Human and hamster sera correlate well in identifying antigenic drift among SARS-CoV-2 variants, including JN.1.

Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, we show that neutralization titers and breadth of matched human and hamster pre-Omicron variant primary infection sera correlate well and generate similar antigenic maps. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with fivefold to sixfold antigenic differences between these variants and XBB.1.5. Compared to sera following only ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, XBB.1.5 booster sera had the broadest neutralization against XBB sub-lineage variants, although a fivefold titer difference was still observed between JN.1 and XBB.1.5 variants. These findings suggest that antibody coverage of antigenically divergent JN.1 could be improved with a matched vaccine antigen.IMPORTANCEUpdates to COVID-19 vaccine antigens depend on assessing how much vaccine antigens differ antigenically from newer SARS-CoV-2 variants. Human sera from single variant infections are ideal for discriminating antigenic differences among variants, but such primary infection sera are now rare due to high population immunity. It remains unclear whether sera from experimentally infected animals could substitute for human sera for antigenic assessments. This report shows that neutralization titers of variant-matched human and hamster primary infection sera correlate well and recognize variants similarly, indicating that hamster sera can be a proxy for human sera for antigenic assessments. We further show that human sera following an XBB.1.5 booster vaccine broadly neutralized XBB sub-lineage variants but titers were fivefold lower against the more recent JN.1 variant. These findings support updating the current COVID-19 vaccine variant composition and developing a framework for assessing antigenic differences in future variants using hamster primary infection sera.

A novel orf virus vector-based COVID-19 booster vaccine shows cross-neutralizing activity in the absence of anti-vector neutralizing immunity.

Next-generation COVID-19 vaccines are being developed to expand the breadth of coverage against existing and future variants and to extend the duration of protection. Prime-2-CoV_Beta is an orf virus (ORFV) based multi-antigen COVID-19 vaccine that co-expresses Spike (S) and Nucleocapsid (N) antigens. The safety and immunogenicity of Prime-2-CoV_Beta is investigated in a phase 1 first-in-human (FIH) dose-finding trial (ORFEUS study, ClinicalTrials.gov: NCT05367843). Participants of two age groups (18-55 and 65-85 years) who previously completed at least two doses of mRNA vaccines were enrolled and sequentially assigned to different dose groups to receive one intramuscular dose of 3 × 105, 3 × 106, 1.5 × 107, or 3 × 107 plaque-forming units (PFU) of Prime-2-CoV_Beta on day 1 and a second dose on day 29. Here, we report safety and immunogenicity data collected up to 6 months after the first study vaccination. Prime-2-CoV_Beta is safe and well tolerated and elicits immune responses at higher dose levels in participants aged 18-55. A single dose of 3 × 107 PFU boosted binding and cross-neutralizing antibody responses that are maintained through 6 months after the first booster vaccination. Polyfunctional S-specific CD4+ and CD8+ T cell responses are observed after vaccination. No pre-existing or vaccine-induced neutralizing anti-vector antibodies are detected. Our findings highlight the potential of the ORFV vector as a safe platform for future vaccine design, which provides the ability to deliver multiple antigens and allows for repeat immunization.

Escape of SARS-CoV-2 Variants KP.1.1, LB.1, and KP3.3 From Approved Monoclonal Antibodies.

Background: First-generation anti-SARS-CoV-2 monoclonal antibodies (mAbs) used for prophylaxis or therapeutic purposes in immunocompromised patients have been withdrawn because of the emergence of resistant Omicron variants. In 2024, 2 novel mAbs, VYD222/Pemivibart and AZD3152/Sipavibart, were approved by health authorities, but their activity against contemporary JN.1 sublineages is poorly characterized. Methods: We isolated authentic JN.1.1, KP.1.1, LB.1, and KP.3.3 viruses and evaluated their sensitivity to neutralization by these mAbs in 2 target cell lines. Results: Compared to ancestral strains, VYD222/Pemivibart remained moderately active against JN.1 subvariants, with a strong increase of 50% Inhibitory Concentration (IC50), reaching up to 3 to 15 µg/mL for KP3.3. AZD3152/Sipavibart neutralized JN.1.1 but lost antiviral efficacy against KP.1.1, LB.1, and KP3.3. Conclusions: Our results highlight the need for a close clinical monitoring of VYD222/Pemivibart and raise concerns about the clinical efficacy of AZD3152/Sipavibart.

