Relative Effectiveness and Waning of a Third Dose of mRNA COVID-19 Vaccine in Medicare Beneficiaries Aged 65 Years and Older during the BA.1/BA.2 Omicron Period.

BACKGROUND: We assessed the added benefit and waning effectiveness of a third COVID-19 vaccine dose (original formula) for preventing COVID-19-related outcomes. METHODS: We used Medicare claims data to conduct a retrospective cohort study in U.S. community-dwelling Medicare Fee-for-Service beneficiaries aged ≥65 years during the BA.1/BA.2 Omicron period (December 19, 2021 - March 26, 2022). We estimated relative vaccine effectiveness (RVE) of 3 versus 2 doses of mRNA COVID-19 vaccines using marginal structural Cox regression models. RESULTS: Among 8,135,020 eligible beneficiaries, 73.3% were 3-dose vaccinated by March 26, 2022. At 14-60 days since vaccination, a third dose provided significant added benefit against COVID-19-related hospitalization for Moderna (RVE: 77.2%; 95% confidence interval (CI): 76.0%, 78.4%) and Pfizer-BioNTech (RVE: 72.5%; 95% CI: 70.8%, 74.0%). Added benefit was lower >120 days. For those with prior medically attended COVID-19 diagnoses, Pfizer-BioNTech provided an added benefit for 120 days, while Moderna provided some added benefit >120 days. Added benefit for either vaccine was higher against death compared to less severe outcomes, which still decreased >120 days. CONCLUSIONS: A third dose COVID-19 vaccine provided significant added benefit against COVID-19-related hospitalization and death, even for beneficiaries with prior medically attended COVID-19 diagnoses. This added benefit decreased after 4 months.

Viral load dynamics in asymptomatic and symptomatic patients during Omicron BA.2 outbreak in Shanghai, China, 2022: a longitudinal cohort study.

The SARS-CoV-2 virus, particularly the Omicron BA.2 variant, led to a significant surge in Shanghai, 2022. However, the viral load dynamic in Omicron infections with varying clinical severities remain unclear. This prospective cohort included 48,830 hospitalized coronavirus disease 2019 (COVID-19) patients across three hospitals in Shanghai, China, between 23 March and 15 May 2022. Systematic nucleic acid testing was performed using RT-PCR Cycle threshold (Ct) value as a proxy of viral load. We analyzed the kinetic characteristics of viral shedding by clinical severity and identified associated risk factors. The study comprised 31.06% asymptomatic cases, 67.66% mild-moderate cases, 1.00% severe cases, 0.29% critical and fatal cases. Upon admission, 57% of patients tested positive, with peak viral load observed at 4 days (median Ct value 27.5), followed by a decrease and an average viral shedding time (VST) of 6.1 days (Interquartile range, 4.0-8.8 days). Although viral load exhibited variation by age and clinical severity, peak Ct values occurred at similar times. Unvaccinated status, age exceeding 60, and comorbidities including hypertension, renal issues kidney dialysis and kidney transplantation, neurological disorders, rheumatism, and psychotic conditions were found to correlate with elevated peak viral load and extended VST. Asymptomatic cases demonstrated a 40% likelihood of contagiousness within 6 days of detection, while mild-moderate and severe cases exhibited post-symptom resolution infectious probabilities of 27% and over 50%, respectively. These findings revealed that the initial Ct values serve as a predictive indicator of severe outcomes. Unvaccinated elderly individuals with particular comorbidities are at high-risk for elevated viral load and prolonged VST.

A quadri-fluorescence SARS-CoV-2 pseudovirus system for efficient antigenic characterization of multiple circulating variants.

The ongoing co-circulation of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains necessitates advanced methods such as high-throughput multiplex pseudovirus systems for evaluating immune responses to different variants, crucial for developing updated vaccines and neutralizing antibodies (nAbs). We have developed a quadri-fluorescence (qFluo) pseudovirus platform by four fluorescent reporters with different spectra, allowing simultaneous measurement of the nAbs against four variants in a single test. qFluo shows high concordance with the classical single-reporter assay when testing monoclonal antibodies and human plasma. Utilizing qFluo, we assessed the immunogenicities of the spike of BA.5, BQ.1.1, XBB.1.5, and CH.1.1 in hamsters. An analysis of cross-neutralization against 51 variants demonstrated superior protective immunity from XBB.1.5, especially against prevalent strains such as "FLip" and JN.1, compared to BA.5. Our finding partially fills the knowledge gap concerning the immunogenic efficacy of the XBB.1.5 vaccine against current dominant variants, being instrumental in vaccine-strain decisions and insight into the evolutionary path of SARS-CoV-2.

