Search Results (842)

Despite the current level of public immunity to SARS-CoV-2, the early inflammatory events associated with respiratory distress in COVID-19 patients are not fully elucidated. Syrian golden hamsters, facultative hibernators, recapitulate the phenotype of SARS-CoV-2-induced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—induced severe acute lung injury seen in patients. In this study, we describe the predominance of the innate immune response in hamsters inoculated with four different SARS-CoV-2 variants, underscoring phenotypic differences among them. Severe inflammatory lung injury was chronologically associated with acute and significant weight loss, mainly in animals inoculated with A.2 and Delta variants. Omicron-infected animals had lower overall histopathology scores compared to other variants. We highlight the central role of endothelial injury and activation in the pathogenesis of experimental SARS-CoV-2 infection in hamsters, characterised by the presence of proliferative type I and type II pneumocytes with abundant surfactant expression, thereby maintaining hyperinflated alveolar fields. Additionally, there was evidence of intrapulmonary lymphatic vessel proliferation, which was accompanied by a lack of detectable microthrombosis in the lung parenchyma. However, white microthrombi were observed in lymphatic vessels. Our findings suggest that the physiological compensatory mechanisms that maintain respiratory homeostasis in Golden Syrian hamsters prevent severe respiratory distress and death after SARS-CoV-2 infection. Full article

The COVID-19 pandemic accelerated the rapid development and distribution of various vaccine platforms, resulting in a significant reduction in disease severity, hospitalizations, and mortality. However, persistent challenges remain concerning the durability and breadth of vaccine-induced protection, especially in the face of emerging SARS-CoV-2 variants. This review aimed to evaluate the factors influencing the immunogenicity and effectiveness of COVID-19 vaccines to inform future vaccine advancement strategies. A narrative review with systematic approach was conducted following PRISMA guidelines for narrative review. Literature was sourced from databases including PubMed, Embase, and Web of Science for studies published between December 2019 and May 2025. Encompassed studies assessed vaccine efficacy, immunogenicity, and safety across various populations and vaccine platforms. Data were collected qualitatively, with quantitative data from reviews highlighted where available. We have uncovered a decline in vaccine efficacy over time and weakened protection against novel variants such as Delta and Omicron. Booster doses, specifically heterologous regimens, improved immunogenicity and increased protection. Vaccine-induced neutralizing antibody titers have been found to correlate with clinical protection, although the long-term correlates of immunity remain poorly defined. The induction of IgG4 antibodies after repeated mRNA vaccinations raised concerns about potential modulation of the immune response. COVID-19 vaccines have contributed significantly to pandemic control; however, their efficacy is limited by the evolution of the virus and declining immunity. Forthcoming vaccine strategies should focus on broad-spectrum, variant-adapted formulations and defining robust comparisons of protection. Recognizing the immunological basis of vaccine response, including the role of specific antibody subclasses, is fundamental for optimizing long-term protection. Full article

Background: Kidney transplant recipients (KTRs) exhibit a significantly diminished immune response to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccines compared with the general population, primarily due to ongoing immunosuppressive therapy. This study evaluated the immunogenicity of a third SARS-CoV-2 mRNA vaccine dose in KTRs and assessed the association between antibody response and protection against SARS-CoV-2 breakthrough infection. Additionally, the clinical and immunological correlates of post-vaccination SARS-CoV-2 infection were examined. Methods: A prospective cohort of 135 KTRs received a third vaccine dose approximately six months following the second dose. Plasma samples were collected at baseline (pre-vaccination), six months after the second dose, and six weeks following the third dose. Humoral responses were assessed using SARS-CoV-2-specific Immunoglobulin G (IgG) titers and virus neutralization assays against wild-type (WT) and viral strains, including multiple Omicron sub-lineages. Results: After the third vaccine dose, 74% of the KTRs had detectable SARS-CoV-2-specific IgG antibodies, compared with 48% following the second dose. The mean IgG titers increased approximately ten-fold post-booster. Despite this increase, neutralizing activity against the Omicron variants remained significantly lower than that against the WT strain. KTRs who subsequently experienced a SARS-CoV-2 breakthrough infection demonstrated reduced neutralizing antibody activity across all variants tested. Additionally, individuals receiving triple immunosuppressive therapy had a significantly higher risk of SARS-CoV-2 breakthrough infection compared with those on dual or monotherapy. A multivariate machine learning analysis identified age and neutralizing activity against WT, Delta, and Omicron BA.2 as the most robust correlates of SARS-CoV-2 breakthrough infection. Conclusions: A third SARS-CoV-2 mRNA vaccine dose significantly improves SARS-CoV-2-specific IgG levels in KTRs; however, the neutralizing response against Omicron variants remains suboptimal. Diminished neutralizing capacity and intensified immunosuppression are key determinants of SARS-CoV-2 breakthrough infection in this immunocompromised population. Full article

