The “vaccine” hubbub: Viral load comparisons of SARS-CoV-2 Delta and Omicron variants against different vaccine–booster vaccine combinations

There is a significant body of evidence showing that efficient vaccination schemes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is helping control the coronavirus disease 2019 (COVID-19) pandemic. However, this goal cannot be achieved without real world data highlighting the impact of vaccines against viral spread. In this study, we have aimed at differentially investigating the impact of COVID-19 vaccines (CoronaVac, Pfizer/BioNTech, Astra/Zeneca Oxford, Janssen) used in North Cyprus in limiting the viral load of Delta and Omicron variants of SARS-COV-2. We have utilized real-time quantitative polymerase chain reaction cycle threshold values (Ct values) as a proxy of viral load of the two SARS-CoV-2 variants. Our results indicate that the administration of at least two doses of the messenger RNA-based Pfizer/BioNTech vaccine leads to the lowest viral load (highest Ct values) obtained for both Omicron and Delta variants. Interestingly, regardless of the vaccine type used, our study revealed that Delta variant produced significantly higher viral loads (lower Ct values) compared with the Omicron variant, where the latter was more commonly associated with younger patients. Viral spread is a crucial factor that can help determine the future of the pandemic. Thus, prioritizing vaccines that will play a role in not only preventing severe disease but also in limiting viral load and spread may contribute to infection control strategies.     

Vaccine effectiveness against Delta,Omicron BA.1, and BA.2 in a highly vaccinated Asian setting: a test-negative design study

ObjectivesWe compared the vaccine effectiveness over time of the primary series and booster against infection and severe disease with the Delta, Omicron BA.1, and BA.2 variants in Singapore, an Asian setting with high vaccination coverage.MethodsWe conducted a test-negative case-control study on all adult residents in Singapore who underwent PCR testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in acute hospitals. Individuals with a negative PCR from 1 September, 2021, to 30 November, 2021, and 1 December, 2021, to 25 April, 2022, served as controls for the Delta and Omicron variants respectively, and PCR-positive individuals within these two time periods served as cases. Associations between vaccination status and SARS-CoV-2 infection and severe disease with the Delta or Omicron variants were measured using Poisson regressions. Vaccine effectiveness was calculated by taking 1 minus risk ratio.ResultsThere were 68 114 individuals comprising 58 495 controls and 9619 cases for the Delta period, of whom 53 093 completed the primary series and 9161 were boosted. For the Omicron period, 104 601 individuals comprising 80 428 controls, 8643 BA.1 cases, and 15 530 BA.2 cases were included, of whom 29 183 and 71 513 were vaccinated with the primary series and boosted, respectively. The primary series provided greater protection against infection with Delta (45%, 95% CI 40–50%) than against infection with Omicron (21%, 95% CI 7–34% for BA.1; 18%, 95% CI 6–29% for BA.2) at <2 months from vaccination. Vaccine effectiveness of the booster was similar against infection with BA.1 (44%, 95% CI 38–50%) and BA.2 (40%, 95% CI 35–40%). Protection against severe disease by the booster for BA.1 (83%, 95% CI 76–88%) and BA.2 (78%, 95% CI 73–82%) was comparable to that by the primary series for Delta (80%, 95% CI 73–85%).ConclusionOur findings support the use of a booster dose to reduce the risk of severe disease and mitigate the impact on the healthcare system in an Omicron-predominant epidemic.     

