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The binding of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein to the host cell receptor angiotensin-converting enzyme 2 (ACE2) is the first step in human viral infection. Therefore, understanding the mechanism of interaction between RBD and ACE2 at the molecular level is critical for the prevention of COVID-19, as more variants of concern, such as Omicron, appear. Recently, atomic force microscopy has been applied to characterize the free energy landscape of the RBD–ACE2 complex, including estimation of the distance between the transition state and the bound state, xu. Here, using a coarse-grained model and replica-exchange umbrella sampling, we studied the free energy landscape of both the wild type and Omicron subvariants BA.1 and XBB.1.5 interacting with ACE2. In agreement with experiment, we find that the wild type and Omicron subvariants have similar xu values, but Omicron binds ACE2 more strongly than the wild type, having a lower dissociation constant KD. [ABSTRACT FROM AUTHOR]

Accurate diagnostic and serology assays are required for the continued management of the COVID-19 pandemic yet spike protein mutations and intellectual property concerns with antigens and antibodies used in various test kits render comparability assessments difficult. As the use of common, well-characterized reagents can help address this lack of standardization, the National Research Council Canada has produced two protein reference materials (RMs) for use in SARS-CoV-2 serology assays: biotinylated human angiotensin-converting enzyme 2 RM, ACE2-1, and SARS-CoV-2 Omicron BA.4/5 spike protein RM, OMIC-1. Reference values were assigned through a combination of amino acid analysis via isotope dilution liquid chromatography tandem mass spectrometry following acid hydrolysis, and ultraviolet–visible (UV–Vis) spectrophotometry at 280 nm. Vial-to-vial homogeneity was established using UV–Vis measurements, and protein oligomeric status, monitored by size exclusion liquid chromatography (LC-SEC), was used to evaluate transportation, storage, and freeze–thaw stabilities. The molar protein concentration in ACE2-1 was 25.3 ± 1.7 µmol L−1 (k = 2, 95% CI) and consisted almost exclusively (98%) of monomeric ACE2, while OMIC-1 contained 5.4 ± 0.5 µmol L−1 (k = 2) spike protein in a mostly (82%) trimeric form. Glycoprotein molar mass determination by LC-SEC with multi-angle light scattering detection facilitated calculation of corresponding mass concentrations. To confirm protein functionality, the binding of OMIC-1 to immobilized ACE2-1 was investigated with surface plasmon resonance and the resulting dissociation constant, KD ~ 4.4 nM, was consistent with literature values. [ABSTRACT FROM AUTHOR]

Two new bis-Schiff base metal(II) complexes viz., bis{N′-[(6-methoxynaphthalen-2-yl)methylidene]-N-methylcarbamohydrazonothioato}-copper(II) complex [Cu(L)2](1) and bis{N′-[(6-methoxynaphthalen-2-yl)methylidene]-N-methylcarbamohydrazonothioato}-nickel(II) complex [Ni(L)2](2), were synthesized and designed from a bidentate-N,S donor Schiff base ligand (HL), and characterized via a single crystal X-ray diffraction (SC-XRD) study, FT-IR, UV-visible and fluorescence spectroscopy, thermal analysis and DFT calculations. Single crystal X-ray diffraction analysis established the perfect square-planar geometry around the metal(II) ions obtained by the coordination of the two N and two S atoms from the two deprotonated HL ligands. Non-covalent intermolecular interactions, which are the main features of the supramolecular assembly, were investigated via Hirshfeld surface (HSs) analysis and 2D-fingerprint plots (FPs) for both the complexes. The supramolecular architecture within the crystal packing is stabilized by C–H⋯S, C–H⋯O and N–H⋯O type hydrogen bonds for the copper(II) complex [Cu(L)2](1), while C–H⋯S, C–H⋯N and N–H⋯O connecting units stabilize the supramolecular assembly for the nickel(II) complex [Ni(L)2](2). The thermal properties of the synthesized complexes offer valuable details on the stability of the complexes. The intermolecular interaction energies have been estimated and their topologies were explored using energy framework analysis. Their interactions with calf-thymus DNA (CT-DNA) and bovine serum albumin (BSA) proteins were also evaluated using UV-visible and fluorescence spectroscopic methods. Absorption titration studies revealed that they interacted strongly with CT-DNA. To gain insight into the potential antiviral applications, we examined the molecular docking of the copper(II) complex [Cu(L)2](1) and nickel(II) complex [Ni(L)2](2) with SARS-CoV-2 RNA binding protein (PDB ID: 6WKP), the Omicron RBD protein (PDB ID: 7WRL) and HIV-1 protease (PDB ID: 8CI7) viruses. They bind to the active positions of viral proteins and show good inhibition performance with target viral proteins. A stronger binding was predicted between the complexes and the SARS-CoV-2 RNA, Omicron and HIV-1 viruses through the negative values of binding affinity. The binding free energies computed using a molecular docking approach were analyzed in detail and the importance of specific interactions was outlined. Furthermore, molecular docking calculations of the complexes against DNA binding protein (PDB ID: 7UV6) were also evaluated. The calculated docking results suggested that they could be adopted as potential inhibitors for the development of new anti-SARS-CoV-2 Omicron and anti-HIV drugs. [ABSTRACT FROM AUTHOR]

Genomic surveillance of pathogen evolution is essential for public health response, treatment strategies, and vaccine development. In the context of SARS-COV-2, multiple models have been developed including Multinomial Logistic Regression (MLR) describing variant frequency growth as well as Fixed Growth Advantage (FGA), Growth Advantage Random Walk (GARW) and Piantham parameterizations describing variant Rt. These models provide estimates of variant fitness and can be used to forecast changes in variant frequency. We introduce a framework for evaluating real-time forecasts of variant frequencies, and apply this framework to the evolution of SARS-CoV-2 during 2022 in which multiple new viral variants emerged and rapidly spread through the population. We compare models across representative countries with different intensities of genomic surveillance. Retrospective assessment of model accuracy highlights that most models of variant frequency perform well and are able to produce reasonable forecasts. We find that the simple MLR model provides ∼0.6% median absolute error and ∼6% mean absolute error when forecasting 30 days out for countries with robust genomic surveillance. We investigate impacts of sequence quantity and quality across countries on forecast accuracy and conduct systematic downsampling to identify that 1000 sequences per week is fully sufficient for accurate short-term forecasts. We conclude that fitness models represent a useful prognostic tool for short-term evolutionary forecasting. Author summary: Over the course of the COVID-19 pandemic, SARS-CoV-2 evolved into many different genetic variants such as the well known Alpha, Beta, Gamma and Delta variants in early 2021 and the Omicron variant in late 2021. These genetic variants could more easily spread from person to person and so outcompeted previous versions of the virus. Even if they aren't being given Greek letter names, new variants are still arising with recent waves of COVID-19 caused by variants such as XBB and JN.1. Predicting which variants will increase in frequency and which variants will decrease in frequency is important for public health, particularly in terms of updating the formulation of the annual COVID-19 vaccine. In this paper, we investigate statistical models that use observed frequencies of different variants in the past weeks to estimate the frequency of different variants today and to forecast the frequency of different variants in 30 days time. We find that in countries with sufficient amounts and timeliness of genetic sequence data, that models forecast well and can be a useful tool for public health. [ABSTRACT FROM AUTHOR]

Grasping the roles of epitopes in viral glycoproteins is essential for unraveling the structure and function of these proteins. Up to now, all identified epitopes have been found to either neutralize, have no effect on, or enhance viral entry into cells. Here, we used nanobodies (single-domain antibodies) as probes to investigate a unique epitope on the SARS-CoV-2 spike protein, located outside the protein's receptor-binding domain. Nanobody binding to this epitope enhances the cell entry of prototypic SARS-CoV-2, while neutralizing the cell entry of SARS-CoV-2 Omicron variant. Moreover, nanobody binding to this epitope enhances both receptor binding activity and post-attachment activity of prototypic spike, explaining the enhanced viral entry. The opposite occurs with Omicron spike, explaining the neutralized viral entry. This study reveals a unique epitope that can both enhance and neutralize viral entry across distinct viral variants, suggesting that epitopes may vary their roles depending on the viral context. Consequently, antibody therapies should be assessed across different viral variants to confirm their efficacy and safety. Author summary: Antibodies bind to specific epitopes on viral surface glycoproteins to perform their function: inhibiting viral infection, having no effect, or, in rare cases, enhancing viral infection. In our research, we used nanobodies (small, single-domain antibodies from camelid animals) as probes and identified a unique epitope on the SARS-CoV-2 spike protein with opposing functions across different SARS-CoV-2 variants. It enhances viral infection in pre-Omicron variants but inhibits it in the Omicron variant. We further investigated the molecular mechanism underlying these opposing effects. Although this epitope is not directly involved in receptor binding, nanobody binding to it modulates receptor binding and post-receptor-binding activities. This study marks the first discovery of a dual-function epitope on the SARS-CoV-2 spike protein that both enhances and inhibits viral infection across different viral variants. This discovery challenges the traditional categorization of epitopes, underscores the complex evolution of the SARS-CoV-2 spike protein, and offers new insights into antiviral antibody therapies. [ABSTRACT FROM AUTHOR]

