Emerging Invasive Group A Streptococcus M1UK Lineage Detected by Allele-Specific PCR, England, 20201.

Increasing reports of invasive Streptococcus pyogenes infections mandate surveillance for toxigenic lineage M1UK. An allele-specific PCR was developed to distinguish M1UK from other emm1 strains. The M1UK lineage represented 91% of invasive emm1 isolates in England in 2020. Allele-specific PCR will permit surveillance for M1UK without need for genome sequencing.

SARS-CoV-2 Omicron variants: burden of disease, impact on vaccine effectiveness and need for variant-adapted vaccines.

The highly transmissible Omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in late 2021. Initial Omicron waves were primarily made up of sub-lineages BA.1 and/or BA.2, BA.4, and BA.5 subsequently became dominant in mid-2022, and several descendants of these sub-lineages have since emerged. Omicron infections have generally caused less severe disease on average than those caused by earlier variants of concern in healthy adult populations, at least, in part, due to increased population immunity. Nevertheless, healthcare systems in many countries, particularly those with low population immunity, have been overwhelmed by unprecedented surges in disease prevalence during Omicron waves. Pediatric admissions were also higher during Omicron waves compared with waves of previous variants of concern. All Omicron sub-lineages exhibit partial escape from wild-type (Wuhan-Hu 1) spike-based vaccine-elicited neutralizing antibodies, with sub-lineages with more enhanced immuno-evasive properties emerging over time. Evaluating vaccine effectiveness (VE) against Omicron sub-lineages has become challenging against a complex background of varying vaccine coverage, vaccine platforms, prior infection rates, and hybrid immunity. Original messenger RNA vaccine booster doses substantially improved VE against BA.1 or BA.2 symptomatic disease. However, protection against symptomatic disease waned, with reductions detected from 2 months after booster administration. While original vaccine-elicited CD8+ and CD4+ T-cell responses cross-recognize Omicron sub-lineages, thereby retaining protection against severe outcomes, variant-adapted vaccines are required to expand the breadth of B-cell responses and improve durability of protection. Variant-adapted vaccines were rolled out in late 2022 to increase overall protection against symptomatic and severe infections caused by Omicron sub-lineages and antigenically aligned variants with enhanced immune escape mechanisms.

Genomic surveillance of severe acute respiratory syndrome coronavirus 2 in Burundi, from May 2021 to January 2022.

BACKGROUND: The emergence and rapid spread of new severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) variants have challenged the control of the COVID-19 pandemic globally. Burundi was not spared by that pandemic, but the genetic diversity, evolution, and epidemiology of those variants in the country remained poorly understood. The present study sought to investigate the role of different SARS-COV-2 variants in the successive COVID-19 waves experienced in Burundi and the impact of their evolution on the course of that pandemic. We conducted a cross-sectional descriptive study using positive SARS-COV-2 samples for genomic sequencing. Subsequently, we performed statistical and bioinformatics analyses of the genome sequences in light of available metadata. RESULTS: In total, we documented 27 PANGO lineages of which BA.1, B.1.617.2, AY.46, AY.122, and BA.1.1, all VOCs, accounted for 83.15% of all the genomes isolated in Burundi from May 2021 to January 2022. Delta (B.1.617.2) and its descendants predominated the peak observed in July-October 2021. It replaced the previously predominant B.1.351 lineage. It was itself subsequently replaced by Omicron (B.1.1.529, BA.1, and BA.1.1). Furthermore, we identified amino acid mutations including E484K, D614G, and L452R known to increase infectivity and immune escape in the spike proteins of Delta and Omicron variants isolated in Burundi. The SARS-COV-2 genomes from imported and community-detected cases were genetically closely related. CONCLUSION: The global emergence of SARS-COV-2 VOCs and their subsequent introductions in Burundi was accompanied by new peaks (waves) of COVID-19. The relaxation of travel restrictions and the mutations occurring in the virus genome played an important role in the introduction and the spread of new SARS-COV-2 variants in the country. It is of utmost importance to strengthen the genomic surveillance of SARS-COV-2, enhance the protection by increasing the SARS-COV-2 vaccine coverage, and adjust the public health and social measures ahead of the emergence or introduction of new SARS-COV-2 VOCs in the country.