SARS-CoV-2 evolves to reduce but not abolish neutralizing action

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have prolonged coronavirus disease 2019 (COVID-19) pandemic by escaping pre-existing immunity acquired by natural infection or vaccination. Elucidation of VOCs' mutation trends and evasion of neutralization is required to update current control measures. Mutations and the prevalence of VOCs were analyzed in the global immunization coverage rate context. Lentivirus-based pseudovirus neutralization analysis platforms for SARS-CoV-2 prototype strain (PS) and VOCs, containing Alpha, Beta, Gamma, Delta, and Omicron, were constructed based on the spike protein of each variant and HEK 293T cell line expressing the human angiotensin-converting enzyme 2 (hACE2) receptor on the surface, and an enhanced green fluorescent protein reporter. Serum samples from 65 convalescent individuals and 20 WIBP-CorV vaccine recipients and four therapeutic monoclonal antibodies (mAbs) namely imdevimab, casirivimab, bamlanivimab, and etesevimab were used to evaluate the neutralization potency against the variants. Pseudovirus-based neutralization assay platforms for PS and VOCs were established, and multiplicity of infection (MOI) was the key factor influencing the assay result. Compared to PS, VOCs may enhance the infectivity of hACE2-293T cells. Except for Alpha, other VOCs escaped neutralization to varying degrees. Attributed to favorable and emerging mutations, the current pandemic Omicron variant of all VOCs demonstrated the most significant neutralization-escaping ability to the sera and mAbs. Compared with the PS pseudovirus, Omicron had 15.7- and 3.71-fold decreases in the NT50 value (the highest serum dilution corresponding to a neutralization rate of 50%); and correspondingly, 90% and 43% of immunization or convalescent serum samples lost their neutralizing activity against the Omicron variant, respectively. Therefore, SARS-CoV-2 has evolved persistently with a strong ability to escape neutralization and prevailing against the established immune barrier. Our findings provide important clues to controlling the COVID-19 pandemic caused by new variants.     

SARS-CoV-2 Omicron variant (B.1.1.529): A concern with immune escape

Omicron, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant that is now spreading across the world, is the most altered version to emerge so far, with mutations comparable to changes reported in earlier variants of concern linked with increased transmissibility and partial resistance to vaccine-induced immunity. This article provides an overview of the SARS-CoV-2 variant Omicron (B.1.1.529) by reviewing the literature from major scientific databases. Although clear immunological and clinical data are not yet available, we extrapolated from what is known about mutations present in the Omicron variant of SARS-CoV-2 and offer preliminary indications on transmissibility, severity, and immune escape through existing research and databases.     

SARS-CoV-2 infection in children evaluated in an ambulatory setting during Delta and Omicron time periods

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and re-emergence of other respiratory viruses highlight the need to understand the presentation of and factors associated with SARS-CoV-2 in pediatric populations over time. The objective of this study was to evaluate the sociodemographic characteristics, symptoms, and epidemiological risk factors associated with ambulatory SARS-CoV-2 infection in children and determine if factors differ by variant type. We conducted a retrospective cohort study of outpatient children undergoing SARS-CoV-2 polymerase chain reaction testing between November 2020 and January 2022. Test-positive were compared with test-negative children to evaluate symptoms, exposure risk, demographics, and comparisons between Omicron, Delta, and pre-Delta time periods. Among 2264 encounters, 361 (15.9%) were positive for SARS-CoV-2. The cohort was predominantly Hispanic (51%), 5–11 years (44%), and 53% male; 5% had received two coronavirus disease 2019 (COVID-19) vaccine doses. Factors associated with a positive test include loss of taste/smell (adjusted odds ratio [aOR]: 6.71, [95% confidence interval, CI: 2.99–15.08]), new cough (aOR: 2.38, [95% CI: 1.69–3.36]), headache (aOR: 1.90, [95% CI: 1.28–2.81), fever (aOR: 1.83, [95% CI: 1.29–2.60]), contact with a positive case (aOR: 5.12, [95% CI: 3.75–6.97]), or household contact (aOR: 2.66, [95% CI: 1.96–3.62]). Among positive children, loss of taste/smell was more predominant during the Delta versus Omicron and pre-Delta periods (12% vs. 2% and 3%, respectively, p = 0.0017), cough predominated during Delta/Omicron periods more than the pre-Delta period (69% and 65% vs. 41%, p = 0.0002), and there were more asymptomatic children in the pre-Delta period (30% vs. 18% and 10%, p = 0.0023). These findings demonstrate that the presentation of COVID-19 in children and most susceptible age groups has changed over time.     