Development of new RT-PCR assays for the specific detection of BA.2.86 SARS-CoV-2 and its descendent sublineages.

The SARS-CoV-2 BA.2.86 variant, also known as Pirola, has acquired over 30 amino acid changes in the Spike protein, evolving into >150 sublineages within ten months of its emergence. Among these, the JN.1, has been rapidly increasing globally becoming the most prevalent variant. To facilitate the identification of BA.2.86 sublineages, we designed the PiroMet-1 and PiroMet-2 assays in silico and validated them using BA.2.86 viral RNA and clinical samples to ascertain analytical specificity and sensitivity. Both assays resulted very specific with limit of detection of about 1-2 RNA copies/µL. The assays were then applied in a digital RT-PCR format to wastewater samples, combined with the OmMet assay (which identifies Omicron sublineages except BA.2.86 and its descendants) and the JRC-UCE.2 assay (which can universally recognize all SARS-CoV-2 variants). When used together with the OmMet and JRC-CoV-UCE.2 assays, the PiroMet assays accurately quantified BA.2.86 sublineages in wastewater samples. Our findings support the integration of these assays into routine SARS-CoV-2 wastewater surveillance as a timely and cost-effective complement to sequencing for monitoring the prevalence and spread of BA.2.86 sublineages within communities.

Preventing future zoonosis: SARS-CoV-2 mutations enhance human-animal cross-transmission.

The COVID-19 pandemic has driven substantial evolution of the SARS-CoV-2 virus, yielding subvariants that exhibit enhanced infectiousness in humans. However, this adaptive advantage may not universally extend to zoonotic transmission. In this work, we hypothesize that viral adaptations favoring animal hosts do not necessarily correlate with increased human infectivity. In addition, we consider the potential for gain-of-function mutations that could facilitate the virus's rapid evolution in humans following adaptation in animal hosts. Specifically, we identify the SARS-CoV-2 receptor-binding domain (RBD) mutations that enhance human-animal cross-transmission. To this end, we construct a multitask deep learning model, MT-TopLap trained on multiple deep mutational scanning datasets, to accurately predict the binding free energy changes upon mutation for the RBD to ACE2 of various species, including humans, cats, bats, deer, and hamsters. By analyzing these changes, we identified key RBD mutations such as Q498H in SARS-CoV-2 and R493K in the BA.2 variant that are likely to increase the potential for human-animal cross-transmission.

Growth of Ba2CoWO6single crystals and their magnetic, thermodynamic and electronic properties.

This study explores the bulk crystal growth, structural characterization, and physical property measurements of the cubic double perovskite Ba2CoWO6(BCWO). In BCWO, Co2+ions form a face-centred cubic lattice with non-distorted cobalt octahedra. The compound exhibits long-range antiferromagnetic order belowTN= 14 K. Magnetization data indicated a slight anisotropy along with a spin-flop transition at 10 kOe, a saturation field of 310 kOe and an ordered moment of 2.17µB atT= 1.6 K. Heat capacity measurements indicate an effectivej= 1/2 ground state configuration, resulting from the combined effects of the crystal electric field and spin-orbit interaction. Surface photovoltage analysis reveals two optical gaps in the UV-Visible region, suggesting potential applications in photocatalysis and photovoltaics. The magnetic and optical properties highlight the significant role of orbital contributions within BCWO, indicating various other potential applications.

Structural and genomic evolutionary dynamics of Omicron variant of SARS-CoV-2 circulating in Madhya Pradesh, India.

The SARS-CoV-2 Omicron (B.1.1.529) variant emerged in early November 2021 and its rapid spread created fear worldwide. This was attributed to its increased infectivity and escaping immune mechanisms. The spike protein of Omicron has more mutations (>30) than any other previous variants and was declared as the variant of concern (VOC) by the WHO. The concern among the scientific community was huge about this variant, and a piece of updated information on circulating viral strains is important in order to better understand the epidemiology, virus pathogenicity, transmission, therapeutic interventions, and vaccine development. A total of 710 samples were processed for sequencing and identification up to a resolution of sub-lineage. The sequence analysis revealed Omicron variant with distribution as follows: B.1.1, B.1.1.529, BA.1, BA.2, BA.2.10, BA.2.10.1, BA.2.23, BA.2.37, BA.2.38, BA.2.43, BA.2.74, BA.2.75, BA.2.76, and BA.4 sub-lineages. There is a shift noted in circulating lineage from BA.1 to BA.2 to BA.4 over a period from January to September 2022. Multiple signature mutations were identified in S protein T376A, D405N, and R408S mutations, which were new and common to all BA.2 variants. Additionally, R346T was seen in emerging BA.2.74 and BA.2.76 variants. The emerging BA.4 retained the common T376A, D405N, and R408S mutations of BA.2 along with a new mutation F486V. The samples sequenced were from different districts of Madhya Pradesh and showed a predominance of BA.2 and its variants circulating in this region. The current study identified circulation of BA.1 and BA.1.1 variants during initial phase. The predominant Delta strain of the second wave has been replaced by the Omicron variant in this region over a period of time. This study successfully deciphers the dynamics of the emergence and replacement of various sub-lineages of SARS-CoV-2 in central India on real real-time basis.