An inducible hACE2 transgenic mouse model recapitulates SARS-CoV-2 infection and pathogenesis in vivo.

The classical manifestation of COVID-19 is pulmonary infection. After host cell entry via human angiotensin-converting enzyme II (hACE2), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can infect pulmonary epithelial cells, especially the AT2 (alveolar type II) cells that are crucial for maintaining normal lung function. However, previous hACE2 transgenic models have failed to specifically and efficiently target the cell types that express hACE2 in humans, especially AT2 cells. In this study, we report an inducible, transgenic hACE2 mouse line and showcase three examples for specifically expressing hACE2 in three different lung epithelial cells, including AT2 cells, club cells, and ciliated cells. Moreover, all these mice models develop severe pneumonia after SARS-CoV-2 infection. This study demonstrates that the hACE2 model can be used to precisely study any cell type of interest with regard to COVID-19-related pathologies.

British Society for Rheumatology Annual Conference 2023 Abstracts

The proceedings contain 343 papers. The topics discussed include: implementation of a disease modifying anti-rheumatic drug blood monitoring software: 8 years of experience in a single center;effectiveness of colchicine among patients with COVID-19 infection: a randomized, open labelled, clinical trial;rheumatic autoimmune diseases following COVID-19 infection: an observational study in Iraqi Kurdistan region;COVID-19 in male elite Irish-based athletes at a national sports institute;the effects of a pain management program for patients with an inflammatory arthritis;a retrospective analysis of the effectiveness safety of platelet rich plasma injections in primary osteoarthritis in knee joint, in patients attending a tertiary care hospital, Sri Lanka;a cohort study;do proformas used in fracture liaison service appointments reflect national osteoporosis clinical standards? a content analysis;calcium pyrophosphate dihydrate crystal in operated rheumatoid arthritis of the knee;cardiac amyloidosis: a case series of 31 patients with a comprehensive literature review;scoping review for the application of center of pressure for patient or intervention assessment in rheumatoid conditions;and four SNPs associated with monocyte/macrophage cell lineage uniquely associated with CRPS-1 in discovery and replication cohorts and suggest predisposition to regional osteopenia and digit misperception.

PHASE 1 CLINICAL TRIALS OF A Q-GRIFFITHSIN NASAL SPRAY FOR SARS-CoV-2 PROPHYLAXIS

Background: The currently approved vaccines do not induce sterilizing immunity against SAR-CoV-2 infection, and immunity wanes over time. A robust broad spectrum topical prophylaxis strategy could protect vulnerable populations in the face of continuous evolution of SARS-CoV-2. The algal antiviral lectin Griffithsin (GRFT), and an engineered oxidation-resistant variant Q-GRFT have robust entry inhibitory activity against SARS-CoV variants of concern, in addition to other respiratory viruses with pandemic potential. We designed a nasal spray to deliver Q-GRFT to the upper respiratory tract mucosa for on-demand use as a broad-spectrum prophylactic. Two clinical trials (Phase 1a and 1b) were conducted to assess safety, tolerability, and pharmacokinetics of Q-GRFT nasal spray in healthy adults. Method(s): Healthy adult volunteers were enrolled in a Phase 1a double blinded, randomized study to receive a single dose of either intranasal Q-GRFT (3.0 mg, 2 sprays per nostril) or placebo at 2:1 ratio. Following a safety review, the Phase 1b study was initiated. Eleven volunteers in Group 1 received 3.0 mg dose once daily, for 7 days. After a safety review, 11 volunteers in Group 2 received a total of 6.0 mg Q-GRFT (3.0 mg twice daily for 7 days). Topical Q-GRFT concentrations were measured by ELISA in collected nasal and nasopharyngeal fluids. Drug levels in plasma were assayed to determine systemic exposure. Viral microneutralization cytopathic effect (CPE) assays were performed against SARS-CoV-2 Omicron BA-5 and MERS-CoV. Result(s): Eighteen adults (24-54 years;Males 58.3%, Females 41.7%;12 Q-GRFT, 6 Placebo), and 22 adults (aged 23-59 years;Males 52.4%, Females 47.6%) were enrolled in Phase 1a and 1b, respectively. In Phase 1a, a single dose of Q-GRFT maintained quantifiable levels in nasal passages and nasopharynx for up to 24 hours. Similarly, Q-GRFT was quantifiable in nasal and nasopharyngeal regions in the Phase 1b study. No dose accumulation effect or systemic exposure was observed. Nasal and nasopharyngeal swab eluates inhibited SARS-CoV-2 Omicron BA.5 and MERS-CoV in CPE assays. Q-GRFT did not modify olfactory sensation. No severe adverse events were reported. Thus, the nasal spray was deemed safe. Conclusion(s): Intranasal Q-GRFT was safe and enhanced mucosal SARSCoV-2 inhibitory activity in human volunteers. The results support further development of Q-GRFT as a broad-spectrum prophylactic against coronaviruses to curb ongoing infections, and for future pandemic preparedness.