Immunogenicity and efficacy of XBB.1.5 rS vaccine against the EG.5.1 variant of SARS-CoV-2 in Syrian hamsters.

The continued emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants necessitates updating coronavirus disease 2019 (COVID-19) vaccines to match circulating strains. The immunogenicity and efficacy of these vaccines must be tested in pre-clinical animal models. In Syrian hamsters, we measured the humoral and cellular immune response after immunization with the nanoparticle recombinant Spike (S) protein-based COVID-19 vaccine (Novavax, Inc.). We also compared the efficacy of the updated monovalent XBB.1.5 variant vaccine with previous COVID-19 vaccines for the induction of XBB.1.5 and EG.5.1 neutralizing antibodies and protection against a challenge with the EG.5.1 variant of SARS-CoV-2. Immunization induced high levels of S-specific IgG and IgA antibody-secreting cells and antigen-specific CD4+ T cells. The XBB.1.5 and XBB.1.16 vaccines, but not the Prototype vaccine, induced high levels of neutralizing antibodies against the XBB.1.5, EG.5.1, and JN.1 variants of SARS-CoV-2. Upon challenge with the Omicron EG.5.1 variant, the XBB.1.5 and XBB.1.16 vaccines reduced the virus load in the lungs, nasal turbinates, trachea, and nasal washes. The bivalent vaccine (Prototype rS + BA.5 rS) continued to offer protection in the trachea and lungs, but protection was reduced in the upper airways. By contrast, the monovalent Prototype vaccine no longer offered good protection, and breakthrough infections were observed in all animals and tissues. Thus, based on these study results, the protein-based XBB.1.5 vaccine is immunogenic and increased the breadth of protection against the Omicron EG.5.1 variant in the Syrian hamster model. IMPORTANCE: As SARS-CoV-2 continues to evolve, there is a need to assess the immunogenicity and efficacy of updated vaccines against newly emerging variants in pre-clinical models such as mice and hamsters. Here, we compared the immunogenicity and efficacy between the updated XBB.1.5, the original Prototype Wuhan-1, and the bivalent Prototype + BA.5 vaccine against a challenge with the EG.5.1 Omicron variant of SARS-CoV-2 in hamsters. The XBB.1.5 and bivalent vaccine, but not the Prototype, induced serum-neutralizing antibodies against EG.5.1, albeit the titers were higher in the XBB.1.5 immunized hamsters. The presence of neutralizing antibodies was associated with complete protection against EG.5.1 infection in the lower airways and reduced virus titers in the upper airways. Compared with the bivalent vaccine, immunization with XBB.1.5 improved viral control in the nasal turbinates. Together, our data show that the updated vaccine is immunogenic and that it offers better protection against recent variants of SARS-CoV-2.

Reduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection by blocking the epidermal growth factor receptor (EGFR) pathway.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants presents challenges in global efforts to transition from the pandemic to an endemic stage. The spike protein of the SARS-CoV-2 virus, which is pivotal for cell entry, exhibits significant mutations in its variants, potentially affecting infectivity and therapeutic efficacy. Recent findings indicate upregulation of the epidermal growth factor receptor (EGFR) pathway, a key target in cancer therapy, by the spike protein of SARS-CoV-2. This study aimed to investigate the activity of the EGFR pathway against SARS-CoV-2 variants and to assess the inhibitory effects of EGFR inhibitors using SARS-CoV variant pseudoviral particles to guide future therapeutic strategies. Omicron variant SARS-CoV pseudoviral particles exhibited heightened infectivity in human angiotensin-converting enzyme 2 (hACE2)-expressing HEK293 and A549 lung cancer cells accompanied by increased EGFR pathway activation in infected cells. Using the EGFR tyrosine kinase inhibitor, osimertinib, we observed a reduction in viral infection rates in hACE2-HEK293 and A549 cells infected with the SARS-CoV-2 variant pseudoviral particles. We conducted further experiments to confirm that the reduction in infection efficacy with osimertinib treatment was not associated to a decrease in cell viability. Furthermore, this inhibitory effect of osimertinib in cell lines was corroborated in a spheroid cell culture model derived from hACE2-A549 cells. These findings suggest the potential application of EGFR-targeted antiviral therapy against highly infectious SARS-CoV-2 variants.IMPORTANCEThe emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is concerning as vaccines designed for one variant need not essentially protect against other novel variants. Therefore, there is an urgent need to identify therapies that can act against multiple novel variants that have heightened virulence compared with the wild type. It has been reported that the spike protein of the SARS-CoV-2 virus elicits an increased expression of the epidermal growth factor receptor (EGFR) pathway. We used this information and examined whether treatment with an EGFR inhibitor, osimertinib, which is already approved for clinical use in cancer therapy, can reduce the infection caused by SARS-CoV-2, wild type, and Omicron and Delta variants, in two cell lines and one spheroid model. The results showed that osimertinib treatment successfully reduced infection efficacy, particularly in variants, and that this effect was not related to a reduction in cell viability, making this a promising strategy for treating SARS-CoV-2 infections.

Characteristics and predictors of Long Covid in children: a 3-year prospective cohort study.

Background: Children can develop Long Covid, however long term outcomes and their predictors are poorly described in these patients. The primary aim is to describe characteristics and predictors of Long Covid in children assessed in-clinics up to 36 months post-SARS-CoV-2 infection, as well as investigate the role of vaccines in preventing Long Covid, risk of reinfections and development of autoimmune diseases. Methods: Children aged 0-18 years old with confirmed SARS-CoV-2 infection were invited for a prospective follow-up assessment at a peadiatric post-covid clinic in Rome, Italy, at serial intervals (3-, 6-, 12-, 18-, 24- and 36-months post-infection onset, between 01/02/2020 and 28/02/2024). Long Covid was defined as persistence of otherwise unexplained symptoms for at least three months after initial infection. Findings: 1319 patients were initially included, 1296 reached the 3 months follow-up or more. Of the patients who underwent multiple follow-ups, 23.2% (301), 169 (13.2%), 89 (7.9%), 67 (6.1%), 47 (7.1%) were diagnosed with Long Covid at 3-6-12-18-24 months, respectively For the primary outcome of Long Covid at three months, age >12 years (P < 0.001, OR 11.33, 95% CI 4.2; 15.15), comorbidities (P = 0.008, OR 1.83, 95% CI 1.06; 2.44), being infected with original variants (P < 0.001, OR 4.77, 95% CI 2.46; 14.47), female sex (P < 0.001, OR 1.62, 95% CI 1.02; 1.89) were statistically significant risk factors. Age >12 years (P = 0.002, OR 9.37, 95% CI 1.58; 8.64), and infection with original (P = 0.012, OR 3.52, 95% CI 1.32; 8.64) and alfa (P < 0.001, OR 4.09, 95% CI 2.01; 8.3) SARS-CoV-2 variants remained statistically significant risk factors for Long Covid duration for at least 18 months. Vaccination was associated with a lower risk of long covid at 3, 6 and 12 months for older children and a lower risk of reinfections. Being infected with the original SARS-CoV-2 variant was associated with a higher risk of new-onset autoimmune diseases ((P = 0.035, 95% CI 1.12; 2.4). One patient was diagnosed with Long Covid after a re-infection. Interpretation: This is the longest follow-up study of children with SARS-CoV-2 infection, showing a significant and long-lasting burden of Long Covid in the pediatric population. Our findings highlight the urgent need of investing in pediatric Long Covid in order to find effective diagnostic and therapeutic approaches, as well can inform preventive strategies in case of future pandemics. Funding: This study has been funde by Pfizer non-competitive grant, granted to DB (#65925795).

