Evidence of Copper Nanoparticles and Poly I:C Modulating Cas9 Interaction and Cleavage of COR (Conserved Omicron RNA).

Conserved omicron RNA (COR) is a 40 base long 99.9% conserved sequence in SARS-CoV-2 Omicron variant, predicted to form a stable stem loop, the targeted cleavage of which can be an ideal next step in controlling the spread of variants. The Cas9 enzyme has been traditionally utilized for gene editing and DNA cleavage. Previously Cas9 has been shown to be capable of RNA editing under certain conditions. Here we investigated the ability of Cas9 to bind to single-stranded conserved omicron RNA (COR) and examined the effect of copper nanoparticles (Cu NPs) and/or polyinosinic-polycytidilic acid (poly I:C) on the RNA cleavage ability of Cas9. The interaction of the Cas9 enzyme and COR with Cu NPs was shown by dynamic light scattering (DLS) and zeta potential measurements and was confirmed by two-dimensional fluorescence difference spectroscopy (2-D FDS). The interaction with and enhanced cleavage of COR by Cas9 in the presence of Cu NPs and poly I:C was shown by agarose gel electrophoresis. These data suggest that Cas9-mediated RNA cleavage may be potentiated at the nanoscale level in the presence of nanoparticles and a secondary RNA component. Further explorations in vitro and in vivo may contribute to the development of a better cellular delivery platform for Cas9.

[Clinical features of 23 neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2]. / æ–°ç”Ÿå„¿æ–°åž‹å† çŠ¶ç— æ¯’Omicronå˜å¼‚æ ªæ„ŸæŸ“23例临床分析.

OBJECTIVES: To summarize the clinical features of neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The medical data of 23 neonates with Omicron variant of SARS-CoV-2 infection admitted to the City North Campus of Urumqi First People's Hospital from October to December 2022 were retrospectively reviewed. RESULTS: All 23 infants had a history of exposure to confirmed caregivers with SARS-CoV-2 infection after birth, and none of them was vertically transmitted. Clinical classification: 5 cases of asymptomatic infection, 18 cases of mild infection, and no cases of moderate, severe, or critically ill. The first symptoms were fever in 13 cases, cough in 3 cases, nasal congestion in 1 case, and diarrhea in 1 case. Blood white blood cell counts decreased in 2 cases, and C-reactive protein increased in 1 case. Seven infants underwent chest X-ray examination due to cough or shortness of breath, and one of which showed focal exudative changes, while the rest showed no abnormal changes. All infants were discharged after symptomatic treatment and the median hospital stay was 6 days. The duration of nucleic acid positivity of SARS-CoV-2 was negatively correlated with N gene Ct values and ORF1ab gene Ct values (rs=-0.719 and -0.699, respectively; P<0.05). One month after discharge, all infants had no symptoms or signs of nucleic acid re-positivity. CONCLUSIONS: The clinical manifestations are usually mild or asymptomatic in neonates infected with SARS-CoV-2 Omicron variant. The lower the Ct values of the N and ORF1ab genes of SARS-CoV-2, the longer the duration of nucleic acid positivity. Neonates infected with SARS-CoV-2 Omicron variant can have a good prognosis after symptomatic treatment.

Tracking the first SARS-CoV-2 Omicron BA.5.1.3 outbreak in China.

The SARS-CoV-2 is still undergoing rapid evolution, resulting in the emergence of several variants of concern, especially the Omicron variants (B.1.1.529), which are surging worldwide. In this study, we tracked Omicron subvariant BA.5.1.3 as the causative agent in the Hainan Province wave in China, which started on 1 August 2022. This was China's first case of Omicron subvariant BA.5.1.3 and led to an indefinite total lockdown in Hainan with more than 8,500 confirmed cases. We obtained 391 whole genomes from positive nasopharyngeal swab samples in the city of Sanya in Hainan Province, which was the center of this outbreak. More than half of the infected cases were female (58%, 227/391) with a median age of 37.0 years (IQR 23.0-53.0). Median Ct values were 24.9 (IQR 22.6-27.3) and 25.2 (IQR 22.9-27.6) for ORF1ab and N genes, respectively. The total single-nucleotide polymorphism (SNP) numbers of Omicron BA.5.1.3 sampled in Sanya (median 69.0, IQR = 69.0-70.0) compared to those worldwide (median 63.0, IQR = 61.0-64.0) showed a significant difference (p < 0.05). Unique core mutations, including three non-synonymous mutations in ORF1ab (Y1064N, S2844G, and R3574K) and one synonymous mutation in ORF3a (S74S), were found. Phylogenetic analysis showed that virus from Sanya formed an independent sub-clade within the BA.5.1.3 subvariant, and could be divided into 15 haplotypes based on the S gene. The most recent common ancestor for the virus from Sanya was estimated as appearing on 5 July 2022, with 95% HPD ranging from 15 May to 20 September 2022. Thanks to our results, we were also able to delineate the mutational profile of this outbreak and highlight the importance of global genomic surveillance and data sharing.

