SARS-CoV-2 impairs interferon production via NSP2-induced repression of mRNA translation.

Viruses evade the innate immune response by suppressing the production or activity of cytokines such as type I interferons (IFNs). Here we report the discovery of a mechanism by which the SARS-CoV-2 virus coopts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-ß. We reveal that the SARS-CoV-2 encoded nonstructural protein 2 (NSP2) directly interacts with the cellular GIGYF2 protein. This interaction enhances the binding of GIGYF2 to the mRNA cap-binding protein 4EHP, thereby repressing the translation of the Ifnb1 mRNA. Depletion of GIGYF2 or 4EHP significantly enhances IFN-ß production, which inhibits SARS-CoV-2 replication. Our findings reveal a target for rescuing the antiviral innate immune response to SARS-CoV-2 and other RNA viruses.

Interim analysis from a phase 2 randomized trial of EuCorVac-19: a recombinant protein SARS-CoV-2 RBD nanoliposome vaccine.

BACKGROUND: Numerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the SARS-CoV-2 receptor-binding domain (RBD) on immunogenic nanoliposomes. METHODS: Initial study of a phase 2 randomized, observer-blind, placebo-controlled trial to assess the immunogenicity, safety, and tolerance of ECV19 was carried out between July and October 2021. Two hundred twenty-nine participants were enrolled at 5 hospital sites in South Korea. Healthy adults aged 19-75 without prior known exposure to COVID-19 were vaccinated intramuscularly on day 0 and day 21. Of the participants who received two vaccine doses according to protocol, 100 received high-dose ECV19 (20 µg RBD), 96 received low-dose ECV19 (10 µg RBD), and 27 received placebo. Local and systemic adverse events were monitored. Serum was assessed on days 0, 21, and 42 for immunogenicity analysis by ELISA and neutralizing antibody response by focus reduction neutralization test (FRNT). RESULTS: Low-grade injection site tenderness and pain were observed in most participants. Solicited systemic adverse events were less frequent, and mostly involved low-grade fatigue/malaise, myalgia, and headache. No clinical laboratory abnormalities were observed. Adverse events did not increase with the second injection and no serious adverse events were solicited by ECV19. On day 42, Spike IgG geometric mean ELISA titers were 0.8, 211, and 590 Spike binding antibody units (BAU/mL) for placebo, low-dose and high-dose ECV19, respectively (p < 0.001 between groups). Neutralizing antibodies levels of the low-dose and high-dose ECV19 groups had FRNT50 geometric mean values of 129 and 316, respectively. Boosting responses and dose responses were observed. Antibodies against the RBD correlated with antibodies against the Spike and with virus neutralization. CONCLUSIONS: ECV19 was generally well-tolerated and induced antibodies in a dose-dependent manner that neutralized SARS-CoV-2. The unique liposome display approach of ECV19, which lacks any immunogenic protein components besides the antigen itself, coupled with the lack of increased adverse events during boosting suggest the vaccine platform may be amenable to multiple boosting regimes in the future. Taken together, these findings motivate further investigation of ECV19 in larger scale clinical testing that is underway. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov as # NCT04783311.

Risk factors and clinical impact of COVID-19-associated pulmonary aspergillosis: Multicenter retrospective cohort study.