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, in December 2019, it has evolved, leading to variants that differ in their transmissibility, severity of disease, and susceptibility to therapy. Our goal was to describe the dynamics of the emergence of SARS-CoV-2 variants among the population of the southern part of Poland (Silesia) in the period from September 2021 to August 2022. Our results showed that, like in the rest of Poland or in neighboring countries (Czech Republic, Slovakia), Delta was replaced by the Omicron BA.1 variant, isolated for the first time in December 2021, and subsequently Omicron BA.2 and its derivative subvariants acquiring further mutations. Finally, in August 2022, only the BA.5.2.26 subvariant was present in Silesia. However, we noted differences in the dynamics of emergence and spread of some Omicron subvariants compared to the rest of Poland and the neighboring countries, which may be due to differences in population density or import of the virus from other regions. Full article

Understanding how hospital length of stay (LoS) evolves with successive SARS-CoV-2 variants is central to the multiscale modeling and forecasting of COVID-19 and other respiratory virus dynamics. Using records from 1249 COVID-19 patients admitted to Chungbuk National University Hospital (2021–2023), we quantified LoS across three distinct variant phases (Pre-Delta, Delta, and Omicron) and three age groups (0–39, 40–64, and 65+ years). A gamma-distributed multi-state model—capturing transitions between semi-critical and critical wards—incorporated variant phase and age as log-linear covariates. Parameters were estimated via maximum likelihood with 95% confidence intervals derived from bootstrap resampling, and Monte Carlo iterations yielded detailed LoS distributions. Omicron-phase stays were 5–8 days, shorter than the 10–14 days observed in earlier phases, reflecting improved treatment protocols and reduced virulence. Younger adults typically stayed 3–5 days, whereas older cohorts required 8–12 days, with prolonged admissions (over 30 days) clustering in the oldest group. These time-dependent transition probabilities can be integrated with real-time bed-availability alert systems, highlighting the need for variant-specific ward/ICU resource planning and underscoring the importance of targeted management for elderly patients during current and future pandemics. Full article

The study aimed to identify the variants of SARS-CoV-2 (Severe Acute Respiratory Syndrome related coronavirus-2) virus isolates within the window of March 2021 to February 2022 in Bangladesh and investigate their comparative mutational profiles, preferences and phylogenetics. After the collection of the sample specimen and RNA extraction, the genome was sequenced using Illumina COVID Seq, and NGS data analysis was performed in DRAGEN COVID Lineage software (version 3.5.9). Among the 96 virus isolates, 24 (25%) were from Delta (clade 21A (n = 21) and 21J (n = 3)) and 72 (75%) were from Omicron (clade 20A (n = 6) and 20B (n = 66)). In Omicron and Delta, substitutions were much higher than deletions and insertions. High-frequency nucleotide change patterns were similar (for C > T, and A > G) in both of the variants, but different in some (i.e., G > T, G > A). Preferences for specific amino acids over the other amino acids in substitutions and deletions were observed to vary in different proteins of these variants. Phylogenetic analysis showed that the most ancestral variants were from clade 21A and clade 20A, and then the other variants emerged. The study demonstrates noteworthy variations of Omicron and Delta in mutational pattern and preferences for amino acids and protein, and further study on their biological functional impact might unveil the reason behind their mutational strategies and behavioral changes. Full article