Bivalent COVID-19 vaccine antibody responses to Omicron variants suggest that responses to divergent variants would be improved with matched vaccine antigens.

We compared neutralizing antibody responses to BA.4/5, BQ.1.1, XBB, and XBB.1.5 Omicron SARS-CoV-2 variants after a bivalent or ancestral COVID-19 mRNA booster vaccine or post-vaccination infection. We found that the bivalent booster elicited moderately high antibody titers against BA.4/5 that were approximately two-fold higher against all Omicron variants than titers elicited by the monovalent booster. The bivalent booster elicited low but similar titers against both XBB and XBB.1.5 variants. These findings inform risk assessments for future COVID-19 vaccine recommendations and suggest that updated COVID-19 vaccines containing matched vaccine antigens to circulating divergent variants may be needed.

Identification of key mutations responsible for the enhancement of receptor-binding affinity and immune escape of SARS-CoV-2 Omicron variant.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised concerns worldwide due to its enhanced transmissibility and immune escapability. The first dominant Omicron BA.1 subvariant harbors more than 30 mutations in the spike protein from the prototype virus, of which 15 mutations are located at the receptor binding domain (RBD). These mutations in the RBD region attracted significant attention, which potentially enhance the binding of the receptor human angiotensin-converting enzyme 2 (hACE2) and decrease the potency of neutralizing antibodies/nanobodies. This study applied the molecular dynamics simulations combined with the molecular mechanics-generalized Born surface area (MMGBSA) method, to investigate the molecular mechanism behind the impact of the mutations acquired by Omicron on the binding affinity between RBD and hACE2. Our results indicate that five key mutations, i.e., N440K, T478K, E484A, Q493R, and G496S, contributed significantly to the enhancement of the binding affinity by increasing the electrostatic interactions of the RBD-hACE2 complex. Moreover, fourteen neutralizing antibodies/nanobodies complexed with RBD were used to explore the effects of the mutations in Omicron RBD on their binding affinities. The calculation results indicate that the key mutations E484A and Y505H reduce the binding affinities to RBD for most of the studied neutralizing antibodies/nanobodies, mainly attributed to the elimination of the original favorable gas-phase electrostatic and hydrophobic interactions between them, respectively. Our results provide valuable information for developing effective vaccines and antibody/nanobody drugs.

Multi-omics blood atlas reveals unique features of immune and platelet responses to SARS-CoV-2 Omicron breakthrough infection.

Although host responses to the ancestral SARS-CoV-2 strain are well described, those to the new Omicron variants are less resolved. We profiled the clinical phenomes, transcriptomes, proteomes, metabolomes, and immune repertoires of >1,000 blood cell or plasma specimens from SARS-CoV-2 Omicron patients. Using in-depth integrated multi-omics, we dissected the host response dynamics during multiple disease phases to reveal the molecular and cellular landscapes in the blood. Specifically, we detected enhanced interferon-mediated antiviral signatures of platelets in Omicron-infected patients, and platelets preferentially formed widespread aggregates with leukocytes to modulate immune cell functions. In addition, patients who were re-tested positive for viral RNA showed marked reductions in B cell receptor clones, antibody generation, and neutralizing capacity against Omicron. Finally, we developed a machine learning model that accurately predicted the probability of re-positivity in Omicron patients. Our study may inspire a paradigm shift in studying systemic diseases and emerging public health concerns.

