Within-Host Evolution of SARS-CoV-2 in a B-Cell Depleted Patient With Successful Treatment.

Prolonged viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an immunocompromised host is a challenge as the treatment and infection control for chronic coronavirus disease 2019 infection is not well established and there is a potential risk of new variants emerging. A 48-year-old woman who underwent chemotherapy, including rituximab and steroid, had reactivation of SARS-CoV-2 68 days after the virus was first detected. She successfully recovered after receiving convalescent plasma and intravenous immunoglobulin. Genomic analysis demonstrated that viruses collected from the nasopharyngeal specimens at day 0 and day 68 had 18 different nucleotide mutations, implying within-host evolution after in-depth epidemiologic investigation.

Insomnia during coronavirus disease 2019 pandemic in Korea: a National sleep survey.

Coronavirus disease 2019 (COVID-19) pandemic has caused widespread increase in stress and affected sleep quality and quantity, with up to 30% prevalence of sleep disorders being reported after the declaration of the pandemic. This study aimed to assess perceived changes due to the pandemic in the prevalence of insomnia and excessive daytime sleepiness (EDS) in Korea, and identify the associated factors. An online survey was conducted among 4000 participants (2035 men and 1965 women) aged 20-69 years enrolled using stratified multistage random sampling according to age, sex, and residential area, between January, 2021 and February, 2022. The questionnaire included various items, such as socio-demographics, Insomnia Severity Index, and Epworth Sleepiness Scale (ESS). Insomnia was defined as difficulty falling asleep and difficulty maintaining sleep more than twice a week. EDS was classified as an ESS score ≥ 11. Insomnia was reported by 32.9% (n = 1316) of the participants (37.3% among women and 28.6% among men). Multivariate logistic regression revealed that insomnia was associated with female sex [odds ratio (OR) = 1.526, 95% confidence interval (CI) = 1.297-1.796], night workers (OR 1.561, 95% CI 1.160-2.101), and being unmarried (OR 1.256, 95% CI 1.007-1.566). EDS was reported by 12.8% (n = 510) of the participants (14.7% among men and 10.7% among women). EDS was associated with male sex (OR 1.333, 95% CI 1.062-1.674), and being employed (OR 1.292, 95% CI 1.017-1.641). During the COVID-19 pandemic, the prevalence of insomnia increased in Korea, while there was no significant change in EDS compared with pre-pandemic evidence.

Digital Healthcare for Airway Diseases from Personal Environmental Exposure.

Digital technologies have emerged in various dimensions of human life, ranging from education to professional services to well-being. In particular, health products and services have expanded by the use and development of artificial intelligence, mobile health applications, and wearable electronic devices. Such advancements have enabled accurate and updated tracking and modeling of health conditions. For instance, digital health technologies are capable of measuring environmental pollution and predicting its adverse health effects. Several health conditions, including chronic airway diseases such as asthma and chronic obstructive pulmonary disease, can be exacerbated by pollution. These diseases impose substantial health burdens with high morbidity and mortality. Recently, efforts have been made to develop digital technologies to alleviate such conditions. Moreover, the COVID-19 pandemic has facilitated the application of telemedicine and telemonitoring for patients with chronic airway diseases. This article reviews current trends and studies in digital technology utilization for investigating and managing environmental exposure and chronic airway diseases. First, we discussed the recent progression of digital technologies in general environmental healthcare. Then, we summarized the capacity of digital technologies in predicting exacerbation and self-management of airway diseases. Concluding these reviews, we provided suggestions to improve digital health technologies' abilities to reduce the adverse effects of environmental exposure in chronic airway diseases, based on personal exposure-response modeling.

B.1.617.2 (Delta) Variant of SARS-CoV-2: features, transmission and potential strategies.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic. With the continuous evolution of the viral genome, SARS-CoV-2 has evolved many variants. B.1.617.2, also called Delta, is one of the most concerned variants. The Delta variant was first reported in India at the end of 2020 but has spread globally, by now, to 135 countries and is not stand still. Delta shared some mutations with other variants, and owned its special mutations on spike proteins, which may be responsible for its strong transmission and increasing virulence. Under these circumstances, a systematic summary of Delta is necessary. This review will focus on the Delta variant. We will describe all the characteristics of Delta (including biological features and clinical characteristics), analyze potential reasons for its strong transmission, and provide potential protective ways for combating Delta.

