The asymptomatic proportion of SARS-CoV-2 Omicron-variant infections in households: A systematic review (preprint)

Background Understanding the clinical spectrum of SARS-CoV-2 infection, including the asymptomatic fraction, is important as asymptomatic individuals are still able to infect other individuals and contribute to ongoing transmission. The WHO Unity Household transmission investigation (HHTI) protocol provides a platform for the prospective and systematic collection of high-quality clinical, epidemiological, serological, and virological data from SARS-CoV-2 confirmed cases and their household contacts. These data can be used to understand key severity and transmissibility parameters - including the asymptomatic proportion - in relation to local epidemic context and help inform public health response. Methods We aimed to estimate the asymptomatic proportion of SARS-CoV-2 Omicron-variant infections in Unity-aligned HHTIs. We conducted a systematic review and meta-analysis in alignment with the PRISMA 2020 guidelines and registered our systematic review on PROSPERO (CRD42022378648). We searched EMBASE, Web of Science, MEDLINE, and bioRxiv and medRxiv from 1 November 2021 to 22 August 2023. Results We identified 8,368 records, of which 98 underwent full text review. We identified only three studies for data extraction, with substantial variation in study design and corresponding estimates of the asymptomatic proportion. As a result, we did not generate a pooled estimate or I2 metric. Conclusions The limited number of quality studies that we identified highlights the need for improved preparedness and response capabilities to facilitate robust HHTI implementation, analysis and reporting, to better inform national, regional and global risk assessments and policy making.

Effectiveness of the 2023-2024 Omicron XBB.1.5-containing mRNA COVID-19 vaccine (mRNA-1273.815) in preventing COVID-19-related hospitalizations and medical encounters among adults in the United States: An interim analysis (preprint)

Background/ObjectivesCOVID-19 continues to pose a significant burden that impacts public health and the healthcare system as the SARS-CoV-2 virus continues to evolve. Regularly updated vaccines are anticipated to boost waning immunity and provide protection against circulating variants. This study evaluated vaccine effectiveness (VE) of mRNA-1273.815, a 2023-2024 Omicron XBB.1.5-containing mRNA COVID-19 vaccine, at preventing COVID-19-related hospitalizations and any medically attended COVID-19 in adults [≥]18 years, overall, and by age and underlying medical conditions. MethodsThis retrospective cohort study used the Veradigm Network EHR linked to claims data to identify US adults [≥]18 years of age who received the mRNA-1273.815 vaccine (exposed) matched 1:1 to individuals who did not receive a 2023-2024 updated COVID-19 vaccine (unexposed). Patients in the unexposed cohort were randomly matched to eligible mRNA-1273.815 recipients. Inverse probability of treatment weighting was used to adjust for differences between the two cohorts. The exposed cohort was vaccinated between September 12, 2023, and December 15, 2023, and individuals in both cohorts were followed up for COVID-19-related hospitalizations and medically attended COVID-19 until December 31, 2023. A Cox regression model was used to estimate the hazard ratio (HR). VE of the mRNA-1273.815 vaccine in preventing COVID-19-related hospitalizations and any medically attended COVID-19 was estimated as 100*(1-HR). Subgroup analyses were performed for adults [≥]50, adults [≥]65, and individuals with underlying medical conditions associated with severe COVID-19 outcomes. ResultsOverall, 859,335 matched pairs of mRNA-1273.815 recipients and unexposed adults were identified. The mean age was 63 years, and 80% of the study population was [≥]50 years old. 61.5% of the mRNA-1273.815 cohort and 66.4% of the unexposed cohort had an underlying medical condition. Among the overall adult population ([≥]18 years), VE was 60.2% (53.4-66.0%) against COVID-19-related hospitalization and 33.1% (30.2%-35.9%) against medically attended COVID-19 over a median follow-up of 63 (IQR: 44-78) days. VE estimates by age and underlying medical conditions were similar. ConclusionsThese results demonstrate the significant protection provided by mRNA-1273.815 against COVID-19-related hospitalizations and any medically attended COVID-19 in adults 18 years and older, regardless of their vaccination history, and support CDC recommendations for vaccination with the 2023-2024 Omicron XBB.1.5-containing COVID-19 vaccine to prevent COVID-19-related outcomes, including hospitalizations.