Clinical Features of COVID-19 in Pediatric Rheumatic Diseases: 2020-2022 Survey of the Pediatric Rheumatology Association of Japan.

Coronavirus disease 2019 (COVID-19) in children can be compounded by concurrent diseases and immunosuppressants. For the first time, we aimed to report the clinical features of concurrent COVID-19 and pediatric rheumatic disease (PRD) in Japan. Pediatric Rheumatology Association of Japan members were surveyed between 1 April 2020 and 31 August 2022. Outcome measurements included the clinical features of concurrent PRD and COVID-19. Questionnaire responses were obtained from 38 hospitals. Thirty-one hospitals (82%) had children with PRD and COVID-19. The female-to-male ratio in these children (n = 156) was 7:3, with half aged 11-15 years. The highest proportion of children with PRD and COVID-19 was accounted for by juvenile idiopathic arthritis (52%), followed by systemic lupus erythematosus (24%), juvenile dermatomyositis (5%), scleroderma (4%), and Takayasu arteritis (3%). Of children with PRD, a significant majority (97%) were found to be asymptomatic (10%) or presented with mild symptoms (87%) of the COVID-19 infection. No severe cases or deaths were observed. Regarding the use of glucocorticoids, immunosuppressants, or biologics for PRD treatment before COVID-19, no significant difference was found between asymptomatic/mild and moderate COVID-19 in children with PRD. Therefore, COVID-19 is not a threat to children with PRD in Japan.

Poor neutralizing antibody responses against SARS-CoV-2 Omicron BQ.1.1 and XBB in Norway in October 2022.

New immune evasive variants of SARS-CoV-2 continue to emerge, potentially causing new waves of covid-19 disease. Here, we evaluate levels of neutralizing antibodies against isolates of Omicron variants, including BQ.1.1 and XBB, in sera harvested 3-4 weeks after vaccination or breakthrough infections. In addition, we evaluate neutralizing antibodies in 32 sera from October 2022, to evaluate immunity in Norwegian donors prior to the winter season. Most serum samples harvested in October 2022 had low levels of neutralizing antibodies against BQ.1.1 and especially XBB, explaining why these variants and their descendants have dominated in Norway during the 2022 and 2023 winter season.

Balancing Functional Tradeoffs between Protein Stability and ACE2 Binding in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB Lineages: Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic and Energetic Changes.

Evolutionary and functional studies suggested that the emergence of the Omicron variants can be determined by multiple fitness trade-offs including the immune escape, binding affinity for ACE2, conformational plasticity, protein stability and allosteric modulation. In this study, we systematically characterize conformational dynamics, structural stability and binding affinities of the SARS-CoV-2 Spike Omicron complexes with the host receptor ACE2 for BA.2, BA.2.75, XBB.1 and XBB.1.5 variants. We combined multiscale molecular simulations and dynamic analysis of allosteric interactions together with the ensemble-based mutational scanning of the protein residues and network modeling of epistatic interactions. This multifaceted computational study characterized molecular mechanisms and identified energetic hotspots that can mediate the predicted increased stability and the enhanced binding affinity of the BA.2.75 and XBB.1.5 complexes. The results suggested a mechanism driven by the stability hotspots and a spatially localized group of the Omicron binding affinity centers, while allowing for functionally beneficial neutral Omicron mutations in other binding interface positions. A network-based community model for the analysis of epistatic contributions in the Omicron complexes is proposed revealing the key role of the binding hotspots R498 and Y501 in mediating community-based epistatic couplings with other Omicron sites and allowing for compensatory dynamics and binding energetic changes. The results also showed that mutations in the convergent evolutionary hotspot F486 can modulate not only local interactions but also rewire the global network of local communities in this region allowing the F486P mutation to restore both the stability and binding affinity of the XBB.1.5 variant which may explain the growth advantages over the XBB.1 variant. The results of this study are consistent with a broad range of functional studies rationalizing functional roles of the Omicron mutation sites that form a coordinated network of hotspots enabling a balance of multiple fitness tradeoffs and shaping up a complex functional landscape of virus transmissibility.