West Nile virus infections in Hungary: Epidemiological update and phylogenetic analysis of the Hungarian virus strains between 2015 and 2022.

Following the introduction of the West Nile virus (WNV) into Hungary in 2004, it has shortly become one of the most important human arbovirus infections, with a gradually increasing number of cases. The study aimed to summarize the current epidemiological situation in Hungary and sequence the WNV PCR-positive clinical specimens and virus isolates by next-generation whole genome sequencing (NGS) to obtain a detailed phylogenetic analysis of the circulating virus strains. Whole blood and urine samples from confirmed WNV-infected patients and WNV isolates were investigated by reverse transcription PCR assays. Genome sequencing was carried out by Sanger-method, followed by NGS on the Illumina MiSeq platform. Altogether 499 human infections were diagnosed between 2004 and 2022. A particularly remarkable increase in human WNV infections was observed in 2018, while the number of reported cases significantly decreased during the COVID-19 pandemic. Between 2015 and 2022, 15 WNV isolates, and 10 PCR-positive clinical specimens were investigated by NGS. Phylogenetic analysis revealed that the major European WNV lineage 2 clades, namely the Eastern European (or Russian) and the Central European (or Hungarian) clades, are presented in Hungary. Strains of the Balkan and other European clusters within the Central European clade are co-circulating in the country, following a characteristic geographical distribution. In Hungary, the presence and co-circulation of multiple lineage 2 WNV strains could be identified in the last few years. Therefore, in light of the 2018 WNV outbreak, sequence-based typing of the currently circulating strains could highly support outbreak investigations.

Pathogenicity evaluation of GVI-1 lineage infectious bronchitis virus and its long-term effects on reproductive system development in SPF hens.

Infectious bronchitis virus (IBV) has gained increasing attention in the poultry industry due to its ability to cause tissue injuries not only in the respiratory system and kidney but also in the reproductive system of layers. Recently, the GVI-1 lineage IBVs have spread widely in China, whereas their pathogenicity in egg-laying chickens has rarely been studied, especially its long-term influence in egg production upon the early infection in chicks. In this study, 10-day-old SPF chicks were infected with the GVI-1 lineage JX181 strain and monitored over a 170-day period after infection. The pathogenicity evaluation of the JX181 strain included clinical observations, immunohistochemical assay, viral load, viral shedding, gross autopsy, and laying rate. The results showed that JX181 has a high pathogenicity, causing severe system lesions, and the decrease in egg production. In summary, this study describes the long-term damages caused by the early infection with the IBV GVI-1 lineage on the reproductive system of hens, providing a comprehensive understanding of the pathogenicity of the IBV GVI-1 lineage and emphasizing the importance of its early prevention.

Analyzing and Comparing Omicron Lineage Variants Protein-Protein Interaction Network Using Centrality Measure.