Reaction Times in Modern Virology: "This is not a Drill".

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of interest BA.2.87.1 has not driven any Coronavirus disease 2019 (COVID-19) pandemic wave. Nevertheless, it has served to test the reaction times of modern virology laboratories. In this commentary, we highlight how fast the reaction has been at characterizing this sublineage, leading at an unprecedented pace to almost as many papers as the number of viral sequences.

Concerted deletions eliminate a neutralizing supersite in SARS-CoV-2 BA.2.87.1 spike.

BA.2.87.1 represents a major shift in the BA.2 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is unusual in having two lengthy deletions of polypeptide in the spike (S) protein, one of which removes a beta-strand. Here we investigate its neutralization by a variety of sera from infected and vaccinated individuals and determine its spike (S) ectodomain structure. The BA.2.87.1 receptor binding domain (RBD) is structurally conserved and the RBDs are tightly packed in an "all-down" conformation with a small rotation relative to the trimer axis as compared to the closest previously observed conformation. The N-terminal domain (NTD) maintains a remarkably similar structure overall; however, the rearrangements resulting from the deletions essentially destroy the so-called supersite epitope and eliminate one glycan site, while a mutation creates an additional glycan site, effectively shielding another NTD epitope. BA.2.87.1 is relatively easily neutralized but acquisition of additional mutations in the RBD could increase antibody escape allowing it to become a dominant sub-lineage.

Efficient control of root-knot nematodes by expressing Bt nematicidal proteins in root leucoplasts.

Root-knot nematodes (RKNs) are plant pests that infect the roots of host plants. Bacillus thuringiensis (Bt) nematicidal proteins exhibited toxicity to nematodes. However, the application of nematicidal proteins for plant protection is hampered by the lack of effective delivery systems in transgenic plants. In this study, we discovered the accumulation of leucoplasts (root plastids) in galls and RKN-induced giant cells. RKN infection causes the degradation of leucoplasts into small vesicle-like structures, which are responsible for delivering proteins to RKNs, as observed through confocal microscopy and immunoelectron microscopy. We showed that different-sized proteins from leucoplasts could be taken up by Meloidogyne incognita female. To further explore the potential applications of leucoplasts, we introduced the Bt crystal protein Cry5Ba2 into tobacco and tomato leucoplasts by fusing it with a transit peptide. The transgenic plants showed significant resistance to RKNs. Intriguingly, RKN females preferentially took up Cry5Ba2 protein when delivered through plastids rather than the cytosol. The decrease in progeny was positively correlated with the delivery efficiency of the nematicidal protein. In conclusion, this study offers new insights into the feeding behavior of RKNs and their ability to ingest leucoplast proteins, and demonstrates that root leucoplasts can be used for delivering nematicidal proteins, thereby offering a promising approach for nematode control.

The significance of recurrent de novo amino acid substitutions that emerged during chronic SARS-CoV-2 infection: an observational study.