Clinical characteristics of 1139 mild cases of the SARS-CoV-2 Omicron variant infected patients in Shanghai

In March 2022, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surged during the Coronavirus Disease 2019 (COVID-19) pandemic in Shanghai, but over 90% of patients were mild. This study included 1139 COVID-19 patients mildly infected with the Omicron variant of SARS-CoV-2 in Shanghai from May 1 to 10, 2022, aiming to clarify the demographic characteristics and clinical symptoms of patients with mild Omicron infection. The clinical phenotypes of Omicron infection were identified by model-based cluster analysis to explore the features of different clusters. The median age of the patients was 41.0 years [IQR: 31.0–52.0 years] and 73.0% were male. The top three clinical manifestations are cough (57.5%), expectoration (48.3%), and nasal congestion and runny nose (43.4%). The prevalence of nasal congestion and runny nose varied significantly across the doses of vaccinations, with 23.1% in the unvaccinated population and 30%, 45.9%, and 44.3% in the 1-dose, 2-dose and 3-dose vaccinated populations, respectively. In addition, there were significant differences for fever (23.1%, 26.0%, 28.6%, 18.4%), head and body heaviness (15.4%, 14.0%, 26.7%, 22.4%), and loss of appetite (25.6%, 30.0%, 33.6%, 27.7%). The unvaccinated population had a lower incidence of symptoms than the vaccinated population. Cluster analysis revealed that all four clusters had multisystemic symptoms and were dominated by both general and respiratory symptoms. The more severe the degree of the symptoms was, the higher the prevalence of multisystemic symptoms will be. The Omicron variant produced a lower incidence of symptoms in mildly infected patients than previous SARS-CoV-2 variants, but the clinical symptoms caused by the Omicron variant are more complex, so that it needs to be differentiated from influenza.     

Cartography of SARS-CoV-2 variants based on the susceptibility to therapeutic monoclonal antibodies

A comprehensive picture of a phenotypic relationship among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has been poorly studied. Here, this study presents cartography showing how the wild-type strain of SARS-CoV-2 and 14 variants are alike or different from the perspective of the susceptibility to 12 therapeutic monoclonal antibodies. The Alpha variant is close to the wild-type strain, whereas the Beta, Gamma, and Delta variants diverge from the wild-type. The map highlights the very unique property of the Omicron variant. Interestingly, sublineages of the Omicron variants, BA.1, BA.2, and BA.4/5, differ substantially in the cartography.     

Evidence of co-infections during Delta and Omicron SARS-CoV-2 variants co-circulation through prospective screening and sequencing

ObjectivesTo describe Delta/Omicron SARS-CoV-2 variants co-infection detection and confirmation during the fifth wave of COVID-19 pandemics in France in 7 immunocompetent and epidemiologically unrelated patients.MethodsSince December 2021, the surveillance of Delta/Omicron SARS-CoV-2 variants of concern (VOC) circulation was performed through prospective screening of positive-samples using single nucleotide polymorphism (SNP) PCR assays targeting SARS-CoV-2 S-gene mutations K417N (Omicron specific) and L452R (Delta specific). Samples showing unexpected mutational profiles were further submitted to whole genome sequencing (WGS) using three different primer sets.ResultsBetween weeks 49-2021 and 02-2022, SARS-CoV-2 genome was detected in 3831 respiratory samples, of which 3237 (84.5%) were screened for VOC specific SNPs. Unexpected mutation profiles suggesting a dual Delta/Omicron population were observed in 7 nasopharyngeal samples (0.2%). These co-infections were confirmed by WGS. For 2 patients, the sequence analyses of longitudinal samples collected 7 to 11 days apart showed that Delta or Omicron can outcompete the other variant during dual infection. Additionally, for one of these samples, a recombination event between Delta and Omicron was detected.ConclusionsThis work demonstrates that SARS-CoV-2 Delta/Omicron co-infections are not rare in high virus co-circulation periods. Moreover, co-infections can further lead to genetic recombination which may generate new chimeric variants with unpredictable epidemic or pathogenic properties that could represent a serious health threat.     

GSK3326595 is a promising drug to prevent SARS-CoV-2 Omicron and other variants infection by inhibiting ACE2-R671 di-methylation