The SARS-CoV-2 ORF8 protein is a unique accessory viral protein among human coronaviruses, characterized by recurrent deletions and mutations with functional consequences. In this short report, we demonstrate that several dominant SARS-CoV-2 strains, despite encoding ORF8, fail to secrete the protein, revealing a recurring pattern of ORF8 functional impairment that cannot be detected by sequence analysis alone. In agreement with other studies, several high-frequency mutations were identified using the Nextstrain/augur pipeline, including G8Stop, Q27Stop, D119-/F120- double deletions, and nucleotide substitution C27889U, which occurred in XBB.1.5, Alpha, Delta, and BA.5.2 variants, respectively. Notably, the D119-/F120- deletions and C27889U substitution do not introduce premature stop codons, yet ORF8 secretion was lost in Delta and BA.5.2 virus-infected cultures. This indicates that the extracellular ORF8 function is impaired in these variants, resulting in ORF8 deficiency. Our findings highlight that the impairment of ORF8 secretion arises not only from premature stop codons but also from other mutations. Therefore, the functional validation of ORF8 secretion and activity is essential following sequence analysis to accurately assess ORF8’s role in SARS-CoV-2 infection. Full article

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has rapidly evolved, giving rise to multiple Variants of Concern—including Alpha, Beta, Gamma, Delta, and Omicron—which emerged independently across different regions. Licensed COVID-19 vaccines primarily target the highly mutable spike protein, resulting in reduced efficacy due to immune escape by emerging variants. Previously, we developed a live attenuated Francisella tularensis LVS ΔcapB single-vector platform COVID-19 vaccine, rLVS ΔcapB/MN, expressing the conserved membrane (M) and nucleocapsid (N) proteins from the early SARS-CoV-2 WA-01/2020 strain. In this study, we evaluate the efficacy of rLVS ΔcapB/MN and an enhanced version, rLVS ΔcapB::RdRp/MN, which additionally expresses the conserved RNA-dependent RNA polymerase (RdRp) protein from the same strain, in a hamster model. Methods: Both vaccine candidates were administered orally or intranasally to golden Syrian hamsters (equal numbers of males and females) and evaluated against intranasal challenge with SARS-CoV-2 Delta (B.1.617.2-AY.1) and Omicron (BA.5) variants. Results: Vaccinated animals developed robust, TH1-biased IgG responses specific to the nucleocapsid protein. Following SARS-CoV-2 challenge, immunized hamsters exhibited reduced weight loss, lower oropharyngeal and lung viral titers, and improved lung pathology scores compared with unvaccinated controls. Conclusion: These findings support the potential of this universal vaccine to provide broad protection against current and future SARS-CoV-2 variants, with minimal need for updating. Full article

Background/Objectives: To evaluate how immune responses compare among ethnic groups approximately 2 years after receiving a third dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1or BBIBP-CorV), we tested T cell responses and Spike-specific RBD-antibody titer, and neutralized antibody titer levels utilizing Spectral Flow cytometry, ELISA, and SARS-CoV-2 pseudotyped-based neutralization assays, respectively. Methods: Forty-four individuals from January–December 2023 were identified within the cohort and were classified into different ethnic backgrounds; Black (N = 13), Asian (N = 14), Caucasian (N = 17). We recognize that the “Asian” group includes diverse subpopulations with distinct genetic and environmental backgrounds, which could not be further stratified due to sample-size limitations. Spike-specific AIM+, CD4+, and CD8+ T cell responses were assessed and evaluated against SARS-CoV-2 variants, including the ancestral Wuhan, Delta, and multiple Omicron subvariants (B1.1529, BA2.86, BA.4/5, and XBB.1). Alongside we tested the RBD-IgG and neutralizing antibody titers against the ancestral Wuhan. Spearman’s correlation analysis was utilized to determine corelative relationships among the AIM+ and CD4+ T cell responses, as well as the RBD-IgG and neutralizing antibody titers. Results: Our results show robust and comparable RBD-IgG and neutralizing antibody titers across all groups, with a significant positive correlation between these two measurements. Significant differences were observed in T-cell activation, with Asian participants exhibiting lower frequencies of Spike-specific CD4+ T cells against SARS-CoV-2 Omicron subvariants and higher frequencies of cytokine-producing CD4+ T cells (TNF-α, IFN-γ, and IL-2) as compared to the Caucasian group. Breakthrough infection status was not fully controlled and may influence these findings. Conclusion: Despite a small sample size and potential confounding by natural infections within our long-time-span sampling, our data suggest persistent cellular and humoral immunity 2 years after vaccination across ethnicities, with notable differences in T cell activation and cytokine profile. These preliminary observations highlight the need for larger, more detailed studies that consider intra-ethnic diversity and hybrid immunity to better understand ethnic differences in COVID-19 vaccine responses. Full article

