Distinct Molecular Mechanisms Characterizing Pathogenesis of SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has continued for over 2 years, following the outbreak of coronavirus-19 (COVID-19) in 2019. It has resulted in enormous casualties and severe economic crises. The rapid development of vaccines and therapeutics against SARS-CoV-2 has helped slow the spread. In the meantime, various mutations in the SARS-CoV-2 have emerged to evade current vaccines and therapeutics. A better understanding of SARS-CoV-2 pathogenesis is a prerequisite for developing efficient, advanced vaccines and therapeutics. Since the outbreak of COVID-19, a tremendous amount of research has been conducted to unveil SARSCoV-2 pathogenesis, from clinical observations to biochemical analysis at the molecular level upon viral infection. In this review, we discuss the molecular mechanisms of SARS-CoV-2 propagation and pathogenesis, with an update on recent advances.

Immunological and Pathological Peculiarity of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant.

Diverse severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged since the beginning of the COVID-19 pandemic. We investigated the immunological and pathological peculiarity of the SARS-CoV-2 beta variant of concern (VoC) compared to the ancestral strain. Comparative analysis of phenotype and pathology revealed that the beta VoC induces slower disease progression and a prolonged presymptomatic period in the early stages of SARS-CoV-2 infection but ultimately causes sudden death in the late stages of infection in the K18-hACE2 mouse model. The beta VoC induced enhanced activation of CXCL1/2-CXCR2-NLRP3-IL-1ß signal cascade accelerating neutrophil recruitment and lung pathology in beta variant-infected mice, as evidenced by multiple analyses of SARS-CoV-2-induced inflammatory cytokines and transcriptomes. CCL2 was one of the most highly secreted cytokines in the early stages of infection. Its blockade reduced virus-induced weight loss and delayed mortality. Our study provides a better understanding of the variant characteristics and need for treatment. IMPORTANCE Since the outbreak of COVID-19, diverse SARS-CoV-2 variants have been identified. These variants have different infectivity and transmissibility from the ancestral strains. However, underlying molecular mechanisms have not yet been fully elucidated. In our study, the beta variant showed distinct pathological conditions and cytokine release kinetics from an ancestral strain in a mouse model. It was associated with higher neutrophil recruitment by increased levels of CXCL1/2, CXCR2, and interleukin 1ß (IL-1ß) at a later stage of viral infection. Our study will provide a better understanding of SARS-CoV-2 pathogenesis.

Risk factors influencing COVID-19 mortality rate in OECD countries: A cross-sectional study.

SUMMARY: The coronavirus disease (COVID-19) has spread globally; however, the COVID-19 mortality rate varies largely across countries. The purpose of this study was to investigate the factors affecting mortality and increase in mortality rate by time trends in 30 member countries of the Organization for Economic Co-operation and Development (OECD). These countries have different national health and medical characteristics in terms of health care use, health equipment, health resource, health risk, and health status at different time points. The results revealed that the lower 25% of countries had an increase in the mortality rate of 27.21% which was higher than the upper 25% of countries' increase in the mortality rate of 20.51%. Therefore, the affected countries should strengthen their medical infrastructure to prepare for such large-scale outbreaks in the future. It is imperative to reduce the health inequality between population groups and achieve health equity, regardless of the income gap, rather than vaccination of specific countries. This will require the management of non-communicable diseases, a solid health insurance system, a stable supply of medical supplies, and strengthening the competency of health care workers.

Infection control in operating rooms for COVID-19 patients

Background Surgeries performed for patients with coronavirus disease 2019 (COVID-19) place the medical staff at very high risk of infection. We suggest recommendations for appropriate operation preparation, anesthetic management, and infection control for COVID-19 patients in operating rooms. Current Concepts Surgeries must be performed in an airborne infection isolation room, such as a negative-pressure operating room. It is recommended that scheduled surgeries for COVID-19 patients be postponed to an acceptable extent, with the exception of emergency cases. Moreover, the number of medical staff participating in the surgery should be minimized. Medical staffs should practice proper hand hygiene and wear an appropriate level of personal protective equipment depending on the infection risk. While performing surgery and inducing anesthesia in COVID-19 patients, endotracheal intubation should be performed by trained anesthesiologists with a video laryngoscope, preferably using high-efficiency viral filters, which can prevent contamination in the anesthesia machine. Use of disposable equipment or COVID-19 patient-specific devices is recommended to prevent the spread of infection, but instruments that require sharing among multiple patients must be thoroughly cleaned and disinfected before their use for the next patient. Discussion and Conclusion: Medical staff performing surgeries for COVID-19 patients are at very high risk of infection. Therefore, the use of appropriate personal protective equipment, high-efficiency viral filters in breathing circuits during anesthesia, and disinfection of contaminated equipment after the operation are mandatory.

Possible Benefit of Angiotensin II Receptor Blockers in COVID-19 Patients: A Case Series.