Distinct Responses of Cystic Fibrosis Epithelial Cells to SARS-CoV-2 and Influenza A Virus.

The COVID-19 pandemic has underscored the impact of viral infections on individuals with cystic fibrosis (CF). Initial observations suggested lower COVID-19 rates among CF populations; however, subsequent clinical data have presented a more complex scenario. This study aimed to investigate how bronchial epithelial cells from CF and non-CF individuals, including various CF transmembrane conductance regulator (CFTR) mutations, respond to in vitro infection with SARS-CoV-2 variants and SARS-CoV. Comparisons with the Influenza A virus (IAV) were included based on evidence that CF patients experience heightened morbidity from IAV infection. Our findings showed that CF epithelial cells exhibited reduced replication of SARS-CoV-2, regardless of the type of CFTR mutation or SARS-CoV-2 variant, as well as the original 2003 SARS-Cove. In contrast, these cells displayed more efficient IAV replication compared to non-CF cells. Interestingly, the reduced susceptibility to SARS-CoV-2 in CF was not linked to the expression of angiotensin converting enzyme 2 (ACE2) receptor nor to CFTR dysfunction, as pharmacological treatments to restore CFTR function did not normalize the viral response. Both SARS-CoV-2 infection and CFTR function influenced the levels of certain cytokines and chemokines, although these effects were not correlated. Overall, this study reveals a unique viral response in CF epithelial cells, characterized by reduced replication for some viruses like SARS-CoV-2, while showing increased susceptibility to others such as IAV. This research offers a new perspective on CF and viral interactions, emphasizing the need for further investigation into the mechanisms underlying these differences. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

SARS-CoV-2 detection in COVID-19 patients' sample using Wooden quoit conformation structural aptamer (WQCSA)-Based electronic bio-sensing system.

The COVID-19 epidemic and its continuous spread pose a serious threat to public health. Coronavirus strains known as SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) variants have undergone genomic changes. The severity of the symptoms, the efficiency of vaccinations, and the transmission capacity of the virus can be impacted by these alterations. Point-of-care diagnostic assays can identify particular genetic or protein sequences that are exclusive to each variety. Currently, ultrafast, responsive, and accurate antibody detection faces several challenges. Here, we outline the fabrication, implementation, and sensing performance benchmarking of an ultrafast (5 s) and inexpensive (0.15 USD) assay with label-free sensing of SARS-CoV-2 S (Spike)/N (Nucleocapsid) protein and other variants in real patient samples. A label-free DNA aptameric capacitive bio-sensing device was used to detect SARS-CoV-2 variants. Our novel, cutting-edge bio-sensing device contains a Wooden quoits conformation structural aptamer (WQCSA)-based inter-digitated capacitor electronic (WQCSA-IDCE) system. WQCSA-aptamer was used as a switch-turn on response to achieve ultrasensitivity in the variable area of the SARS-CoV-2. The molecular beacon (MB) method was also used to measure the fluorescently colored SARS-CoV-2 S/N protein. These sensors can be used with several types of label-free DNA aptamers to act as rapid, affordable, and label-free biosensors for a variety of critical acute respiratory virus syndrome disorders.

Variant-specific neutralising antibodies levels induced by the PHH-1 V SARS-CoV-2 vaccine (Bimervax®) by HIPRA.

SARS-CoV-2 virus variants continue to emerge at an alarming rate due to spontaneous genetic mutations, particularly in the spike protein receptor-binding domain (RBD) portion, which render the virus more likely to escape immunity. So far, the immunity obtained through global primary and/or booster immunisation campaigns has been sufficient to protect the population from new emerging variants of the Omicron lineage. The current approach to update vaccines' antigen composition to new variants to boost immunity may not be sustainable in the long term. It might also be potentially redundant if the mutations are giving rise to variants which induce milder infections and existing vaccines, such as Bimervax®, are still sufficiently protective, as Covid is slowly becoming a seasonal illness. Through measuring neutralising antibody titres in sera from subjects boosted with Bimervax®, we have demonstrated the ability of Bimervax® to induce immune responses against a variety of SARS-CoV-2 variants, ranging from earlier variants inducing more serious infections to more recent variants which have been found to produce milder infections.

