-19 cases from massive surveillance, including 129 551 individuals screened at fever clinics or returning from Hubei and 3710 close contacts of confirmed COVID-19 patients. Among them, 17 patients were asymptomatic at initial clinical assessment. These asymptomatic patients on admission accounted for a small proportion of all patients (5.54%) with relatively weak transmissibility, and the detection rate was 0.35 per 100 close contacts. Moreover, the dynamics of symptoms of the 307 patients showed that the interval from symptom remission to the final negativity of viral nucleic acid was 5.0 days (interquartile range 2.0 to 11.0 days), with 14 patients (4.56%) having re-detectable viral RNA after discharge. Overall, our findings suggested asymptomatic carriers and presymptomatic patients only accounted for a small proportion of COVID-19 patients. Also, the asymptomatic phase during recovery from COVID-19 implied that negativity in viral RNA is necessary as a de-isolation criterion and follow-up is recommended.

Clinical outcomes of different therapeutic options for COVID-19 in two Chinese case cohorts: A propensity-score analysis.

BACKGROUND: The timing of administration of agents and use of combination treatments in COVID-19 remain unclear. We assessed the effectiveness of therapeutics in cohorts in Hong Kong SAR and Anhui, China. METHODS: We conducted propensity-score analysis of 4771 symptomatic patients from Hong Kong between 21st January and 6th December 2020, and 648 symptomatic patients from Anhui between 1st January and 27th February 2020. We censored all observations as at 13st December 2020. Time from hospital admission to discharge, and composite outcome of death, invasive mechanical ventilation or intensive care unit admission across 1) all therapeutic options including lopinavir-ritonavir, ribavirin, umifenovir, interferon-alpha-2b, interferon-beta-1b, corticosteroids, antibiotics, and Chinese medicines, and 2) four interferon-beta-1b combination treatment groups were investigated. FINDINGS: Interferon-beta-1b was associated with an improved composite outcome (OR=0.55, 95%CI 0.38, 0.80) and earlier discharge (-8.8 days, 95%CI -9.7, -7.9) compared to those not administered interferon-beta-1b. Oral ribavirin initiated within 7 days from onset was associated with lower risk of the composite outcome in Hong Kong (OR=0.51, 95%CI 0.29, 0.90). Lopinavir-ritonavir, intravenous ribavirin, umifenovir, corticosteroids, interferon-alpha-2b, antibiotics or Chinese medicines failed to show consistent clinical benefit. Interferon-beta-1b co-administered with ribavirin was associated with improved composite outcome (OR=0.50, 95%CI 0.32, 0.78) and earlier discharge (-2.35 days, 95%CI -3.65, -1.06) compared to interferon-beta-1b monotherapy. INTERPRETATION: Our findings support the early administration of interferon-beta-1b alone or in combination with oral ribavirin for COVID-19 patients. FUNDING: Hong Kong Health and Medical Research Fund; Hong Kong Innovation and Technology Commission; Chinese Fundamental Research Funds for the Central Universities.

Glycemic control in children and teenagers with type 1 diabetes around lockdown for COVID-19: A continuous glucose monitoring-based observational study.