Complex analysis of the personalized pharmacotherapy in the management of COVID-19 patients and suggestions for applications of predictive, preventive, and personalized medicine attitude.

AIMS: Coronavirus disease 2019 (COVID-19) is rapidly spreading worldwide. Drug therapy is one of the major treatments, but contradictory results of clinical trials have been reported among different individuals. Furthermore, comprehensive analysis of personalized pharmacotherapy is still lacking. In this study, analyses were performed on 47 well-characterized COVID-19 drugs used in the personalized treatment of COVID-19. METHODS: Clinical trials with published results of drugs use for COVID-19 treatment were collected to evaluate drug efficacy. Drug-to-Drug Interactions (DDIs) were summarized and classified. Functional variations in actionable pharmacogenes were collected and systematically analysed. "Gene Score" and "Drug Score" were defined and calculated to systematically analyse ethnicity-based genetic differences, which are important for the safer use of COVID-19 drugs. RESULTS: Our results indicated that four antiviral agents (ritonavir, darunavir, daclatasvir and sofosbuvir) and three immune regulators (budesonide, colchicine and prednisone) as well as heparin and enalapril could generate the highest number of DDIs with common concomitantly utilized drugs. Eight drugs (ritonavir, daclatasvir, sofosbuvir, ribavirin, interferon alpha-2b, chloroquine, hydroxychloroquine (HCQ) and ceftriaxone had actionable pharmacogenomics (PGx) biomarkers among all ethnic groups. Fourteen drugs (ritonavir, daclatasvir, prednisone, dexamethasone, ribavirin, HCQ, ceftriaxone, zinc, interferon beta-1a, remdesivir, levofloxacin, lopinavir, human immunoglobulin G and losartan) showed significantly different pharmacogenomic characteristics in relation to the ethnic origin of the patient. CONCLUSION: We recommend that particularly for patients with comorbidities to avoid serious DDIs, the predictive, preventive, and personalized medicine (PPPM, 3 PM) strategies have to be applied for COVID-19 treatment, and genetic tests should be performed for drugs with actionable pharmacogenes, especially in some ethnic groups with a higher frequency of functional variations, as our analysis showed. We also suggest that drugs associated with higher ethnic genetic differences should be given priority in future pharmacogenetic studies for COVID-19 management. To facilitate translation of our results into clinical practice, an approach conform with PPPM/3 PM principles was suggested. In summary, the proposed PPPM/3 PM attitude should be obligatory considered for the overall COVID-19 management. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-021-00247-0.

Association between Inhaled Corticosteroid Use and SARS-CoV-2 Infection: A Nationwide Population-Based Study in South Korea.

BACKGROUND: Although it is known that inhaled corticosteroid (ICS) use may increase the risk of respiratory infection, its influence on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Thus, the aim of this study was to investigate the association between ICS use and the positivity of SARS-CoV-2 infection among patients with chronic respiratory diseases. METHODS: Nationwide data of 44,968 individuals with chronic respiratory diseases tested for SARS-CoV-2 until May 15, 2021 were obtained from the Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea. The positivity of SARS-CoV-2 infection was retrospectively analysed according to the prescription, type, and dose of ICS taken one year before SARS-CoV-2 test. RESULTS: Among 44,968 individuals tested, 931 (2.1%) were positive for SARS-CoV-2. A total of 7,019 patients (15.6%) were prescribed ICS one year prior to being tested for SARS-CoV-2. Low, medium, and high doses of ICS were prescribed in 7.5%, 1.6%, and 6.5% of total cases, respectively. Among types of ICS, budesonide, fluticasone, beclomethasone, and ciclesonide were prescribed in 3.7%, 8.9%, 2.3%, and 0.6% of total cases, respectively. A multivariate analysis showed no significant increase in infection with ICS use (odds ratio, 0.84; 95% confidence interval, 0.66-1.03). Moreover, there were no associations between the positivity of infection and the dose or type of ICS prescribed. CONCLUSION: Prior ICS use did not increase the positivity for SARS-CoV-2 infection. Moreover, different doses or types of ICS did not affect this positivity.

