Clinical Characteristics of 40 Patients Infected With the SARS-CoV-2 Omicron Variant in Korea

Since severe acute respiratory syndrome-coronavirus-2 variant B.1.1.529 (omicron) was first reported to the World Health Organization on November 24, 2021, the cases of the omicron variant have been detected in more than 90 countries over the last month. We investigated the clinical and epidemiological characteristics of the first 40 patients with the omicron variant who had been isolated at the National Medical Center in South Korea during December 4–17, 2021. The median age of the patients was 39.5 years. Twenty-two patients (55%) were women. Seventeen patients (42.5%) were fully vaccinated, and none were reinfected with the omicron. Eighteen (45%) had recent international travel history. Half of the patients (19, 47.5%) were asymptomatic, while the others had mild symptoms. Six patients (15%) showed lung infiltrations on chest image; however, none required supplemental oxygen. These mild clinical features are consistent with recent case reports on the omicron variant from other countries.     

Immunity,virus evolution,and effectiveness of SARS-CoV-2 vaccines

Phylogenetic and pathogenesis studies of the severe acute respiratory syndrome-related coronaviruses (SARS-CoVs) strains have highlighted some specific mutations that could confer the RNA genome fitness advantages and immunological resistance for their rapid spread in the human population. The analyses of 30 kb RNA SARS-CoVs genome sequences, protein structures, and functions have provided us a perspective of how host-virus protein-protein complexes act to mediate virus infection. The open reading frame (ORF)1a and ORF1b translation yields 16 non-structural (nsp1-16) and 6 accessory proteins (p6, p7a, p8ab, p9b) with multiple functional domains. Viral proteins recruit over 300 host partners forming hetero-oligomeric complexes enabling the viral RNA synthesis, packing, and virion release. Many cellular host factors and the innate immune cells through pattern-recognition receptors and intracellular RNA sensor molecules act to inhibit virus entry and intracellular replication. However, non-structural ORF proteins hijack them and suppress interferon synthesis and its antiviral effects. Pro-inflammatory chemokines and cytokines storm leads to dysfunctional inflammation, lung injury, and several clinical symptoms in patients. During the global pandemic, COVID-19 patients were identified with non-synonymous substitution of G614D in the spike protein, indicating virus co-evolution in host cells. We review findings that suggest that host RNA editing and DNA repair systems, while carrying on recombination, mutation, and repair of viral RNA intermediates, may facilitate virus evolution. Understanding how the host cell RNA replication process may be driven by SARS-CoV-2 RNA genome fitness will help the testing of vaccines effectiveness to multiple independent mutated coronavirus strains that will emerge.     

Booster BNT162b2 COVID-19 Vaccination Increases Neutralizing Antibody Titers Against the SARS-CoV-2 Omicron Variant in Both Young and Elderly Adults

Concerns about the effectiveness of current vaccines against the rapidly spreading severe acute respiratory syndrome-coronavirus-2 omicron (B.1.1.529) variant are increasing. This study aimed to assess neutralizing antibody activity against the wild-type (BetaCoV/Korea/KCDC03/2020), delta, and omicron variants after full primary and booster vaccinations with BNT162b2. A plaque reduction neutralization test was employed to determine 50% neutralizing dilution (ND₅₀) titers in serum samples. ND₅₀ titers against the omicron variant (median [interquartile range], 5.3 [< 5.0–12.7]) after full primary vaccination were lower than those against the wild-type (144.8 [44.7–294.0]) and delta (24.3 [14.3–81.1]) variants. Furthermore, 19/30 participants (63.3%) displayed lower ND₅₀ titers than the detection threshold (< 10.0) against omicron after full primary vaccination. However, the booster vaccine significantly increased ND₅₀ titers against BetaCoV/Korea/KCDC03/2020, delta, and omicron, although titers against omicron remained lower than those against the other variants (P < 0.001). Our study suggests that booster vaccination with BNT162b2 significantly increases humoral immunity against the omicron variant.     