Neutralizing Antibodies against 10 SARS-CoV-2 Variants at Two Years Post-COVISHIELD Vaccination with Special Reference to Omicron Subvariants and Booster Administration.

To study the durability of neutralizing antibodies (NAbs) against ten SARS-CoV-2 variants among COVISHIELD vaccine recipients from Pune, India, 184 vaccinee samples with (pre-positives) or without (pre-negatives) prior antibody positivity were evaluated. To estimate NAb levels, a validated ten-plex MSD ACE2 neutralization assay was used. NAbs against Alpha, Beta, Delta, and Omicron/subvariants were assessed at 1 month (PD2-1) and 6 months (PD2-6) post-vaccination, post-booster dose, and 2 years (2Y) post-vaccination. In pre-negatives, the seropositivity declined from PD2-1 to PD2-6 for all variants (Omicron variants: 14-54% to 0%; non-Omicron variants: 66-100% to 8-44%). In pre-positives, the decline in seropositivity from PD2-1 to PD2-6 was seen only for Omicron variants (14-39%). At PD2-6, a significant reduction in NAb levels was observed in all vaccinees against all the variants. Irrespective of prior exposure, the diminished anti-variant antibody levels at PD2-6 increased significantly following the administration of the booster. In conclusion, the COVISHIELD vaccine booster dose did provide cross-neutralizing antibodies against broad-range SARS-CoV-2 variants with improved durability up to [16 (15-18)] months post-booster dose and two years post-vaccination.

Hybrid Immunity against SARS-CoV-2 Variants: A Narrative Review of the Literature.

The emergence of SARS-CoV-2 led to a global health crisis and the burden of the disease continues to persist. The rapid development and emergency authorization of various vaccines, including mRNA-based vaccines, played a pivotal role in mitigating severe illness and mortality. However, rapid viral mutations, leading to several variants of concern, challenged vaccine effectiveness, particularly concerning immune evasion. Research on immunity, both from natural infection and vaccination, revealed that while neutralizing antibodies provide protection against infection, their effect is short-lived. The primary defense against severe COVID-19 is derived from the cellular immune response. Hybrid immunity, developed from a combination of natural infection and vaccination, offers enhanced protection, with convalescent vaccinated individuals showing significantly higher levels of neutralizing antibodies. As SARS-CoV-2 continues to evolve, understanding the durability and breadth of hybrid immunity becomes crucial. This narrative review examines the latest data on humoral and cellular immunity from both natural infection and vaccination, discussing how hybrid immunity could inform and optimize future vaccination strategies in the ongoing battle against COVID-19 and in fear of a new pandemic.

Genomic analysis of the SARS-CoV-2 variants circulated in the Philippines, 2020-2024.

Purpose: Genomic sequencing has been an invaluable tool to determine the evolution of SARS-CoV-2. In the present study, we provided a comprehensive description of the SARS-CoV-2 variants circulated in the Philippines. Methods: The dataset from the human COVID-19 infections was acquired by downloading the sequences and their associated metadata spanning from March 2020 to April 2024. Then, we executed several filtering criteria to acquire the final dataset for the Philippine samples and performed spatial distribution analysis and phylogenetic tree construction of the reported SARS-CoV-2 sequences. Results: A total of 16,679,203 SARS-CoV sequences were obtained, of which 17,393 (0.10 %) were sampled in the Philippines. Western Visayas reported the highest SARS-CoV-2 sequences (21.33 %), while the Bangsamoro Autonomous Region in Muslim Mindanao reported the least (0.48 %). The phylogenetic tree revealed the evolution of the detected SARS-CoV-2 variants circulating in the Philippines with 19 A as the first reported case (based on the GISAID submission), and 24 A (JN.1) as the currently circulating variant. Omicron variants have dominated the Philippines with 21 L (Omicron, BA.2) having 5102 cases (29.33 %), followed by 22B (BA.5) having 2184 cases (12.57 %). Using Pearson's Chi-square test of independence, we showed that there is a significant association between the age-groups and gender with the detection years. Conclusion: Altogether, this analysis showed the updated epidemiological trends of the reported SARS-CoV-2 variants in the Philippines. This increases the importance of conducting surveillance on viral infectious diseases such as COVID-19 to provide the scope and trajectory of viral spread in a country.