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 epidemic is worsening. Binding of the Spike1 protein of SARS-CoV-2 with the angiotensin-converting enzyme 2 (ACE2) receptor mediates entry of the virus into host cells. Many reports show that protein arginine methylation by protein arginine methyltransferases (PRMTs) is important for the functions of these proteins, but it remains unclear whether ACE2 is methylated by PRMTs. Here, we show that PRMT5 catalyses ACE2 symmetric dimethylation at residue R671 (meR671-ACE2). We indicate that PRMT5-mediated meR671-ACE2 promotes SARS-CoV-2 receptor-binding domain (RBD) binding with ACE2 probably by enhancing ACE2 N-glycosylation modification. We also reveal that the PRMT5-specific inhibitor GSK3326595 is able to dramatically reduce ACE2 binding with RBD. Moreover, we discovered that meR671-ACE2 plays an important role in ACE2 binding with Spike1 of the SARS-CoV-2 Omicron, Delta, and Beta variants; and we found that GSK3326595 strongly attenuates ACE2 interaction with Spike1 of the SARS-CoV-2 Omicron, Delta, and Beta variants. Finally, SARS-CoV-2 pseudovirus infection assays uncovered that PRMT5-mediated meR671-ACE2 is essential for SARS-CoV-2 infection in human cells, and pseudovirus infection experiments confirmed that GSK3326595 can strongly suppress SARS-CoV-2 infection of host cells. Our findings suggest that as a clinical phase II drug for several kinds of cancers, GSK3326595 is a promising candidate to decrease SARS-CoV-2 infection by inhibiting ACE2 methylation and ACE2-Spike1 interaction.     

Effectiveness of MRNA booster vaccine among healthcare workers in New York City during the Omicron surge,December 2021 to January 2022

ObjectiveTo describe effectiveness of mRNA vaccines by comparing 2-dose (2D) and 3-dose (3D) healthcare worker (HCW) recipients in the setting of Omicron variant dominance. Performance of 2D and 3D vaccine series against SARS-CoV-2 variants and the clinical outcomes of HCWs may inform return-to-work guidance.MethodsIn a retrospective study from December 15, 2020 to January 15, 2022, SARS-CoV-2 infections among HCWs at a large tertiary cancer centre in New York City were examined to estimate infection rates (aggregated positive tests / person-days) and 95% CIs over the Omicron period in 3D and 2D mRNA vaccinated HCWs and were compared using rate ratios. We described the clinical features of post-vaccine infections and impact of prior (pre-Omicron) COVID infection on vaccine effectiveness.ResultsAmong the 20857 HCWs in our cohort, 20,660 completed the 2D series with an mRNA vaccine during our study period and 12461 had received a third dose by January 15, 2022. The infection rate ratio for 3D versus 2D vaccinated HCWs was 0.667 (95% CI 0.623, 0.713) for an estimated 3D vaccine effectiveness of 33.3% compared to two doses only during the Omicron dominant period from December 15, 2021 to January 15, 2022. Breakthrough Omicron infections after 3D + 14 days occurred in 1,315 HCWs. Omicron infections were mild, with 16% of 3D and 11% 2D HCWs being asymptomatic.DiscussionStudy demonstrates improved vaccine-derived protection against COVID-19 infection in 3D versus 2D mRNA vaccinees during the Omicron surge. The advantage of 3D vaccination was maintained irrespective of prior COVID-19 infection status.     