First-generation oral antivirals against SARS-CoV-2

BackgroundOral drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have received emergency use authorization for the treatment of mild-to-moderate COVID-19 in non-hospitalized patients who are at high risk for clinical progression.ObjectivesTo provide a clinical practice overview of first-generation oral antiviral agents against SARS-CoV-2.SourcesReferences for this review were identified through searches of PubMed, Google Scholar, bioRxiv, medRxiv, regulatory drug agencies, and pharmaceutical companies' websites up to 16 February 2022.ContentMolnupiravir and nirmatrelvir and ritonavir have been authorized for use in nonhospitalized individuals with mild-to-moderate COVID-19 who are at high risk for progression. In clinical trials, molnupiravir reduced the frequency of hospitalization or death by 3% (relative risk reduction 30%), and nirmatrelvir and ritonavir by 6% (relative risk reduction 89%). Their use in clinical practice requires early administration, review of drug-drug interactions (nirmatrelvir and ritonavir), considerations of embryo-fetal toxicity (molnupiravir), and compliance with ingestion of a high number of pills. Knowledge gaps include the efficacy of these agents in vaccinated, hospitalized, or immunosuppressed individuals with prolonged SARS-CoV-2 persistence.ImplicationsFirst-generation oral antivirals represent progress in therapeutics against SARS-CoV-2, but also pose new challenges in clinical practice. Further advances in the development of new drugs are required.     

Immunogenicity of SARS-CoV-2 Vaccine in Kidney Transplant Recipients: A Cross-Sectional Study in Korea

Eighty-five Korean kidney transplant recipients who received three doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine were tested with anti-receptor binding domain (RBD) antibody and neutralizing antibody. High anti-RBD antibody (≥ 100 U/mL) and neutralizing antibody responses (≥ 30%) were detected in 51/85 (60.0%) patients. When we divided the patients with the time from transplantation to vaccination (< 1, 1–2.4, 2.5–4.9, and ≥ 5-year), anti-RBD antibody titers were 3.2 U/mL, 27.8 U/mL, 370.2 U/mL, and 5,094.2 U/mL (P < 0.001) and anti-neutralizing antibody levels were 2.2%, 11.6%, 45.6%, and 93.0% (P < 0.001), respectively. Multivariate analysis revealed increased antibody responses when the time from transplantation to vaccination was five years or longer (odds ratio, 12.0; confidence interval, 2.7–52.8). Korean kidney transplant recipients had suboptimal antibody responses after the third dose of SARS-CoV-2 vaccine. A shorter time from transplantation to vaccination was a risk factor for a low antibody response.     

Evidence of Long-Distance Droplet Transmission of SARS-CoV-2 by Direct Air Flow in a Restaurant in Korea

BackgroundThe transmission mode of severe acute respiratory syndrome coronavirus 2 is primarily known as droplet transmission. However, a recent argument has emerged about the possibility of airborne transmission. On June 17, there was a coronavirus disease 2019 (COVID-19) outbreak in Korea associated with long distance droplet transmission.MethodsThe epidemiological investigation was implemented based on personal interviews and data collection on closed-circuit television images, and cell phone location data. The epidemic investigation support system developed by the Korea Disease Control and Prevention Agency was used for contact tracing. At the restaurant considered the site of exposure, air flow direction and velocity, distances between cases, and movement of visitors were investigated.ResultsA total of 3 cases were identified in this outbreak, and maximum air flow velocity of 1.2 m/s was measured between the infector and infectee in a restaurant equipped with ceiling-type air conditioners. The index case was infected at a 6.5 m away from the infector and 5 minutes exposure without any direct or indirect contact.ConclusionDroplet transmission can occur at a distance greater than 2 m if there is direct air flow from an infected person. Therefore, updated guidelines involving prevention, contact tracing, and quarantine for COVID-19 are required for control of this highly contagious disease.     

Clinical Characteristics and Outcomes of Children With SARS-CoV-2 Infection During the Delta and Omicron Variant-Dominant Periods in Korea

