Accurate Diagnosis of COVID-19 from Self-Collectable Biospecimens Using Synthetic Apolipoprotein H Peptide-Coated Nanoparticle Assay.

A high-throughput, accurate screening is crucial for the prevention and control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current methods, which involve sampling from the nasopharyngeal (NP) area by medical staffs, constitute a fundamental bottleneck in expanding the testing capacity. To meet the scales required for population-level surveillance, self-collectable specimens can be used; however, its low viral load has hindered its clinical adoption. Here, we describe a magnetic nanoparticle functionalized with synthetic apolipoprotein H (ApoH) peptides to capture, concentrate, and purify viruses. The ApoH assay demonstrates a viral enrichment efficiency of >90% for both SARS-CoV-2 and its variants, leading to an order of magnitude improvement in analytical sensitivity. For validation, we apply the assay to a total of 84 clinical specimens including nasal, oral, and mouth gargles obtained from COVID-19 patients. As a result, a 100% positivity rate is achieved from the patient-collected nasal and gargle samples, which exceeds that of the traditional NP swab method. The simple 12 min pre-enrichment assay enabling the use of self-collectable samples will be a practical solution to overcome the overwhelming diagnostic capacity. Furthermore, the methodology can easily be built on various clinical protocols, allowing its broad applicability to various disease diagnoses.

SARS-CoV-2 Omicron Variant of Concern: Everything You Wanted to Know about Omicron but Were Afraid to Ask.

As soon as the first case of the omicron variant of severe acute respiratory syndrome coronavirus 2 was reported in November 2021, it quickly spread worldwide with the emergence of several subvariants. Compared to previous variants, omicron was heavily mutated, especially for those in the Spike (S) protein and its receptor-binding domain. These mutations allowed the viruses to evade immune responses (i.e., previous infections and vaccine-elicited) and increase in transmissibility. Although vaccine effectiveness is decreased for omicron, boosters remain effective for protecting against severe diseases. Also, bivalent vaccines have been developed to increase vaccine effectiveness. Interestingly, although omicron is highly infectious, it has less morbidity and mortality compared to previously identified variants, such as delta. Additionally, the mutations that allow the virus to evade immune responses also allow it to evade many of the monoclonal antibodies developed at the beginning of the pandemic for treatment. Here, we reviewed the omicron variant's epidemiology, genetics, transmissibility, disease severity, and responsiveness to vaccine and treatments.

Trends in Confirmed COVID-19 Cases in the Korean Military Before and After the Emergence of the Omicron Variant.

BACKGROUND: Due to the higher transmissibility and increased immune escape of the omicron variant of severe acute respiratory syndrome coronavirus 2, the number of patients with coronavirus disease 2019 (COVID-19) has skyrocketed in the Republic of Korea. Here, we analyzed the change in trend of the number of confirmed COVID-19 cases in the Korean military after the emergence of the omicron variant on December 5, 2021. METHODS: An interrupted time-series analysis was performed of the daily number of newly confirmed COVID-19 cases in the Korean military from September 1, 2021 to April 10, 2022, before and after the emergence of the omicron variant. Moreover, the daily number of newly confirmed COVID-19 cases in the Korean military and in the population of Korean civilians adjusted to the same with military were compared. RESULTS: The trends of COVID-19 occurrence in the military after emergence of the omicron variant was significantly increased (regression coefficient, 23.071; 95% confidence interval, 16.122-30.020; P < 0.001). The COVID-19 incidence rate in the Korean military was lower than that in the civilians, but after the emergence of the omicron variant, the increased incidence rate in the military followed that of the civilian population. CONCLUSION: The outbreak of the omicron variant occurred in the Korean military despite maintaining high vaccination coverage and intensive non-pharmacological interventions.

Amelioration of SARS-CoV-2 infection by ANO6 phospholipid scramblase inhibition.

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).

TMED3 Complex Mediates ER Stress-Associated Secretion of CFTR, Pendrin, and SARS-CoV-2 Spike.

Under ER stress conditions, the ER form of transmembrane proteins can reach the plasma membrane via a Golgi-independent unconventional protein secretion (UPS) pathway. However, the targeting mechanisms of membrane proteins for UPS are unknown. Here, this study reports that TMED proteins play a critical role in the ER stress-associated UPS of transmembrane proteins. The gene silencing results reveal that TMED2, TMED3, TMED9 and TMED10 are involved in the UPS of transmembrane proteins, such as CFTR, pendrin and SARS-CoV-2 Spike. Subsequent mechanistic analyses indicate that TMED3 recognizes the ER core-glycosylated protein cargos and that the heteromeric TMED2/3/9/10 complex mediates their UPS. Co-expression of all four TMEDs improves, while each single expression reduces, the UPS and ion transport function of trafficking-deficient ΔF508-CFTR and p.H723R-pendrin, which cause cystic fibrosis and Pendred syndrome, respectively. In contrast, TMED2/3/9/10 silencing reduces SARS-CoV-2 viral release. These results provide evidence for a common role of TMED3 and related TMEDs in the ER stress-associated, Golgi-independent secretion of transmembrane proteins.

