Single-cell transcriptomic analysis of B cells reveals new insights into atypical memory B cells in COVID-19.

Here, we performed single-cell RNA sequencing of S1 and receptor binding domain protein-specific B cells from convalescent COVID-19 patients with different clinical manifestations. This study aimed to evaluate the role and developmental pathway of atypical memory B cells (MBCs) in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The results revealed a proinflammatory signature across B cell subsets associated with disease severity, as evidenced by the upregulation of genes such as GADD45B, MAP3K8, and NFKBIA in critical and severe individuals. Furthermore, the analysis of atypical MBCs suggested a developmental pathway similar to that of conventional MBCs through germinal centers, as indicated by the expression of several genes involved in germinal center processes, including CXCR4, CXCR5, BCL2, and MYC. Additionally, the upregulation of genes characteristic of the immune response in COVID-19, such as ZFP36 and DUSP1, suggested that the differentiation and activation of atypical MBCs may be influenced by exposure to SARS-CoV-2 and that these genes may contribute to the immune response for COVID-19 recovery. Our study contributes to a better understanding of atypical MBCs in COVID-19 and the role of other B cell subsets across different clinical manifestations.

Anti-PF4 positivity and platelet activation after Ad26.COV2·S vaccination in Brazil.

INTRODUCTION: The Ad26.COV2·S (Janssen/Johnson & Johnson) COVID-19 vaccine, has been rarely associated with vaccine-induced immune thrombocytopenia and thrombosis (VITT). We investigated the prevalence of anti-PF4 antibody positivity, thrombocytopenia, D-dimer elevation, plasmatic thromboinflammatory markers, and platelet functional assays following Ad26.COV2·S vaccination in Rio de Janeiro, Brazil. METHODS: From July to September 2021, participants were assessed prior, 1, and 3 weeks post-vaccination. Platelet count and D-dimer were measured at each visit and anti-PF4 at week 3. A positive anti-PF4 prompted retrospective testing of the sample from week 0. Individuals with new thrombocytopenia or elevated D-dimer, positive anti-PF4, and 38 matched controls without laboratory abnormalities were evaluated for plasmatic p-selectin, tissue factor, and functional platelet activation assays. RESULTS: 630 individuals were included; 306 (48.57%) females, median age 28 years. Forty-two (6.67%) presented ≥1 laboratory abnormality in week 1 or 3. Five (0.79%) had thrombocytopenia, 31 (4.91%) elevated D-dimer, and 9 (1.57%) had positive anti-PF4 at week 3. Individuals with laboratory abnormalities and controls showed a slight increase in plasmatic p-selectin and tissue factor. Ten individuals with laboratory abnormalities yielded increased surface expression of p-selectin, and their ability to activate platelets in a FcγRIIa dependent manner was further evaluated. Two were partially inhibited by high concentrations of heparin and blockage of FcγRII with IV.3 antibody. Plasma obtained before vaccination produced similar results, suggesting a lack of association with vaccination. CONCLUSIONS: Vaccination with Ad26.COV2·S vaccine led to a very low frequency of low-titer positive anti-PF4 antibodies, elevation of D-dimer, and mild thrombocytopenia, with no associated clinically relevant increase in thromboinflammatory markers and platelet activation.

Preeclampsia in the Context of COVID-19: Mechanisms, Pathophysiology, and Clinical Outcomes.

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the global COVID-19 pandemic, significantly impacting the health of pregnant women. Obstetric populations, already vulnerable, face increased morbidity and mortality related to COVID-19, aggravated by preexisting comorbidities. Recent studies have shed light on the potential correlation between COVID-19 and preeclampsia (PE), a leading cause of maternal and perinatal morbidity worldwide, emphasizing the significance of exploring the relationship between these two conditions. Here, we review the pathophysiological similarities that PE shares with COVID-19, with a particular focus on severe COVID-19 cases and in PE-like syndrome cases related with SARS-CoV-2 infection. We highlight cellular and molecular mechanistic inter-connectivity between these two conditions, for example, regulation of renin-angiotensin system, tight junction and barrier integrity, and the complement system. Finally, we discuss how COVID-19 pandemic dynamics, including the emergence of variants and vaccination efforts, has shaped the clinical scenario and influenced the severity and management of both COVID-19 and PE. Continued research on the mechanisms of SARS-CoV-2 infection during pregnancy and the potential risk of developing PE from previous infections is warranted to delineate the complexities of COVID-19 and PE interactions and to improve clinical management of both conditions.