AIMS/INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic urged authorities to impose rigorous quarantines and brought considerable changes to people's lifestyles. The impact of these changes on glycemic control has remained unclear, especially the long-term effect. We aimed to investigate the impact of COVID-19 lockdown on glycemic control in children and adolescents with type 1 diabetes. MATERIALS AND METHODS: This observational study enrolled children with type 1 diabetes using continuous glucose monitoring. Continuous glucose monitoring data were extracted from the cloud-based platform before, during and after lockdown. Demographics and lifestyle change-related information were collected from the database or questionnaires. We compared these data before, during and after lockdown. RESULTS: A total of 43 children with type 1 diabetes were recruited (20 girls; mean age 7.45 years; median diabetes duration 1.05 years). We collected 41,784 h of continuous glucose monitoring data. Although time in range (3.9-10.0 mmol/L) was similar before, during and after lockdown, the median time below range <3.9 mmol/L decreased from 3.70% (interquartile range [IQR] 2.25-9.53%) before lockdown to 2.91% (IQR 1.43-5.95%) during lockdown, but reversed to 4.95% (IQR 2.11-9.42%) after lockdown (P = 0.004). Time below range <3.0 mmol/L was 0.59% (IQR 0.14-2.21%), 0.38% (IQR 0.05-1.35%) and 0.82% (IQR 0.22-1.69%), respectively (P = 0.008). The amelioration of hypoglycemia during lockdown was more prominent among those who had less time spent <3.9 mmol/L at baseline. During lockdown, individuals reduced their physical activity, received longer sleep duration and spent more time on diabetes management. In addition, they attended outpatient clinics less and turned to telemedicine more frequently. CONCLUSION: Glycemic control did not deteriorate in children and teenagers with type 1 diabetes around the COVID-19 pandemic. Hypoglycemia declined during lockdown, but reversed after lockdown, and the changes related to lifestyle might not provide a long-term effect.

Effects of sources of social support and resilience on the mental health of different age groups during the COVID-19 pandemic.

BACKGROUND: A pandemic is a very stressful event, especially for highly vulnerable people (e.g., older adults). The purpose of the current study was to investigate the main and interactive relationships of social support and resilience on individual mental health during the COVID-19 pandemic across three age groups: emerging adults, adults, and older adults. METHODS: A survey was conducted with 23,192 participants aged 18-85. Respondents completed a questionnaire, including items on the COVID-19-related support they perceived from different sources, the abbreviated version of the Connor-Davidson Resilience Scale, and the Mental Health Inventory. RESULTS: Latent profile analysis identified five profiles of social support, and the patterns of potential profiles were similar in all groups. However, category distribution in the five profiles was significantly different among the age groups. Furthermore, analysis using the BCH command showed significant differences in mental health among these profiles. Lastly, interactive analyses indicated resilience had a positive relationship with mental health, and social support served as a buffer against the negative impact of low resilience on mental health. CONCLUSIONS: This study provides quantitative evidence for socioemotional selectivity theory (SST) and enables several practical implications for helping different age groups protecting mental health during pandemic.

Redefining Cardiac Biomarkers in Predicting Mortality of Inpatients With COVID-19.

The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for hs-cTnI (high-sensitivity cardiac troponin I) was 7.12 ([95% CI, 4.60-11.03] P<0.001), (NT-pro)BNP (N-terminal pro-B-type natriuretic peptide or brain natriuretic peptide) was 5.11 ([95% CI, 3.50-7.47] P<0.001), CK (creatine phosphokinase)-MB was 4.86 ([95% CI, 3.33-7.09] P<0.001), MYO (myoglobin) was 4.50 ([95% CI, 3.18-6.36] P<0.001), and CK was 3.56 ([95% CI, 2.53-5.02] P<0.001). The cutoffs of those cardiac biomarkers for effective prognosis of 28-day mortality of COVID-19 were found to be much lower than for regular heart disease at about 19%-50% of the currently recommended thresholds. Patients with elevated cardiac injury markers above the newly established cutoffs were associated with significantly increased risk of COVID-19 death. In conclusion, cardiac biomarker elevations are significantly associated with 28-day death in patients with COVID-19. The prognostic cutoff values of these biomarkers might be much lower than the current reference standards. These findings can assist in better management of COVID-19 patients to improve outcomes. Importantly, the newly established cutoff levels of COVID-19-associated cardiac biomarkers may serve as useful criteria for the future prospective studies and clinical trials.

Elevated fasting blood glucose within the first week of hospitalization was associated with progression to severe illness of COVID-19 in patients with preexisting diabetes: A multicenter observational study.