INTRODUCTION: Dysfunction in the renin-angiotensin-aldosterone system (RAAS) has been observed in patients with coronavirus disease 2019 (COVID-19). It is presumed that the effect of reducing interleukin-6 (IL-6) levels by angiotensin II receptor blockers (ARBs) by RAAS modulation. We investigated changes in angiotensin II and IL-6 levels in four COVID-19 patients treated with ARBs. Case Presentation. Cases 1 and 2 were who had not received ARBs before and were newly administered ARBs. Case 3 restarted ARBs after discontinuation for 7 days, and case 4 received an increased dose of ARBs. The mean in angiotensin II levels (607.5 pg/mL, range: 488-850 pg/mL, reference range < 100 pg/mL), C-reactive protein (CRP) (10.58 mg/dL, range 4.45-18.05 mg/dL), and IL-6 (55.78 pg/mL, range: 12.86-144.82 pg/mL, reference range < 7 pg/mL) was observed at the admission in all patients. Upon clinical improvement, the mean decrease in CRP (1.02 mg/dL, range 0.06-3.78 mg/dL) and IL-6 (5.63 pg/mL, range 0.17-20.87 pg/mL) was observed in all patients. Conversely, angiotensin II levels gradually increased. CONCLUSION: This report supports the potential benefit of ARBs to improve the clinical outcomes of COVID-19 patients by controlling RAAS dysfunction.

Effectiveness of Steroid Treatment for SARS-CoV-2 Pneumonia With Cryptogenic Organizing Pneumonia-Like Reaction: A Case Report.

Several studies on the treatment of coronavirus disease 2019 (COVID-19) are being conducted, and various drugs are being tried; however, the results have not been uniform. Steroids have been widely used in the treatment of COVID-19, but their effects are controversial. As immunosuppressive and anti-inflammatory agents, steroids are considered to reduce lung damage by regulating various inflammatory responses. We report a case of severe acute respiratory syndrome coronavirus-2 pneumonia manifesting as a cryptogenic organizing pneumonia-like reaction and discuss its treatment, clinical course, and favorable outcomes after steroid administration.

Comparison of Serologic Response of Hospitalized COVID-19 Patients Using 8 Immunoassays.

BACKGROUND: In Korea, there were issues regarding the use of immunoassays for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies to detect infection. So, we compared antibody results of eight kinds of commercial immunoassays using clinical remnant specimens. METHODS: We compared the results of several immunoassay kits tested on 40 serum samples from 15 confirmed patients and 86 remnant serum samples from clinical laboratory. Eight kinds of IVD kits-four enzyme-linked immunosorbent assay, two lateral flow rapid immunochromatographic assays, and two chemiluminescent immunoassays with one RUO kit were tested. RESULTS: Among 40 serum samples from 15 coronavirus disease 2019 (COVID-19) patients, 35 yielded at least one positive result for detecting antibodies in the combined assessment. There were inconsistent results in 12 (28%) samples by single immunoassay. Forty samples collected in 2019 before the first COVID-19 Korean case showed negative results except for one equivocal result. CONCLUSION: The discrepant results obtained with different immunoassay kits in this study show that serological assessment of SARS-CoV-2 by a single immunoassay requires caution not only in detecting infection but also in assessing immunologic status.

Response System for and Epidemiological Features of COVID-19 in Gyeongsangnam-do Province in South Korea.

BACKGROUND: The South Korean government has been combating the coronavirus disease 2019 (COVID-19) outbreak using public information and extensive viral screening. We describe the application of the Korean response system in Gyeongsangnam-do province and outline the epidemiological features of COVID-19 in the cohort. METHODS: A Rapid Response Team tracked the patients' activities and identified close contacts. A Patient Management Team made decisions regarding the severity of illness, hospital allocation depending on severity, and time of discharge. A national medical center with 155 beds and 4 university-affiliated hospitals with 48 negative-pressure isolation rooms were dedicated for patients with COVID-19. RESULTS: As of 15 April, 17 400 residents were tested, of whom 111 were confirmed positive cases. Of the 111 patients, 78 were cured and discharged, 2 recovered after mechanical ventilation, and none died. One healthcare worker at the national center tested positive for SARS-CoV-2. All 412 staff members at the center were tested, but there were no additional infections. Cough (30.0%) was the most common initial symptom, whereas anosmia and ageusia were the first symptoms in 14.7% and 15.7% of the patients, respectively. Overall, 25 patients (22.5%) reported having no symptoms at admission and 7 (6.3%) remained asymptomatic at discharge. CONCLUSIONS: A response system that enabled the early detection of COVID-19 cases, including asymptomatic and presymptomatic cases, and timely quarantine of these patients and their contacts, along with efficient allocation of medical resources, was the key to curbing the COVID-19 outbreak in Gyeongsangnam-do Province.