Contribution of memory T cells to the generation of long-lasting immunity against COVID-19.

Humans are exposed every day to innumerable external stimuli, both environmental and microbial. Immunological memory recalls each specific stimulus and mounts a secondary response that is faster and of a larger magnitude than the primary response; this process constitutes the basis for vaccine development. The COVID-19 pandemic offers a unique opportunity to study the development of immune memory against an emergent microorganism. Memory T cells have an important role in the resolution of COVID-19, and they are key pillars of immunological memory. In this review, we summarize the main findings regarding anti-SARS-CoV-2 memory T cells after infection, after vaccination, and after the combination of these two events ("hybrid immunity"), and analyze how these cells can contribute to long-term protection against the infection with SARS-CoV-2 variants.

Los humanos se exponen cada día a innumerables estímulos externos, tanto ambientales como microbianos. La memoria inmunológica registra de manera específica un estímulo y articula una respuesta secundaria más rápida y de mayor magnitud que la respuesta primaria; este proceso constituye la base del desarrollo de vacunas. La pandemia de COVID-19 ofreció la oportunidad de estudiar el desarrollo de la memoria inmunológica contra un microorganismo emergente. Las células T de memoria tienen un papel importante en la resolución de COVID-19 y son pilares importantes de la memoria inmunológica. En esta revisión se resumen los principales hallazgos de la respuesta de las células T de memoria contra la infección por SARS-CoV-2, a la vacunación o a la combinación de ambos procesos ("inmunidad híbrida"), y se discute cómo estas células pueden contribuir a la protección a largo plazo contra distintas variantes del virus.

Efficacy, immunogenicity and safety of CoronaVac® in children and adolescents aged 6 months to 17 years: a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial.

Safe and effective vaccines against COVID-19 for children and adolescents are needed. This international multicenter, randomized, double-blind, placebo-controlled, phase III clinical trial assessed the efficacy, immunogenicity, and safety of CoronaVac® in children and adolescents (NCT04992260). The study was carried out in Chile, South Africa, Malaysia, and the Philippines. The enrollment ran from September 10, 2021 to March 25, 2022. For efficacy assessment, the median follow-up duration from 14 days after the second dose was 169 days. A total of 11,349 subjects were enrolled. Two 3-µg injections of CoronaVac® or placebo were given 28 days apart. The primary endpoint was the efficacy of the CoronaVac®. The secondary endpoints were the immunogenicity and safety. The vaccine efficacy was 21.02% (95% CI: 1.65, 36.67). The level of neutralizing antibody in the vaccine group was significantly higher than that in the placebo group (GMT: 390.80 vs. 62.20, P <0.0001). Most adverse reactions were mild or moderate. All the severe adverse events were determined to be unrelated to the investigational products. In conclusion, in the Omicron-dominate period, a two-dose schedule of 3 µg CoronaVac® was found to be safe and immunogenic, and showed potential against symptomatic COVID-19 in healthy children and adolescents.

4th booster-dose SARS-CoV-2 heterologous and homologous vaccination in rheumatological patients.

Objective: to evaluate the immune response to the SARS-CoV-2 vaccines in adults with immune-mediated rheumatic diseases (IMRDs) in comparison to healthy individuals, observed 1-20 weeks following the fourth vaccine dose. Additionally, to evaluate the impact of immunosuppressive therapies, vaccination schedules, the time interval between vaccination and sample collection on the vaccine's immune response. Methods: We designed a longitudinal observational study conducted at the rheumatology department of Hospital de Copiapó. Neutralizing antibodies (Nabs) titers against the Wuhan and Omicron variant were analyzed between 1-20 weeks after administration of the fourth dose of the SARS-CoV-2 vaccine to 341 participants (218 IMRD patients and 123 healthy controls). 218 IMRD patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), systemic vasculitis (VS) and systemic scleroderma (SS) were analyzed. Results: Performing a comparison between the variants, Wuhan vs Omicron, we noticed that there were significant differences (p<0.05) in the level of the ID50, both for healthy controls and for patients with IMRDs. The humoral response of patients with IMRDs is significantly lower compared to healthy controls for the Omicron variant of SARS-CoV-2 (p = 0.0015). The humoral response of patients with IMRDs decreases significantly when the time interval between vaccination and sample collection is greater than 35 days. This difference was observed in the response, both for the Wuhan variant and for the Omicron variant. Conclusion: The IMRDs patients, the humoral response variation in the SARS-CoV-2 vaccine depends on doses and type of vaccine administered, the humoral response times and the treatment that these patients are receiving.