Background: After a 920-day hiatus, COVID-19 resurged in the Tibet Autonomous Region of China in August 2022. This study compares the characteristics of COVID-19 between high-altitude residents and newcomers, as well as between newcomers and lowlanders. Methods: This multi-center cohort study conducted at the Third People's Hospital of Tibet Autonomous Region and Beijing University Shenzhen Hospital, included 520 high-altitude resident patients, 53 high-altitude newcomer patients, and 265 lowlander patients infected with the Omicron variant. Initially, we documented epidemiological, clinical, and treatment data across varying residency at admission. We compared the severity of COVID-19 and various laboratory indicators, including hemoglobin concentration and SpO2%, over a 14-day period from the date of the first positive nucleic acid test, as well as the differences in treatment methods and disease outcomes between highlanders and high-altitude newcomers. We also compared several characteristics of COVID-19 between high-altitude newcomers and lowlanders. Univariate analysis, multivariable logistic regression, and the generalized linear mixed model were utilized for the analysis. Results: No fatalities were observed. The study found no significant differences in COVID-19 severity or in the physiological measures of hemoglobin concentration and SpO2% between high-altitude and lowland residents. Similarly, there were no statistically significant differences in the values or trends of hemoglobin and SpO2% between high-altitude residents and newcomers throughout the 14-day observation period. However, compared to age- and sex-matched lowlander patients (1:5 ratio), high-altitude newcomers exhibited higher heart rates, respiratory rates, and average hemoglobin concentrations, along with lower platelet counts. There were no significant differences in hospital stays between the two groups. Conclusions: High-altitude residents and newcomer patients exhibit clinical similarities. However, the clinical characteristics of high-altitude newcomers and lowlander patients differ due to the impact of the high-altitude environment. These results highlight potential considerations for public health strategies in high-altitude regions such as Tibet. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 cell-mediated immunity remains understudied during pregnancy in unvaccinated Black African women living with HIV (WLWH) from low- and middle-income countries. We investigated SARS-CoV-2-specific T-cell responses 1 month following infection in 24 HIV-uninfected women and 15 WLWH at any stage during pregnancy or postpartum. The full-length spike (FLS) glycoprotein and nucleocapsid (N) protein of wild-type (WT) SARS-CoV-2, as well as mutated spike protein regions found in the Omicron variant (B.1.1.529) were targeted by flow cytometry. WT-specific CD4+ and CD8+ T cells elicited similar FLS- and N-specific responses in HIV-uninfected women and WLWH. SARS-CoV-2-specific T-lymphocytes were predominantly TNF-α monofunctional in pregnant and postpartum women living with and without HIV, with fever cells producing either IFN-γ or IL-2. Furthermore, T-cell responses were unaffected by Omicron-specific spike mutations as similar responses between Omicron and the ancestral virus were detected for CD4+ and CD8+ T cells. Our results collectively demonstrate comparable T-cell responses between WLWH on antiretroviral therapy and HIV-uninfected pregnant and postpartum women who were naïve to Covid-19 vaccination. Additionally, we show that T cells from women infected with the ancestral virus, Beta variant (B.1.351), or Delta variant (B.1.617.2) can cross-recognize Omicron, suggesting an overall preservation of T-cell immunity. [ABSTRACT FROM AUTHOR]

Introduction: Various COVID-19 vaccine trials have shown that vaccines can successfully prevent symptomatic cases of COVID-19 and death. Head-to-head comparisons help to better understand the immune response characteristics of different COVID-19 vaccines in humans. Methods: We randomly selected 20 participants from each of five ongoing Phase II trials of COVID-19 vaccines. Here, SARS-CoV 2-specific immune responses to DNA vaccine (INO-4800), mRNA vaccine (BNT162b2), Adenovirus-vectored vaccine (CONVIDECIA), Protein subunit vaccine (Recombinant COVID- 19 Vaccine (Sf9 Cells)), Inactivated Vaccine (KCONVAC) were examined longitudinally in healthy adults between Jan 15, 2021 and July 5, 2021 for 6 months. RBD-IgG titres were detected by ELISA, neutralising antibody titer were detected by pseudoviral neutralization and immune cell response were detected by flow cytometry. Results: At the first visit (V1), 100% of individuals who received the BNT162b2, CONVIDECIA, or KCONVAC vaccines experienced seroconversion of neutralizing and binding antibodies in the serum. Except for the Recombinant COVID-19 Vaccine (Sf9 Cells) vaccine having the highest neutralizing antibody GMT at the second visit (although there was no statistically significant difference in geometric mean titers between V1 and V2), the rest of the vaccines had the highest levels of binding antibodies and neutralizing antibodies at V1. The neutralizing antibodies GMT of all vaccines showed a significant decrease at V3 compared to V1. The neutralizing antibody GMT against the omicron variant of all vaccines at V1 showed a significant decrease compared to the wild strain. We observed statistically significant differences in Tcm cells and RBD-specific memory B cells among various vaccines. Discussion: BNT162b2 (mRNA vaccine) exhibits the highest antibody levels among the five vaccines evaluated, regardless of whether the target is the wild-type virus or its variants. However, its cellular immune response may be weaker compared to CONVIDECIA (adenovirus type 5 vector vaccine). [ABSTRACT FROM AUTHOR]

Introduction: This study measures the COVID-19 vaccine effectiveness (CVE) against hospital admission and severe COVID-19. Methods: This study is a test-negative case-control design using data from eight provinces in April, 2021 until March, 2022. The individuals were classified as cases and controls based on the results of the RT-PCR test for SARS-CoV-2 and matched based on the timing of the test being conducted as well as the timing of hospital admission. The measure of association was an odds ratio (OR) by univariate and multiple logistic regression. The multiple logistic regression has been carried out to take confounding factors and potential effect modifiers into account. The CVE was computed as CVE = (1 – OR)*100 with 95% confidence interval. Results: Among 19314 admitted patients, of whom 13216 (68.4%) were cases and 6098 (31.6%) were controls, 1313 (6.8%) died. From total, 5959 (30.8%) patients had received the vaccine in which one, two, and booster doses were 2443 (12.6%), 2796 (14.5٪), and 720 (3.7٪), respectively. The estimated adjusted effectiveness of only one dose, two doses and booter vaccination were 22% (95% CI: 14%-29%), 35% (95% CI: 29%-41%) and 33% (95% CI: 16%-47%), respectively. In addition, the adjusted vaccine effectiveness against severe outcome was 33% (95% CI: 19%- 44%), 34% (95% CI: 20%- 45%) and 20% (95% CI: -29%- 50%) for those who received one, two and booster vaccinations, respectively. Conclusion: Our study concluded that full vaccination, though less effective compared to similar studies elsewhere, decreased hospital admissions and deaths from COVID-19 in Iran, particularly during the Delta variant period, with an observed decline during the Omicron variant dominance. [ABSTRACT FROM AUTHOR]

While first-generation, spike (S)-based COVID-19 vaccines were effective against early SARS-CoV-2 strains, the rapid evolution of novel Omicron subvariants have substantially reduced vaccine efficacy. As such, broadly protective vaccines against SARS-CoV-2 are needed to prevent future viral emergence. In addition, it remains less clear whether peripheral immunization, especially with mRNA vaccines, elicits effective respiratory immunity. Our group has developed a nucleoside-modified mRNA vaccine expressing the nucleocapsid (N) protein of the ancestral SARS-CoV-2 virus and has tested its use in combination with the S-based mRNA vaccine (mRNA-S). In this study, we examined efficacy of mRNA-N alone or in combination with mRNA-S (mRNA-S+N) against more immune evasive Omicron variants in hamsters. Our data show that mRNA-N alone induces a modest but significant protection against BA.5 and that dual mRNA-S+N vaccination confers complete protection against both BA.5 and BQ.1, preventing detection of virus in the hamster lungs. Analysis of respiratory immune response in mice shows that intramuscular mRNA-S+N immunization effectively induces respiratory S- and N-specific T cell responses in the lungs and in bronchoalveolar lavage (BAL), as well as antigen-specific binding IgG in BAL. Together, our data further support mRNA-S+N as a potential pan-COVID-19 vaccine for broad protection against current and emerging SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Introduction: There are no reports in LATAM related to longitudinal humoral and cellular response to adenovirus based COVID-19 vaccines in people with Multiple Sclerosis (pwMS) under different disease modifying therapies (DMTs) and neutralization of the Omicron and Wuhan variants of SARS-COV-2. Methods: IgG anti- SARS-COV-2 spike titer were measured in a cohort of 101 pwMS under fingolimod, dimethyl fumarate, cladribine and antiCD20, as well as 28 healthy controls (HC) were measured 6 weeks after vaccination with 2nd dose (Sputnik V or AZD1222) and 3nd dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed.Results: Multivariate regression analysis showed anti-cd20 (β= -,349, 95% CI: -3655.6 - -369.01, p=0.017) and fingolimod (β=-,399, 95% CI: -3363.8 - -250.9, p=0.023) treatments as an independent factor associated with low antibody response (r² adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p<0.001; slope 0.8, 95% CI:0.4-1.3), with no differences between DMTs. Neutralization capacity was lower for BA.1 (slope 0.3, 95%CI:0.1-0.4). After the 3rd dose, neutralization of BA.1 improved (slope: 0.9 95%CI:0.6-1.2), without differences between DMTs. A fraction of pwMS generated anti-Spike CD4+ and CD8+ T cell response. In contrast, pwMS under antiCD20 generated CD8+TNF+IL2+ response without differences with HC, even in the absence of humoral response. The 3rd dose significantly increased the neutralization against the Omicron, as observed in the immunocompetent population. Discussion: Findings regarding humoral and cellular response are consistent with previous reports [ABSTRACT FROM AUTHOR]