BACKGROUND: De novo amino acid substitutions (DNS) frequently emerge among immunocompromised patients with chronic SARS-CoV-2 infection. While previous studies have reported these DNS, their significance has not been systematically studied. METHODS: We performed a review of DNS that emerged during chronic SARS-CoV-2 infection. We searched PubMed until June 2023 using the keywords "(SARS-CoV-2 or COVID-19) and (mutation or sequencing) and ((prolonged infection) or (chronic infection) or (long term))". We included patients with chronic SARS-CoV-2 infection who had SARS-CoV-2 sequencing performed for at least 3 time points over at least 60 days. We also included 4 additional SARS-CoV-2 patients with chronic infection of our hospital not reported previously. We determined recurrent DNS that has appeared in multiple patients and determined the significance of these mutations among epidemiologically-significant variants. FINDINGS: A total of 34 cases were analyzed, including 30 that were published previously and 4 from our hospital. Twenty two DNS appeared in ≥3 patients, with 14 (64%) belonging to lineage-defining mutations (LDMs) of epidemiologically-significant variants and 10 (45%) emerging among chronically-infected patients before the appearance of the corresponding variant. Notably, nsp9-T35I substitution (Orf1a T4175I) emerged in all three patients with BA.2.2 infection in 2022 before the appearance of Variants of Interest that carry nsp9-T35I as LDM (EG.5 and BA.2.86/JN.1). Structural analysis suggests that nsp9-T35I substitution may affect nsp9-nsp12 interaction, which could be critical for the function of the replication and transcription complex. INTERPRETATION: DNS that emerges recurrently in different chronically-infected patients may be used as a marker for potential epidemiologically-significant variants. FUNDING: Theme-Based Research Scheme [T11/709/21-N] of the Research Grants Council (See acknowledgements for full list).

Colorimetric IPN hydrogels embedded with colloidal photonic crystals: A novel approach for the detection of ethanol and Ba2+ ions in water.

A critical bottleneck in sensor technology is the rapid and precise detection of specific analytes in complex matrices, hindering advancements in environmental monitoring, healthcare, and industrial process control. This study addresses this challenge by introducing a novel composite hydrogel sensor designed for rapid and selective detection of ethanol and barium ions (Ba2+) in aqueous environments. The sensor integrates interpenetrating network (IPN) hydrogels with embedded colloidal photonic crystals (CPCs), synthesized via a solution-based polymerization approach. This innovative configuration allows CPCs to dynamically adjust their photonic bandgap in response to environmental changes, manifesting as a visible, colorimetric shift. This response stems from the synergy between the mechanical properties of the IPN hydrogel and the optical sensitivity of CPCs. Upon exposure to analytes such as ethanol and Ba2+, the sensor exhibits a rapid and reversible color transition that is directly proportional to their concentration. Notably, ethanol (0 vol%-80 vol%) and Ba2+ (5-17.5 mM) induce a distinct blueshift in the photonic bandgap and trigger a color change from red-orange to green due to the alteration in the swelling behavior of the IPN hydrogel, affecting its lattice constant. The IPN hydrogel-CPC composite demonstrates exceptional operational stability and facilitates rapid detection, making it ideal for on-site applications without the need for complex equipment. These characteristics make the composite hydrogel sensor a promising candidate for environmental monitoring, industrial process control, and public health diagnostics, paving the way for the development of next-generation responsive sensor materials.

Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity-IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

BACKGROUND: Assessing variant-specific COVID-19 vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages. METHODS: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. RESULTS: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. CONCLUSIONS: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB.

Clinical Evaluation of the Accuracy of the Panbio™ COVID-19/Flu A&B Rapid Panel: A Combination Antigen Rapid Diagnostic Test for the Omicron Variant and Influenza A Virus.

It is difficult to differentiate between coronavirus disease 2019 (COVID-19) and influenza based on the symptoms. In the present study, a newly developed antigen rapid diagnostic test (Ag-RDT) called Panbio™ COVID-19/Flu A&B that can simultaneously detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A/B virus was evaluated. Its accuracy was evaluated using 235 pairs of nasopharyngeal samples collected from patients with respiratory symptoms and fever (>37.5°C). Reverse transcription polymerase chain reaction was used as a reference method to evaluate the accuracy of the SARS-CoV-2 detection. We confirmed the accuracy of the developed Ag-RDT against the Omicron variant where the sensitivity and specificity were 94.8% and 100%, respectively. In addition, to identify the influenza A virus, a noninferiority test was conducted using a commercial Ag-RDT, which has a sensitivity and specificity in comparison with viral culture of 94.8% and 98.4%, respectively. The positive and negative predictive values for influenza A virus were 98.5% and 98.1%, respectively, for the Panbio COVID-19/Flu A&B test. The evaluation of this newly developed Ag-RDT using clinical samples suggests that it has a high efficacy in clinical settings.

Spike structures, receptor binding, and immune escape of recently circulating SARS-CoV-2 Omicron BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 sub-variants.