Comparison of Adverse Events and Antibody Responses Among Different COVID-19 Vaccination Schedules.

Global investment in developing COVID-19 vaccines has been substantial, but vaccine hesitancy has emerged due to misinformation. Concerns about adverse events, vaccine shortages, dosing confusion, mixing vaccines, and access issues contribute to hesitancy. Initially, the WHO recommended homologous vaccination (same vaccine for both doses), but evolving factors led to consideration of heterologous vaccination (different vaccines). The study compared reactogenicity and antibody response for both viral protein spike (S) and nucleocapsid (N) in 205 participants who received three vaccination regimens: same vaccine for all doses (Pfizer), two initial doses of the same vaccine (CoronaVac or AstraZeneca), and a Pfizer booster. ChAdOx1 and BNT162b2 vaccines were the most reactogenic vaccines, while CoronaVac vaccine was the least. ChAdOx1 and BNT162b2 achieved 100% of S-IgG seropositivity with one dose, while CoronaVac required two doses, emphasizing the importance of the second dose in achieving complete immunization across the population with different vaccine regimes. Pfizer recipients showed the highest S-IgG antibody titers, followed by AstraZeneca recipients, both after the first and second doses. A third vaccine dose was essential to boost the S-IgG antibodies and equalize the antibody levels among the different vaccine schedules. CoronaVac induced N-IgG antibodies, while in the Pfizer and AstraZeneca groups, they were induced by a natural infection, reinforcing the role of N protein as a biomarker of infection.

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.

Advancement in the development of mRNA-based vaccines for respiratory viruses.

Acute respiratory infections are the leading cause of death and illness in children under 5 years old and represent a significant burden in older adults. Primarily caused by viruses infecting the lower respiratory tract, symptoms include cough, congestion, and low-grade fever, potentially leading to bronchiolitis and pneumonia. Messenger ribonucleic acid (mRNA)-based vaccines are biopharmaceutical formulations that employ mRNA molecules to induce specific immune responses, facilitating the expression of viral or bacterial antigens and promoting immunization against infectious diseases. Notably, this technology had significant relevance during the COVID-19 pandemic, as these formulations helped to limit SARS-CoV-2 virus infections, hospitalizations, and deaths. Importantly, mRNA vaccines promise to be implemented as new alternatives for fighting other respiratory viruses, such as influenza, human respiratory syncytial virus, and human metapneumovirus. This review article analyzes mRNA-based vaccines' main contributions, perspectives, challenges, and implications against respiratory viruses.

Immune Stimulation with Imiquimod to Best Face SARS-CoV-2 Infection and Prevent Long COVID.

Through widespread immunization against SARS-CoV-2 prior to or post-infection, a substantial segment of the global population has acquired both humoral and cellular immunity, and there has been a notable reduction in the incidence of severe and fatal cases linked to this virus and accelerated recovery times for those infected. Nonetheless, a significant demographic, comprising around 20% to 30% of the adult population, remains unimmunized due to diverse factors. Furthermore, alongside those recovered from the infection, there is a subset of the population experiencing persistent symptoms referred to as Long COVID. This condition is more prevalent among individuals with underlying health conditions and immune system impairments. Some Long COVID pathologies stem from direct damage inflicted by the viral infection, whereas others arise from inadequate immune system control over the infection or suboptimal immunoregulation. There are differences in the serum cytokines and miRNA profiles between infected individuals who develop severe COVID-19 or Long COVID and those who control adequately the infection. This review delves into the advantages and constraints associated with employing imiquimod in human subjects to enhance the immune response during SARS-CoV-2 immunization. Restoration of the immune system can modify it towards a profile of non-susceptibility to SARS-CoV-2. An adequate immune system has the potential to curb viral propagation, mitigate symptoms, and ameliorate the severe consequences of the infection.

The effect of previous SARS-CoV-2 infection on systemic immune responses in individuals with tuberculosis.