Objective Mild symptoms are the norm for children with coronavirus disease-2019 (COVID-19), but data on the Omicron form are few. One of the most frequent neurological symptoms of COVID-19 in children is febrile seizure (FS). Methods Patients with FS who visited the pediatric fever clinic between December 6 and December 31, 2022, when the Omicron version of SARS-CoV-2 was the predominant strain, were included in this retrospective, single-center analysis. Results Children who tested positive for COVID-19 had a 5.58% incidence of FSs. Compared to patients without COVID-19, a greater percentage of COVID-19 patients (29.5 vs. 7.5%, p < 0.01) experienced complex FSs. In the COVID-19-positive group, four cases were critically unwell and were admitted to the Intensive Care Unit (1.4 vs. 0%, p < 0.01), and the admission proportion was greater (18.9 vs. 1.9%, p < 0.01). The proportion of lactic acid and IL-6 increase was larger in the COVID-19-positive group (33.5 vs. 21.5%, 22.1 vs. 17.8%, p = 0.022, p = 0.006, respectively). Conclusion Infections with COVID-19 in children have been linked to FSs in the Omicron era. To fully understand the neuropathogenesis of seizures in children with COVID-19, more research is required. [ABSTRACT FROM AUTHOR]

An observational and retrospective study was carried out to analyse HCoV positivity from a multiplex PCR respiratory panel and RT‐PCR for SARS‐CoV‐2 in respiratory samples from 1 June 2020 to 31 July 2023 at the Príncipe de Asturias University Hospital (HUPA) in Alcalá de Henares, Madrid, Spain. Out of 2802 respiratory panels, 1258 (44.8%) turned out positive. HCoV was detected in 114 (4%) cases (range 0–23; median 1.5; IQR 0–3.75) with positivity rates ranging from 0% to 14%. All four variants of HCoV circulated, and OC‐43 was the most common in 62.3% of cases. After the onset of the pandemic, the HCoV season was delayed 22 weeks, with a peak positivity of 9% in the summer of 2021, showing an inverse relationship with the alpha and delta waves of SARS‐CoV‐2. In the two subsequent autumn–winter seasons, HCoV positivity increased (11–14%) with a reduction in the summer of 2022 and 2023 following the emergence of the omicron variant and the relaxation of social distancing measures. The seasonal spread pattern of endemic HCoV might be returning to normal in our region and likely in other temperate zones of the northern hemisphere after 3 years of the pandemic. [ABSTRACT FROM AUTHOR]

During the 2023 Danish COVID-19 vaccination campaign, an updated monovalent mRNA vaccine targeting the SARS-CoV-2 omicron XBB.1.5 subvariant was administered. However, the rapid spread of a genetically divergent omicron BA.2.86 subvariant, JN.1, since September, 2023, poses potential challenges due to its rapid dominance and possible immune escape. Using national electronic health registry data from all regions of Denmark, we aimed to investigate whether the SARS-CoV-2 subvariant BA.2.86, and its descendant JN.1, differed from other circulating variants in terms of their ability to escape vaccine protection, the risk of infection leading to severe disease, and self-reported symptoms among infected people. In this observational study, we included all residents of Denmark aged 65 years and older who tested positive for SARS-CoV-2 by PCR between Oct 1 and Dec 31, 2023, and for whom genomic data on the SARS-CoV-2 variant that had caused their infection were available. Data from clinical testing, sentinel, and self-sampling-based surveillance were linked with national electronic civil, vaccination, and hospitalisation registers. The relative protection of the XBB.1.5 updated COVID-19 vaccine against BA.2.86 infections versus infections with other variants was analysed in a case-only study, and the relative risk of hospitalisation in people infected with BA.2.86 versus other variants was analysed in a case–control study. Both analyses were adjusted for time, comorbidities, and previous vaccination history, among other potential confounders. Additionally, prevalence patterns in self-reported symptoms among people of all ages infected with SARS-CoV-2 were reported separately by subvariant. Of the 7581 people in Denmark aged 65 years or older who tested positive for SARS-CoV-2 by PCR during the study period, 5882 (78%) samples were eligible for sequencing. 3862 (66%) of these passed quality control, were successfully sequenced, and the SARS-CoV-2 variant and subvariant identified, and these individuals were included in the study. Of these 3862 people, 2184 (57%) were infected with the BA.2.86 subvariant, including 1615 JN.1 infections. Participants infected with BA.2.86 had 1·52 (95% CI 1·25–1·86) times the odds, and those infected with JN.1 had 1·60 (1·27–2·02) times the odds, of having received the XBB.1.5 vaccine at least 7 days before their infection compared with participants infected with a non-BA.2.86 variant. The severity analysis showed no evidence of association between the infecting variant and the risk of COVID-19 hospitalisation (odds ratio 1·04 [95% CI 0·86–1·26] for BA.2.86 and 1·07 [0·85–1·34] for JN.1). Similarly, there was no evidence of differences in self-reported symptoms by variant strain. Compared with other SARS-CoV-2 variants, BA.2.86 and the JN.1 sublineage were less sensitive to vaccine-induced immune protection from the XBB.1.5 updated COVID-19 vaccine; however, we found no evidence that infection with BA.2.86 or JN.1 resulted in increased disease severity or different symptom profiles. Although less effective against the new variants, XBB.1.5 vaccination remains protective and reduces the risk of infection and COVID-19 disease. The Danish Government and the EU's EU4Health programme. [ABSTRACT FROM AUTHOR]

At the end of 2021, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) took over from the preceding Delta variant as the dominant strain, causing a huge wave of infection and death due to its high transmissibility and immune escape. The Omicron wave was the fifth of the pandemic in Hong Kong Special Administrative Region, China. Given the huge variability in the mortality and vaccination rates associated with coronavirus disease (COVID-19) across age groups in the fifth wave, we constructed a two-age-group transmission model with time-varying transmission, vaccination, and death rates to assess the dynamics of the Omicron variant in two age groups (a younger group aged 0-59 years and a group of older adults aged ≥ 60 years). We calibrated the model to eight sets of epidemic data from Hong Kong using the Markov Chain Monte Carlo algorithm to disentangle the transmission degree and disease severity for the two age groups. The calibrated model was then used to explore counterfactual scenarios in which the booster vaccination campaign was modified to assess the direct and indirect effects of booster doses in the two age groups. We also performed sensitivity analyses by varying key model parameters so as to evaluate the uncertainty of some parameters on the epidemic trend. The results indicated a high degree of assortativity (intra-group contact) in the two age groups, and the intra-group transmission rate was much higher than the inter-group transmission rate. Younger individuals showed a slightly higher transmission advantage in the fifth of the pandemic in Hong Kong. Moreover, the average mortality rate in the older group was 87 times higher than that in the younger group. We confirmed that administering booster doses of vaccines offered substantial protection to the target population, particularly against death. There are vast infection-suppression benefits of vaccinating younger individuals that play an important role in transmission. Meanwhile, vaccination in the older individuals has vast benefits in reducing deaths. Vaccination campaigns targeting a particular age group are far less effective than boosting wider segments of the population. This study provides a retrospective understanding of Hong Kong's fifth wave of the pandemic, which is crucial for future projections and the planning of interventions. • The full-spectrum dynamics of Omicron in older and younger age groups of Hong Kong are reconstructed. • The transmission degree, disease severity, and the effects of booster doses in Hong Kong, are revealed. • Younger individuals show a slightly higher transmission advantage. • There is a high degree of assortativity (intra-group contact) in the two age groups. • The average death rate of the older group is 26 times that of the younger group in Hong Kong, China. [ABSTRACT FROM AUTHOR]

Antivirals with proven effectiveness against the Omicron SARS-CoV-2 variant are required for COVID-19 treatment in hospitalized patients, particularly those with severe underlying conditions. Ensitrelvir, a 3C-like protease inhibitor, received emergency approval in Japan in November 2022, based on evidence of rapid symptom resolution in non-hospitalized patients, but confirmation of its effectiveness in hospitalized patients is lacking. This retrospective chart review reports outcomes for all patients who received ensitrelvir whilst hospitalized with SARS-CoV-2 infection at Rinku General Medical Center, Japan (November 2022–April 2023). Thirty-two hospitalized patients received 5 days of ensitrelvir treatment (375 mg loading dose, 125 mg as maintenance dose). Patients' mean age was 73.5 years and most had mild COVID-19. Patients exhibited various underlying diseases, most commonly hypertension (78.1%) and chronic kidney disease (25.0%). Seven (21.9%) patients were on hemodialysis. The most common concomitant medications were antihypertensives (59.4%) and corticosteroids (31.3%); 2 (6.3%) patients were being treated with rituximab; 28 (87.5%) patients had viral persistence following pre-treatment by remdesivir. Following ensitrelvir treatment, viral clearance was recorded in 18 (56.3%) patients by Day 6 and 25 (78.1%) patients at final measurement. All patients experienced clinical improvement as assessed by the investigator at Day 5. No intensive care unit admissions or deaths due to COVID-19 occurred. No new safety signals were observed. In conclusion, positive virological outcomes were observed following ensitrelvir treatment, in hospitalized patients with SARS-CoV-2 in a real-world setting, including high-risk patients, who failed previous antiviral therapy. These results require confirmation in more extensive studies. UMIN000051300. [ABSTRACT FROM AUTHOR]

The article focuses on evaluating the effectiveness of four clinical drugs—nirmatrelvir (NTV), ensitrelvir (ETV), leritrelvir (LTV), and GC376—against the main protease (Mpro) of SARS-CoV-2 and other coronaviruses. Topics include the impact of mutations on drug resistance, the comparative efficacy of these inhibitors against resistant Mpro mutants, and the role of pharmacokinetics in drug effectiveness.