Kinetics of Viral Shedding for Outbreak Surveillance of Emerging Infectious Diseases: Modeling Approach to SARS-CoV-2 Alpha and Omicron Infection.

BACKGROUND: Previous studies have highlighted the importance of viral shedding using cycle threshold (Ct) values obtained via reverse transcription polymerase chain reaction to understand the epidemic trajectories of SARS-CoV-2 infections. However, it is rare to elucidate the transition kinetics of Ct values from the asymptomatic or presymptomatic phase to the symptomatic phase before recovery using individual repeated Ct values. OBJECTIVE: This study proposes a novel Ct-enshrined compartment model to provide a series of quantitative measures for delineating the full trajectories of the dynamics of viral load from infection until recovery. METHODS: This Ct-enshrined compartment model was constructed by leveraging Ct-classified states within and between presymptomatic and symptomatic compartments before recovery or death among people with infections. A series of recovery indices were developed to assess the net kinetic movement of Ct-up toward and Ct-down off recovery. The model was applied to (1) a small-scale community-acquired Alpha variant outbreak under the "zero-COVID-19" policy without vaccines in May 2021 and (2) a large-scale community-acquired Omicron variant outbreak with high booster vaccination rates following the lifting of the "zero-COVID-19" policy in April 2022 in Taiwan. The model used Bayesian Markov chain Monte Carlo methods with the Metropolis-Hastings algorithm for parameter estimation. Sensitivity analyses were conducted by varying Ct cutoff values to assess the robustness of the model. RESULTS: The kinetic indicators revealed a marked difference in viral shedding dynamics between the Alpha and Omicron variants. The Alpha variant exhibited slower viral shedding and lower recovery rates, but the Omicron variant demonstrated swifter viral shedding and higher recovery rates. Specifically, the Alpha variant showed gradual Ct-up transitions and moderate recovery rates, yielding a presymptomatic recovery index slightly higher than 1 (1.10), whereas the Omicron variant had remarkable Ct-up transitions and significantly higher asymptomatic recovery rates, resulting in a presymptomatic recovery index much higher than 1 (152.5). Sensitivity analysis confirmed the robustness of the chosen Ct values of 18 and 25 across different recovery phases. Regarding the impact of vaccination, individuals without booster vaccination had a 19% higher presymptomatic incidence rate compared to those with booster vaccination. Breakthrough infections in boosted individuals initially showed similar Ct-up transition rates but higher rates in later stages compared to nonboosted individuals. Overall, booster vaccination improved recovery rates, particularly during the symptomatic phase, although recovery rates for persistent asymptomatic infection were similar regardless of vaccination status once the Ct level exceeded 25. CONCLUSIONS: The study provides new insights into dynamic Ct transitions, with the notable finding that Ct-up transitions toward recovery outpaced Ct-down and symptom-surfacing transitions during the presymptomatic phase. The Ct-up against Ct-down transition varies with variants and vaccination status. The proposed Ct-enshrined compartment model is useful for the surveillance of emerging infectious diseases in the future to prevent community-acquired outbreaks.

Enhanced Assessment of Cross-Reactive Antigenic Determinants within the Spike Protein.