Transmission Patterns of Co-Circulation of Omicron Sub-Lineages in Hong Kong SAR, China, a City with Rigorous Social Distancing Measures, in 2022 (preprint)

Objective: The study aimed to characterize the changing landscape of circulating SARS-CoV-2 lineages in the local community of Hong Kong throughout 2022. We examined how adjustments to quarantine arrangements influenced the transmission pattern of Omicron variants in a city with relatively rigorous social distancing measures at that time. Methods: In 2022, a total of 4,684 local SARS-CoV-2 genomes were sequenced using the Oxford Nanopore GridION sequencer. SARS-CoV-2 consensus genomes were generated by MAFFT, and the maximum likelihood phylogeny of these genomes were determined using IQ-TREE. The dynamic changes in lineages were depicted in a time tree created by Nextstrain. Statistical analysis was conducted to assess the correlation between changes in the number of lineages and adjustments to quarantine arrangements. Results: By the end of 2022, a total of 83 SARS-CoV-2 lineages were identified in the community. The increase in the number of new lineages was significantly associated with the relaxation of quarantine arrangements (One-way ANOVA, F(5,47)=18.233, p<0.001)). Over time, Omicron BA.5 sub-lineages replaced BA.2.2 and became the predominant Omicron variants in Hong Kong. The influx of new lineages reshaped the dynamics of Omicron variants in the community without fluctuating the death rate and hospitalization rate (One-way ANOVA, F(5,47)=2.037, p=0.091). Conclusion: The study revealed that even with an extended mandatory quarantine period for incoming travelers, it may not be feasible to completely prevent the introduction and subsequent community spread of highly contagious Omicron variants. Ongoing molecular surveillance of COVID-19 remains essential to monitor the emergence of new recombinant variants.

Ipsilateral or contralateral boosting of mice with mRNA vaccines confers equivalent immunity and protection against a SARS-CoV-2 Omicron strain (preprint)

Boosting with mRNA vaccines encoding variant-matched spike proteins has been implemented to mitigate their reduced efficacy against emerging SARS-CoV-2 variants. Nonetheless, in humans, it remains unclear whether boosting in the ipsilateral or contralateral arm with respect to the priming doses impacts immunity and protection. Here, we boosted K18-hACE2 mice with either monovalent mRNA-1273 (Wuhan-1 spike) or bivalent mRNA-1273.214 (Wuhan-1 + BA.1 spike) vaccine in the ipsilateral or contralateral leg relative to a two-dose priming series with mRNA-1273. Boosting in the ipsilateral or contralateral leg elicited equivalent levels of serum IgG and neutralizing antibody responses against Wuhan-1 and BA.1. While contralateral boosting with mRNA vaccines resulted in expansion of spike-specific B and T cells beyond the ipsilateral draining lymph node (DLN) to the contralateral DLN, administration of a third mRNA vaccine dose at either site resulted in similar levels of antigen-specific germinal center B cells, plasmablasts/plasma cells, T follicular helper cells and CD8+ T cells in the DLNs and the spleen. Furthermore, ipsilateral and contralateral boosting with mRNA-1273 or mRNA-1273.214 vaccines conferred similar homologous or heterologous immune protection against SARS-CoV-2 BA.1 virus challenge with equivalent reductions in viral RNA and infectious virus in the nasal turbinates and lungs. Collectively, our data show limited differences in B and T cell immune responses after ipsilateral and contralateral site boosting by mRNA vaccines that do not substantively impact protection against an Omicron strain.

Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals. (preprint)

Background: SARS-CoV-2 vaccines have been shown to be safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. We performed this study to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. Methods and Findings: We performed a retrospective clinical cohort study utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. Our primary outcome was incidence and time to first positive SARS-CoV-2 molecular test in the Omicron predominant era. We performed multivariable analyses stratified by calendar time using Cox modeling to determine hazard of SARS-CoV-2. In total, 133,191 patients were analyzed. Having 3+ comorbidities was associated with increased hazard for breakthrough (HR=1.2 CI 1.2-1.6). During the second half of the study, having 2 comorbidities (HR= 1.1 95% CI 1.02-1.2) and having 3+ comorbidities (HR 1.7, 95% CI 1.5-1.9) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in the first 6 months of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age related behavioral factors play an important role in breakthrough infection with the highest incidence among young adults. Our findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.