Evaluation of Neutralizing Activity against Omicron Subvariants in BA.5 Breakthrough Infection and Three-Dose Vaccination Using a Novel Chemiluminescence-Based, Virus-Mediated Cytopathic Assay.

Neutralizing potency of humoral immune responses induced by prior infection or vaccination is vital for protecting of individuals and population against severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). However, the emergence of viral variants that can evade neutralization by vaccine- or infection-induced immunity is a significant public health threat and requires continuous monitoring. Here, we have developed a novel scalable chemiluminescence-based assay for assessing SARS-CoV-2-induced cytopathic effect to quantify the neutralizing activity of antisera. The assay leverages the correlation between host cell viability and ATP levels in culture to measure the cytopathic effect on target cells induced by clinically isolated, replication-competent, authentic SARS-CoV-2. With this assay, we demonstrate that the recently arisen Omicron subvariants BQ.1.1 and XBB.1 display a significant decrease in sensitivity to neutralization by antibodies elicited from breakthrough infections with Omicron BA.5 and from receipt of three doses of mRNA vaccines. Thus, this scalable neutralizing assay provides a useful platform to assess the potency of acquired humoral immunity against newly emerging SARS-CoV-2 variants. IMPORTANCE The ongoing global pandemic of SARS-CoV-2 has emphasized the importance of neutralizing immunity in protecting individuals and populations against severe respiratory illness. In light of the emergence of viral variants with the potential to evade immunity, continuous monitoring is imperative. A virus plaque reduction neutralization test (PRNT) is a "gold standard" assay for analyzing neutralizing activity for authentic viruses that form plaques, like influenza virus, dengue virus, and SARS-CoV-2. However, this method is labor intensive and is not efficient for performing large-scale neutralization assays on patient specimens. The assay system established in this study allows for the detection of a patient's neutralizing activity by simply adding an ATP detection reagent, providing a simple evaluation system for neutralizing activity of antisera as an alternative to the plaque reduction method. Our extended analysis of the Omicron subvariants highlights their increasing capability to evade neutralization by both vaccine- and infection-induced humoral immunity.

Association between vaccination status and severe health consequences among community-dwelling COVID-19 patients during Omicron BA.1/BA.2 and BA.5-predominant periods in Japan.

BACKGROUND: Many previous studies have reported that COVID-19 vaccine effectiveness decreased over time and declined with newly emerging variants. However, there are few such studies in Japan. Using data from a community-based retrospective study, we aimed to assess the association between vaccination status and severe COVID-19 outcomes caused by the Omicron variant, considering the length of time since the last vaccination dose. METHODS: We included all persons aged ≥12 diagnosed with COVID-19 by a doctor and notified to the Chuwa Public Health Center of Nara Prefectural Government during the Omicron BA.1/BA.2 and BA.5-predominant periods in Japan (January 1 to September 25, 2022). The outcome variable was severe health consequences (SHC) (i.e., COVID-19-related hospitalization or death). The explanatory variable was vaccination status of the individuals (i.e., the number of vaccinations and length of time since last dose). Covariates included gender, age, risk factors for aggravation, and the number of hospital beds per population. Using the generalized estimating equations of the multivariable Poisson regression models, we estimated the cumulative incidence ratio (CIR) and 95% confidence interval (CI) for SHC, with stratified analyses by period (BA.1/BA.2 or BA.5) and age (65 and older or 12-64 years). RESULTS: Of the 69,827 participants, 2,224 (3.2%) had SHC, 12,154 (17.4%) were unvaccinated, and 29,032 (41.6%) received ≥3 vaccine doses. Regardless of period or age, there was a significant dose-response relationship in which adjusted CIR for SHC decreased with an increased number of vaccinations and a longer time since the last vaccination. On the one hand, in the BA.5 period, those with ≥175 days after the third dose had no significant difference in people aged 65 and older (CIR 0.77; 95% CI, 0.53-1.12), but significantly lower CIR for SHC in people aged 12-64 (CIR 0.47; 95% CI, 0.26-0.84), compared with those with ≥14 days after the second dose. CONCLUSION: A higher number of vaccinations were associated with lower risk of SHC against both BA.1/BA.2 and BA.5 sublineages. Our findings suggest that increasing the number of doses of COVID-19 vaccine can prevent severe COVID-19 outcomes, and that a biannual vaccination is recommended for older people.