Despite successful vaccination efforts, the emergence of new SARS-CoV-2 variants poses ongoing challenges to control COVID-19. Understanding humoral responses regarding SARS-CoV-2 infections and their impact is crucial for developing future vaccines that are effective worldwide. Here, we identified 41 immunodominant linear B-cell epitopes in its spike glycoprotein with an SPOT synthesis peptide array probed with a pool of serum from hospitalized COVID-19 patients. The bioinformatics showed a restricted set of epitopes unique to SARS-CoV-2 compared to other coronavirus family members. Potential crosstalk was also detected with Dengue virus (DENV), which was confirmed by screening individuals infected with DENV before the COVID-19 pandemic in a commercial ELISA for anti-SARS-CoV-2 antibodies. A high-resolution evaluation of antibody reactivity against peptides representing epitopes in the spike protein identified ten sequences in the NTD, RBD, and S2 domains. Functionally, antibody-dependent enhancement (ADE) in SARS-CoV-2 infections of monocytes was observed in vitro with pre-pandemic Dengue-positive sera. A significant increase in viral load was measured compared to that of the controls, with no detectable neutralization or considerable cell death, suggesting its role in viral entry. Cross-reactivity against peptides from spike proteins was observed for the pre-pandemic sera. This study highlights the importance of identifying specific epitopes generated during the humoral response to a pathogenic infection to understand the potential interplay of previous and future infections on diseases and their impact on vaccinations and immunodiagnostics.

Effectiveness of COVID-19 Vaccination against Severe Symptoms and Death Among Geriatric Inpatients: A Retrospective Cohort Study in Macao.

Monitoring the effectiveness of COVID-19 vaccination is critical for understanding if the vaccinated population, especially the elderly, is adequately protected from the emergence of new SARS-CoV-2 variants. This study aimed to investigate the effects of COVID-19 vaccination on the severity of symptoms and mortality in hospitalized geriatric patients during the Omicron BF.7 surge in Macao. Data from electronic health records and vaccination registry of inpatients aged 60 years or above admitted to Kiang Wu Hospital from 12 December 2022 to 12 March 2023 were retrospectively analyzed. The study involved 848 people, including 426 vaccinated and 422 unvaccinated individuals. The mean CXR scores (8.95 ± 9.49 vs. 11.41 ± 10.81, p < 0.001) and the mean MEWS scores (0.96 ± 2.01 vs. 1.49 ± 2.45, p < 0.001) were lower in the vaccinated group. By comparing the dose counts, no significant difference was seen in the odds of death. Based on the time of the last vaccination, 128 people were categorized as complete and 298 as incomplete vaccination. The complete vaccination group showed a 54% (95% CI 0.23-0.91) reduction in mortality risk (p = 0.026). The study findings not only reconfirm the effectiveness of COVID-19 vaccination but, more importantly, highlight the importance of vaccination timing to maximize vaccines' protective effect.

SARS-CoV-2 Variants and Clinical Outcomes of Special Populations: A Scoping Review of the Literature.

The ongoing COVID-19 pandemic has significantly impacted special populations, including immunocompromised individuals, people living with HIV (PLWHIV), pediatric patients, and those with chronic liver disease (CLD). This scoping review aims to map the clinical outcomes of these vulnerable groups when infected with various SARS-CoV-2 variants. The review identifies trends and patterns, noting that early variants, such as Alpha and Delta, are associated with more severe outcomes, including higher hospitalization and mortality rates. In contrast, the Omicron variant, despite its increased transmissibility, tends to cause milder clinical manifestations. The review highlights the necessity for ongoing surveillance and tailored healthcare interventions due to the heterogeneity of patient populations and the evolving nature of the virus. Continuous monitoring and adaptive healthcare strategies are essential to mitigate the impact of COVID-19 on these high-risk groups.

Comprehensive Analysis of SARS-CoV-2 Dynamics in Bangladesh: Infection Trends and Variants (2020-2023).