Predicting Functional Conformational Ensembles and Binding Mechanisms of Convergent Evolution for SARS-CoV-2 Spike Omicron Variants Using AlphaFold2 Sequence Scanning Adaptations and Molecular Dynamics Simulations (preprint)

In this study, we combined AlphaFold-based approaches for atomistic modeling of multiple protein states and microsecond molecular simulations to accurately characterize conformational ensembles and binding mechanisms of convergent evolution for the SARS-CoV-2 Spike Omicron variants BA.1, BA.2, BA.2.75, BA.3, BA.4/BA.5 and BQ.1.1. We employed and validated several different adaptations of the AlphaFold methodology for modeling of conformational ensembles including the introduced randomized full sequence scanning for manipulation of sequence variations to systematically explore conformational dynamics of Omicron Spike protein complexes with the ACE2 receptor. Microsecond atomistic molecular dynamic simulations provide a detailed characterization of the conformational landscapes and thermodynamic stability of the Omicron variant complexes. By integrating the predictions of conformational ensembles from different AlphaFold adaptations and applying statistical confidence metrics we can expand characterization of the conformational ensembles and identify functional protein conformations that determine the equilibrium dynamics for the Omicron Spike complexes with the ACE2. Conformational ensembles of the Omicron RBD-ACE2 complexes obtained using AlphaFold-based approaches for modeling protein states and molecular dynamics simulations are employed for accurate comparative prediction of the binding energetics revealing an excellent agreement with the experimental data. In particular, the results demonstrated that AlphaFold-generated extended conformational ensembles can produce accurate binding energies for the Omicron RBD-ACE2 complexes. The results of this study suggested complementarities and potential synergies between AlphaFold predictions of protein conformational ensembles and molecular dynamics simulations showing that integrating information from both methods can potentially yield a more adequate characterization of the conformational landscapes for the Omicron RBD-ACE2 complexes. This study provides insights in the interplay between conformational dynamics and binding, showing that evolution of Omicron variants through acquisition of convergent mutational sites may leverage conformational adaptability and dynamic couplings between key binding energy hotspots to optimize ACE2 binding affinity and enable immune evasion.

Mutational pressure drives enhanced release of proteasome-generated public CD8+ T cell epitopes from SARS-CoV-2 RBD of Omicron and its current lineages (preprint)

The COVID-19 pandemic was the most dramatic in the newest history with nearly 7 million deaths and global impact on mankind. Here we report binding index of 305 HLA class I molecules from 18,771 unique haplotypes of 28,104 individuals to 821 peptides experimentally observed from spike protein RBD of 5 main SARS-CoV-2 strains hydrolyzed by human proteasomes with constitutive and immune catalytic phenotypes. Our data read that 4 point mutations in the hACE2-binding region RBD496-513 of Omicron B1.1.529 strain results in a dramatic increase of proteasome-mediated release of two public HLA class I epitopes. Global population analysis of HLA class I haplotypes, specific to these peptides, demonstrated decreased mortality of human populations enriched in these haplotypes from COVID-19 after but not before December, 2021, when Omicron became dominant SARS-CoV-2 strain. Noteworthy, currently circulating BA.2.86 and JN.1 lineages contain no amino acid substitutions in RBD496-513 thus preserving identified core epitopes.

Immune imprinting revealed by SARS-CoV-2 Omicron infection prior to vaccination (preprint)

Immune imprinting or original antigenic sin (OAS) originally referred to a phenomenon of suboptimal immune response to a repeat exposure to a virus that was antigenically distinct from the original virus infection. OAS has been implicated in higher mortality in young people during the 2009-10 H1N1 pandemic where the elderly (H1N1 exposure in childhood) appeared relatively well protected compared to younger individuals whose first influenza infection was not H1N1. Immune imprinting is part of a rapid recall system and is highly effective against a slowly evolving virus (drifting) but not antigenically shifting viruses such as influenza and SARS CoV-2. As predicted by OAS, suboptimal neutralization responses to the highly divergent SARS-COV-2 lineage Omicron have been observed in animal models and individuals previously vaccinated with primary course of ancestral (Wu-1) vaccine. Due to the rapid scale up of vaccine before emergence of the antigenically distinct Omicron variant, it is unknown whether immunological imprinting for occurs in the context of SARS-COV-2 infection itself. We longitudinally assessed humoral responses to primary two dose Ad26.COV2.S Wu-hu-1 based vaccination in a Nigerian population following the global emergence of Omicron. At study entry in Jan 2023, we found 93% and 58% of pre-vaccination participants previously exposed to ancestral Wu-1 and Omicron virus respectively by anti-N IgG and anti-receptor binding domain (RBD) IgG Wu-1 and Omicron -specific antibodies. In participants with no evidence of prior exposure to Omicron, neutralisation against Wu-1 was significantly higher than Omicron variants as expected. However, serum neutralisation titres in participants who were anti-RBD Omicron IgG positive were paradoxically 2-fold lower for Omicron BA.1 as compared to Wu-1. This is clear evidence for imprinted immunity from the ancestral pre-omicron lineage viruses, and remarkably these old responses to Wu-1 were able to dominate over more recent, likely multiple, Omicron lineage infections. Furthermore, in these participants with prior exposure to Omicron and evidence of imprinting, we observed that further Omicron infection and Wu-1 based vaccine was associated with boosting of responses across variants with equalisation of neutralisation titres for Wu-1 and Omicron variants. However, omicron responses did not surpass ancestral responses, suggesting persistence of imprinting and only partial mitigation. Although neutralization responses at high titres were observed post dose 1 vaccination against ancestral and Omicron variants BA.1, BA.2, BA.4 in nearly all participants, neutralisation against the highly immune evasive XBB recombinant variant remained substantially lower, with a second vaccine dose providing very modest boosting. These data highlight immune imprinting against SARS-CoV-2 prior to vaccination and its persistence thereafter. In present day unvaccinated populations where serum neutralisation responses to pre-Omicron variants dominate, use of an omicron variant based vaccine should be used in preference to Wu-1 based vaccine to override imprinting and provide broader protection for vulnerable populations such as the elderly or those with compromised immunity.