SARS-CoV-2 Omicron Specific Mutations Affecting Infectivity, Fusogenicity, and Partial TMPRSS2-Independency.

The COVID-19 pandemic resulted from the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its first appearance in 2019, new SARS-CoV-2 variants of concern (VOCs) have emerged frequently, changing the infection's dynamic. SARS-CoV-2 infects cells via two distinct entry routes; receptor-mediated endocytosis or membrane fusion, depending on the absence or presence of transmembrane serine protease 2 (TMPRSS2), respectively. In laboratory conditions, the Omicron SARS-CoV-2 strain inefficiently infects cells predominantly via endocytosis and is phenotypically characterized by decreased syncytia formation compared to the earlier Delta variant. Thus, it is important to characterize Omicron's unique mutations and their phenotypic manifestations. Here, by utilizing SARS-CoV-2 pseudovirions, we report that the specific Omicron Spike F375 residue decreases infectivity, and its conversion to the Delta S375 sequence significantly increases Omicron infectivity. Further, we identified that residue Y655 decreases Omicron's TMPRSS2 dependency and entry via membrane fusion. The Y655H, K764N, K856N and K969N Omicron revertant mutations, bearing the Delta variant sequence, increased the cytopathic effect of cell-cell fusion, suggesting these Omicron-specific residues reduced the severity of SARS-CoV-2. This study of the correlation of the mutational profile with the phenotypic outcome should sensitize our alertness towards emerging VOCs.

Changes in SARS-CoV-2 seroprevalence and population immunity in Finland, 2020-2022.

Studying the prevalence of SARS-CoV-2 specific antibodies (seroprevalence) allows for assessing the impact of epidemic containment measures and vaccinations and estimating the number of infections regardless of viral testing. We assessed antibody-mediated immunity to SARS-CoV-2 induced by infections and vaccinations from April 2020 to December 2022 in Finland by measuring serum IgG to SARS-CoV-2 nucleoprotein (N-IgG) and spike glycoprotein from randomly selected 18-85-year-old subjects (n = 9794). N-IgG seroprevalence remained at <7% until the last quartile (Q) of 2021. After the emergence of the Omicron variant, N-IgG seroprevalence increased rapidly and was 31% in Q1/2022 and 54% in Q4/2022. Seroprevalence was highest in the youngest age groups from Q2/2022 onwards. We did not observe regional differences in seroprevalence in 2022. We estimated that 51% of the Finnish 18-85-year-old population had antibody-mediated hybrid immunity induced by a combination of vaccinations and infections by the end of 2022. In conclusion, major shifts in the COVID-19 pandemic and resulting population immunity could be observed by serological testing.

A comprehensive insight on the challenges for COVID-19 vaccine: A lesson learnt from other viral vaccines.

The aim of this study is to comprehensively analyze previous viral vaccine programs and identify potential challenges and effective measures for the COVID-19 vaccine program. Previous viral vaccine programs, such as those for HIV, Zika, Influenza, Ebola, Dengue, SARS, and MERS, were evaluated. Paramount challenges were identified, including quasi-species, cross-reactivity, duration of immunity, revaccination, mutation, immunosenescence, and adverse events related to viral vaccines. Although a large population has been vaccinated, mutations in SARS-CoV-2 and adverse events related to vaccines pose significant challenges. Previous vaccine programs have taught us that predicting the final outcome of the current vaccine program for COVID-19 cannot be determined at a given state. Long-term follow-up studies are essential. Validated preclinical studies, long-term follow-up studies, alternative therapeutic approaches, and alternative vaccines are necessary.