The Worldwide spread of the Omicron lineage variants has now been confirmed. It is crucial to understand the process of cellular life and to discover new drugs need to identify the important proteins in a protein interaction network (PPIN). PPINs are often represented by graphs in bioinformatics, which describe cell processes. There are some proteins that have significant influences on these tissues, and which play a crucial role in regulating them. The discovery of new drugs is aided by the study of significant proteins. These significant proteins can be found by reducing the graph and using graph analysis. Studies examining protein interactions in the Omicron lineage (B.1.1.529) and its variants (BA.5, BA.4, BA.3, BA.2, BA.1.1, BA.1) are not yet available. Studying Omicron has been intended to find a significant protein. 68 nodes represent 68 proteins and 52 edges represent the relationship among the protein in the network. A few centrality measures are computed namely page rank centrality (PRC), degree centrality (DC), closeness centrality (CC), and betweenness centrality (BC) together with node degree and Local clustering coefficient (LCC). We also discover 18 network clusters using Markov clustering. 8 significant proteins (candidate gene of Omicron lineage variants) were detected among the 68 proteins, including AHSG, KCNK1, KCNQ1, MAPT, NR1H4, PSMC2, PTPN11 and, UBE21 which scored the highest among the Omicron proteins. It is found that in the variant of Omicron protein-protein interaction networks, the MAPT protein's impact is the most significant.

Phylogenetic Changes in SARS-CoV-2 Virus in Bosnian-Herzegovinian Population Over the Period of Two Years.

Background: All viral genomes, including the SARS-CoV-2 virus, mutate over time, and some of these mutations can affect the characteristics of the virus, such as the ease of spread, the severity of the patient's clinical picture, or the effect of vaccines, therapeutic drugs, diagnostic tools or other measures of public health and social protection. Because of all the above, it is imperative to carry out continuous sequencing of this pathogen. Objective: The main goal of this research was to obtain the highest quality genomic sequences of the SARS-CoV-2 virus, to compare the obtained sequences with the reference Wuhan-Hu-1 sequence and to obtain a high-quality genomic alignment in order to reconstruct the appropriate phylogenetic tree. Methods: For the purposes of this research, a next-generation semiconductor sequencing method was chosen. In this research, a total of 47 samples of nasopharyngeal and oropharyngeal swabs from patients from the human population of Bosnia and Herzegovina with a clinical diagnosis of COVID-19 were collected. Results: In the processed 47 samples, there are several monophyletic groups on the constructed phylogenetic tree, of which one sample belongs to the same monophyletic group as the Wuhan-Hu-1 reference sequence. Conclusion: The greater number of samples is needed for a more comprehensive approach. Therefore, the results of this research can act as a guideline for the design of effective measures and strategies in order to solve problems regarding future pandemics as efficiently as possible.

SARS-CoV-2 Neutralizing Antibodies to B.1 and to BA.5 Variant after Booster Dose of BNT162b2 Vaccine in HIV Patients COVID-Naïve and on Successful Antiretroviral Therapy.

Live virus neutralization is the gold standard to investigate immunity. This prospective observational study aimed to determine the magnitude of response against the original B.1 lineage and against the BA.5 lineage six months after the third BNT162b2 mRNA vaccine dose in patients with HIV infection on successful antiretroviral treatment and no previous SARS-CoV-2 infection. A total of 100 subjects (M/F 83/17, median age 54 years) were included in the analysis: 95 had plasma HIV RNA <40 copies/mL, the median CD4+ T cell count at the administration of the third dose was 580 cells/mm3, and the median nadir CD4+ T cell count was 258 cells/mm3. Neutralizing antibodies (NtAb) against B.1 were detectable in all the subjects, but those to BA.5 were only detected in 88 (p < 0.001). The median NtAb titer to B.1 was significantly higher than that to BA.5 (393 vs. 60, p < 0.0001), and there was a strong positive correlation between the paired measurements (p < 0.0001). Linear regression on a subset of 87 patients excluding outlier NtAb titers showed that 48% of the changes in NtAb titers to BA.5 are related to the changes in value titers to B.1. SARS-CoV-2 variants evolve rapidly, challenging the efficacy of vaccines, and data on comparative NtAb responses may help in tailoring intervals between vaccine doses and in predicting vaccine efficacy.