Soluble IL-2R Levels Predict in-Hospital Mortality in COVID-19 Patients with Respiratory Failure.

Acute respiratory distress syndrome is the primary cause of death in patients with coronavirus disease 2019 (COVID-19) pneumonia. Our study aims to determine the association between serum markers and mortality in COVID-19 patients with respiratory failure. This retrospective study was conducted in a tertiary care hospital in South Korea. Forty-nine patients with COVID-19, who required high flow nasal cannulation or mechanical ventilation from February 2020 to April 2021, were included. Demographic and laboratory data were analyzed at baseline and on Day 7 of admission. We found that serum creatinine, troponin, procalcitonin, and soluble interleukin-2 receptor (sIL-2R) at baseline were more elevated in the non-survivor group, but were not associated with mechanical ventilator use on Day 7. Older age, PaO2/FiO2 ratio, lymphocyte and platelet counts, lactate dehydrogenase, IL-6, C-reactive protein, and sIL-2R on Day 7 were significantly associated with mortality. Delta sIL-2R (Day 7-Day 0) per standard deviation was significantly higher in the non-survivor group (adjusted hazard ratio 3.225, 95% confidence interval (CI) 1.151-9.037, p = 0.026). Therefore, sIL-2R could predict mortality in COVID-19 patients with respiratory failure. Its sustained elevation suggests a hyper-inflammatory state, and mirrors the severity of COVID-19 in patients with respiratory failure, thereby warranting further attention.

Soluble IL-2R Levels Predict in-Hospital Mortality in COVID-19 Patients with Respiratory Failure (preprint)

Acute respiratory distress syndrome is the primary cause of death in patients with coronavirus disease 2019 (COVID-19) pneumonia. Our study aims to determine the association between serum markers and mortality in COVID-19 patients with respiratory failure. This retrospective study was conducted in a tertiary care hospital in South Korea. Forty-three patients with COVID-19, who required high flow nasal cannulation or mechanical ventilation from Feb 2020-Jan 2021, were included. Demographic and laboratory data were analyzed at baseline and on Day 7 of admission. Older age was associated with mortality. Serum creatinine, troponin, procalcitonin, and soluble interleukin-2 receptor (sIL-2R) at baseline were more elevated in the non-survivor group; however, were not associated with mechanical ventilator use on Day 7 PaO 2 /FiO 2 ratio, lymphocyte and platelet counts, lactate dehydrogenase, IL-6, c-reactive protein, and sIL-2R on Day 7 were significantly associated with mortality. Delta sIL-2R (Day 7-Day 0) per standard deviation was significantly higher in the non-survivor group (adjusted hazard ratio 3.225, 95% CI 1.151-9.037, p=0.026). sIL-2R could predict mortality in COVID-19 patients with respiratory failure, not mechanical ventilator use. Its sustained elevation suggests a hyper-inflammatory state, and mirrors the severity of COVID-19 in patients with respiratory failure; therefore, warrants further attention.

COVID-19 one year later: a retrospect of CRISPR-Cas system in combating COVID-19.

Coronavirus disease 2019 (COVID-19), an infectious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a persistent global threat. The transmission of SARS-CoV-2 is wide and swift. Rapid detection of the viral RNA and effective therapy are imperative to prevent the worldwide spread of the new infectious disease. Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR)- CRISPR-associated protein (Cas) system is an RNA-directed adaptive immune system, and it has been transformed into a gene editing tool. Applications of CRISPR-Cas system involves in many fields, such as human gene therapy, drug discovery and disease diagnosis. Under the background of COVID-19 pandemic, CRISPR-Cas system shows hidden capacity to fight the emergency in many aspects. This review will focus on the role of gene editing in COVID-19 diagnosis and treatment. We will describe the potential use of CRISPR-Cas-based system in combating COVID-19, from diagnosis to treatment. Furthermore, the limitation and perspectives of this novel technology are also evaluated.