Highlights Fasting blood glucose < 10 mmol/L was proposed as a target of glycemic control during the first week of hospitalization in patients with preexisting diabetes. Poor HbA1c levels prior to coronavirus disease 2019 (COVID-19) might not be associated with severity among patients with preexisting diabetes. Mean blood glucose seemed not to be associated with poor prognosis of COVID-19.

GSTM3 variant is a novel genetic modifier in Brugada syndrome, a disease with risk of sudden cardiac death

BACKGROUND: Brugada syndrome (BrS) is a rare inherited disease causing sudden cardiac death (SCD). Copy number variants (CNVs) can contribute to disease susceptibility, but their role in Brugada syndrome (BrS) is unknown. We aimed to identify a CNV associated with BrS and elucidated its clinical implications. METHODS: We enrolled 335 unrelated BrS patients from 2000 to 2018 in the Taiwanese population. Microarray and exome sequencing were used for discovery phase whereas Sanger sequencing was used for the validation phase. HEK cells and zebrafish were used to characterize the function of the CNV variant. FINDINGS: A copy number deletion of GSTM3 (chr1:109737011-109737301, hg38) containing the eighth exon and the transcription stop codon was observed in 23.9% of BrS patients versus 0.8% of 15,829 controls in Taiwan Biobank (P <0.001), and 0% in gnomAD. Co-segregation analysis showed that the co-segregation rate was 20%. Patch clamp experiments showed that in an oxidative stress environment, GSTM3 down-regulation leads to a significant decrease of cardiac sodium channel current amplitude. Ventricular arrhythmia incidence was significantly greater in gstm3 knockout zebrafish at baseline and after flecainide, but was reduced after quinidine, consistent with clinical observations. BrS patients carrying the GSTM3 deletion had higher rates of sudden cardiac arrest and syncope compared to those without (OR: 3.18 (1.77-5.74), P<0.001;OR: 1.76 (1.02-3.05), P = 0.04, respectively). INTERPRETATION: This GSTM3 deletion is frequently observed in BrS patients and is associated with reduced INa, pointing to this as a novel potential genetic modifier/risk predictor for the development of the electrocardiographic and arrhythmic manifestations of BrS. FUNDING: This work was supported by the Ministry of Science and Technology (107-2314-B-002-261-MY3 to J.M.J. Juang), and by grants HL47678, HL138103 and HL152201 from the National Institutes of Health to CA.

Expression of SARS-CoV-2 receptor ACE2 and TMPRSS2 in human primary conjunctival and pterygium cell lines and in mouse cornea.

PURPOSE: To determine the expressions of SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2) genes in human and mouse ocular cells and comparison to other tissue cells. METHODS: Human conjunctiva and primary pterygium tissues were collected from pterygium patients who underwent surgery. The expression of ACE2 and TMPRSS2 genes was determined in human primary conjunctival and pterygium cells, human ocular and other tissue cell lines, mesenchymal stem cells as well as mouse ocular and other tissues by reverse transcription-polymerase chain reaction (RT-PCR) and SYBR green PCR. RESULTS: RT-PCR analysis showed consistent expression by 2 ACE2 gene primers in 2 out of 3 human conjunctival cells and pterygium cell lines. Expression by 2 TMPRSS2 gene primers could only be found in 1 out of 3 pterygium cell lines, but not in any conjunctival cells. Compared with the lung A549 cells, similar expression was noted in conjunctival and pterygium cells. In addition, mouse cornea had comparable expression of Tmprss2 gene and lower but prominent Ace2 gene expression compared with the lung tissue. CONCLUSION: Considering the necessity of both ACE2 and TMPRSS2 for SARS-CoV-2 infection, our results suggest that conjunctiva would be less likely to be infected by SARS-CoV-2, whereas pterygium possesses some possibility of SARS-CoV-2 infection. With high and consistent expression of Ace2 and Tmprss2 in cornea, cornea rather than conjunctiva has higher potential to be infected by SARS-CoV-2. Precaution is necessary to prevent possible SARS-CoV-2 infection through ocular surface in clinical practice.