Trends of Mismatches in Real-Time RT-PCR Assays Developed by the National Institute of Infectious Diseases, Japan for Omicron Variant of Severe Acute Respiratory Syndrome Coronavirus 2.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2021 and gradually overtook the Delta variant, which was the predominant variant at that time. The Omicron variant has been consecutively replaced by related sublineages. The real-time RT-PCR assays developed by the National Institute of Infectious Diseases (NIID), Japan (i.e., the NIID-N2 and NIID-S2 assays) are the reference assays that have been used in Japan since the outbreak of SARS-CoV-2. To evaluate the applicability of the NIID assays for the Omicron variants, trends in the prevalence of nucleotide mismatches in the primer/probe sequences were traced using sequences registered in the Global Initiative on Sharing Avian Influenza Data database. Approximately 99% of the deposited Omicron variant sequences did not have any mismatches in the NIID assay primer/probes from January to August 2022. This indicates that the NIID assays have been able to detect the changing SARS-CoV-2 Omicron variants.

Molecular Epidemiology of SARS-CoV-2 Omicron Sub-Lineages Isolated from Turkish Patients Infected with COVID-19.

Early detection and characterization of new variants and their impacts enable improved genomic surveillance. This study aims to evaluate the subvariant distribution of Omicron strains isolated from Turkish cases to determine the rate of antiviral resistance of RdRp and 3CLpro inhibitors. The Stanford University Coronavirus Antiviral & Resistance Database online tool was used for variant analyses of the strains uploaded to GISAID as Omicron (n = 20.959) between January 2021 and February,2023. Out of 288 different Omicron subvariants, B.1, BA.1, BA.2, BA.4, BE.1, BF.1, BM.1, BN.1, BQ.1, CK.1, CL.1, and XBB.1 were the main determined subvariants, and BA.1 (34.7%), BA.2 (30.8%), and BA.5 (23.6%) were reported most frequently. RdRp and 3CLPro-related resistance mutations were determined in n = 150, 0.72% sequences, while the rates of resistance against RdRp and 3CLpro inhibitors were reported at 0.1% and 0.6%, respectively. Mutations that were previously associated with a reduced susceptibility to remdesivir, nirmatrelvir/r, and ensitrelvir were most frequently detected in BA.2 (51.3%). The mutations detected at the highest rate were A449A/D/G/V (10.5%), T21I (10%), and L50L/F/I/V (6%). Our findings suggest that continuous monitoring of variants, due to the diversity of Omicron lineages, is necessary for global risk assessment. Although drug-resistant mutations do not pose a threat, the tracking of drug mutations will be necessary due to variant heterogenicity.

The relative prevalence of the Omicron variant within SARS-CoV-2 infected cohorts in different countries: A systematic review.

The Omicron variant of SARS-CoV-2 was detected in October 2021 and exhibited high transmissibility, immune evasion, and reduced severity when compared to the earlier variants. The lesser vaccine effectiveness against Omicron and its reduced severity created vaccination hesitancy among the public. This review compiled data reporting the relative prevalence of Omicron as compared to the early variants to give an insight into the existing variants, which may shape the decisions regarding the targets of the newly developed vaccines. Complied data revealed more than 90% prevalence within the infected cohorts in some countries. The BA.1 subvariant predominated over the BA.2 during the early stages of the Omicron wave. Moreover, BA.4/BA.5 subvariants were detected in South Africa, USA and Italy between October 2021 and April 2022. It is therefore important to develop vaccines that protect against Omicron as well as the early variants, which are known to cause more severe complications.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Variants on Inpatient Clinical Outcome.

BACKGROUND: Prior observation has shown differences in COVID-19 hospitalization risk between SARS-CoV-2 variants, but limited information describes hospitalization outcomes. METHODS: Inpatients with COVID-19 at 5 hospitals in the eastern United States were included if they had hypoxia, tachypnea, tachycardia, or fever, and SARS-CoV-2 variant data, determined from whole-genome sequencing or local surveillance inference. Analyses were stratified by history of SARS-CoV-2 vaccination or infection. The average effect of SARS-CoV-2 variant on 28-day risk of severe disease, defined by advanced respiratory support needs, or death was evaluated using models weighted on propensity scores derived from baseline clinical features. RESULTS: Severe disease or death within 28 days occurred for 977 (29%) of 3369 unvaccinated patients and 269 (22%) of 1230 patients with history of vaccination or prior SARS-CoV-2 infection. Among unvaccinated patients, the relative risk of severe disease or death for Delta variant compared with ancestral lineages was 1.30 (95% confidence interval [CI]: 1.11-1.49). Compared with Delta, the risk for Omicron patients was .72 (95% CI: .59-.88) and compared with ancestral lineages was .94 (.78-1.1). Among Omicron and Delta infections, patients with history of vaccination or prior SARS-CoV-2 infection had half the risk of severe disease or death (adjusted hazard ratio: .40; 95% CI: .30-.54), but no significant outcome difference by variant. CONCLUSIONS: Although risk of severe disease or death for unvaccinated inpatients with Omicron was lower than with Delta, it was similar to ancestral lineages. Severe outcomes were less common in vaccinated inpatients, with no difference between Delta and Omicron infections.