The recently emerged BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 variants have a growth advantage. In this study, we explore the structural bases of receptor binding and immune evasion for the Omicron BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 sub-variants. Our findings reveal that BA.2.86 exhibits strong receptor binding, whereas its JN.1 sub-lineage displays a decreased binding affinity to human ACE2 (hACE2). Through complex structure analyses, we observed that the reversion of R493Q in BA.2.86 receptor binding domain (RBD) plays a facilitating role in receptor binding, while the L455S substitution in JN.1 RBD restores optimal affinity. Furthermore, the structure of monoclonal antibody (mAb) S309 complexed with BA.2.86 RBD highlights the importance of the K356T mutation, which brings a new N-glycosylation motif, altering the binding pattern of mAbs belonging to RBD-5 represented by S309. These findings emphasize the importance of closely monitoring BA.2.86 and its sub-lineages to prevent another wave of SARS-CoV-2 infections.

Characteristics and outcomes of patients with COVID-19 at high risk of disease progression receiving sotrovimab, oral antivirals, or no treatment: a retrospective cohort study.

BACKGROUND: The clinical benefit of coronavirus disease 2019 (COVID-19) treatments against new circulating variants remains unclear. We sought to describe characteristics and clinical outcomes of highest risk patients with COVID-19 receiving early COVID-19 treatments in Scotland. METHODS: Retrospective cohort study of non-hospitalized patients diagnosed with COVID-19 from December 1, 2021-October 25, 2022, using Scottish administrative health data. We included adult patients who met ≥ 1 of the National Health Service highest risk criteria for early COVID-19 treatment and received outpatient treatment with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or no early COVID-19 treatment. Index date was defined as the earliest of COVID-19 diagnosis or early COVID-19 treatment. Baseline characteristics and acute clinical outcomes in the 28 days following index were reported. Values of ≤ 5 were suppressed. RESULTS: In total, 2548 patients were included (492: sotrovimab, 276: nirmatrelvir/ritonavir, 71: molnupiravir, and 1709: eligible highest risk untreated). Patients aged ≥ 75 years accounted for 6.9% (n = 34/492), 21.0% (n = 58/276), 16.9% (n = 12/71) and 13.2% (n = 225/1709) of the cohorts, respectively. Advanced renal disease was reported in 6.7% (n = 33/492) of sotrovimab-treated and 4.7% (n = 81/1709) of untreated patients, and ≤ 5 nirmatrelvir/ritonavir-treated and molnupiravir-treated patients. All-cause hospitalizations were experienced by 5.3% (n = 25/476) of sotrovimab-treated patients, 6.9% (n = 12/175) of nirmatrelvir/ritonavir-treated patients, ≤ 5 (suppressed number) molnupiravir-treated patients and 13.3% (n = 216/1622) of untreated patients. There were no deaths in the treated cohorts; mortality was 4.3% (n = 70/1622) among untreated patients. CONCLUSIONS: Sotrovimab was often used by patients who were aged < 75 years. Among patients receiving early COVID-19 treatment, proportions of 28-day all-cause hospitalization and death were low.

Immunogenicity of the Monovalent Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine against XBB.1.5, BA.2.86, and JN.1 Sublineages: A Phase 2/3 Trial.

We report neutralization titer data against contemporary SARS-CoV-2 sublineages from an ongoing, phase 2/3, open-label, clinical trial of a single dose (30 µg) of an Omicron XBB.1.5-adapted BNT162b2 monovalent mRNA vaccine. The trial included healthy participants who had received at least three previous doses of an mRNA vaccine authorized in the United States, with the most recent authorized vaccine dose being a bivalent Omicron BA.4/BA.5-adapted vaccine given at least 150 days before the study vaccination. In this analysis, Omicron XBB.1.5, BA.2.86, and JN.1 serum neutralizing titers were assessed at baseline and at 1 month after vaccination. Analyses were conducted in a subset of participants who were at least 18 years of age (N = 40) and who had evidence of previous SARS-CoV-2 infection. Immunogenicity was also evaluated in a group of participants who received bivalent BA.4/BA.5-adapted BNT162b2 in another study (ClinicalTrials.gov Identifier: NCT05472038) and who were matched demographically to the participants in the current trial. In this analysis, monovalent XBB.1.5-adapted BNT162b2 vaccine elicited higher XBB.1.5, BA.2.86, and JN.1 neutralizing titers than those elicited by bivalent BA.4/BA.5-adapted BNT162b2. Overall geometric mean fold rises in neutralizing titers from baseline to 1 month after vaccination were higher among participants who received XBB.1.5-adapted BNT162b2 than those who received bivalent BA.4/BA.5-adapted BNT162b2 for XBB.1.5 (7.6 vs. 5.6), slightly higher for JN.1 (3.9 vs. 3.5), and similar for BA.2.86 (4.8 vs. 4.9). ClinicalTrials.gov Identifier: NCT05997290.