The first case of COVID-19 was detected in Bangladesh on 8 March 2020. Since then, the Government of Bangladesh (GoB) has implemented various measures to limit the transmission of COVID-19, including widespread testing facilities across the nation through a laboratory network for COVID-19 molecular testing. This study aimed to analyze the dynamics of SARS-CoV-2 in Bangladesh by conducting COVID-19 testing and genomic surveillance of the virus variants throughout the pandemic. Nasopharyngeal swabs were collected from authorized GoB collection centers between April 2020 and June 2023. The viral RNA was extracted and subjected to real-time PCR analysis in icddr,b's Virology laboratory. A subset of positive samples underwent whole-genome sequencing to track the evolutionary footprint of SARS-CoV-2 variants. We tested 149,270 suspected COVID-19 cases from Dhaka (n = 81,782) and other districts (n = 67,488). Of these, 63% were male. The highest positivity rate, 27%, was found in the >60 years age group, followed by 26%, 51-60 years, 25% in 41-50 years, and the lowest, 9% in under five children. Notably, the sequencing of 2742 SARS-CoV-2 genomes displayed a pattern of globally circulating variants, Alpha, Beta, Delta, and Omicron, successively replacing each other over time and causing peaks of COVID-19 infection. Regarding the risk of SARS-CoV-2 infection, it was observed that the positivity rate increased with age compared to the under-5 age group in 2020 and 2021. However, these trends did not remain consistent in 2022, where older age groups, particularly those over 60, had a lower positivity rate compared to other age groups due to vaccination. The study findings generated data on the real-time circulation of different SARS-CoV-2 variants and the upsurge of COVID-19 cases in Bangladesh, which impacted identifying hotspots and restricting the virus from further transmission. Even though there is currently a low circulation of SARS-CoV-2 in Bangladesh, similar approaches of genomic surveillance remain essential for monitoring the emergence of new SARS-CoV-2 variants or other potential pathogens that could lead to future pandemics.

Immune signature in vaccinated versus non-vaccinated aged people with COVID-19 pneumonia.

BACKGROUND: A definition of the immunological features of COVID-19 pneumonia is needed to support clinical management of aged patients. In this study, we characterized the humoral and cellular immune responses in presence or absence of SARS-CoV-2 vaccination, in aged patients admitted to the IRCCS San Raffaele Hospital (Italy) for COVID-19 pneumonia between November 2021 and March 2022. METHODS: The study was approved by local authorities. Disease severity was evaluated according to WHO guidelines. We tested: (A) anti-SARS-CoV-2 humoral response (anti-RBD-S IgG, anti-S IgM, anti-N IgG, neutralizing activity against Delta, BA1, BA4/5 variants); (B) Lymphocyte B, CD4 and CD8 T-cell phenotype; (C) plasma cytokines. The impact of vaccine administration and different variants on the immunological responses was evaluated using standard linear regression models and Tobit models for censored outcomes adjusted for age, vaccine doses and gender. RESULT: We studied 47 aged patients (median age 78.41), 22 (47%) female, 33 (70%) older than 70 years (elderly). At hospital admission, 36% were unvaccinated (VACno), whilst 63% had received 2 (VAC2) or 3 doses (VAC3) of vaccine. During hospitalization, WHO score > 5 was higher in unvaccinated (14% in VAC3 vs. 43% in VAC2 and 44% VACno). Independently from vaccination doses and gender, elderly had overall reduced anti-SARS-CoV-2 humoral response (IgG-RBD-S, p = 0.0075). By linear regression, the anti-RBD-S (p = 0.0060), B (p = 0.0079), CD8 (p = 0.0043) and Th2 cell counts (p = 0.0131) were higher in VAC2 + 3 compared to VACno. Delta variant was the most representative in VAC2 (n = 13/18, 72%), detected in 41% of VACno, whereas undetected in VAC3, and anti-RBD-S production was higher in VAC2 vs. VACno (p = 0.0001), alongside neutralization against Delta (p = 0141), BA1 (p = 0.0255), BA4/5 (p = 0.0162). Infections with Delta also drove an increase of pro-inflammatory cytokines (IFN-α, p = 0.0463; IL-6, p = 0.0010). CONCLUSIONS: Administration of 3 vaccination doses reduces the severe symptomatology in aged and elderly. Vaccination showed a strong association with anti-SARS-CoV-2 humoral response and an expansion of Th2 T-cells populations, independently of age. Delta variants and number of vaccine doses affected the magnitude of the humoral response against the original SARS-CoV-2 and emerging variants. A systematic surveillance of the emerging variants is paramount to define future vaccination strategies.

Trends in symptom prevalence and sequential onset of SARS-CoV-2 infection from 2020 to 2022 in East and Southeast Asia: a trajectory pattern exploration based on summary data.

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