In Cali, Colombia, 405,689 COVID-19 cases were reported until March 2023, with 2463 complete genome sequences available for analysis. SARS-CoV-2 genomic data from Cali were analyzed to determine the prevalence of variants as well as the mutation frequencies. This study identified Nextstrain clades, Pango lineages, and specific mutations in key viral proteins. A total of 23 Nextstrain clades and 118 Pango lineages were detected, including variants of interest (Lambda, Mu) and variants of concern (Alpha, Gamma, Delta, Omicron). Analysis identified 2424 missense mutations, with notable frequencies in NSP3 (465), S (367), NSP2 (205), N (180), ORF3a (144), NSP12b (113), and NSP13 (108). The study also observed a high prevalence of simultaneous transmission of multiple variants. The COVID-19 epidemic waves in Cali were shaped more by social and economic dynamics than by the emergence of specific SARS-CoV-2 variants. These findings highlight the importance of context-specific public health interventions to mitigate future outbreaks effectively. Full article

Background/Objectives: Patients suffering from inflammatory bowel diseases (IBDs) undergoing treatment with anti-TNF antibodies mount a diminished humoral immune response to vaccination against SARS-CoV-2 compared to healthy controls. The characterization of variant-specific immune responses is particularly warranted among immunosuppressed patients, where reduced responses may necessitate further medical interventions. Methods: This pilot study investigated the humoral immune response of vaccinated IBD patients on anti-TNF medication and a comparable group of healthy individuals against the viral variants Alpha, Beta, Gamma, Delta, and Omicron BA.1 and BA.5. While total IgG antibodies targeting the receptor binding site of the spike protein of SARS-CoV-2 were quantified using a chemiluminescence microparticle immunoassay (CMIA), their potential neutralizing capacity was determined using commercial and variant-specific in-house surrogate virus neutralization tests (sVNTs) against a variant-specific in-house VSV-pseudotyped virus neutralization test (pVNT) as the gold standard. Results: Employing variant-specific assays recapitulated the immune escape functions of virus variants. Conspicuously, antibody reactivity against Alpha and Omicron BA.1 and BA.5 was strikingly poor in IBD patient sera post-initial vaccination compared to healthy individuals. A comparison of the diagnostic performance of assays with the pVNT revealed that identification of patients with inadequate humoral responses by CMIA and sVNT may require adjustments to cut-off values and end-point titration of sera. Following adaptation of cut-off values, patient sera exhibited reduced reactivity against all tested variants. The assay panel used substantiated the impact of anti-TNF therapy in IBD patients as to reduced strength, function, and breadth of the immune response to several SARS-CoV-2 variants. The immune response measured following the second vaccination was comparable to the antibody response observed in healthy individuals following the first vaccination. Conclusion: Variant-specific sVNTs and pVNTs have the potential to serve as valuable tools for evaluating the efficacy of adapted vaccines and to inform clinical interventions in the care of immunosuppressed patients. Anti-TNF-treated individuals with antibody levels below the optimized CMIA threshold should be considered for early booster vaccination and/or close immunological monitoring. Full article

