Interferon antagonists encoded by SARS-CoV-2 at a glance.

The innate immune system is a powerful barrier against invading pathogens. Interferons (IFNs) are a major part of the cytokine-mediated anti-viral innate immune response. After recognition of a pathogen by immune sensors, signaling cascades are activated that culminate in the release of IFNs. These activate cells in an autocrine or paracrine fashion eventually setting cells in an anti-viral state via upregulation of hundreds of interferon-stimulated genes (ISGs). To evade the anti-viral effect of the IFN system, successful viruses like the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolved strategies to counteract both IFN induction and signaling. In fact, more than half of the about 30 proteins encoded by SARS-CoV-2 target the IFN system at multiple levels to escape IFN-mediated restriction. Here, we review recent insights into the molecular mechanisms used by SARS-CoV-2 proteins to suppress IFN production and the establishment of an anti-viral state.

Endogenous IFITMs boost SARS-Coronavirus 1 and 2 replication while overexpression inhibits infection by relocalizing ACE2

Opposing effects of Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) on SARS-CoV-2 infection have been reported. The reasons for this are unclear and the role of IFITMs in infection of other human coronaviruses (hCoVs) remains poorly understood. Here, we show that endogenous expression of IFITM2 and/or IFITM3 is critical for efficient replication of SARS-CoV-1, SARS-CoV-2 and hCoV-OC43 but has little effect on MERS-, NL63- and 229E-CoVs. In contrast, overexpression of IFITMs inhibits all these hCoVs, as well as the corresponding Spike-containing pseudo-particles, except OC43, which is enhanced by IFITM3. We further demonstrate that overexpression of IFITMs impairs cell surface expression of ACE2 representing the entry receptor of SARS-CoVs and hCoV-NL63 but not hCoV-OC43. Our results explain the inhibitory effects of artificial IFITM overexpression on ACE2-tropic SARS-CoVs and show that three hCoVs, including major causative agents of severe respiratory disease, hijack IFITMs for efficient infection of human cells. Graphical abstract Opposing effects of IFITM proteins on infection by human coronaviruses including SARS-CoV-2 have been reported. Here, Xie and colleagues resolved these seeming controversies and show that endogenous expression of IFITMs has little if any inhibitory effects but strongly enhances replication of SARS-CoV-1, SARS-CoV-2 and hCoV-OC43.

Endogenous IFITMs boost SARS-coronavirus 1 and 2 replication whereas overexpression inhibits infection by relocalizing ACE2.

Opposing effects of interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) on SARS-CoV-2 infection have been reported. The reasons for this are unclear and the role of IFITMs in infection of other human coronaviruses (hCoVs) remains poorly understood. Here, we demonstrate that endogenous expression of IFITM2 and/or IFITM3 is critical for efficient replication of SARS-CoV-1, SARS-CoV-2 and hCoV-OC43 but has little effect on MERS-, NL63-and 229E-hCoVs. In contrast, overexpression of IFITMs inhibits all these hCoVs, and the corresponding spike-containing pseudo-particles, except OC43, which is enhanced by IFITM3. We further demonstrate that overexpression of IFITMs impairs cell surface expression of ACE2 representing the entry receptor of SARS-CoVs and hCoV-NL63 but not hCoV-OC43. Our results explain the inhibitory effects of artificial IFITM overexpression on ACE2-tropic SARS-CoVs and show that three hCoVs, including major causative agents of severe respiratory disease, hijack IFITMs for efficient infection of human cells.

Stress Experience of COVID-19 Patients as Reported by Psychological Supporters in South Korea: A Qualitative Study.

Background: COVID-19 patients experience various stressors during the quarantine period and after release from quarantine. However, stressors experienced during each period remain unclear. Methods: A total of 15 mental health experts from the integrated psychological support group for COVID-19participated in this study. Psychological support was provided for the total 932 confirmed COVID-19 patients and their families. Qualitative data were collected using Focus Group Interview (FGI). The participants were divided into two groups and semi-structured questions were used to allow participants to speak their minds. Results: During the quarantine period, difficulties of being diagnosed with COVID-19, concerns about recovery from COVID-19, stress related to quarantine, issues related to the treatment environment, and limited information about COVID-19 and communication were frequently reported. After release from quarantine, the reported main stressors include reinfection or reactivation, concerns about complications, and financial difficulties. Confusion as vectors and victims, stigma and discrimination, and conflicts within a family were observed during both periods. Conclusions: COVID-19 patients suffered various stressors during the quarantine period and after release from quarantine. Moreover, returning to their daily life required timely psychosocial support, intervention, and treatment for COVID-19 infection.