Molecular evolution of SARS-CoV-2 from December 2019 to August 2022

Severe acute respiratorysyndrome coronavirus-2 (SARS-CoV-2) pandemic spread rapidly and this scenario is concerning worldwide, presenting more than 590 million coronavirus disease 2019 cases and 6.4 million deaths. The emergence of novel lineages carrying several mutations in the spike protein has raised additional public health concerns worldwide during the pandemic. The present study review and summarizes the temporal spreading and molecular evolution of SARS-CoV-2 clades and variants worldwide. The evaluation of these data is important for understanding the evolutionary histories of SARSCoV-2 lineages, allowing us to identify the origins of each lineage of this virus responsible for one of the biggest pandemics in history. A total of 2897 SARS-CoV-2 whole-genome sequences with available information from the country and sampling date (December 2019 to August 2022), were obtained and were evaluated by Bayesian approach. The results demonstrated that the SARS-CoV-2 the time to the most recent common ancestor (tMRCA) in Asia was 2019-12-26 (highest posterior density 95% [HPD95%]: 2019-12-18; 2019-12-29), in Oceania 2020-01-24 (HPD95%: 2020-01-15; 2020-01-30), in Africa 2020-02-27 (HPD95%: 2020-02-21; 2020-03-04), in Europe 2020-02-27 (HPD95%: 2020-02-20; 2020-03-06), in North America 2020-03-12 (HPD95%: 2020-03-05; 2020-03-18), and in South America 2020-03-15 (HPD95%: 2020-03-09; 2020-03-28). Between December 2019 and June 2020, 11 clades were detected (20I [Alpha] and 19A, 19B, 20B, 20C, 20A, 20D, 20E [EU1], 20F, 20H [Beta]). From July to December 2020, 4 clades were identified (20J [Gamma, V3], 21 C [Epsilon], 21D [Eta], and 21G [Lambda]). Between January and June 2021, 3 clades of the Delta variant were detected (21A, 21I, and 21J). Between July and December 2021, two variants were detected, Delta (21A, 21I, and 21J) and Omicron (21K, 21L, 22B, and 22C). Between January and June 2022, the Delta (21I and 21J) and Omicron (21K, 21L, and 22A) variants were detected. Finally, between July and August 2022, 3 clades of Omicron were detected (22B, 22C, and 22D). Clade 19A was first detected in the SARS-CoV-2 pandemic (Wuhan strain) with origin in 2019-12-16 (HPD95%: 2019-12-15; 2019-12-25); 20I (Alpha) in 2020-11-24 (HPD95%: 2020-11-15; 2021-12-02); 20H (Beta) in 2020-11-25 (HPD95%: 2020-11-13; 2020-11-29); 20J (Gamma) was 2020-12-21 (HPD95%: 2020-11-05; 2021-01-15); 21A (Delta) in 2020-09-20 (HPD95%: 2020-05-17; 2021-02-03); 21J (Delta) in 2021-02-26 (2020-11-02; 2021-04-24); 21M (Omicron) in 2021-01-25 (HPD95%: 2020-09-16; 2021-08-08); 21K (Omicron) in 2021-07-30 (HPD95%: 2021-05-30; 2021-10-19); 21L (Omicron) in 2021-10-03 (HPD95%: 2021-04-16; 2021-12-23); 22B (Omicron) in 2022-01-25 (HPD95%: 2022-01-10; 2022-02-05); 21L in 2021-12-20 (HPD95%: 2021-05-16; 2021-12-31). Currently, the Omicron variant predominates worldwide, with the 21L clade branching into 3 (22A, 22B, and 22C). Phylogeographic data showed that Alpha variant originated in the United Kingdom, Beta in South Africa, Gamma in Brazil, Delta in India, Omicron in South Africa, Mu in Colombia, Epsilon in the United States of America, and Lambda in Peru. The COVID-19 pandemic has had a significant impact on global health worldwide and the present study provides an overview of the molecular evolution of SARS-CoV-2 lineage clades (from the Wuhan strain to the currently circulating lineages of the Omicron).     

Outbreak of SARS-CoV-2 B.1.617.2 (delta) variant in a nursing home 28 weeks after two doses of mRNA anti-COVID-19 vaccines: evidence of a waning immunity

ObjectivesTo describe a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.617.2 (Delta) variant outbreak among residents (n = 69) and health workers (n = 69) of a small nursing home in northeastern Italy, with full vaccination coverage of 91% and 82%, respectively. Evaluation of the anti-Spike IgG titres 28 weeks after the mRNA vaccine booster dose against SARS-CoV-2 infection and severe coronavirus disease 2019 (COVID-19).Materials and methodsSera were collected within 48 hours from the index case; anti-Spike IgG was determined (expressed as WHO binding antibody units (BAU)/mL) through a commercial quantitative assay; SARS-CoV-2 was diagnosed using RT-PCR, and full-genome sequencing was performed for lineage characterization. Residents were grouped according to anti-Spike IgG titres (≤50, 51–1000 and > 1000 BAU/mL) and the resulting protection against infection and severe disease was measured.ResultsNone of the health workers and 14 of the 59 (24%) residents fully vaccinated and without a previous SARS-CoV-2 infection showed anti-Spike IgG ≤50 BAU/mL (one-sided Fisher exact test, p 0.011). Among these residents, a level of anti-Spike IgG ≤50 BAU/mL resulted in a higher risk of SARS-CoV-2 infection (relative risk 1.55, 95% CI 1.17–2.05) and severe COVID-19 (relative risk 5.33, 95% CI 1.83–15.57).ConclusionLow levels of SARS-CoV-2 neutralizing anti-Spike IgG in serum 28 weeks after the administration of the second dose parallel the waning of vaccine protection.     