Virological characteristics of SARS-CoV-2 Omicron BA.5.2.48 (preprint)

With the prevalence of sequentially-emerged sublineages including BA.1, BA.2 and BA.5, SARS-CoV-2 Omicron infection has transformed into a regional epidemic disease. As a sublineage of BA.5, the BA.5.2.48 outbreak and evolved into multi-subvariants in China without clearly established virological characteristics, especially the pathogenicity. Though reduced airborne transmission and pathogenicity of former Omicron sublineages have been revealed in animal models, the virological characteristics of BA.5.2.48 was unidentified. Here, we evaluated the in vitro and in vivo virological characteristics of two isolates of the prevalent BA.5.2.48 subvariant, DY.2 and DY.1.1 (a subvariant of DY.1). DY.2 replicates more efficiently than DY.1.1 in HelahACE2+ cells and Calu-3 cells. The A570S mutation (of DY.1) in a normal BA.5 spike protein (DY.2) leads to a 20% improvement in the hACE2 binding affinity, which is slightly reduced by a further K147E mutation (of DY.1.1). Compared to the normal BA.5 spike, the double-mutated protein demonstrates efficient cleavage and reduced fusogenicity. BA.5.2.48 demonstrated enhanced airborne transmission capacity in hamsters than BA.2. The pathogenicity of BA.5.2.48 is greater than BA.2, as revealed in K18-hACE2 rodents. Under immune selection pressure, DY.1.1 shows stronger fitness than DY.2 in hamster turbinates. Thus the outbreaking prevalent BA.5.2.48 multisubvariants exhibites divergent virological features.

Bivalent COVID-19 vaccines boost the capacity of pre-existing SARS-CoV-2-specific memory B cells to cross-recognize Omicron subvariants (preprint)

Bivalent COVID-19 vaccines comprising ancestral Wuhan-Hu-1 (WH1) and the Omicron BA.1 or BA.5 subvariant elicit enhanced serum antibody responses to emerging Omicron subvariants. We characterized the memory B-cell (Bmem) response following a fourth dose with a BA.1 or BA.5 bivalent vaccine, and compared the immunogenicity with a WH1 monovalent fourth dose. Healthcare workers previously immunized with mRNA or adenoviral vector monovalent vaccines were sampled before and one-month after a monovalent, BA.1 or BA.5 bivalent fourth dose COVID-19 vaccine. RBD-specific Bmem were quantified with an in-depth spectral flow cytometry panel including recombinant RBD proteins of the WH1, BA.1, BA.5, BQ.1.1, and XBB.1.5 variants. All recipients had slightly increased WH1 RBD-specific Bmem numbers. Recognition of Omicron subvariants was not enhanced following monovalent vaccination, while both bivalent vaccines significantly increased WH1 RBD-specific Bmem cross-recognition of all Omicron subvariants tested by flow cytometry. Thus, Omicron-based bivalent vaccines can improve recognition of descendent Omicron subvariants by pre-existing, WH1-specific Bmem, beyond that of a conventional, monovalent vaccine. This provides new insights into the capacity of variant-based mRNA booster vaccines to improve immune memory against emerging SARS-CoV-2 variants.