CoVe-Tracker: An Interactive SARS-CoV-2 Pan Proteome Evolution Tracker.

SARS-CoV-2 has significantly mutated its genome during the past 3 years, leading to the periodic emergence of several variants. Some of the variants possess enhanced fitness advantage, transmissibility, and pathogenicity and can also reduce vaccine efficacy. Thus, it is important to track the viral evolution to prevent and protect the mankind from SARS-CoV-2 infection. To this end, an interactive web-GUI platform, namely, CoVe-tracker (SARS-CoV-2 evolution tracker), is developed to track its pan proteome evolutionary dynamics (https://project.iith.ac.in/cove-tracker/). CoVe-tracker provides an opportunity for the user to fetch the country-wise and protein-wise amino acid mutations (currently, 44139) of SARS-CoV-2 and their month-wise distribution. It also provides position-wise evolution observed in the SARS-CoV-2 proteome. Importantly, CoVe-tracker provides month- and country-wise distributions of 2065 phylogenetic assignment of named global outbreak (PANGO) lineages and their 177564 variants. It further provides periodic updates on SARS-CoV-2 variant(s) evolution. CoVe-tracker provides the results in a user-friendly interactive fashion by projecting the results onto the world map (for country-wise distribution) and protein 3D structure (for protein-wise mutation). The application of CoVe-tracker in tracking the closest cousin(s) of a variant is demonstrated by considering BA.4 and BA.5 PANGO lineages as test cases. Thus, CoVe-tracker would be useful in the quick surveillance of newly emerging mutations/variants/lineages to facilitate the understanding of viral evolution, transmission, and disease epidemiology.

Temporal dynamics and fatality of SARS-CoV-2 variants in Bangladesh.

Background and Aims: Since the beginning of the SARS-CoV-2 pandemic, multiple new variants have emerged posing an increased risk to global public health. This study aimed to investigate SARS-CoV-2 variants, their temporal dynamics, infection rate (IFR) and case fatality rate (CFR) in Bangladesh by analyzing the published genomes. Methods: We retrieved 6610 complete whole genome sequences of the SARS-CoV-2 from the GISAID (Global Initiative on Sharing all Influenza Data) platform from March 2020 to October 2022, and performed different in-silico bioinformatics analyses. The clade and Pango lineages were assigned by using Nextclade v2.8.1. SARS-CoV-2 infections and fatality data were collected from the Institute of Epidemiology Disease Control and Research (IEDCR), Bangladesh. The average IFR was calculated from the monthly COVID-19 cases and population size while average CFR was calculated from the number of monthly deaths and number of confirmed COVID-19 cases. Results: SARS-CoV-2 first emerged in Bangladesh on March 3, 2020 and created three pandemic waves so far. The phylogenetic analysis revealed multiple introductions of SARS-CoV-2 variant(s) into Bangladesh with at least 22 Nextstrain clades and 107 Pangolin lineages with respect to the SARS-CoV-2 reference genome of Wuhan/Hu-1/2019. The Delta variant was detected as the most predominant (48.06%) variant followed by Omicron (27.88%), Beta (7.65%), Alpha (1.56%), Eta (0.33%) and Gamma (0.03%) variant. The overall IFR and CFR from circulating variants were 13.59% and 1.45%, respectively. A time-dependent monthly analysis showed significant variations in the IFR (p = 0.012, Kruskal-Wallis test) and CFR (p = 0.032, Kruskal-Wallis test) throughout the study period. We found the highest IFR (14.35%) in 2020 while Delta (20A) and Beta (20H) variants were circulating in Bangladesh. Remarkably, the highest CFR (1.91%) from SARS-CoV-2 variants was recorded in 2021. Conclusion: Our findings highlight the importance of genomic surveillance for careful monitoring of variants of concern emergence to interpret correctly their relative IFR and CFR, and thus, for implementation of strengthened public health and social measures to control the spread of the virus. Furthermore, the results of the present study may provide important context for sequence-based inference in SARS-CoV-2 variant(s) evolution and clinical epidemiology beyond Bangladesh.

Prediction models for neutralization activity against emerging SARS-CoV-2 variants: A cross-sectional study.

