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1.
Cell Rep ; 40(3): 111117, 2022 07 19.
Article in English | MEDLINE | ID: covidwho-1914214

ABSTRACT

As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delivers its viral genome into host cells via fusion of the viral and cell membranes. Here, we show that ANO6/TMEM16F-mediated cell surface exposure of phosphatidylserine is critical for SARS-CoV-2 entry and that ANO6-selective inhibitors are effective against SARS-CoV-2 infections. Application of the SARS-CoV-2 Spike pseudotyped virus (SARS2-PsV) evokes a cytosolic Ca2+ elevation and ANO6-dependent phosphatidylserine externalization in ACE2/TMPRSS2-positive mammalian cells. A high-throughput screening of drug-like chemical libraries identifies three different structural classes of chemicals showing ANO6 inhibitory effects. Among them, A6-001 displays the highest potency and ANO6 selectivity and it inhibits the single-round infection of SARS2-PsV in ACE2/TMPRSS2-positive HEK 293T cells. More importantly, A6-001 strongly inhibits authentic SARS-CoV-2-induced phosphatidylserine scrambling and SARS-CoV-2 viral replications in Vero, Calu-3, and primarily cultured human nasal epithelial cells. These results provide mechanistic insights into the viral entry process and offer a potential target for pharmacological intervention to protect against coronavirus disease 2019 (COVID-19).


Subject(s)
COVID-19 Drug Treatment , Angiotensin-Converting Enzyme 2 , Animals , Anoctamins , Humans , Mammals/metabolism , Phosphatidylserines , Phospholipid Transfer Proteins/metabolism , SARS-CoV-2 , Virus Internalization
2.
Front Psychiatry ; 12: 685445, 2021.
Article in English | MEDLINE | ID: covidwho-1323094

ABSTRACT

Experiences of infectious diseases cause stressful and traumatic life events, hence, coronavirus disease 2019 (COVID-19) patients could suffer from various mental health problems requiring psychological support services. This study investigates the severity of mental health problems among confirmed COVID-19 patients. From March to November 2020, we collected the data from 118 COVID-19 patients who voluntarily participated in the National Center for Disaster Trauma's online mental health assessment consisting of self-report scales like Primary Care of Posttraumatic Stress Disorder screen (PC-PTSD), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Patient Health Questionnaire-15 (PHQ-15), and P4 Suicidality Screener. For control, 116 other disaster-experienced and 386 non-COVID-19-experienced participants were recruited. The COVID-19 patients showed more severe symptoms including post-traumatic symptoms, depression, anxiety, and somatic symptoms than control groups across all four screening scales (p < 0.001). Regarding high-risk, COVID-19 patients had an increased association with high-risk compared to the comparison groups (PC-PTSD: OR = 24.16, 95% CI = 13.52-43.16 p < 0.001; PHQ-9: OR = 14.45, 95% CI = 8.29-25.19, p < 0.001; GAD-7: OR=20.71, 95% CI = 10.74-39.96, p < 0.001; PHQ-15: OR = 5.65, 95% CI = 3.44-9.25, p < 0.001; P4: OR = 14.67, 95% CI = 8.95-25.07, p < 0.001). This study's results imply that there is a high-risk of overall mental health problems, especially stronger associations of post-traumatic stress symptoms, in COVID-19 patients. These findings help inform practitioners about the psychological responses to COVID-19 experiences and to prepare appropriate interventions and services for the incremental number of confirmed cases.

3.
Epidemiol Health ; 42: e2020035, 2020.
Article in English | MEDLINE | ID: covidwho-665563

ABSTRACT

OBJECTIVES: To describe and evaluate epidemiological investigation results and containment measures implemented in Busan, where 108 cases were confirmed with coronavirus disease 2019 (COVID-19) between February 21, 2020 and March 24, 2020. METHODS: Any individual who tested positive for COVID-19 was classified as a confirmed case. Measures were taken to identify the source of infection and trace and quarantine contacts. Serial intervals were estimated and the effective reproduction number was computed. RESULTS: Of the total 18,303 COVID-19 tests performed between January 16, 2020 and March 24, 2020 in Busan, 108 yielded positive results (positive test rate, 0.6%). All confirmed cases were placed in isolation at hospitals. Of the 108 confirmed cases, 59 (54.6%) were female. The most common age group was 20-29 years with 37 cases (34.3%). Regarding symptoms at the time of diagnosis, cough (n=38, 35.2%) and fever (n=34, 31.5%) were most common; 12 cases (11.1%) were asymptomatic. The source of infection was identified in 99 cases (91.7%). A total of 3,223 contacts were identified and quarantined. Household contacts accounted for 196, and the household secondary attack rate was 8.2% (95% confidence interval [CI], 4.7 to 12.9). The mean serial interval was estimated to be 5.54 days (95% CI, 4.08 to 7.01). After February 26, (Rt) remained below 1 in Busan. CONCLUSIONS: The early containment strategy implemented in Busan shows that control is possible if outbreaks are of limited scope. In preparation for future outbreaks, public health and healthcare systems should be re-examined and put in a ready state.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Disease Outbreaks/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Adolescent , Adult , Aged , COVID-19 , Child , Child, Preschool , Contact Tracing , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Quarantine , Republic of Korea/epidemiology , Young Adult
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