Background/Objectives: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has resulted in 777 million cases worldwide. Various vaccines have been approved to control the spread of COVID-19, with mRNA vaccines (Pfizer and Moderna) being widely used in the USA. We conducted a prospective longitudinal study to analyze the immune response elicited by two/three and four doses of monovalent mRNA vaccines in both vaccinated individuals and those who experienced breakthrough infections. Participants were stratified into different age groups: 18–40, 41–60, and over 60 years. Methods: We assessed cross-variant neutralization responses in two cohorts—Cohort I: n = 167 (serum), Cohort II: n = 92 (serum and nasal swab) samples—using infectious virus microneutralization assay (MN) and antibody (IgG or IgA) binding ELISA titers to the spike protein receptor binding domain (RBD). Samples were collected from the Louisville Metro–Jefferson County Co-Immunity Project, a federally funded, population-based study for the surveillance of SARS-CoV-2 in Jefferson County, Kentucky during 2020–2022, involving both health care workers and a local community. Results: Individuals who received two doses of the mRNA vaccine exhibited reduced neutralization against Beta, Delta, and Omicron BA.1 variants compared to wildtype Wuhan, with further decline observed six months post-booster vaccination. However, individuals who experienced natural COVID-19 infection (breakthrough) after receiving two vaccine doses showed enhanced neutralization and antibody responses, particularly against Omicron BA.1. Following the 3rd dose, antibodies and neutralization responses were restored. Among triple-vaccinated individuals, reduced neutralization was observed against Omicron variants BA.1, BA.5, and BA.2 compared to Wuhan. Neutralization responses were better against BA.2 variant compared to BA.1 and BA.5. However, individuals who received three doses of vaccine and experienced a breakthrough infection (n = 45) elicited significantly higher neutralizing antibodies responses against all Omicron subvariants compared to vaccinated individuals. Interestingly, nasal swab samples collected from volunteers with breakthrough infection showed significantly elevated spike-reactive mucosal IgA antibodies and enhanced cross neutralization against BA.1, BA.2, and BA.5 compared to individuals who received only three vaccine doses. Conclusions: mRNA vaccination elicits a strong systemic immune response by boosting serum neutralizing antibodies (NAb), although this protection wanes over time, allowing new variants to escape neutralization. Breakthrough individuals have extra enrichment in nasal NAb offering protection against emerging variants. This longitudinal immune profiling underscores the strengthening of pandemic preparedness and supports the development of durable mucosal vaccines against respiratory infectious disease. Full article

(1) Background: The currently circulating variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits resistance to antibodies induced by vaccines. The World Health Organization recommended the use of monovalent XBB.1 sublineages (e.g., XBB.1.5) as an antigenic component in 2023. (2) Objective: In this study, we aimed to develop vaccines based on the XBB.1.5 receptor-binding domain (RBD) to combat the recently emerged SARS-CoV-2 XBB and JN.1 variants, as well as previously circulating variants. (3) Methods: Glycoengineered Pichia pastoris was utilized to produce a recombinant XBB.1.5 RBD protein with mammalian-like and fucose-free N-glycosylation. The XBB.1.5 RBD was mixed with Al(OH)₃:CpG adjuvants to prepare monovalent vaccines. Thereafter, the XBB.1.5 RBD was mixed with the Beta (B.1.351), Delta (B.1.617.2), or Omicron (BA.2) RBDs (1:1 ratio), along with Al(OH)₃:CpG, to prepare bivalent vaccines. BALB/c mice were immunized with the monovalent and bivalent vaccines. Neutralizing antibody titers were assessed via pseudovirus and authentic virus assays; humoral immune responses were analyzed by RBD-binding IgG subtypes. (4) Results: The monovalent vaccine induced higher neutralizing antibody titers against Delta, BA.2, XBB.1.5, and JN.1 compared to those in mice immunized solely with Al(OH)₃:CpG, as demonstrated by pseudovirus virus assays. The XBB.1.5/Delta RBD and XBB.1.5/Beta RBD-based bivalent vaccines provided potent protection against the BA.2, XBB.1.5, JN.1, and KP.2 variants, as well as the previously circulating Delta and Beta variants. All monovalent and bivalent vaccines induced high levels of RBD-binding IgG (IgG1, IgG2a, IgG2b, and IgG3) antibodies in mice, suggesting that they elicited robust humoral immune responses. The serum samples from mice immunized with the XBB.1.5 RBD-based and XBB.1.5/Delta RBD-based vaccines could neutralize the authentic XBB.1.16 virus. (5) Conclusions: The XBB.1.5/Beta and XBB.1.5/Delta RBD-based bivalent vaccines are considered as potential candidates for broad-spectrum vaccines against SARS-CoV-2 variants. Full article