Objective: Despite extensive vaccination campaigns to combat the coronavirus disease (COVID-19) pandemic, variants of concern, particularly the Omicron variant (B.1.1.529 or BA.1), may escape the antibodies elicited by vaccination against SARS-CoV-2. Therefore, this study aimed to evaluate 50% neutralizing activity (NT50) against SARS-CoV-2 D614G, Delta, Omicron BA.1, and Omicron BA.2 and to develop prediction models to predict the risk of infection in a general population in Japan. Methods: We used a random 10% of samples from 1,277 participants in a population-based cross-sectional survey conducted in January and February 2022 in Yokohama City, the most populous municipality in Japan. We measured NT50 against D614G as a reference and three variants (Delta, Omicron BA.1, and BA.2) and immunoglobulin G against SARS-CoV-2 spike protein (SP-IgG). Results: Among 123 participants aged 20-74, 93% had received two doses of SARS-CoV-2 vaccine. The geometric means (95% confidence intervals) of NT50 were 65.5 (51.8-82.8) for D614G, 34.3 (27.1-43.4) for Delta, 14.9 (12.2-18.0) for Omicron BA.1, and 12.9 (11.3-14.7) for Omicron BA.2. The prediction model with SP-IgG titers for Omicron BA.1 performed better than the model for Omicron BA.2 (bias-corrected R 2 with bootstrapping: 0.721 vs. 0.588). The models also performed better for BA.1 than for BA.2 (R 2 = 0.850 vs. 0.150) in a validation study with 20 independent samples. Conclusion: In a general Japanese population with 93% of the population vaccinated with two doses of SARS-CoV-2 vaccine, neutralizing activity against Omicron BA.1 and BA.2 were substantially lower than those against D614G or the Delta variant. The prediction models for Omicron BA.1 and BA.2 showed moderate predictive ability and the model for BA.1 performed well in validation data.

Reinfection rate and disease severity of the BA.5 Omicron SARS-CoV-2 lineage compared to previously circulating variants of concern in the Canary Islands (Spain).

ABSTRACTThe emergence of the Omicron SARS-CoV-2 variant of concern has changed the COVID-19 scenario as this variant is characterized by high transmissibility and immune evasion ability. To evaluate the impact of this variant on the Canary Islands (Spain) population, we determined the reinfection rates and disease severity associated with the Omicron sublineages and the previously circulating variants of concern. We performed a retrospective observational study on 21,745 SARS-CoV-2 viral genomes collected from December 2020 to July 2022 in the Canary Islands (Spain). We compared the reinfection rates between lineages using pairwise proportion and Fisher's exact tests. To assess disease severity, we studied the association of Alpha, Delta, BA.1, BA.2, BA.5, and other risk factors on 28-day hospital mortality using logistic regression and Cox proportional hazard models. We observed 127 bona fide reinfection cases throughout the study period. We found that BA.5 had the highest reinfection rate compared to other lineages (vs. Delta p = 2.89 × 10-25; vs. BA.1 p = 5.17 × 10-11; vs. BA.2 p = 0.002). Among the 1,094 hospitalized patients, multivariate logistic regression showed that Alpha (Odds Ratio [OR] = 0.45, 95% Confidence Interval [CI] = 0.23-0.87, p = 0.02), BA.2 (OR = 0.38, 95% CI = 0.22-0.63, p = 1.91 × 10-4), and BA.5 (OR = 0.30, 95% CI = 0.16-0.55, p = 1.05 × 10-4) had lower 28-day hospital mortality compared to Delta. These results were confirmed by using Cox proportional hazard models. Omicron lineages, and in particular BA.5, were associated with higher reinfection rates and lower disease severity (28-day hospital mortality) than previously circulating variants of concern.