SARS-CoV-2 Vaccine Breakthrough Infections of Omicron and Delta Variants in Healthcare Workers.

Understanding SARS-CoV-2 breakthrough infections in vaccinated healthcare workers is of key importance in mitigating the effects of the COVID-19 pandemic in healthcare facilities. An observational prospective cohort study was conducted in vaccinated employees with acute SARS-CoV-2 infection between October 2021 and February 2022. Serological and molecular testing was performed to determine SARS-CoV-2 viral load, lineage, antibody levels, and neutralizing antibody titers. A total of 571 (9.7%) employees experienced SARS-CoV-2 breakthrough infections during the enrolment period, of which 81 were included. The majority (n = 79, 97.5%) were symptomatic and most (n = 75, 92.6%) showed Ct values < 30 in RT-PCR assays. Twenty-four (30%) remained PCR-positive for > 15 days. Neutralizing antibody titers were strongest for the wildtype, intermediate for Delta, and lowest for Omicron variants. Omicron infections occurred at higher anti-RBD-IgG serum levels (p = 0.00001) and showed a trend for higher viral loads (p = 0.14, median Ct difference 4.3, 95% CI [-2.5-10.5]). For both variants, viral loads were significantly higher in participants with lower anti-RBD-IgG serum levels (p = 0.02). In conclusion, while the clinical course of infection with both the Omicron and Delta variants was predominantly mild to moderate in our study population, waning immune response over time and prolonged viral shedding were observed.

Comparison between original SARS-CoV-2 strain and omicron variant on thin-section chest CT imaging of COVID-19 pneumonia.

OBJECTIVES: We investigated different computed tomography (CT) features between Omicron-variant and original-strain SARS-CoV­2 pneumonia to facilitate the clinical management. MATERIALS AND METHODS: Medical records were retrospectively reviewed to select patients with original-strain SARS-CoV­2 pneumonia from February 22 to April 22, 2020, or Omicron-variant SARS-CoV­2 pneumonia from March 26 to May 31, 2022. Data on the demographics, comorbidities, symptoms, clinical types, and CT features were compared between the two groups. RESULTS: There were 62 and 78 patients with original-strain or Omicron-variant SARS-CoV­2 pneumonia, respectively. There were no differences between the two groups in terms of age, sex, clinical types, symptoms, and comorbidities. The main CT features differed between the two groups (p = 0.003). There were 37 (59.7%) and 20 (25.6%) patients with ground-glass opacities (GGO) in the original-strain and Omicron-variant pneumonia, respectively. A consolidation pattern was more frequently observed in the Omicron-variant than original-strain pneumonia (62.8% vs. 24.2%). There was no difference in crazy-paving pattern between the original-strain and Omicron-variant pneumonia (16.1% vs. 11.6%). Pleural effusion was observed more often in Omicron-variant pneumonia, while subpleural lesions were more common in the original-strain pneumonia. The CT score in the Omicron-variant group was higher than that in the original-strain group for critical-type (17.00, 16.00-18.00 vs. 16.00, 14.00-17.00, p = 0.031) and for severe-type (13.00, 12.00-14.00 vs 12.00, 10.75-13.00, p = 0.027) pneumonia. CONCLUSION: The main CT finding of the Omicron-variant SARS-CoV­2 pneumonia included consolidations and pleural effusion. By contrast, CT findings of original-strain SARS-CoV­2 pneumonia showed frequent GGO and subpleural lesions, but without pleural effusion. The CT scores were also higher in the critical and severe types of Omicron-variant than original-strain pneumonia.