Background: The impact of previous SARS-CoV-2 infection on the systemic immune response during tuberculosis (TB) disease has not been explored. Methods: An observational, cross-sectional cohort was established to evaluate the systemic immune response in persons with pulmonary tuberculosis with or without previous SARS-CoV-2 infection. Those participants were recruited in an outpatient referral clinic in Rio de Janeiro, Brazil. TB was defined as a positive Xpert-MTB/RIF Ultra and/or a positive culture of Mycobacterium tuberculosis from sputum. Stored plasma was used to perform specific serology to identify previous SARS-CoV-2 infection (TB/Prex-SCoV-2 group) and confirm the non- infection of the tuberculosis group (TB group). Plasmatic cytokine/chemokine/growth factor profiling was performed using Luminex technology. Tuberculosis severity was assessed by clinical and laboratory parameters. Participants from TB group (4.55%) and TB/Prex-SCoV-2 (0.00%) received the complete COVID-19 vaccination. Results: Among 35 participants with pulmonary TB, 22 were classified as TB/Prex-SCoV-2. The parameters associated with TB severity, together with hematologic and biochemical data were similar between the TB and TB/Prex-SCoV-2 groups. Among the signs and symptoms, fever and dyspnea were significantly more frequent in the TB group than the TB/Prex-SCoV-2 group (p < 0,05). A signature based on lower amount of plasma EGF, G-CSF, GM-CSF, IFN-α2, IL-12(p70), IL-13, IL-15, IL-17, IL-1ß, IL-5, IL-7, and TNF-ß was observed in the TB/Prex-SCoV-2 group. In contrast, MIP-1ß was significantly higher in the TB/Prex-SCoV-2 group than the TB group. Conclusion: TB patients previously infected with SARS-CoV-2 had an immunomodulation that was associated with lower plasma concentrations of soluble factors associated with systemic inflammation. This signature was associated with a lower frequency of symptoms such as fever and dyspnea but did not reflect significant differences in TB severity parameters observed at baseline.

Atypical hemolytic-uremic syndrome after COVID-19 vaccine: A case report.

BACKGROUND: The emergence of new SARS-CoV-2 variants and the global COVID-19 pandemic spurred urgent vaccine development. While common vaccine side effects are well-documented, rare adverse events necessitate post-marketing surveillance. Recent research linked messenger RNA vaccines to thrombotic microangiopathy (TMA), a group of syndromes characterized by microvascular hemolytic anemia and thrombocytopenia. This report describes a new-onset atypical hemolytic-uremic syndrome (aHUS) occurring after COVID-19 vaccination and complements recent literature. CASE PRESENTATION: A previously healthy 25-year-old woman developed malaise, nausea, edema, and renal dysfunction 60 days postvaccination. Laboratory findings confirmed TMA diagnosis. Genetic testing for complement system mutations was negative. Kidney biopsy supported the diagnosis, and the patient required hemodialysis. CONCLUSION: This case illustrates the rare occurrence of aHUS following COVID-19 vaccination, with unique characteristics compared to previous reports. Despite the critical role of vaccination in pandemic control, emerging adverse events, such as vaccine-related TMA, must be recognized and investigated. Additional clinical trials are imperative to comprehend the clinical features and pathophysiological mechanisms underlying TMA associated with COVID-19 vaccination.

Real-world effectiveness of original BNT162b2 mRNA COVID-19 against symptomatic Omicron infection among children 5-11 years of age in Brazil: A prospective test-negative design study.

OBJECTIVE: To estimate original wild-type BNT162b2 effectiveness against symptomatic Omicron infection among children 5-11 years of age. METHODS: This prospective test-negative, case-control study was conducted in Toledo, southern Brazil, from June 2022 to July 2023. Patients were included if they were aged 5-11 years, sought care for acute respiratory symptoms in the public health system, and were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. In the primary analysis, we determined the effectiveness of two doses of original wild-type BNT162b2 against symptomatic COVID-19. The reference exposure group was the unvaccinated. RESULTS: A total of 757 children were enrolled; of these, 461 (25 cases; 436 controls) were included in the primary analysis. Mean age was 7.4 years, 49.7 % were female, 34.6 % were obese, and 14.1 % had chronic pulmonary disease. Omicron accounted for 100 % of all identified SARS-CoV-2 variants with BA.5, BQ.1, and XBB.1 accounting for 35.7 %, 21.4 % and 21.4 %, respectively. The adjusted estimate of two-dose vaccine effectiveness against symptomatic Omicron was 3.1 % (95 % CI, -133.7 % to 61.8 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 192.5 days (interquartile range, 99 to 242 days). CONCLUSION: In this study with children 5-11 years of age, a two dose-schedule of original wild-type BNT162b2 was not associated with a significant protection against symptomatic Omicron infection after a median time between the second dose and the beginning of COVID-19 symptoms of 192 days, although the study may have been underpowered to detect a clinically important difference. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT05403307 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT05403307).