BackgroundData on the clinical characteristics of pediatric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection are limited. We aimed to evaluate the clinical features and outcomes of children with SARS-CoV-2 infection before and after omicron variant dominance in Korea.MethodsA multicenter retrospective cohort study was conducted in hospitalized patients aged ≤ 18 years with laboratory-confirmed SARS-CoV-2 infection at five university hospitals in South Korea. The study periods were divided into the delta (from August 23, 2021 to January 2, 2022) and omicron (from January 30 to March 31, 2022).ResultsIn total, 612 hospitalized patients were identified (211, delta; 401, omicron). During the omicron and delta periods, the proportions of individuals with serious illness (moderate, severe, and critical severity) were 21.2% and 11.8%, respectively (P = 0.034). Compared with the delta period, the proportions of patients with moderate illness increased significantly in the age groups of 0–4 years (14.2% vs. 3.4%) and 5–11 years (18.6% vs. 4.2%) during the omicron period. During the two periods, the proportions of patients with complex chronic diseases (delta, 16.0% vs. 4.3%, P = 0.040; omicron, 27.1% vs. 12.7%; P = 0.002), respiratory diseases except for asthma (delta, 8.0% vs. 0.0%, P = 0.013; omicron, 9.4% vs. 1.6%; P = 0.001), and neurologic diseases (delta, 28.0% vs. 3.2%, P < 0.001; omicron, 40.0% vs. 5.1%, P < 0.001) were significantly higher in patients with serious illness than in those with non-serious illness. During the delta period, the risk for serious illness was higher among patients with obesity (adjusted odds ratio [aOR], 8.18; 95% confidence interval [CI], 2.80–27.36) and neurologic diseases (aOR, 39.43; 95% CI, 6.90–268.3) and aged 12–18 years (aOR, 3.92; 95% CI, 1.46–10.85). However, the presence of neurologic disease (aOR, 9.80; 95% CI, 4.50–22.57) was the only risk factor for serious illness during the omicron period. During the omicron period, the proportions of patients with croup (11.0% vs. 0.5%) and seizures (13.2% vs. 2.8%) increased significantly compared with the delta period.ConclusionCompared with the delta period, the proportions of young children and patients with complex comorbidities were higher during the omicron period in Korea. Patients with complex chronic diseases, especially neurologic diseases, had a high risk of severe coronavirus disease 2019 in the two distinct variant-dominant periods.     

Olfactory disorder in patients infected with SARS-CoV-2

Three (60%) of five patients with coronavirus disease 2019 (COVID-19) had olfactory disorder. Two exhibited anosmia at the onset of COVID-19, while one had hyposmia 4 days after the onset of COVID-19. All patients with olfactory disorder were completely recovered with a mean recovery length of 11.3 days.     

Importation and Transmission of SARS-CoV-2 B.1.1.529 (Omicron) Variant of Concern in Korea,November 2021

In November 2021, 14 international travel-related severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant of concern (VOC) patients were detected in South Korea. Epidemiologic investigation revealed community transmission of the omicron VOC. A total of 80 SARS-CoV-2 omicron VOC-positive patients were identified until December 10, 2021 and 66 of them reported no relation to the international travel. There may be more transmissions with this VOC in Korea than reported.     

SARS-CoV-2 and natural infection in animals

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of the novel coronavirus disease (COVID-19) pandemic, which has caused serious challenges for public health systems worldwide. Due to the close relationship between animals and humans, confirmed transmission from humans to numerous animal species has been reported. Understanding the cross-species transmission of SARS-CoV-2 and the infection and transmission dynamics of SARS-CoV-2 in different animals is crucial to control COVID-19 and protect animal health. In this review, the possible animal origins of SARS-CoV-2 and animal species naturally susceptible to SARS-CoV-2 infection are discussed. Furthermore, this review categorizes the SARS-CoV-2 susceptible animals by families, so as to better understand the relationship between SARS-CoV-2 and animals.     

High neutralizing potency of swine glyco-humanized polyclonal antibodies against SARS-CoV-2

Heterologous polyclonal antibodies might represent an alternative to the use of convalescent plasma or monoclonal antibodies (mAbs) in coronavirus disease (COVID-19) by targeting multiple antigen epitopes. However, heterologous antibodies trigger human natural xenogeneic antibody responses particularly directed against animal-type carbohydrates, mainly the N-glycolyl form of the neuraminic acid (Neu5Gc) and the α1,3-galactose, potentially leading to serum sickness or allergy. Here, we immunized cytidine monophosphate-N-acetylneuraminic acid hydroxylase and α1,3-galactosyl-transferase (GGTA1) double KO pigs with the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor binding domain to produce glyco-humanized polyclonal neutralizing antibodies lacking Neu5Gc and α1,3-galactose epitopes. Animals rapidly developed a hyperimmune response with anti-SARS-CoV-2 end-titers binding dilutions over one to a million and end-titers neutralizing dilutions of 1:10 000. The IgG fraction purified and formulated following clinical Good Manufacturing Practices, named XAV-19, neutralized spike/angiotensin converting enzyme-2 interaction at a concentration <1 μg/mL, and inhibited infection of human cells by SARS-CoV-2 in cytopathic assays. We also found that pig GH-pAb Fc domains fail to interact with human Fc receptors, thereby avoiding macrophage-dependent exacerbated inflammatory responses and a possible antibody-dependent enhancement. These data and the accumulating safety advantages of using GH-pAbs in humans warrant clinical assessment of XAV-19 against COVID-19.     