Epidemiological and transmission characteristics comparison analysis between Delta and Omicron variants of the SARS-CoV-2 (BA.2.1, BA.2.2, BA.2.76, BA.5.2) (preprint)

Since the outbreak of coronavirus disease 2019 (COVID-19), the virus has undergone three mutations, with Delta and Omicron being the most affected.This study aimed to understand the epidemiology and transmission differences between the Delta and Omicron variants, and to analyze the infection characteristics of different variants, providing a scientific theoretical basis for prevention and control strategies.We conducted a comparative analysis by selecting six local outbreaks of the Delta variant that occurred in Hunan Province in July 2021 and six local outbreaks of different sub-lineages of the Omicron variant that occurred in 2022. The results showed that asymptomatic cases were more prevalent in Omicron variant infections, with BA.5.2 having the highest proportion. The Delta and Omicron variants have identical median incubation periods of 2–3 days. In terms of secondary situations, the secondary attack rate of the Delta variant is 0.85%, while that of the Omicron variant is 1.69%. For specific Omicron subvariants, Omicron BA.2.1 has a secondary attack rate of 0.89%, Omicron BA.2.2 is 0.71%, Omicron BA.2.76 is 2.51%, and Omicron BA.5.2 has a secondary attack rate of 4.63%. The predominant mode of exposure for cases with recurrent infections of the Delta variant is cohabitation, while for Omicron variant outbreaks, cohabitation remains predominant, followed by spatial proximity and dining together.The Delta variant and the Omicron variant are both make it prone to causing multiple generations of cases in a short period, leading to a wider impact. The secondary attack rates of Omicron and Delta variants in this study were much lower than in other countries, indicating that strengthening personnel control and social regulations are beneficial for the prevention and control of newly emerging severe infectious diseases. Meanwhile, the exposure types of Omicron variant secondary cases were more diverse, and the symptoms of infected individuals were milder, indicating its greater stealthiness. Therefore, it is crucial to focus on virus mutations, strengthen surveillance, and increase prevention and control efforts if enhanced transmissibility of the variant is detected.

Real-Life Practice of Kelleni’s Protocol in Treatment and Post Exposure Prophylaxis of SARS CoV-2 Omicron HV.1 and JN.1 Subvariants (preprint)

This brief report discusses the ongoing real-world practice using nitazxoanide, NSAIDs and/or azithromycin (Kelleni’s protocol) to manage the evolving manifestations of SARS CoV-2 Omicron EG.5.1, its descendant HV.1 as well as BA.2.86 and its descendant JN.1 subvariants in Egypt. These subvariants are well-known for their highly evolved immune-evasive properties and the manifestations include some peculiar manifestations as persistent cough besides high fever in young children as well as persistent severe cough, high fever, change of voice and marked bone aches in high risk groups of adults. It’s suggested that the ongoing SARS CoV-2 evolution is continuing to mostly affect the high risk groups of patients, to some of whom we’ve also successfully prescribed nitazoxanide and/or NSAIDs for post-exposure prophylaxis of all household contacts. We also continue to recommend starting the immune-modulatory antiviral Kelleni’s protocol as soon as possible in the course of infection and adjusting it in a personalized manner to be more aggressive from the beginning for the high risk patients, at least until the currently encountered surge of infections subsides.

A Comparative Experimental and Computational Study on the Nature of the Pangolin-CoV and COVID-19 Omicron (preprint)

The relationship between pangolin-CoV and SARS-CoV-2 has been a subject of debate. Further evidence of a special relationship between the two viruses can be found by the fact that all known COVID-19 viruses have abnormally hard outer shell (low M disorder; i.e., low content of intrinsically disordered residues in the membrane (M) protein) that so far was found in CoVs associated with burrowing animals, such as rabbits and pangolins, in which transmission involves virus remaining in buried feces for a long time. While a hard outer shell is necessary for viral survival, a harder inner shell could also help. For this reason, the N disorder range of pangolin-CoVs, not bat-CoVs, more closely matches that of SARS-CoV-2 especially when Omicron is included. The low N disorder (i.e., low content of intrinsically disordered residues in the nucleocapsid (N) protein), first observed in pangolin-CoV-2017 amd later in Omicron, is associated with attenuation according to the Shell-Disorder-Model. Our experimental study revealed that pangolin-CoV-2017 and SARS-CoV-2 Omicron (XBB.1.16 subvariant) show similar attenuations with respect to viral growth and plaque formation. Subtle differences have been observed that are consistent with disorder-centric computational analysis.