BACKGROUND/AIMS: The risk factors and clinical impacts of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) remain controversial, and no data have been reported in Korea. This study aimed to investigate the epidemiology and importance of CAPA diagnostic efforts and to identify the predictors of CAPA and the impacts on clinical outcomes. METHODS: Between January 2020 and May 2021, data of severely to critically ill COVID-19 patients were extracted from seven hospitals of the Catholic Medical Center through a clinical data warehouse. Corticosteroid use was subcategorized into total cumulative dose, early 7-day dose, mean daily dose, and duration of use. RESULTS: A total of 2,427 patients were screened, and 218 patients were included. CAPA was diagnosed in 4.6% (10/218) of all hospitalized and 11.2% (10/89) of intensive care unit patients. Total cumulative dose (over 1,000 mg as methylprednisolone) and daily high-dose corticosteroid use (over 60 mg/day) were independent predictors but not early 7-day high-dose corticosteroid use (over 420 mg/week) (odds ratio [OR], 1.731; 95% confidence interval [CI], 0.350 to 8.571) nor prolonged use (OR, 2.794; 95% CI, 0.635 to 13.928). In-hospital overall mortality was 11.9% (26 of 218). CAPA itself did not affect the outcome; rather, daily high-dose steroid use significantly increased the 30-day mortality (hazard ratio, 5.645; 95% CI, 1.225 to 26.091). CONCLUSION: CAPA was not uncommon, especially in critically ill patients. Daily high-dose corticosteroid use was the predictor of CAPA and associated with high mortality rates. High-dose corticosteroids use after early inflammatory phase should be avoided, and active surveillance methods for CAPA are essential for those high-risk patients.

Analysis of a COVID-19 Prescreening Process in an Outpatient Clinic at a University Hospital during the COVID-19 Pandemic.

BACKGROUND: To minimize nosocomial infection against coronavirus disease 2019 (COVID-19), most hospitals conduct a prescreening process to evaluate the patient or guardian of any symptoms suggestive of COVID-19 or exposure to a COVID-19 patient at entrances of hospital buildings. In our hospital, we have implemented a two-level prescreening process in the outpatient clinic: an initial prescreening process at the entrance of the outpatient clinic (PPEO) and a second prescreening process is repeated in each department. If any symptoms or epidemiological history are identified at the second level, an emergency code is announced through the hospital's address system. The patient is then guided outside through a designated aisle. In this study, we analyze the cases missed in the PPEO that caused the emergency code to be applied. METHODS: All cases reported from March 2020 to April 2021 were analyzed retrospectively. We calculated the incidence of cases missed by the PPEO per 1,000 outpatients and compared the incidence between first-time hospital visitors and those visiting for the second time or more; morning and afternoon office hours; and days of the week. RESULTS: During the study period, the emergency code was applied to 449 cases missed by the PPEO. Among those cases, 20.7% were reported in otorhinolaryngology, followed by 11.6% in gastroenterology, 5.8% in urology, and 5.8% in dermatology. Fever was the most common symptom (59.9%), followed by cough (19.8%). The incidence of cases per 1,000 outpatients was significantly higher among first-time visitors than among those visiting for the second time or more (1.77 [confidence interval (CI), 1.44-2.10] vs. 0.59 [CI, 0.52-0.65], respectively) (P < 0.001). CONCLUSION: Fever was the most common symptom missed by the PPEO, and otorhinolaryngology and gastroenterology most frequently reported missed cases. Cases missed by the PPEO were more likely to occur among first-time visitors than returning visitors. The results obtained from this study can provide insights or recommendations to other healthcare facilities in operating prescreening processes during the COVID-19 pandemic.

Surveillance of the infection prevention and control practices of healthcare workers by an infection control surveillance-working group and a team of infection control coordinators during the COVID-19 pandemic.

BACKGROUND: During the ongoing coronavirus disease (COVID-19) pandemic, hospitals have strengthened their guidelines on infection prevention and control (IPC), and a rigorous adherence to these guidelines is crucial. An infection control surveillance-working group (ICS-WG) and infection control coordinators (ICCs) team were created to monitor the IPC practices of the healthcare workers (HCWs) in a regional hospital in Korea. This study analyzed the surveillance results and aimed to identify what IPC practices needed improvement. METHODS: During phase 1 (March to April 2020), the ICS-WG performed random audits, recorded incidences of improper IPC practices, and provided advice to the violators. During phase 2 (April to July), the ICCs inspected the hospital units and proposed practical ideas about IPC. The surveillance and proposals targeted the following practices: patient screening, usage of personal protective equipment (PPE), hand and respiratory hygiene, equipment reprocessing, environmental cleaning, management of medical waste, and social distancing. RESULTS: In phase 1, of the 127 violations observed, most (32.3%) corresponded to hand and respiratory hygiene. In phase 2, the highest proportion of violation per category was observed in the management of medical waste (37.8%); among these, a higher proportion of violation (71.4%) was observed in the collection of medical waste. Of the 106 proposals made by the ICCs, the most addressed practice was patient screening (28.3%). No case of nosocomial infection was reported during the study period. CONCLUSION: Adherence to proper hand and respiratory hygiene was inadequate at the early stage of the COVID-19 pandemic. The results indicate that more attention and further training are needed for the management of medical waste, particularly medical waste collection, and that continuous upgrading of the strategies for patient screening is essential. These results will be useful in helping other healthcare facilities to establish their IPC strategies.