OBJECTIVE: To estimate the prevalence of post--acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) after infection with SARS-CoV-2 during pregnancy and to characterize associated risk factors. METHODS: In a multicenter cohort study (NIH RECOVER [Researching COVID to Enhance Recovery]- Pregnancy Cohort), individuals who were pregnant during their first SARS-CoV-2 infection were enrolled across the United States from December 2021 to September 2023, either within 30 days of their infection or at differential time points thereafter. The primary outcome was PASC, defined as score of 12 or higher based on symptoms and severity as previously published by the NIH RECOVER-Adult Cohort, at the first study visit at least 6 months after the participant's first SARS-CoV-2 infection. Risk factors for PASC were evaluated, including sociodemographic characteristics, clinical characteristics before SARS-CoV-2 infection (baseline comorbidities, trimester of infection, vaccination status), and acute infection severity (classified by need for oxygen therapy). Multivariable logistic regression models were fitted to estimate associations between these characteristics and presence of PASC. RESULTS: Of the 1,502 participants, 61.1% had their first SARS-CoV-2 infection on or after December 1, 2021 (ie, during Omicron variant dominance); 51.4% were fully vaccinated before infection; and 182 (12.1%) were enrolled within 30 days of their acute infection. The prevalence of PASC was 9.3% (95% CI, 7.9--10.9%) measured at a median of 10.3 months (interquartile range 6.1--21.5) after first infection. The most common symptoms among individuals with PASC were postexertional malaise (77.7%), fatigue (76.3%), and gastrointestinal symptoms (61.2%). In a multivariable model, the proportion PASC positive with vs without history of obesity (14.9% vs 7.5%, adjusted odds ratio [aOR] 1.65, 95% CI, 1.12--2.43), depression or anxiety disorder (14.4% vs 6.1%, aOR 2.64, 95% CI, 1.79--3.88) before first infection, economic hardship (self-reported difficulty covering expenses) (12.5% vs 6.9%, aOR 1.57, 95% CI, 1.05--2.34), and treatment with oxygen during acute SARS-CoV-2 infection (18.1% vs 8.7%, aOR 1.86, 95% CI, 1.00--3.44) were associated with increased prevalence of PASC. CONCLUSION: The prevalence of PASC at a median time of 10.3 months after SARS-CoV-2 infection during pregnancy was 9.3% in the NIH RECOVER-Pregnancy Cohort. The predominant symptoms were postexertional malaise, fatigue, and gastrointestinal symptoms. Several socioeconomic and clinical characteristics were associated with PASC after infection during pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05172024. [ABSTRACT FROM AUTHOR]

This study established a novel infield sensing approach based on detection of the volatile compound markers in skin secretions. This was based on analysis of volatile compounds in axillary sweat samples collected from RT-PCR-proven Coronavirus disease 2019 (COVID-19) positive and negative populations using gas chromatography-mass spectrometry (GC–MS). The analysis proposed the possible markers of the monoaromatic compounds and ethyl hexyl acrylate. A portable photo ionization detector (PID) incorporated with the selective material towards the marker compounds was then developed with the pressurized injection approach. This provided the accuracy of 100% in the research phase (n = 125). The developed approach was then applied for screening of 2207 COVID-19 related cases covering the periods of the Alpha, Beta, Delta and Omicron variants of SARS-CoV-2 infection in Bangkok, Thailand. This offered the sensitivity, specificity and accuracy ranges of 92–99, 93–98 and 95–97%, respectively. [ABSTRACT FROM AUTHOR]

Background: New York City (NYC) was the first COVID-19 epicenter in the United States and home to one of the country's largest contact tracing programs, NYC Test & Trace (T2). Understanding points of attrition along the stages of program implementation and follow-up can inform contact tracing efforts for future epidemics or pandemics. The objective of this study was to evaluate the completeness and timeliness of T2 case and contact notification and monitoring using a "cascade of care" approach. Methods: This cross-sectional study included all SARS-CoV-2 cases and contacts reported to T2 from May 31, 2020 to January 1, 2022. Attrition along the "cascade of care" was defined as: (1) attempted, (2) reached, (3) completed intake (main outcome), (4) eligible for monitoring, and (5) successfully monitored. Timeliness was assessed: (1) by median days from a case's date of testing until their positive result was reported to T2, (2) from result until the case was notified by T2, and (3) from a case report of a contact until notification of the contact. Results: A total of 1.45 million cases and 1.38 million contacts were reported to T2 during this period. For cases, attrition occurred evenly across the first three cascade steps (~-12%) and did not change substantially until the Omicron wave in December 2021. During the Omicron wave, the proportion of cases attempted dropped precipitously. For contacts, the largest attrition occurred between attempting and reaching (-27%), and attrition rose with each COVID-19 wave as contact volumes increased. Attempts to reach contacts discontinued entirely during the Omicron wave. Overall, 67% of cases and 49% of contacts completed intake interviews (79% and 57% prior to Omicron). T2 was timely, with a median of 1 day to receive lab results, 2 days to notify cases, and < 1 day to notify contacts. Conclusions: T2 provided a large volume of NYC residents with timely notification and monitoring. Engagement in the program was lower for contacts than cases, with the largest gap coming from inability to reach individuals during call attempts. To strengthen future test-and-trace efforts, strategies are needed to encourage acceptance of local contact tracer outreach attempts. [ABSTRACT FROM AUTHOR]

Introduction: As the SARS-CoV-2 virus continues to evolve and new variants emerge, it becomes crucial to understand the comparative pathological and immunological responses elicited by different strains. This study focuses on the original Wuhan strain and the Omicron variant, which have demonstrated significant differences in clinical outcomes and immune responses. Methods: We employed ferrets as an experimental model to assess the D614G variant (a derivative of the Wuhan strain) and the Omicron BA.5 variant. Each variant was inoculated into separate groups of ferrets to compare disease severity, viral dissemination, and immune responses. Results: The D614G variant induced more severe disease and greater viral spread than the Omicron variant. Notably, ferrets infected with the D614G variant exhibited a robust neutralizing antibody response, whereas those infected with the Omicron variant failed to produce a detectable neutralizing antibody response. Despite the clearance of the virus from nearly all tissues by 7 days post-infection, an increase in pathological lesions was observed from 14 to 21 days, particularly in those infected with the D614G variant, suggesting a sustained immune response even after viral clearance. Discussion: These findings underscore the adaptability of SARS-CoV-2 and illuminate how susceptibility and clinical manifestations vary across different strains and species. The results emphasize the necessity of considering both the direct effects of viral infection and the indirect, often prolonged, impacts of the immune response in evaluating the outcomes of SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) continues its significant health and economic impact globally. Despite the success of spike-protein vaccines in preventing severe disease, long-lasting protection against emerging variants and the prevention of breakthrough infections and transmission remain elusive. We generate an intranasal live-attenuated SARS-CoV-2 vaccine, CDO-7N-1, using codon deoptimization. CDO-7N-1 shows highly attenuated replication and minimal or no lung pathology in vivo over multiple passages. It induces robust mucosal and systemic neutralizing antibody and T-cell subset responses, in mice (female K18-hACE2 and male HFH4-hACE2 mice), hamsters, and macaques triggered by a single immunization. Mice and hamsters vaccinated with CDO-7N-1 are protected from challenge with wild-type (WT) SARS-CoV-2 and other variants of concern. Serum from vaccinated animals neutralizes WT SARS-CoV-2, variants of concern (beta and delta), variants of interest (omicron XBB.1.5) and SARS-CoV-1. Antibody responses are sustained and enhanced by repeated immunization or infection with WT SARS-CoV-2. Immunity against all SARS-CoV-2 proteins by CDO-7N-1 should improve efficacy against future SARS-CoV-2 variants. Current SARS-CoV-2 vaccines require several injections for optimal immune protection. Here, the authors report an intranasal live-attenuated vaccine that induces long-term immunity following a single dose and protects from SARS-CoV-2 wildtype and variants in non-human primate and small animal models. [ABSTRACT FROM AUTHOR]

While severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is characterized by impaired induction of interferons (IFNs) and IFN-stimulated genes (ISGs), the IFNs and ISGs in upper airway is essential to restrict the spread of respiratory virus. Here, we identified the prominent IFN and ISG upregulation in the nasopharynx (NP) of mild and even severe coronavirus disease 2019 (COVID-19) patients (CoV2+) in Omicron era and to compare their clinical outcome depending on the level of IFNs and ISGs. Whereas the induction of IFNB was minimal, transcription of IFNA, IFNG, and IFNLs was significantly increased in the NP of CoV2 + patients. IFNs and ISGs may be more upregulated in the NP of CoV2 + patients at early phases of infection according to viral RNA levels and this is observed even in severe cases. IFN-related innate immune response might be characteristic in macrophages and monocytes at the NP and the CoV2 + patients with higher transcription of IFNs and ISGs in the NP showed a correlation with good prognosis of COVID-19. This study presents that IFNs and ISGs may be upregulated in the NP, even in severe CoV2 + patients depending on viral replication during Omicron-dominant period and the unique IFN-responsiveness in the NP links with COVID-19 clinical outcomes. [ABSTRACT FROM AUTHOR]

Rapid diagnostics are critical infectious disease tools that are designed to detect a known biomarker using antibodies specific to that biomarker. However, a way to detect unknown disease variants has not yet been achieved in a paper test format. We describe here a route to make an adaptable paper immunoassay that can detect an unknown biomarker, demonstrating it on SARS-CoV-2 variants. The immunoassay repurposes cross reactive antibodies raised against the alpha variant. Gold nanoparticles of two different colors conjugated to two different antibodies create a colorimetric signal, and machine learning of the resulting colorimetric pattern is used to train the assay to discriminate between variants of alpha and Omicron BA.5. By using principal component analysis, the colorimetric test patterns can pick up and discriminate an unknown variant that it has not encountered before, Omicron BA.1. The test has an accuracy of 100% and a potential calculated discriminatory power of 900. We show that it can be used adaptively and that it can be used to pick up emerging variants without the need to raise new antibodies. [ABSTRACT FROM AUTHOR]