Incidence, risk factors, and clinical symptom profile of reinfection during Omicron-dominated COVID-19 outbreak in Hong Kong: A retrospective cohort study (preprint)

Background: Despite the declaration from World Health Organization of the end of the COVID-19 pandemic, reinfection persists and continues to strain the global healthcare system. With the emergence of the most recent variant of SARS-CoV-2 named JN.1, retrospective analysis of epidemiological characteristics of previous cases involving the Omicron variant is essential to provide references for preventing reinfection caused by the ongoing new SARS-Cov-2 variants. Methods: This retrospective cohort study included 6325 patients infected with SARS-CoV-2 during the Omicron-dominated outbreak (from December 2021 to May 2022) in Hong Kong. Statistical analysis was conducted to demonstrate the epidemiological characteristics and a logistic regression model was utilized to identify risk factors associated with reinfection. Results: The Omicron reinfection incidence was 5.18% (n = 353). No significant difference was observed in receiving mRNA (BNT162b2) vaccine and inactivated (CoronaVac) vaccine between reinfection and non-reinfection groups (p>0.05). Risk factors were identified as female gender (p<0.001), longer infection duration (p<0.05), comorbidity of eyes, ear, nose, throat disease (p<0.01), and severe post-infection impact on daily life and work (p<0.05), while equal or larger than 70 years old (p<0.05) and vaccination after primary infection (p<0.01) were associated with a lower risk of reinfection. The prevalence of most symptoms after reinfection was lower than the first infection, except for fatigue. Conclusion: No significant difference in mRNA (BNT162b2) vaccine and inactivated (CoronaVac) vaccine against reinfection. Post-infection vaccination could lower the risk of reinfection, which potentially inform the development of preventive measures including vaccination policies against potential new SARS-Cov-2 variants.

Real-word immunogenicity of a recombinant subunit COVID-19 vaccine and effectiveness against omicron infection: a prospective, multi-centre, longitudinal cohort study in Alzheimer's disease patients (preprint)

Introduction Vaccination is an essential strategy against COVID-19 in the current era of emerging variants. This study evaluates the real-world immunogenicity and effectiveness of the recombinant subunit COVID-19 vaccine (Zifivax) in Alzheimer's disease (AD) patients.Methods 249 AD patients were enrolled in a multicentre, longitudinal cohort study. Levels of RBD-IgG, neutralization antibody activity, and cytokines were identified to evaluate the immune responses. Clinical outcomes were assessed within one month following Omicron infection..Results Following three doses, the vaccine induced a robust immune response, elevating neutralizing antibodies and activating T-cells. AD patients exhibited significantly higher humoral immune responses compared to unvaccinated counterparts. Following Omicron infection, unvaccinated patients experienced higher levels of Th1/Th2-type cytokines than vaccinated individuals. Vaccination correlated with increased survival rates and extended survival times after infection..Discussion The findings highlight the vaccine's efficacy in reducing severe illness, and preventing death in AD patients facing Omicron infection.

Tracking inflammation resolution signatures in lungs after SARS-CoV-2 omicron BA.1 infection of K18-hACE2 mice (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which can result in severe disease often characterised by a 'cytokine storm' and the associated acute respiratory distress syndrome. However, many infections with SARS-CoV-2 are mild or asymptomatic throughout the course of infection. Although blood biomarkers of severe disease are well studied, less well understood are the inflammatory signatures in lung tissues associated with mild disease or silent infections, wherein infection and inflammation are rapidly resolved leading to sequelae-free recovery. Herein we described RNA-Seq and histological analyses of lungs over time in an omicron BA.1/K18-hACE2 mouse infection model, which displays these latter features. Although robust infection was evident at 2 days post infection (dpi), viral RNA was largely cleared by 10 dpi. Acute inflammatory signatures showed a slightly different pattern of cytokine signatures compared with severe infection models, but where much diminished 30 dpi and absent by 66 dpi. Cellular deconvolution identified significantly increased abundance scores for a number of anti-inflammatory pro-resolution cell types at 5/10 dpi. These included type II innate lymphoid cells, T regulatory cells, and interstitial macrophages. Genes whose expression trended downwards over 2 - 66 dpi included biomarkers of severe disease and were associated with 'cytokine storm' pathways. Genes whose expression trended upward during this period were associated with recovery of ciliated cells, AT2 to AT1 transition, reticular fibroblasts and innate lymphoid cells, indicating a return to homeostasis. Very few differentially expressed host genes were identified at 66 dpi, suggesting near complete recovery. The parallels between mild or subclinical infections in humans and those observed in this BA.1/K18-hACE2 mouse model are discussed.