In the past 5 years, the COVID-19 pandemic has experienced frequently changing variants contextualizing immune evasion. The emergence of Omicron with >30–50 mutations on the spike gene has shown a sharp divergence from its relative VOCs, such as WT, Alpha, Beta, Gamma, and Delta. The requisition of prime boosting was essential within 3–6 months to improve the Nab response that had been not lasted for longer. Omicron subvariant BA.1.1 was less transmissible, but with an extra nine mutations in next variant BA.2 made it more transmissible. This remarkable heterogeneity was reported in ORF1ab or TRS sites, ORF7a, and 10 regions in the genomic sequences of Omicron BA.2 and its evolving subvariants BA.4.6, BF.7, BQ.2, BF. 7, BA.2.75.2, and BA.5 (BQ.1 and BQ.1.1). The mutational stability of subvariants XBB, XBB 1, XBB 1.5, and XBB 1.6 conferred a similar affinity towards ACE-2. This phenomenon has been reported in breakthrough infections and after booster vaccinations producing hybrid immunity. The reduced pathogenic nature of Omicron has implicated its adaptation either through immunocompromised individuals or other animal hosts. The binding capacity of RBD and ACE-2, including the proteolytic priming via TMPRSS2, reveals its (in-vitro) transmissibility behavior. RBD mutations signify transmissibility, S1/S2 enhances virulence, while S2 infers the effective immunogenic response. Initial mutations D614G, E484A, N501Y, Q493K, K417N, S477N, Y505H, and G496S were found to increase the Ab escape. Some mutations such as, R346K, L452R, and F486Vwere seen delivering immune pressure. HR2 region (S2) displayed mutations R436S, K444T, F486S, and D1199N with altered spike positions. Later on, the booster dose or breakthrough infections contributed to elevating the immune profile. Several other mutations in BA.1.1-N460K, R346T, K444T, and BA.2.75.2-F486S have also conferred the neutralization resistance. The least studied T-cell response in SARS-CoV-2 affects HLA- TCR interactions, thus, it plays a role in limiting the virus clearance. Antigenic cartographic analysis has also shown Omicron’s drift from its predecessor variants. The rapidly evolving SARS-CoV-2 variants and subvariants have driven the population-based immunity escape in fully immunized individuals within short period. This could be an indication that Omicron is heading towards endemicity and may evolve in future with subvariants could lead to outbreaks, which requires regular surveillance. Full article

Background: The 2019 coronavirus disease (COVID-19) pandemic had a severe impact on frail, end-stage kidney disease (ESKD) patients, either on dialysis or transplanted, with a high mortality rate in the early waves. Vaccination against SARS-CoV-2 with mRNA vaccines has led to reduced hospitalization and mortality rates in the general population and ESKD patients. Neutralizing antibodies (NAbs) are a valuable correlate of protection after vaccination, and IgG anti-spike antibodies are considered a surrogate marker of protection. Methods: This study investigated the correlates of protection brought by NAb and anti-spike IgG antibodies against SARS-CoV-2 wild-type Wuhan strain and variants of concern in a cohort of 128 French patients on dialysis after vaccination with the BNT162b2 mRNA vaccine. The correlate was assessed using Receiver Operating Characteristic curves. Results: The level of protection for IgG anti-spike antibodies was set at 917 BAU/mL for the original Wuhan strain and 980 BAU/mL and 1450 BAU/mL, respectively, for the Delta and Omicron BA.1 variants. Conclusions: The level of protection can be regularly monitored by measuring IgG anti-spike antibody concentrations to allow tailored boosters of SARS-CoV-2 vaccination in this frail and immunocompromised ESKD population. Full article