Impact of combination preventative interventions on hospitalization and death under the pandemic of SARS-CoV-2 Omicron variant in China

With a large population most susceptible to Omicron and emerging SARS-CoV-2 variants, China faces uncertain scenarios if reopening its border. Thus, we aimed to predict the impact of combination preventative interventions on hospitalization and death. An age-stratified susceptible-infectious-quarantined-hospitalized-removed-susceptible (SIQHRS) model based on the new guidelines of COVID-19 diagnosis and treatment (the ninth edition) was constructed to simulate the transmission dynamics of Omicron within 365 days. At baseline, we assumed no interventions other than 60% booster vaccination in individuals aged ≤60 years and 80% in individuals aged >60 years, quarantine and hospitalization. Oral antiviral medications for COVID-19 and nonpharmaceutical interventions (NPIs) such as social distancing and antigen self-testing were considered in subsequent scenarios. Sensitivity analyses were conducted to reflect different levels of interventions. A total of 0.73 billion cumulative quarantines (95% CI 0.53–0.83), 33.59 million hospitalizations (22.41–39.31), and 0.62 million deaths (0.40–0.75) are expected in 365 days. The case fatality rate with pneumonia symptoms (moderate, severe and critical illness) is expected to be 1.83% (1.68–1.99%) and the infected fatality rate is 0.38‰ (0.33–0.4‰). The highest existing hospitalization and ICU occupations are 3.11 (0.30–3.85) and 20.33 (2.01–25.20) times of capacity, respectively. Sensitivity analysis showed that interventions can be adjusted to meet certain conditions to reduce the total number of infections and deaths. In conclusion, after sufficient respiratory and ICU beds are prepared and the relaxed NPIs are in place, the SARS-CoV-2 Omicron variant would not seriously impact the health system.     

Cumulative incidence of SARS-CoV-2 infection in the general population of the Valencian Community (Spain) after the surge of the Omicron BA.1 variant

Studies investigating the cumulative incidence of and immune status against SARS-CoV-2 infection provide valuable information for shaping public health decision-making. A cross-sectional study on 935 participants, conducted in the Valencian Community (VC), measuring anti-SARS-CoV-2-receptor binding domain-RBD-total antibodies and anti-Nucleocapsid (N)-IgGs via electrochemiluminescence assays. Quantitation of neutralizing antibodies (NtAb) against ancestral and Omicron BA.1 and BA.2 variants and enumeration of SARS-CoV-2-S specific-IFNγ-producing CD4⁺ and CD8⁺ T cells was performed in 100 and 137 participants, respectively. The weighted cumulative incidence was 51.9% (95% confidence interval [CI]: 48.7–55.1) and was inversely related to age. Anti-RBD total antibodies were detected in 97% of participants; vaccinated and SARS-CoV-2-experienced (VAC-ex; n = 442) presented higher levels (p < 0.001) than vaccinated/naïve (VAC-n; n = 472) and nonvaccinated/experienced (UNVAC-ex; n = 63) subjects. Antibody levels correlated inversely with time elapsed since last vaccine dose in VAC-n (Rho, −0.52; p < 0.001) but not in VAC-ex (rho −0.02; p = 0.57). Heterologous booster shots resulted in increased anti-RBD antibody levels compared with homologous schedules in VAC-n, but not in VAC-ex. NtAbs against Omicron BA.1 were detected in 94%, 75%, and 50% of VAC-ex, VAC-n and UNVAC-ex groups, respectively. For Omicron BA.2, the figures were 97%, 84%, and 40%, respectively. SARS-CoV-2-S-reactive IFN-γ T cells were detected in 73%, 75%, and 64% of VAC-ex, VAC-n and UNVAC-ex, respectively. Median frequencies for both T-cell subsets were comparable across groups. In summary, by April 2022, around half of the VC population had been infected with SARS-CoV-2 and, due to extensive vaccination, displayed hybrid immunity.     