Systemic and Mucosal Immunogenicity of Monovalent XBB.1.5-Adapted COVID-19 mRNA Vaccines in Patients with Inflammatory Bowel Disease.

Recently updated COVID-19 mRNA vaccines encode the spike protein of the omicron subvariant XBB.1.5 and are recommended for patients with inflammatory bowel disease (IBD) on immunosuppressive treatment. Nonetheless, their immunogenicity in patients with IBD against rapidly expanding virus variants remains unknown. This prospective multicenter cohort study is the first study to investigate the immunogenicity of XBB.1.5-adapted vaccines in patients with IBD. Systemic and mucosal antibodies targeting the receptor-binding domains (RBDs) of the omicron subvariants XBB.1.5, EG.5.1, and BA.2.86, as well as their neutralization were quantified before and two to four weeks after vaccination with monovalent XBB.1.5-adapted mRNA vaccines. Vaccination increased levels of serum anti-RBD IgG targeting XBB.1.5, EG.5.1, and BA.2.86 (1.9-fold, 1.8-fold, and 2.6-fold, respectively) and enhanced corresponding neutralization responses (2.3-fold, 3.1-fold, and 3.5-fold, respectively). Following vaccination, anti-TNF-treated patients had reduced virus neutralization compared to patients on treatments with other cellular targets. 11.1% and 16.7% of patients lacked EG.5.1 and BA.2.86 neutralization, respectively; all these patients received anti-TNF treatment. At mucosal sites, vaccination induced variant-specific anti-RBD IgG but failed to induce RBD-targeting IgA. Our findings provide a basis for future vaccine recommendations while highlighting the importance of frequent booster vaccine adaptation and the need for mucosal vaccination strategies in patients with IBD.

Characteristics and outcomes of patients treated with sotrovimab to prevent progression to severe COVID-19 in Belgium.

OBJECTIVE: Sotrovimab, a dual-action, engineered human monoclonal antibody, has been demonstrated to significantly reduce the risk of hospitalisation and death in high-risk patients with COVID-19. Here, we describe the real-world use of, and outcomes from, sotrovimab treatment in Belgium during the Delta and Omicron waves among patients with COVID-19 at high risk of developing severe disease. METHODS: This was a multicentric, single-arm observational cohort study of non-hospitalised patients receiving outpatient sotrovimab treatment between 1 November 2021 and 2 August 2022 at nine hospitals in Belgium. The primary outcomes were all-cause and COVID-19-related hospitalisations and all-cause deaths during the 29-day acute follow-up period from first administration of sotrovimab. RESULTS: A total of 634 patients were included (63.4% aged < 65 years; 50.3% male). A high proportion (67.7%; n = 429/634) of patients were immunocompromised, with 36.9% (n = 234/634) actively treated for malignancy. During the 29-day acute period, 12.5% (n = 79/634) of sotrovimab-treated patients were hospitalised due to any cause (median duration 4 days; median time to hospitalisation 14 days) and 1.1% (n = 7/634) died due to any cause. The proportion of sotrovimab-treated patients experiencing COVID-19-related hospitalisation was highest during the Delta predominance and Delta/BA.1 codominance (both 6.3%) periods. During the BA.1 predominance, BA.1/BA.2 codominance and BA.2/BA.5 codominance periods, COVID-19-related hospitalisations were consistently low (all ≤2.7%). CONCLUSION: This study indicated low rates of COVID-19-related hospitalisations and all-cause deaths in sotrovimab-treated patients in Belgium, including during Omicron subvariant periods, despite over two-thirds of the study population being immunocompromised.

JN.1 and the ongoing battle: unpacking the characteristics of a new dominant COVID-19 variant.

In the fourth year of the COVID-19 occurrence, a new COVID-19 variant, JN.1, has emerged and spread globally and become the dominant strain in several regions. It has some specific mutations in its spike proteins, empowering it with higher transmissibility. Regarding the significance of the issue, understanding the clinical and immunological traits of JN.1 is critical for enhancing health strategies and vaccination efforts globally, with the ultimate goal of bolstering our collective response to the pandemic. In this study, we take a look at the latest findings of JN.1 characteristics and mutations as well as its consequences on bypassing immune system. We demonstrate the importance of continual surveillance and strategic adaptation within healthcare frameworks along with the significance of wastewater sampling for the rapid identification of emerging SARS-CoV-2 variants.