Successful Lung Transplantation From a Donor Who Had Recovered From Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia.

During the present coronavirus disease 2019 (COVID-19) pandemic, transplantation of donor lungs using patients with a history of COVID-19 infection is a critical issue. Donor-derived virus infection and graft dysfunction are possible after transplantation. However use of such lungs could save the lives of patients requiring emergency transplantation. We successfully transplanted lungs from a brain-dead donor who had recovered from severe acute respiratory syndrome coronavirus 2 into a severe respiratory failure patient supported with extracorporeal membrane oxygenation who needed an emergency transplant. At the 3-month follow-up our patient showed no evidence of COVID-19 transmission or graft dysfunction.

The impact of the modified schedules of anatomy education on students' performance and satisfaction: Responding to COVID-19 pandemic in South Korea.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic substantially undermined medical education and healthcare systems. Owing to the pandemic in South Korea, most medical schools needed to be flexible when conducting online and offline classes, but the guidelines did not reflect the specificity of medical schools. This study described the impact of modified anatomy education schedules at the Seoul National University College of Medicine (SNUCM) on students' academic performance and satisfaction. METHODS: Anatomy education in SNUCM is divided into three regional units (the upper and lower limbs, trunk, and head and neck). Owing to the COVID-19 pandemic, the schedule was mixed with simultaneous and rotating schedules. The authors conducted exceptions for online lectures, cadaver dissections, and written and practical examinations in three classes of approximately 50 students each. Furthermore, the authors assessed students' performance using three sets of written and practical examinations, and students completed a questionnaire regarding modified anatomy laboratory schedules. RESULTS: Despite the pandemic events in Seoul and South Korea during the laboratory sessions, all sessions were completed without any confirmed COVID-19 cases among the students, faculty, and staff. Most of the scores on the written and practical examinations significantly decreased in 2020 compared to those in 2019. However, in the trunk session that used the virtual anatomy application, the score on the practical examination in 2020 was significantly higher than that in 2019. Over 70% (79 and 77 out of 105 respondents on the upper and lower limbs and trunk, respectively) and 53% (55/105) students reported that there were no significant difficulties in studying anatomy in a face-to-face laboratory. CONCLUSIONS: In conclusion, an adequate education program for cadaver dissection should be developed and provided to overcome the pandemic restrictions. The study findings could serve as a reference for anatomy education during the COVID-19 pandemic.

Analyses of Confirmed COVID-19 Cases Among Korean Military Personnel After Mass Vaccination.

BACKGROUND: The military was one of the first groups in Korea to complete mass vaccination against the coronavirus disease 2019 (COVID-19) due to their high vulnerability to COVID-19. To confirm the effect of mass vaccination, this study analyzed the patterns of confirmed cases within Korean military units. METHODS: From August 1 to September 15, 2021, all epidemiological data regarding confirmed COVID-19 cases in military units were reviewed. The number of confirmed cases in the units that were believed to have achieved herd immunity (i.e., ≥ 70% vaccination) was compared with the number of cases in the units that were not believed to have reached herd immunity (< 70% vaccination). Additionally, trends in the incidence rates of COVID-19 in the military and the entire Korean population were compared. RESULTS: By August 2021, 85.60% of military personnel were fully vaccinated. During the study period, a total of 174 COVID-19 cases were confirmed in the 39 units. More local transmission (herd immunity group vs. non-herd immunity group [%], 1 [0.91] vs. 39 [60.94]) and hospitalizations (12 [11.01] vs. 13 [27.08]) occurred in the units that were not believed to have achieved herd immunity. The percentage of fully vaccinated individuals among the confirmed COVID-19 cases increased over time, possibly due to the prevalence of the delta variant. Nevertheless, the incidence rate remained lower in military units than in the general Korean population. CONCLUSION: After completing mass vaccination, the incidence rates of COVID-19 infection in the military were lower than those in the national population. New cluster infections did not occur in vaccinated units, thereby suggesting that herd immunity has been achieved in these military units. Further research is needed to determine the extent to which levels of non-pharmacological intervention can be reduced in the future.