COVID-19 vaccine-induced neutralising antibody responses against SARS-CoV-2 Omicron BA.4/5 are diminished in patients with inflammatory bowel disease on anti-TNF or JAK-inhibitor therapy

Background: Patients with Inflammatory bowel disease (IBD) receiving anti-TNF or JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the currently dominant Omicron BA.4/5 variants. Method(s): We prospectively recruited 329 adults (68 healthy controls (HC) and 261 IBD) who had received three doses of COVID-19 vaccine at nine UK centres. The IBD population was established (>12 weeks therapy) on either thiopurine (n=60), infliximab (IFX) (n=43), thiopurine and IFX combination (n=46), ustekinumab (n=43), vedolizumab (n=46) or tofacitinib (n=23). Pseudoneutralisation assays were performed and the half maximal inhibitory concentration (NT50) of participant sera was calculated. The primary outcome was anti-SARSCoV-2 neutralising response against wild-type (WT) virus and the BA.4/5 variant after the second and third doses of anti-SARS-CoV-2 vaccine, stratified by immunosuppressive therapy, adjusting for prior infection, ethnicity, vaccine type and age. Result(s): Heterologous (two doses adenovirus vaccine, third dose mRNA vaccine) and homologous (three doses mRNA vaccine) vaccination strategies significantly increased neutralising titres against both WT SARS-CoV-2 virus and the BA.4/5 variants in HCs and IBD (fig 1). Antibody titres against BA.4/5 were significantly lower than antibodies against WT virus in both groups (Geometric Mean Ratio (GMR) [95% CI], 0.11 [0.09, 0.15], P<0.0001 in healthy participants;GMR 0.07 [0.06, 0.08], P<0.0001 in IBD patients). Multivariable models showed that neutralising antibodies against BA.4/5 after three doses of vaccine were significantly lower in IBD patients on IFX (GMR 0.44 [0.20, 0.97], P=0.042), IFX and thiopurine combination (GMR 0.34 [0.15, 0.77], P=0.0098) or tofacitinib (GMR 0.37 [0.15, 0.92], P=0.032), but not in patients on thiopurine monotherapy, ustekinumab or vedolizumab. Breakthrough infection was associated with lower neutralising antibodies against WT and BA.4/5 (P<0.05). Conclusion(s): A third dose of COVID-19 vaccine based on the WT spike glycoprotein boosts neutralising antibody titres in patients with IBD. However, responses are lower against the currently dominant variant BA.4/5, particularly in patients taking anti-TNF or JAK-inhibitor therapy. Breakthrough infections are associated with lower neutralising antibodies and immunosuppressed IBD patients may receive additional benefit from bivalent vaccine boosters which target Omicron variants. .

Emergence of BA.4/BA.5 Omicron Sub-lineages and Increased SARS-CoV-2 Incidence in Senegal

Background: The Omicron variant B.1.1.529 has led to a new dynamic in the COVID-19 pan-demic, with an increase in cases worldwide. Its rapid propagation favors the emergence of novel sub-lineages, including BA.4 and BA.5. The latter has shown increased transmissibility compared to other Omicron sub-lineages. In Senegal, the emergence of the Omicron variant in December 2021 characterized the triggering of a short and dense epidemiological wave that peaked at the end of February. This wave was followed by a period with a significant drop in the number of COVID-19 cases, but an upsurge in SARS-CoV-2 infection has been noted since mid-June. Objective(s): The purpose of this brief report is to give an update regarding the genomic situation of SARS-CoV-2 in Dakar during this phase of recrudescence of cases. Method(s): We performed amplicon-based SARS-CoV-2 sequencing on nasopharyngeal swab samples from declared COVID-19 patients and outbound travelers that tested positive. Result(s): Ongoing genomic surveillance activities showed that more than half of recent COVID-19 cases were due to the BA.4 and BA.5 sub-lineages that share two critical mutations associated with increased transmissibility and immune response escape. The circulation of recombinants between Omicron sub-lineages was also noted. Conclusion(s): Despite the lack of proven severity of BA.4 and BA.5 sub-lineages, their increased transmis-sibility causes a rapid spread of the virus, hence a surge in the number of cases. This rapid spread consti-tutes a greater risk of exposure for vulnerable patients. To tackle this issue, any increase in the number of cases must be monitored to support public health stakeholders. Therefore, genomic surveillance is an ever-essential element in managing this pandemic.Copyright © 2022 Bentham Science Publishers.