Increased photokeratitis during the coronavirus disease 2019 pandemic: Clinical and epidemiological features and preventive measures.

ABSTRACT: An increased incidence of photokeratitis has occurred during the coronavirus disease 2019 (COVID-19) pandemic due to improper and unprotected use of ultraviolet lamps. Here, we summarize the clinical and epidemiological features of this increased incidence of photokeratitis and share advice in using health education to prevent it.We collected data from patients diagnosed with photokeratitis from October 7, 2019 to December 1, 2019, and from February 17, 2020 to April 12, 2020, and compared the frequency of onset, site of ultraviolet radiation (UVR) exposure, reason for exposure, exposure time, and recovery time. We also implemented and evaluated multiple measures of public health education to prevent increased disease.After the COVID-19 outbreak, the frequency of onset of photokeratitis increased significantly, especially among young women. The main reason for UVR exposure changed from welding to disinfection. The incidence sites varied, and the exposure time was longer. As a result, patients needed a longer time to recover. Positive health education was an useful and convenient measure to prevent the disease.While the COVID-19 pandemic is ongoing, more attention should be paid to public health and implement positive measures to prevent photokeratitis.

Are we ready to deal with a global COVID-19 pandemic? Rethinking countries' capacity based on the Global Health Security Index.

BACKGROUND: The Global Health Security (GHS) Index has been developed to measure a country's capacity to cope with a public health emergency; however, evidence for whether it corresponds to the response to a global pandemic is lacking. This study performed a multidimensional association analysis to explore the correlation between the GHS Index and COVID-19-associated morbidity, mortality, and disease increase rate (DIR) in 178 countries (regions). METHODS: The GHS Index and COVID-19 pandemic data - including total cases per million (TCPM), total deaths per million (TDPM), and daily growth rate - were extracted from online databases. The Spearman correlation coefficient was applied to describe the strength of the association between the GHS Index, sociological characteristics, and the epidemic situation of COVID-19. DIRs were compared, and the impact of the GHS Index on the DIR by the time of "lockdown" was visualized. RESULTS: The overall GHS Index was positively correlated with TCPM and TDPM, with coefficients of 0.34 and 0.41, respectively. Countries categorized into different GHS Indextiers had different DIRs before implementing lockdown measures. However, no significant difference was observed between countries in the middle and upper tiers after implementing lockdown measures. The correlation between GHS Index and DIR was positive five days before lockdown measures were taken, but it became negative 13 days later. CONCLUSIONS: The GHS Index has limited value in assessing a country's capacity to respond to a global pandemic. Nevertheless, it has potential value in determining the country's ability to cope with a local epidemic situation.

Impact of COPD on COVID-19 prognosis: A nationwide population-based study in South Korea.

Underlying chronic respiratory disease may be associated with the severity of coronavirus disease 2019 (COVID-19). This study investigated the impact of chronic obstructive pulmonary disease (COPD) on the risk for respiratory failure and mortality in COVID-19 patients. A nationwide retrospective cohort study was conducted in 4610 patients (≥ 40 years old) infected with COVID-19 between January 20 and May 27, 2020, using data from the Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea. The clinical course and various clinical features were compared between COPD and non-COPD patients, and the risks of respiratory failure and all-cause mortality in COPD patients were analyzed using a multivariate logistic regression model. Among 4610 COVID-19 patients, 4469 (96.9%) and 141 (3.1%) were categorized into the non-COPD and COPD groups, respectively. The COPD group had greater proportions of older (≥ 60 years old) (78.0% vs. 45.2%, P < 0.001) and male (52.5% vs. 36.6%, P < 0.001) patients than the non-COPD group. Relatively greater proportions of patients with COPD received intensive critical care (7.1% vs. 3.7%, P = 0.041) and mechanical ventilation (5.7% vs. 2.4%, P = 0.015). Multivariate analyses showed that COPD was not a risk factor for respiratory failure but was a significant independent risk factor for all-cause mortality (OR = 1.80, 95% CI 1.11-2.93) after adjustment for age, sex, and Charlson Comorbidity Index score. Among COVID-19 patients, relatively greater proportions of patients with COPD received mechanical ventilation and intensive critical care. COPD is an independent risk factor for all-cause mortality in COVID-19 patients in Korea.