Stress Experience of COVID-19 Patients as Reported by Psychological Supporters in South Korea: A Qualitative Study

Background: COVID-19 patients experience various stressors during the quarantine period and after release from quarantine. However, stressors experienced during each period remain unclear. Methods A total of 15 mental health experts from the integrated psychological support group for COVID-19participated in this study. Psychological support was provided for the total 932 confirmed COVID-19 patients and their families. Qualitative data were collected using Focus Group Interview (FGI). The participants were divided into two groups and semi-structured questions were used to allow participants to speak their minds. Results During the quarantine period, difficulties of being diagnosed with COVID-19, concerns about recovery from COVID-19, stress related to quarantine, issues related to the treatment environment, and limited information about COVID-19 and communication were frequently reported. After release from quarantine, the reported main stressors include reinfection or reactivation, concerns about complications, and financial difficulties. Confusion as vectors and victims, stigma and discrimination, and conflicts within a family were observed during both periods. Conclusions COVID-19 patients suffered various stressors during the quarantine period and after release from quarantine. Moreover, returning to their daily life required timely psychosocial support, intervention, and treatment for COVID-19 infection.

Online Mental Health Assessments of COVID-19 Patients in South Korea.

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.

Presenting characteristics and clinical outcome of patients with COVID-19 in South Korea: A nationwide retrospective observational study.

BACKGROUND: More than 13,000 cases were reported to be infected with COVID-19 by RT-PCR in South Korea. Most studies report clinical characteristics of hospitalized patients with COVID-19; the full spectrum of disease severity has thus not yet been well described. METHODS: Using retrospective observational methods, this study analyzed factors affecting early clinical symptoms, clinical progress, and severity of disease for COVID-19 positive patients released from quarantine to provide information on establishing optimized care for new patients. The medical data of 7803 laboratory-confirmed patients who had been discharged or died by April 30, 2020 were analyzed using multivariate logistic regression analysis. FINDINGS: On admission, 7383 (94•5%) patients were asymptomatic or showed mild illness, and 372 (4•8%) patients were severe illness. Also, 48 (0 0•6%) were hospitalized with critically ill when diagnosed. Most patients with asymptomatic or mild illness on admission remained mild until discharge, 253 (3•4%) progressed to severe illness, and 83 (1•1%) died in hospital. However, the case fatality were 29•8% and 62•5% in severe and critically ill patients, respectively. At admission, 73•0% of hospitalized patients had symptoms; most common were cough (42•5%), sputum (28•8%), and fever (20•1%). Only 35•2% of laboratory confirmed patients admitted to the temporary care facility complained of symptoms. Increasing odds of being critically ill was associated with older age (OR 28•93, 95% CI 13•34-62•75 for age >70y, vs. age <50 y; p<0•0001), being male (OR 2•15, 95% CI1•59-2•89; p<0•0001), fever (OR 2•52, 95% CI 1.84-3•45; p<0•0001), and shortness of breath (OR 7•40, 95% CI 5•37-10•19; p<0•0001). Comorbid illness significantly increased risk of critical illness or death. INTERPRETATION: Most cases were discharged as asymptomatic or recovered from mild illness, and only 9•7% developed severe disease requiring oxygen therapy or more. Case fatality rate was 2•9%, and markedly increased in those over age 50. Risk factors such as age, sex, fever, shortness of breath, and underlying disease can be useful in predicting future clinical severity. Additionally, the number of confirmed asymptomatic COVID-19 patients significantly contribute to continued spread. FUNDING: none.

ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity.

Activation of the RIG-I-like receptors, retinoic-acid inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), establishes an antiviral state by upregulating interferon (IFN)-stimulated genes (ISGs). Among these is ISG15, the mechanistic roles of which in innate immunity still remain enigmatic. In the present study, we report that ISG15 conjugation is essential for antiviral IFN responses mediated by the viral RNA sensor MDA5. ISGylation of the caspase activation and recruitment domains of MDA5 promotes its oligomerization and thereby triggers activation of innate immunity against a range of viruses, including coronaviruses, flaviviruses and picornaviruses. The ISG15-dependent activation of MDA5 is antagonized through direct de-ISGylation mediated by the papain-like protease of SARS-CoV-2, a recently emerged coronavirus that has caused the COVID-19 pandemic. Our work demonstrates a crucial role for ISG15 in the MDA5-mediated antiviral response, and also identifies a key immune evasion mechanism of SARS-CoV-2, which may be targeted for the development of new antivirals and vaccines to combat COVID-19.

Psychosocial Support during the COVID-19 Outbreak in Korea: Activities of Multidisciplinary Mental Health Professionals.

As of April 18, 2020, there have been a total of 10,653 confirmed cases and 232 deaths due to coronavirus disease 2019 (COVID-19) in Korea. The pathogen spread quickly, and the outbreak caused nationwide anxiety and shock. This study presented the anecdotal records that provided a detailed process of the multidisciplinary teamwork in mental health during the COVID-19 outbreak in the country. Psychosocial support is no less important than infection control during an epidemic, and collaboration and networking are at the core of disaster management. Thus, a multidisciplinary team of mental health professionals was immediately established and has collaborated effectively with its internal and external stakeholders for psychosocial support during the COVID-19 outbreak.