Things You Should Know in the Performing Echocardiographic Examination in Patients with COVID-19.

Novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has become a pandemic problem. Cardiovascular diseases are common in COVID-19 patients, especially in severe forms of infection, and these are associated with higher mortality. SARS-CoV-2 infection can cause cardiovascular disease and worsen preexisting disease by direct invasion, hypoxia associated with pneumonia, and immunologic mechanisms. Because prompt detection and proper treatment can be critical to COVID-19 patients, echocardiographic examinations are essential diagnostic tools in the diagnosis and determination of treatment options. However, because there is an increased risk of infection during echocardiographic examinations, healthcare providers should pay attention to mitigate the risk of infection during the diagnosis and management of COVID-19 patients.

State Framework for Delivering Targeted Housing Assistance to People and Places Hit Hardest by COVID-19

From the Document: "The COVID-19 [coronavirus disease 2019] pandemic has had devastating health and economic effects nationwide. The economic shocks have been worse for renter households and households of color. For the past couple of months, unemployment insurance benefits and eviction moratoriums in the Coronavirus Aid, Relief, and Economic Security (CARES) Act have kept vulnerable renters in their homes. But these laws have either expired or will soon expire, and many renters face an increasing risk of displacement unless quick action is taken. In this brief, we propose an approach for identifying the hardest-hit places and people who need relief, and we create a method of targeting housing assistance to renters and homeowners in the hardest-hit states. We developed an index using available state data and suggest a race-conscious method of directing resources. Our index weights hard-hit renter households and renters of color who are experiencing disproportionate housing insecurity and greater financial damage but less government support amid the pandemic. The index also offers a state ranking for those most in need."

Containment of a healthcare-associated COVID-19 outbreak in a university hospital in Seoul, Korea: A single-center experience.

BACKGROUND: Our hospital experienced the first healthcare-associated COVID-19 outbreak in Seoul at the time the first COVID-19 cases were confirmed in Korea. The first confirmed COVID-19 patient was a hospital personnel who was in charge of transferring patients inside our hospital. To contain the virus spread, we shutdown our hospital, and tested all inpatients, medical staff members, and employees. METHODS: We retrospectively analyzed the results of SARS-CoV-2 RT-PCR testing according to the contact history, occupation, and presence of respiratory symptoms. Closed-circuit television (CCTV) was reviewed in the presence of an epidemiologist to identify individuals who came into contact with confirmed COVID-19 patients. RESULTS: A total of 3,091 respiratory samples from 2,924 individuals were obtained. Among 2,924 individuals, two inpatients, and one caregiver tested positive (positivity rate, 0.1%). Although all confirmed cases were linked to a general ward designated for pulmonology patients, no medical staff members, medical support personnel, or employees working at the same ward were infected. Contact with confirmed COVID-19 cases was frequent among inpatients and medical support personnel. The most common contact area was the general ward for pulmonology patients and medical support areas, including clinical and imaging examination rooms. Finally, the total number of hospital-associated infections was 14, consisting of four diagnosed at our hospital and ten diagnosed outside the hospital. CONCLUSIONS: The robust control of the COVID-19 outbreak further minimized the transmission of SARS-CoV-2 in the hospital and local communities. However, there was also a debate over the appropriate period of hospital shutdown and testing of all hospital staff and patients. Future studies are required to refine and establish the in-hospital quarantine and de-isolation guidelines based on the epidemiological and clinical settings.