Impact of comorbid asthma on severity of coronavirus disease (COVID-19).

The severity of the coronavirus disease (COVID-19) is associated with various comorbidities. However, no studies have yet demonstrated the potential risk of respiratory failure and mortality in COVID-19 patients with pre-existing asthma. We selected 7272 adult COVID-19 patients from the Korean Health Insurance Review and Assessment COVID-19 database for this nationwide retrospective cohort study. Among these, 686 patients with asthma were assessed by their severities and evaluated by the clinical outcome of COVID-19 compared to patients without asthma. Of 7272 adult COVID-19 patients, 686 with asthma and 6586 without asthma were compared. Asthma was not a significant risk factor for respiratory failure or mortality among all COVID-19 patients (odds ratio [OR] = 0.99, P = 0.997 and OR = 1.06, P = 0.759) after adjusting for age, sex, and the Charlson comorbidity score. However, a history of acute exacerbation (OR = 2.63, P = 0.043) was significant risk factors for death among COVID-19 patients with asthma. Asthma is not a risk factor for poor prognosis of COVID-19. However, asthma patients who had any experience of acute exacerbation in the previous year before COVID-19 showed higher COVID-19-related mortality, especially in case of old age and male sex.

Effective Use of an Advanced Isolation Unit During the COVID-19 Pandemic: A Retrospective Cohort Study (preprint)

Background: Advanced isolation and testing of patients with suspicious symptoms or community-acquired pneumonia of an unknown origin are of prime importance in the current coronavirus disease (COVID-19) pandemic. We describe herein a strategy for preventing virus transmission within hospitals through screening and advanced isolation.Methods: We retrospectively analysed patients screened and admitted to the adult advanced isolation unit at a South Korean hospital, from February to April 2020. Those requiring hospitalization were admitted to the unit. Based on the hospital’s testing capacity for severe acute respiratory syndrome coronavirus 2, we divided patients into groups to identify the relationship between test-running frequency and efficacy of the advanced isolation unit based on the decrease in de-isolation time.Findings: Of the 10,364 screened patients, 5,969 were tested for the virus, and 10 were confirmed to have COVID-19. Of the 338 patients admitted to the unit, one patient was diagnosed with COVID-19. The median de-isolation time from the unit was 2·9 hours (interquartile range: 1·0–6·6), and patients stayed in the unit for a median of 16·6 hours (interquartile range: 9·0–24·1). The group that tested six times per day had the shortest admission to de-isolation time and stay time in the unit.Interpretation: Our process minimized exposure without delaying proper treatment and prevented virus transmission within the hospital. High testing frequencies maximized the efficacy of the advanced isolated unit.Funding Statement: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectorsDeclaration of Interests: No conflicts of interest exist for any author. Ethics Approval Statement: The study protocol was reviewed and approved by the Institutional Review Board of Severance Hospital (IRB No. 4-2020-0374), and the need for informed consent was waived by the committeee.

Association Between Inhaled Corticosteroid Use and the Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Nationwide Population-based Study in South Korea (preprint)