Phylogenetic analysis of the first four SARS-CoV-2 cases in Chile

The current pandemic caused by the new coronavirus is a worldwide public health concern. To aboard this emergency, and like never before, scientific groups around the world have been working in a fast and coordinated way to get the maximum of information about this virus when it has been almost 3 months since the first cases were detected in Wuhan province in China. The complete genome sequences of around 450 isolates are available, and studies about similarities and differences among them and with the close related viruses that caused similar epidemics in this century. In this work, we studied the complete genome of the first four cases of the new coronavirus disease in Chile, from patients who traveled to Europe and Southeast Asia. Our findings reveal at least two different viral variants entries to Chilean territory, coming from Europe and Asia. We also sub-classified the isolates into variants according to punctual mutations in the genome. Our work contributes to global information about transmission dynamics and the importance to take control measures to stop the spread of the infection.     

Omicron-specific mRNA vaccine induced cross-protective immunity against ancestral SARS-CoV-2 infection with low neutralizing antibodies

The major challenge in COVID-19 vaccine effectiveness is immune escape by SARS-CoV-2 variants. To overcome this, an Omicron-specific messenger RNA (mRNA) vaccine was designed. The extracellular domain of the spike of the Omicron variant was fused with a modified GCN4 trimerization domain with low immunogenicity (TSomi). After immunization with TSomi mRNA in hamsters, animals were challenged with SARS-CoV-2 virus. The raised nonneutralizing antibodies or cytokine secretion responses can recognize both Wuhan S and Omicron S. However, the raised antibodies neutralized SARS-CoV-2 Omicron virus infection but failed to generate Wuhan virus neutralizing antibodies. Surprisingly, TSomi mRNA immunization protected animals from Wuhan virus challenge. These data indicated that non-neutralizing antibodies or cellular immunity may play a more important role in vaccine-induced protection than previously believed. Next-generation COVID-19 vaccines using the Omicron S antigen may provide sufficient protection against ancestral or current SARS-CoV-2 variants.     

Prevalence of SARS-CoV-2 Antibody in 2,935 Healthcare Workers at 6 Major Hospitals,Daegu, Korea

BackgroundIn Korea, the first community outbreak of coronavirus disease 2019 (COVID-19) occurred in Daegu on February 18, 2020. This study was performed to investigate the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies in healthcare workers (HCWs) at 6 major hospitals in Daegu.MethodsBlood specimens of 2,935 HCWs at 6 major hospitals in Daegu from January 2021 to February 2021 were collected. Every specimen was tested for antibody against SARS-CoV-2 using both Elecsys Anti-SARS-CoV-2 electrochemiluminescence immunoassay (Roche Diagnostics, Rotkreuz, Switzerland) and R-FIND COVID-19 IgG/M/A enzyme-linked immunosorbent assay kit (SG medical Inc., Seoul, Korea) as screening tests. If 1 or more of these screening test results was positive, 2 additional antibody tests were performed using Abbott Anti-SARS-CoV-2 IgG assay (Abbott, Abbott Park, IL, USA) and cPass SARS-CoV-2 Neutralization Antibody Detection Kit (GenScript USA Inc., Piscataway, NJ, USA). If 2 or more of the total 4 test results were positive, it was determined as positive for the antibody against SARS-CoV-2.ResultsAccording to the criteria of SARS-CoV-2 antibody positivity determination, 12 subjects were determined as positive. The overall positive rate of the SARS-CoV-2 antibody was 0.41% (12/2,935). Of the 12 subjects determined as positive, 7 were diagnosed with COVID-19, and the remaining 5 were nondiagnosed cases of COVID-19.ConclusionIn early 2021, the overall seroprevalence of SARS-CoV-2 antibody among HCW located in Daegu was 0.41%, and 0.17% excluding COVID-19 confirmed subjects. These results were not particularly high compared with the general public and were much lower than HCWs in other countries.