Comparison of secondary attack rate and viable virus shedding between patients with SARS-CoV-2 Delta and Omicron variants: A prospective cohort study

There are limited data comparing the transmission rates and kinetics of viable virus shedding of the Omicron variant to those of the Delta variant. We compared these rates in hospitalized patients infected with Delta and Omicron variants. We prospectively enrolled adult patients with COVID-19 admitted to a tertiary care hospital in South Korea between September 2021 and May 2022. Secondary attack rates were calculated by epidemiologic investigation, and daily saliva samples were collected to evaluate viral shedding kinetics. Genomic and subgenomic SARS-CoV-2 RNA was measured by PCR, and virus culture was performed from daily saliva samples. A total of 88 patients with COVID-19 who agreed to daily sampling and were interviewed, were included. Of the 88 patients, 48 (59%) were infected with Delta, and 34 (41%) with Omicron; a further 5 patients gave undetectable or inconclusive RNA PCR results and 1 was suspected of being coinfected with both variants. Omicron group had a higher secondary attack rate (31% [38/124] vs. 7% [34/456], p < 0.001). Survival analysis revealed that shorter viable virus shedding period was observed in Omicron variant compared with Delta variant (median 4, IQR [1−7], vs. 8.5 days, IQR [5–12 days], p < 0.001). Multivariable analysis revealed that moderate-to-critical disease severity (HR: 1.96), and immunocompromised status (HR: 2.17) were independent predictors of prolonged viral shedding, whereas completion of initial vaccine series or first booster-vaccinated status (HR: 0.49), and Omicron infection (HR: 0.44) were independently associated with shorter viable virus shedding. Patients with Omicron infections had higher transmission rates but shorter periods of transmissible virus shedding than those with Delta infections.     

SARS-CoV-2 Omicron and its current known unknowns: A narrative review

The emergence of the SARS-CoV-2 Omicron variant (B.1.1.529) has created great global distress. This variant of concern shows multiple sublineages, importantly B.1.1.529.1 (BA.1), BA.1 + R346K (BA.1.1), and B.1.1.529.2 (BA.2), each with unique properties. However, little is known about this new variant, specifically its sub-variants. A narrative review was conducted to summarise the latest findings on transmissibility, clinical manifestations, diagnosis, and efficacy of current vaccines and treatments. Omicron has shown two times higher transmission rates than Delta and above ten times more infectious than other variants over a similar period. With more than 30 mutations in the spike protein's receptor-binding domain, there is reduced detection by conventional RT-PCR and rapid antigen tests. Moreover, the two-dose vaccine effectiveness against Delta and Omicron variants was found to be approximately 21%, suggesting an urgent need for a booster dose to prevent the possibility of breakthrough infections. However, the current vaccines remain highly efficacious against severe disease, hospitalisation, and mortality. Japanese preliminary lab data elucidated that the Omicron sublineage BA.2 shows a higher illness severity than BA.1. To date, the clinical management of Omicron remains unchanged, except for monoclonal antibodies. Thus far, only Bebtelovimab could sufficiently treat all three sub-variants of Omicron. Further studies are warranted to understand the complexity of Omicron and its sub-variants. Such research is necessary to improve the management and prevention of Omicron infection.     

National case fatality rates of the COVID-19 pandemic

ObjectivesThe case fatality rate (CFR) of coronavirus disease 2019 (COVID-19) varies significantly between countries. We aimed to describe the associations between health indicators and the national CFRs of COVID-19.MethodsWe identified for each country health indicators potentially associated with the national CFRs of COVID-19. We extracted data for 18 variables from international administrative data sources for 34 member countries of the Organization for Economic Cooperation and Development (OECD). We excluded the collinear variables and examined the 16 variables in multivariable analysis. A dynamic web-based model was developed to analyse and display the associations for the CFRs of COVID-19. We followed the Guideline for Accurate and Transparent Health Estimates Reporting (GATHER).ResultsIn multivariable analysis, the variables significantly associated with the increased CFRs were percentage of obesity in ages >18 years (β = 3.26; 95%CI = 1.20, 5.33; p 0.003), tuberculosis incidence (β = 3.15; 95%CI = 1.09, 5.22; p 0.004), duration (days) since first death due to COVID-19 (β = 2.89; 95%CI = 0.83, 4.96; p 0.008), and median age (β = 2.83; 95%CI = 0.76, 4.89; p 0.009). The COVID-19 test rate (β = –3.54; 95%CI = –5.60, –1.47; p 0.002), hospital bed density (β = –2.47; 95%CI = –4.54, –0.41; p 0.021), and rural population ratio (β = –2.19; 95%CI = –4.25, –0.13; p 0.039) decreased the CFR.ConclusionsThe pandemic hits population-dense cities. Available hospital beds should be increased. Test capacity should be increased to enable more effective diagnostic tests. Older patients and patients with obesity and their caregivers should be warned about a potentially increased risk.