Background Inhaled corticosteroid (ICS) use may increase the risk of respiratory infection, but its influence on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not known. This study aimed to investigate the association between ICS use and the risk of SARS-CoV-2 infection among the patients with chronic respiratory diseases.Methods The Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea provided nationwide data of 44,968 individuals with chronic respiratory diseases tested for SARS-CoV-2 until May 15. The risks of SARS-CoV-2 infection were retrospectively analysed according to the prescription, type, and dose of ICS taken one year before SARS-CoV-2 test.Results Among 44,968 individuals tested, 931 (2.1%) were positive for SARS-CoV-2. A total of 7,019 patients (15.6%) were prescribed ICS one year prior to being tested for SARS-CoV-2. Low, medium, and high doses of ICS were prescribed in 7.5%, 1.6%, and 6.5% of total cases, respectively. Among the types of ICS, budesonide, fluticasone, beclomethasone, and ciclesonide were prescribed in 3.7%, 8.9%, 2.3%, and 0.6% of total cases, respectively. The multivariate analysis showed no significant increase in infection with ICS use (OR, 0.84; 95% CI, 0.66–1.03). Moreover, there were no associations between the risk of infection, and doses or types of ICS prescribed.Conclusion Prior ICS use did not increase the risk of SARS-CoV-2 infection. Moreover, different doses or types of ICS did not affect the risk. This study supports the current guidelines to manage patients taking ICS during the SARS-CoV-2 pandemic.

Epidemiological and clinical features of pediatric COVID-19.

BACKGROUND: COVID-19 is an extremely severe infectious disease. However, few studies have focused on the epidemiological and clinical characteristics of pediatric COVID-19. This study conducted a retrospective review of the epidemiological and clinical features of COVID-19 in children. METHODS: A retrospective study was conducted on children with a definite diagnosis of COVID-19 in mainland China using the web crawler technique to collect anonymous COVID-19 updates published by local health authorities. RESULTS: Three hundred forty-one children aged 4 days to 14 years with a median age of 7 years were included. Sixty-six percent of pediatric patients were infected via family members with COVID-19. The median incubation period was 9 days (interquartile range, 6 to 13). Asymptomatic cases accounted for 5.9%, of which 30% had abnormal chest radiologic findings. A majority of pediatric COVID-19 cases showed mild to moderate clinical features, and only a few developed severe or critical diseases (0.6% and 0.3%, respectively). Fever (77.9%) and cough (32.4%) were the predominant presenting symptoms of pediatric COVID-19. The pediatric patients had fewer underlying diseases and complications than adults. The treatment modalities for pediatric COVID-19 patients were not as complex as those of adult COVID-19 patients. The overall prognosis of pediatric COVID-19 was benign with a decent recovery. The median time from onset to cure was 16 days (interquartile range, 13 to 21). CONCLUSIONS: Compared to adults, COVID-19 in children has distinct features of epidemiology and clinical manifestations. The findings from this study might help to guide the development of measures to prevent and treat this ongoing global pandemic. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( chictr.org.cn ) identifier: ChiCTR2000030464.

The clinical characteristics and mortal causes analysis of COVID-19 death patients (preprint)

Abstract Purpose: Currently, COVID-19 is causing a large number of deaths globally. However, few researches focused on the clinical features of death patients. This study conducted a retrospective analysis of clinical characteristics and mortal causes in Chinese COVID-19 death patients. Patients and methods: The clinical characteristics of death patients were collected from publicized by local health authorities in China. Expressions of virus targets in human organs were obtained from GTEx database. Results: 159 patients from 24 provinces in China were recruited in our study, including 26 young patients under 60 and 133 aged 60 or older. The median age was 71 years, which indicated that most death patients were elderly. More male patients died of COVID-19 than females (1.65 fold). Hypertension was the most common coexisting disorder and respiratory failure was the most common direct cause of death. Fever (71.19%) and cough (55.08%) were the predominant presenting symptoms. There was one asymptomatic patient. In addition, by comparing young and old patients, heart disease was identified as an important risk factor for death in the aged patients. ACE2 and TMPRSS2 were the targets of SARS-CoV-2, we analyzed their expression in different organs. TMPRSS2 and ACE2 had a high expression in the organs which had corresponding clinical features in death patients. Conclusion: Male, age and heart disease were the main risk factors of death. Beside, asymptomatic patients with serious coexisting disorders may also die of SARS-CoV-2. Thus, more attention should be paid to the old patients with heart disease and asymptomatic patients in the treatment . Keywords: COVID-19, SARS-Cov-2, death, coexisting disorder, cause of death