Background: According to Norwegian registries, 91% of individuals ≥ 16 years had received ≥ 1 dose of COVID-19 vaccine by mid-July 2022, whereas less than 2% of children < 12 years were vaccinated. Confirmed COVID-19 was reported for 27% of the population, but relaxation of testing lead to substantial underreporting. We have characterized the humoral immunity to SARS-CoV-2 in Norway in the late summer of 2022 by estimating the seroprevalence and identifying antibody profiles based on reactivity to Wuhan or Omicron-like viruses in a nationwide cross-sectional collection of residual sera, and validated our findings using cohort sera. Methods: 1,914 anonymized convenience sera and 243 NorFlu-cohort sera previously collected from the Oslo-area with reported infection and vaccination status were analyzed for antibodies against spike, the receptor-binding domain (RBD) of the ancestral Wuhan strain and Omicron BA.2 RBD, and nucleocapsid (N). Samples were also tested for antibodies inhibiting RBD-ACE2 interaction. Neutralization assays were performed on subsets of residual sera against B.1, BA.2, XBB.1.5 and BQ.1.1. Results: The national seroprevalence estimate from vaccination and/or infection was 99.1% (95% CrI 97.0-100.0%) based on Wuhan (spike_W and RBD_W) and RBD_BA2 antibodies. Sera from children < 12 years had 2.2 times higher levels of antibodies against RBD_BA2 than RBD_W and their seroprevalence estimate showed a 14.4 percentage points increase when also including anti-RBD_BA2 antibodies compared to Wuhan-antibodies alone. 50.3% (95% CI 45.0-55.5%) of residual sera from children and 38.1% (95% CI 36.0-40.4%) of all residual sera were positive for anti-N-antibodies. By combining measurements of binding- and ACE2-RBD-interaction-inhibiting antibodies, reactivity profiles indicative of infection and vaccination history were identified and validated using cohort sera. Residual sera with a profile indicative of hybrid immunity were able to neutralize newer Omicron variants XBB.1.5 and BQ.1.1. Conclusions: By late summer of 2022, most of the Norwegian population had antibodies to SARS-CoV-2, and almost all children had been infected. Antibody profiles indicated that children mostly had experienced a primary Omicron infection, while hybrid immunity was common among adults. The finding that sera displaying hybrid immunity could neutralize newer Omicron variants indicates that Wuhan-like priming of the immune response did not have a harmful imprinting effect and that infections induce cross-reacting antibodies against future variants. [ABSTRACT FROM AUTHOR]

A cross-sectional study on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seroprevalence among unvaccinated people living with HIV (PLWH) was conducted in Kampala, Uganda, in 2022. Data collection was done using a structured questionnaire. SARS-CoV-2 serologies were done using the Roche Elecsys Anti-SARS-CoV-2 S immunoassay, which assesses the adaptive humoral immune response to the SARS-CoV-2 Spike protein. A total of 575 PLWH (female n=355, 61.7%) with a median age of 49 years (IQR 39-55) were included. SARS-CoV-2 seroprevalence was 93%. The majority had antibody concentration levels ὅ 250 U/ml (n=383, 66.6%). Participants aged >55 years were significantly more likely to have lower antibody concentrations compared to younger participants (p-value < 0.001). A high BMI (= 30 kg/m2) was significantly associated with higher antibody concentrations (p-value 0.001). Concerning COVID-19 history, a small proportion of participants (n=79, 13.6%) reported contact with a known COVID-19 patient. Only 8.1% (n=47) had ever had a nasopharyngeal swab for SARS-CoV-2 RT-PCR done, and 3.1% (n=18) actually had a laboratory-confirmed SARS-CoV-2 infection in the past. SARS-CoV-2 seroprevalence was high among our study population, which may be attributed to the fact that the study took place right after all restrictions were lifted and the population was exposed to the dominant Omicron variant. Interestingly, only a small proportion of infections had been laboratory-confirmed. [ABSTRACT FROM AUTHOR]

Although vaccines have reduced the burden of COVID-19, their efficacy in helminth infection–endemic areas is not well characterized. We evaluated the impact of infection by Heligmosomoides polygyrus bakeri (Hpb), a murine intestinal roundworm, on the efficacy of an mRNA vaccine targeting the Wuhan-1 spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in mice. Although immunization generated similar B cell responses in Hpb-infected and uninfected mice, polyfunctional CD4+ and CD8+ T cell responses were markedly reduced in Hpb-infected mice. Hpb-infected and mRNA-vaccinated mice were protected against the ancestral SARS-CoV-2 strain WA1/2020, but control of lung infection was diminished against an Omicron variant compared with animals immunized without Hpb infection. Helminth-mediated suppression of spike protein–specific CD8+ T cell responses occurred independently of signal transducer and activator of transcription 6 (STAT6) signaling, whereas blockade of interleukin-10 (IL-10) rescued vaccine-induced CD8+ T cell responses. Together, these data show that, in mice, intestinal helminth infection impaired vaccine-induced T cell responses through an IL-10 pathway, which compromised protection against antigenically drifted SARS-CoV-2 variants. Editor's summary: Much of the global population lives in areas endemic to helminths, which are known to affect responses to vaccines. To discern how helminth infection affects responses to SARS-CoV-2 vaccines, Desai et al. infected mice with the hookworm Heligmosomoides polygyrus bakeri (Hpb) during the course of a primary SARS-CoV-2 vaccine series. The authors found that Hpb infection compromised T cell, but not antibody, responses to SARS-CoV-2 in an IL-10–dependent manner. Although Hpb-infected K18-hACE2 mice were protected from ancestral SARS-CoV-2 challenge through their antibody responses, they were more susceptible to challenge with an Omicron variant, which can evade antibodies but is still susceptible to T cell responses. Together, these data highlight the need to keep helminth infections in mind during vaccine development and deployment. —Courtney Malo [ABSTRACT FROM AUTHOR]

Immunological imprinting by ancestral SARS-CoV-2 strains is thought to impede the robust induction of Omicron-specific humoral responses by Omicron-based booster vaccines. Here, we analyzed the specificity and neutralization activity of memory B (Bmem) cells after repeated BA.5 exposure in individuals previously imprinted by ancestral strain–based mRNA vaccines. After a second BA.5 exposure, Bmem cells with BA.5 spike protein–skewed reactivity were promptly elicited, correlating with preexisting antibody titers. Clonal lineage analysis identified BA.5-skewed Bmem cells that had redirected their specificity from the ancestral strain to BA.5 through somatic hypermutations. Moreover, Bmem cells with redirected BA.5 specificity exhibited accelerated development compared with de novo Bmem cells derived from naïve repertoires. This redirected BA.5 specificity demonstrated greater resilience to viral point mutation and adaptation to recent Omicron variants HK.3 and JN.1, months after the second BA.5 exposure, suggesting that existing Bmem cells elicited by older vaccines can redirect their specificity toward newly evolving variants. Editor's summary: As the world's population continues to be reexposed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein through infection or vaccination, immunologists have raised concerns about immune imprinting, where memory B cells directed against older strains prohibit B cells targeting newer strains from emerging. However, Kotaki et al. found that, at least for repeated exposures to the Omicron BA.5 variant spike protein, ancestral strain–primed memory B cell responses are not misdirected; rather, older memory B cells became redirected away from the ancestral strain and toward BA.5. The authors used clonal lineage analysis to confirm that the ancestral strain–skewed B cells became redirected toward BA.5 and were not derived from de novo B cell responses. Antibodies derived from these redirected B cells were also able to neutralize more recent Omicron variants, supporting the continued use of updated SARS-CoV-2 vaccines. —Courtney Malo [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusion We aimed to investigate the effect of metabolic dysfunction‐associated steatotic liver disease (MASLD) on three‐dose BNT162b2 immunogenicity to the omicron variant.Adult recipients of three doses of BNT162b2 were prospectively recruited between May and December 2021. The serology of the neutralizing antibody by live virus microneutralization (vMN) to the omicron variant was measured at baseline, day 180, and day 360 after the first dose. The primary outcome was seroconversion (vMN titer ≥ 10) at day 360. Exposure of interest was MASLD, defined as hepatic steatosis (controlled attenuation parameter ≥ 248 dB/m on transient elastography) plus at least one of five cardiometabolic risk factors. Subjects with prior COVID‐19 were excluded. A multivariable logistic regression model was used to derive the adjusted odds ratio of seroconversion with MASLD by adjusting for age, sex, antibiotic use, and proton pump inhibitor use.One hundred forty‐eight BNT162b2 recipients (male: 48 [32.4%]; median age: 51.0 years [interquartile range, IQR: 44.5–57.3]) were recruited. The median time from the first dose to the third dose was 8.5 months (IQR: 7.9–8.9). MASLD subjects had a lower seroconversion rate than non‐MASLD ones (89.6% vs 99.0%; P = 0.007). MASLD was the only independent risk factor for seroconversion (adjusted odds ratio: 0.051, 95% confidence interval: 0.002–0.440). Subgroup analysis of immunogenicity at 4 months after the third dose shows significantly lower vMN titer (13.06 [IQR: 7.69–22.20] vs 33.49 [IQR: 24.05–46.53]; P = 0.004) and seroconversion rate (76.9% vs 97.4%; P = 0.016) in MASLD than non‐MASLD subjects, but not within 4 months from the third dose (vMN titer: 46.87 [IQR: 33.12–66.02] vs 41.86 [IQR: 34.47–50.91], P = 0.240; seroconversion rate: 94.3% vs 100%, P = 0.131).Metabolic dysfunction‐associated steatotic liver disease was a risk factor for poorer immunogenicity to the omicron variant, with a more pronounced waning effect compared among three‐dose BNT162b2 recipients. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor discussing the need to update the current COVID-19 vaccine due to the emergence of new variants of the SARS-CoV-2 virus. The authors conducted a study to evaluate the neutralizing antibody response against two specific variants, KP.2 and KP.3, in individuals who received a specific booster vaccine. The results showed a significant decrease in neutralizing antibody titers against these variants, indicating the importance of adapting future vaccines to address these emerging variants. The authors emphasize the need for ongoing research and adaptation of the vaccine to stay ahead of evolving viral strains, while also considering the effectiveness of the T cell response against highly mutated variants. [Extracted from the article]

The recombination plays a key role in promoting evolution of RNA viruses and emergence of potentially epidemic variants. Some studies investigated the recombination occurrence among SARS-CoV-2, without exploring its impact on virus-host interaction. In the aim to investigate the burden of recombination in terms of frequency and distribution, the occurrence of recombination was first explored in 44 230 Omicron sequences among BQ subvariants and the under investigation "ML" (Multiple Lineages) denoted sequences, using 3seq software. Second, the recombination impact on interaction between the Spike protein and ACE2 receptor as well as neutralizing antibodies (nAbs), was analyzed using docking tools. Recombination was detected in 56.91% and 82.20% of BQ and ML strains, respectively. It took place mainly in spike and ORF1a genes. For BQ recombinant strains, the docking analysis showed that the spike interacted strongly with ACE2 and weakly with nAbs. The mutations S373P, S375F and T376A constitute a residue network that enhances the RBD interaction with ACE2. Thirteen mutations in RBD (S373P, S375F, T376A, D405N, R408S, K417N, N440K, S477N, P494S, Q498R, N501Y, and Y505H) and NTD (Y240H) seem to be implicated in immune evasion of recombinants by altering spike interaction with nAbs. In conclusion, this "in silico" study demonstrated that the recombination mechanism is frequent among Omicron BQ and ML variants. It highlights new key mutations, that potentially implicated in enhancement of spike binding to ACE2 (F376A) and escape from nAbs (RBD: F376A, D405N, R408S, N440K, S477N, P494S, and Y505H; NTD: Y240H). Our findings present considerable insights for the elaboration of effective prophylaxis and therapeutic strategies against future SARS-CoV-2 waves. [ABSTRACT FROM AUTHOR]

The development of cross-reactive vaccines is one of the central aims of modern vaccinology. Continuous mutation and the emergence of new SARS-CoV-2 variants and subvariants create the problem of universal coronavirus vaccine design. Previously, the authors devised three recombinant coronavirus antigens, which were based on the sequence collected in 2019 (the Wuhan variant) and produced in an E. coli bacterial expression system. The present work has shown, for the first time, that these recombinant antigens induce the production of antibodies that clearly interact with produced in CHO full-length S-protein of the Omicron variant. The immunogenicity of these recombinant antigens was studied in formulations with different adjuvants: Freund's adjuvant, Al(OH)3 and an adjuvant based on spherical particles (SPs), which are structurally modified plant virus. All adjuvanted formulations effectively stimulated Omicron-specific IgG production in mice. These universal coronavirus antigens could be considered the main component for the further development of broad-spectrum coronavirus vaccines for the prevention of SARS-CoV-2 infection. The present work also provides evidence that the synthetic biology approach is a promising strategy for the development of highly cross-reactive vaccines. Moreover, it is important to note that the bacterial expression system might be appropriate for the production of antigenically active universal antigens. [ABSTRACT FROM AUTHOR]

Wastewater-based surveillance has emerged as an important method for monitoring the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This study investigated the presence of SARS-CoV-2 in wastewater in Zambia. We conducted a longitudinal study in the Copperbelt and Eastern provinces of Zambia from October 2023 to December 2023 during which 155 wastewater samples were collected. The samples were subjected to three different concentration methods, namely bag-mediated filtration, skimmed milk flocculation, and polythene glycol-based concentration assays. Molecular detection of SARS-CoV-2 nucleic acid was conducted using real-time Polymerase Chain Reaction (PCR). Whole genome sequencing was conducted using Illumina COVIDSEQ assay. Of the 155 wastewater samples, 62 (40%) tested positive for SARS-CoV-2. Of these, 13 sequences of sufficient length to determine SARS-CoV-2 lineages were obtained and 2 sequences were phylogenetically analyzed. Various Omicron subvariants were detected in wastewater including BA.5, XBB.1.45, BA.2.86, and JN.1. Some of these subvariants have been detected in clinical cases in Zambia. Interestingly, phylogenetic analysis positioned a sequence from the Copperbelt Province in the B.1.1.529 clade, suggesting that earlier Omicron variants detected in late 2021 could still be circulating and may not have been wholly replaced by newer subvariants. This study stresses the need for integrating wastewater surveillance of SARS-CoV-2 into mainstream strategies for monitoring SARS-CoV-2 circulation in Zambia. [ABSTRACT FROM AUTHOR]

The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in 2021 as a variant with heavy amino acid mutations in the spike protein, which is targeted by most vaccines, compared to previous variants. Amino acid substitutions in the spike proteins may alter their affinity for host viral receptors and the host interactome. Here, we found that the receptor-binding domain (RBD) of the omicron variant of SARS-CoV-2 exhibited an increased affinity for human angiotensin-converting enzyme 2, a viral cell receptor, compared to the prototype RBD. Moreover, we identified β- and γ-actin as omicron-specific binding partners of RBD. Protein complex predictions revealed that many omicron-specific amino acid substitutions affected the affinity between RBD of the omicron variant and actin. Our findings indicate that proteins localized to different cellular compartments exhibit strong binding to the omicron RBD. [ABSTRACT FROM AUTHOR]

[Display omitted] Currently approved vaccines have been successful in preventing the severity of COVID-19 and hospitalization. These vaccines primarily induce humoral immune responses; however, highly transmissible and mutated variants, such as the Omicron variant, weaken the neutralization potential of the vaccines, thus, raising serious concerns about their efficacy. Additionally, while neutralizing antibodies (nAbs) tend to wane more rapidly than cell-mediated immunity, long-lasting T cells typically prevent severe viral illness by directly killing infected cells or aiding other immune cells. Importantly, T cells are more cross-reactive than antibodies, thus, highly mutated variants are less likely to escape lasting broadly cross-reactive T cell immunity. Therefore, T cell antigen-based human coronavirus (HCoV) vaccines with the potential to serve as a supplementary weapon to combat emerging SARS-CoV-2 variants with resistance to nAbs are urgently needed. Alternatively, T cell antigens could also be included in B cell antigen-based vaccines to strengthen vaccine efficacy. This review summarizes recent advancements in research and development of vaccines containing T cell antigens or both T and B cell antigens derived from proteins of SARS-CoV-2 variants and/or other HCoVs based on different vaccine platforms. [ABSTRACT FROM AUTHOR]

Background With coronavirus disease 2019 (COVID-19) vaccination no longer mandated by many businesses/organizations, it is now up to individuals to decide whether to get any new boosters/updated vaccines going forward. Methods We developed a Markov model representing the potential clinical/economic outcomes from an individual perspective in the United States of getting versus not getting an annual COVID-19 vaccine. Results For an 18–49 year old, getting vaccinated at its current price ($60) can save the individual on average $ 30–$603 if the individual is uninsured and $4–$437 if the individual has private insurance, as long as the starting vaccine efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is ≥50% and the weekly risk of getting infected is ≥0.2%, corresponding to an individual interacting with 9 other people in a day under Winter 2023–2024 Omicron SARS-CoV-2 variant conditions with an average infection prevalence of 10%. For a 50–64 year old, these cost-savings increase to $111–$1278 and $119–$1706 for someone without and with insurance, respectively. The risk threshold increases to ≥0.4% (interacting with 19 people/day), when the individual has 13.4% preexisting protection against infection (eg, vaccinated 9 months earlier). Conclusions There is both clinical and economic incentive for the individual to continue to get vaccinated against COVID-19 each year. [ABSTRACT FROM AUTHOR]

Background SARS-CoV-2 antigen-detection rapid diagnostic tests (Ag-RDTs) have become widely utilized but longitudinal characterization of their community-based performance remains incompletely understood. Methods This prospective longitudinal study at a large public university in Seattle, WA utilized remote enrollment, online surveys, and self-collected nasal swab specimens to evaluate Ag-RDT performance against real-time reverse transcription polymerase chain reaction (rRT-PCR) in the context of SARS-CoV-2 Omicron. Ag-RDT sensitivity and specificity within 1 day of rRT-PCR were evaluated by symptom status throughout the illness episode and Orf1b cycle threshold (Ct). Results From February to December 2022, 5757 participants reported 17 572 Ag-RDT results and completed 12 674 rRT-PCR tests, of which 995 (7.9%) were rRT-PCR positive. Overall sensitivity and specificity were 53.0% (95% confidence interval [CI], 49.6%–56.4%) and 98.8% (95% CI, 98.5%–99.0%), respectively. Sensitivity was comparatively higher for Ag-RDTs used 1 day after rRT-PCR (69.0%), 4–7 days after symptom onset (70.1%), and Orf1b Ct ≤20 (82.7%). Serial Ag-RDT sensitivity increased with repeat testing ≥ 2 (68.5%) and ≥ 4 (75.8%) days after an initial Ag-RDT-negative result. Conclusions Ag-RDT performance varied by clinical characteristics and temporal testing patterns. Our findings support recommendations for serial testing following an initial Ag-RDT-negative result, especially among recently symptomatic persons or those at high risk for SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background Monovalent Omicron XBB.1.5–containing vaccines were approved for coronavirus disease 2019 (COVID-19) 2023–2024 immunizations. Methods This ongoing, open-label, phase 2/3 study evaluated messenger RNA (mRNA)-1273.815 monovalent (50-µg Omicron XBB.1.5 spike mRNA) and mRNA-1273.231 bivalent (25-µg each Omicron XBB.1.5 and BA.4/BA.5 spike mRNAs) vaccines, administered as fifth doses to adults who previously received primary series, third doses of an original mRNA COVID-19 vaccine, and fourth doses of an Omicron BA.4/BA.5 bivalent vaccine. Interim safety and immunogenicity 29 days after vaccination are reported. Results Participants (randomized 1:1) received 50-µg of mRNA-1273.815 (n = 50) or mRNA-1273.231 (n = 51); median intervals (interquartile range) from prior BA.4/BA.5 bivalent doses were 8.2 (8.1–8.3) and 8.3 (8.1–8.4) months, respectively. Fold increases in neutralizing antibody (nAb) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants from prebooster nAb levels were numerically higher against XBB.1.5, XBB.1.16, EG.5.1, BA.2.86, and JN.1 than BA.4/BA.5, BQ.1.1, or D614G on day 29. Monovalent vaccine also cross-neutralized FL.1.5.1, EG.5.1, BA.2.86, HK.3.1, HV.1, and JN.1 variants in a participant subset (n = 20) 15 days after vaccination. Reactogenicity was similar to that of mRNA-1273 vaccines. Conclusions XBB.1.5-containing mRNA-1273 vaccines elicit robust, diverse nAb responses against more recent SARS-CoV-2 variants, including JN.1, supporting the XBB.1.5-spike update for COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

Background The emergence of rapidly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, coupled with waning vaccine-induced immunity, has contributed to the rise of vaccine breakthrough infections. It is crucial to understand how vaccine-induced protection is mediated. Methods We examined 2 prospective cohorts of mRNA vaccinated and boosted individuals during the Omicron wave of infection in Singapore. Results We found that individuals who remain uninfected over the follow-up period had a higher variant-specific IgA, but not IgG, antibody response at 1 month after booster vaccination, compared with individuals who became infected. Conclusions We conclude that IgA may have a potential contributory role in protection against Omicron infection. Clinical Trials Registration. NCT05142319. [ABSTRACT FROM AUTHOR]

COVID-19 is an infectious disease that continues to spread worldwide. A precise estimation of the cases and deaths due to COVID-19 would allow for appropriate consideration of healthcare resource allocation, public health response, and vaccination and economic planning, to minimize social damage. In this study, we analyzed the progression of COVID-19 cases and deaths until January 2022 in 156 countries using a nonlinear mixed-effect model based on the SIR framework. Given the major changes in mortality from infection, risk of re-infection and social responses, the analysis was limited to the period before the emergence of the Omicron variant. The impact of infection prevention measures in various countries was assessed, with a specific focus on estimating the effectiveness of lockdowns, where the effect was assumed to change over time. By accounting for excess mortality, our analysis allowed the estimation of unreported cases and deaths, and thus providing a more comprehensive understanding of the impact of pandemic. In the analysis, we identified gross domestic product (GDP), proportion of people aged 65 years or older, latitude of the capital city on transmissibility of infection, and city population and cardiovascular death rate on mortality rate as significant influencing factors. Furthermore, the differences in transmissibility and mortality rates by variants and the effect of vaccination on the mortality rate were assessed. The transmissibility has increased by odds ratios of 1.2 to 1.4 in Beta, Gamma, and Delta variants; mortality rate has increased by odds ratios of 1.7, 2.2, and 1.4 in Beta, Gamma, and Delta variants, respectively; and vaccination decreased the mortality rate by odds ratios of 0.4 and 0.1 in Delta and other variants, respectively. [ABSTRACT FROM AUTHOR]

Background: Omicron variant impacts populations with its rapid contagiousness, and part of patients suffered from persistent symptoms termed as long COVID. The molecular and immune mechanisms of this currently dominant global variant leading to long COVID remain unclear, due to long COVID heterogeneity across populations. Methods: We recruited 66 participants in total, 22 out of 66 were healthy control without COVID-19 infection history, and 22 complaining about long COVID symptoms 6 months after first infection of Omicron, referred as long COVID (LC) Group. The left ones were defined as non-long COVID (NLC) Group. We profiled them via plasma neutralizing antibody titer, SARS-CoV-2 viral load, transcriptomic and proteomics screening, and machine learning. Results: No serum residual SARS-CoV-2 was observed in the participants 6 months post COVID-19 infection. No significant difference in neutralizing antibody titers was found between the long COVID (LC) Group and the non-long COVID (NLC) Group. Transcriptomic and proteomic profiling allow the stratification of long COVID into neutrophil function upregulated (NU-LC) and downregulated types (ND-LC). The NU-LC, identifiable through a refined set of 5 blood gene markers (ABCA13, CEACAM6, CRISP3, CTSG and BPI), displays evidence of relatively higher neutrophil counts and function of degranulation than the ND-LC at 6 months after infection, while recovered at 12 months post COVID-19. Conclusion: The transcriptomic and proteomic profiling revealed heterogeneity among long COVID patients. We discovered a subgroup of long COVID population characterized by neutrophil activation, which might associate with the development of psychiatric symptoms and indicate a higher inflammatory state. Meanwhile, a cluster of 5 genes was manually curated as the most potent discriminators of NU-LC from long COVID population. This study can serve as a foundational exploration of the heterogeneity in the pathogenesis of long COVID and assist in therapeutic targeting and detailed epidemiological investigation of long COVID. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 Omicron variant sparked the largest wave of infections worldwide. Mainland China eased its strict COVID-19 measures in late 2022 and experienced two nationwide Omicron waves in 2023. Here, we investigated lineage distribution and virus evolution in Guangdong, China, 2022-2023 by comparing 5813 local viral genomes with the datasets from other regions of China and worldwide. Additionally, we conducted three large-scale serological surveys involving 1696 participants to measure their immune response to the BA.5 and XBB.1.9 before and after the corresponding waves. Our findings revealed the Omicron variants, mainly the BA.5.2.48 lineage, causing infections in over 90% of individuals across different age groups within a month. This rapid spread led to the establishment of widespread immunity, limiting the virus's ability to further adaptive mutation and dissemination. While similar immune responses to BA.5 were observed across all age groups after the initial wave, children aged 3 to 11 developed a stronger cross immune response to the XBB.1.9 strain, possibly explaining their lower infection rates in the following XBB.1 wave. Reinfection with Omicron XBB.1 variant triggered a more potent neutralizing immune response among older adults. These findings highlight the impact of age-specific immune responses on viral spread in potential future waves. Release of the zero-COVID policy in China in late 2022 led to two large Omicron-driven waves of infection in 2023. Here, the authors analyze virus genomes and serology data from before and after the two waves and describe changes in virus lineage distribution and age-specific antibody responses. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic's diverse symptomatology, driven by variants, underscores the critical need for a comprehensive understanding. Employing stochastic models, our study evaluates symptom sequences across SARS-CoV-2 variants on aggregated data, yielding essential insights for targeted interventions. Methods: We conducted a meta-analysis based on research literature published before December 9, 2022, from PubMed, LitCovid, Google Scholar, and CNKI databases, to investigate the prevalence of COVID-19 symptoms during the acute phase. Registered in PROSPERO (CRD42023402568), we performed random-effects meta-analyses using the R software to estimate pooled prevalence and 95% CI. Based on our findings, we introduced the Stochastic Progression Model and Sequential Pattern Discovery using Equivalence classes (SPADE) algorithm to analyze patterns of symptom progression across different variants. Results: Encompassing a total of 430,100 patients from east and southeast Asia, our results reveal the highest pooled estimate for cough/dry cough across wild-type, Delta, and Omicron variants, with fever (78.18%; 95% CI: 67–89%) being the most prominent symptom for the Alpha variant. Symptoms associated with the Omicron variant primarily manifested in upper respiratory tracts, cardiovascular, and neuropsychiatric systems. Stochastic models indicate early symptoms including dry cough and fever, followed by subsequent development of sleep disorders, fatigue, and more. Conclusion: Our study underscores the evolving symptomatology across SARS-CoV-2 variants, emphasizing similarities in fever, cough, and fatigue. The Omicron variant presents a distinct profile characterized by milder symptoms yet heightened neuropsychological challenges. Advanced analytical models validate the observed sequential progression of symptoms, reinforcing the consistency of disease trajectory. [ABSTRACT FROM AUTHOR]

Objective: The current study aimed to investigate the baseline immune and inflammatory features and in-hospital outcomes of patients infected with the Omicron variant (PIWO) who presented with different disease severities during the first wave of mass Omicron infections in the Chinese population has occurred. Method: A cross‐sectional study was conducted on 140 hospitalized PIWO between December 11, 2022, and February 16, 2023. The clinical features, antibodies against SARS-CoV-2, immune cells, and inflammatory cytokines among mildly, severely, and critically ill PIWO at baseline and during follow-up period were compared. Result: Patients with severe (n = 49) and critical (n = 35) disease were primarily male, needed invasive mechanical ventilation treatment, and exhibited higher mortality than those with mild disease (n = 56). During acute infection, SARS-CoV-2-specific antibody levels fluctuated with disease severity, serum antibodies increased and the incidence of severe cases decreased in critically ill PIWO over time. Antibody titers in severe or critical PIWO with no antibody responses at baseline did not increase significantly over time. Meanwhile, CD4+T cell, CD8+T cell, and natural killer cell counts were negatively correlated with disease severity, whereas interleukin (IL)-6 and IL-10 levels were positively correlated. In addition, combined diabetes, immunosuppressive therapy before infection, serum amyloid A, IL-10 and neutrophil counts were independently associated with severe and critical illness in PIWO. Among the 11 nonsurvivors, 8, 2, 1 died of respiratory failure, sudden cardiac death, and renal failure, respectively. Compared with survivors, nonsurvivors exhibited lower seropositivity of SARS-CoV-2-specific antibody, reduced CD3+T and CD4+T cell counts, and higher IL-2R, IL-6, IL-8, and IL-10 levels. Of note, lactate dehydrogenase was a significant risk factor of death in severe or critically ill PIWO. Conclusion: This present study assessed the dynamic changes of SARS-CoV-2-specific antibodies, immune cells and inflammatory indexes between severely and critically ill PIWO. Critical and dead PIWO featured compromised humoral immune response and excessive inflammation, which broadened the understanding of the pathophysiology of Omicron infection and provides warning markers for severe disease and poor prognosis. Highlights : 1. Specific anti-SARS-CoV-2 antibodies showed a trend of increasing first and then decreasing with the progression of disease severity. 2. The severity of infection decreased and the levels of the four antibodies against SARS-CoV-2 increased in critically ill PIWO over time. 3. Negative antibodies in severe/critical PIWO at baseline did not increase significantly with therapeutic intervention. 4. Dead PIWO exhibited disordered features of immunocompromised, hyperinflammatory, abnormal coagulation and myocardial injury. 5. Combined diabetes, immunosuppressive therapy before infection, high levels of SAA, IL-10 and neutrophil counts were the risk factors for severe/critical illness. 6. High LDH was related to death event in severely/critically ill PIWO. [ABSTRACT FROM AUTHOR]

Background: A trial performed among unvaccinated, high-risk outpatients with COVID-19 during the delta period showed remdesivir reduced hospitalization. We used our real-world data platform to determine the effectiveness of remdesivir on reducing 28-day hospitalization among outpatients with mild-moderate COVID-19 during an Omicron period including BQ.1/BQ.1.1/XBB.1.5. Methods: We did a propensity-matched, retrospective cohort study of non-hospitalized adults with SARS-CoV-2 infection between April 7, 2022, and February 7, 2023. Electronic healthcare record data from a large health system in Colorado were linked to statewide vaccination and mortality data. We included patients with a positive SARS-CoV-2 test or outpatient remdesivir administration. Exclusion criteria were other SARS-CoV-2 treatments or positive SARS-CoV-2 test more than seven days before remdesivir. The primary outcome was all-cause hospitalization up to day 28. Secondary outcomes included 28-day COVID-related hospitalization and 28-day all-cause mortality. Results: Among 29,270 patients with SARS-CoV-2 infection, 1,252 remdesivir-treated patients were matched to 2,499 untreated patients. Remdesivir was associated with lower 28-day all-cause hospitalization (1.3% vs. 3.3%, adjusted hazard ratio (aHR) 0.39 [95% CI 0.23–0.67], p < 0.001) than no treatment. All-cause mortality at 28 days was numerically lower among remdesivir-treated patients (0.1% vs. 0.4%; aOR 0.32 [95% CI 0.03–1.40]). Similar benefit of RDV treatment on 28-day all-cause hospitalization was observed across Omicron periods, aOR (95% CI): BA.2/BA2.12.1 (0.77[0.19–2.41]), BA.4/5 (0.50[95% CI 0.50–1.01]), BQ.1/BQ.1.1/XBB.1.5 (0.21[95% CI 0.08–0.57]. Conclusion: Among outpatients with SARS-CoV-2 during recent Omicron surges, remdesivir was associated with lower hospitalization than no treatment, supporting current National Institutes of Health Guidelines. [ABSTRACT FROM AUTHOR]

BACKGROUND Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) can affect many organ systems. However, temporal changes during the coronavirus disease 2019 (Covid-19) pandemic, including the evolution of SARS-CoV-2, may have affected the risk and burden of PASC. Whether the risk and burden of PASC have changed over the course of the pandemic is unclear. METHODS We used health records of the Department of Veterans Affairs to build a study population of 441,583 veterans with SARS-CoV-2 infection between March 1, 2020, and January 31, 2022, and 4,748,504 noninfected contemporaneous controls. We estimated the cumulative incidence of PASC at 1 year after SARS-CoV-2 infection during the pre-delta, delta, and omicron eras of the Covid-19 pandemic. RESULTS Among unvaccinated persons infected with SARS-CoV-2, the cumulative incidence of PASC during the first year after infection was 10.42 events per 100 persons (95% confidence interval [CI], 10.22 to 10.64) in the pre-delta era, 9.51 events per 100 persons (95% CI, 9.26 to 9.75) in the delta era, and 7.76 events per 100 persons (95% CI, 7.57 to 7.98) in the omicron era (difference between the omicron and pre-delta eras, -2.66 events per 100 persons [95% CI, -2.93 to -2.36]; difference between the omicron and delta eras, -1.75 events per 100 persons [95% CI, -2.08 to -1.42]). Among vaccinated persons, the cumulative incidence of PASC at 1 year was 5.34 events per 100 persons (95% CI, 5.10 to 5.58) during the delta era and 3.50 events per 100 persons (95% CI, 3.31 to 3.71) during the omicron era (difference between the omicron and delta eras, -1.83 events per 100 persons; 95% CI, -2.14 to -1.52). Vaccinated persons had a lower cumulative incidence of PASC at 1 year than unvaccinated persons (difference during the delta era, -4.18 events per 100 persons [95% CI, -4.47 to -3.88]; difference during the omicron era, -4.26 events per 100 persons [95% CI, -4.49 to -4.05]). Decomposition analyses showed 5.23 (95% CI, 4.97 to 5.47) fewer PASC events per 100 persons at 1 year during the omicron era than during the pre-delta and delta eras combined; 28.11% of the decrease (95% CI, 25.57 to 30.50) was attributable to era-related effects (changes in the virus and other temporal effects), and 71.89% (95% CI, 69.50 to 74.43) was attributable to vaccines. CONCLUSIONS The cumulative incidence of PASC during the first year after SARS-CoV-2 infection decreased over the course of the pandemic, but the risk of PASC remained substantial even among vaccinated persons who had SARS-CoV-2 infection in the omicron era. (Supported by the Department of Veterans Affairs.) [ABSTRACT FROM AUTHOR]

Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Objective: to evaluate the immune response to the SARS-CoV-2 vaccines in adults with immune-mediated rheumatic diseases (IMRDs) in comparison to healthy individuals, observed 1-20 weeks following the fourth vaccine dose. Additionally, to evaluate the impact of immunosuppressive therapies, vaccination schedules, the time interval between vaccination and sample collection on the vaccine's immune response. Methods: We designed a longitudinal observational study conducted at the rheumatology department of Hospital de Copiapó. Neutralizing antibodies (Nabs) titers against the Wuhan and Omicron variant were analyzed between 1-20 weeks after administration of the fourth dose of the SARS-CoV-2 vaccine to 341 participants (218 IMRD patients and 123 healthy controls). 218 IMRD patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), systemic vasculitis (VS) and systemic scleroderma (SS) were analyzed. Results: Performing a comparison between the variants, Wuhan vs Omicron, we noticed that there were significant differences (p<0.05) in the level of the ID50, both for healthy controls and for patients with IMRDs. The humoral response of patients with IMRDs is significantly lower compared to healthy controls for the Omicron variant of SARS-CoV-2 (p = 0.0015). The humoral response of patients with IMRDs decreases significantly when the time interval between vaccination and sample collection is greater than 35 days. This difference was observed in the response, both for the Wuhan variant and for the Omicron variant. Conclusion: The IMRDs patients, the humoral response variation in the SARS-CoV-2 vaccine depends on doses and type of vaccine administered, the humoral response times and the treatment that these patients are receiving. [ABSTRACT FROM AUTHOR]

Current vaccines against COVID-19 elicit immune responses that are overall strong but wane rapidly. As a consequence, the necessary booster shots have contributed to vaccine fatigue. Hence, vaccines that would provide lasting protection against COVID-19 are needed, but are still unavailable. Cytomegaloviruses (CMVs) elicit lasting and uniquely strong immune responses. Used as vaccine vectors, they may be attractive tools that obviate the need for boosters. Therefore, we tested the murine CMV (MCMV) as a vaccine vector against COVID-19 in relevant preclinical models of immunization and challenge. We have previously developed a recombinant MCMV vaccine vector expressing the spike protein of the ancestral SARS-CoV-2 (MCMVS). In this study, we show that the MCMVS elicits a robust and lasting protection in young and aged mice. Notably, spike-specific humoral and cellular immunity was not only maintained but also even increased over a period of at least 6 months. During that time, antibody avidity continuously increased and expanded in breadth, resulting in neutralization of genetically distant variants, like Omicron BA.1. A single dose of MCMVS conferred rapid virus clearance upon challenge. Moreover, MCMVS vaccination controlled two variants of concern (VOCs), the Beta (B.1.135) and the Omicron (BA.1) variants. Thus, CMV vectors provide unique advantages over other vaccine technologies, eliciting broadly reactive and long-lasting immune responses against COVID-19. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has developed substantial antigenic variability. As the majority of the population now has pre-existing immunity due to infection or vaccination, the use of experimentally generated animal immune sera can be valuable for measuring antigenic differences between virus variants. Here, we immunized Syrian hamsters by two successive infections with one of nine SARS-CoV-2 variants. Their sera were titrated against 16 SARS-CoV-2 variants, and the resulting titers were visualized using antigenic cartography. The antigenic map shows a condensed cluster containing all pre-Omicron variants (D614G, Alpha, Delta, Beta, Mu, and an engineered B.1+E484K variant) and considerably more diversity among a selected panel of Omicron subvariants (BA.1, BA.2, BA.4/BA.5, the BA.5 descendants BF.7 and BQ.1.18, the BA.2.75 descendant BN.1.3.1, the BA.2-derived recombinants XBB.2 and EG.5.1, and the BA.2.86 descendant JN.1). Some Omicron subvariants were as antigenically distinct from each other as the wildtype is from the Omicron BA.1 variant. Compared to titers measured in human sera, titers in hamster sera are of higher magnitude, show less fold change, and result in a more compact antigenic map topology. The results highlight the potential of sera from hamsters for the continued antigenic characterization of SARS-CoV-2. [ABSTRACT FROM AUTHOR]