Differential epitope prediction across diverse circulating variants of SARS-COV-2 in Brazil.

COVID-19, caused by the SARS-COV-2 virus, induces numerous immunological reactions linked to the severity of the clinical condition of those infected. The surface Spike protein (S protein) present in Sars-CoV-2 is responsible for the infection of host cells. This protein presents a high rate of mutations, which can increase virus transmissibility, infectivity, and immune evasion. Therefore, we propose to evaluate, using immunoinformatic techniques, the predicted epitopes for the S protein of seven variants of Sars-CoV-2. MHC class I and II epitopes were predicted and further assessed for their immunogenicity, interferon-gamma (IFN-γ) inducing capacity, and antigenicity. For B cells, linear and structural epitopes were predicted. For class I MHC epitopes, 40 epitopes were found for the clades of Wuhan, Clade 2, Clade 3, and 20AEU.1, Gamma, and Delta, in addition to 38 epitopes for Alpha and 44 for Omicron. For MHC II, there were differentially predicted epitopes for all variants and eight equally predicted epitopes. These were evaluated for differences in the MHC II alleles to which they would bind. Regarding B cell epitopes, 16 were found in the Wuhan variant, 14 in 22AEU.1 and in Clade 3, 15 in Clade 2, 11 in Alpha and Delta, 13 in Gamma, and 9 in Omicron. When compared, there was a reduction in the number of predicted epitopes concerning the Spike protein, mainly in the Delta and Omicron variants. These findings corroborate the need for updates seen today in bivalent mRNA vaccines against COVID-19 to promote a targeted immune response to the main circulating variant, Omicron, leading to more robust protection against this virus and avoiding cases of reinfection. When analyzing the specific epitopes for the RBD region of the spike protein, the Omicron variant did not present a B lymphocyte epitope from position 390, whereas the epitope at position 493 for MHC was predicted only for the Alpha, Gamma, and Omicron variants.

Persistence of lung structural and functional alterations at one year post-COVID-19 is associated with increased serum PD-L2 levels and altered CD4/CD8 ratio.

BACKGROUND: Persistent respiratory symptoms and lung abnormalities post-COVID-19 are public health problems. This study evaluated biomarkers to stratify high-risk patients to the development or persistence of post-COVID-19 interstitial lung disease. METHODS: One hundred eighteen patients discharged with residual lung abnormalities compatible with interstitial lung disease (COVID-ILD patients) after a severe COVID-19 were followed for 1 year (post-COVID-ILD patients). Physical examination, pulmonary function tests, and chest high-resolution computed tomography (HRCT) were performed. Soluble forms (s) of PD-L1, PD-L2, TIM-3, and GAL-9 were evaluated in serum and cell culture supernatant, as well as T-cells subsets and the transmembrane expression of PD-L1 and PD-L2 on the cell surface. RESULTS: Eighty percent of the post-COVID-ILD patients normalized their lung function at 1-year follow-up, 8% presented COVID-independent ILD, and 12% still showed functional and HRCT alterations. PD-L2 levels were heterogeneous during acute COVID-19 (aCOVID); patients who increased (at least 30%) their sPD-L2 levels at 1 year post-COVID-19 and exhibited altered CD4/CD8 ratio showed persistence of chest tomographic and functional alterations. By contrast, patients who decreased sPD-L2 displayed a complete lung recovery. sPD-L1, sTIM-3, and sGAL-9 increased significantly during aCOVID and decreased in all patients after 1-year follow-up. CONCLUSION: Increased sPD-L2 and an altered CD4/CD8 ratio after 12 months of aCOVID are associated with the persistence of lung lesions, suggesting that they may contribute to lung damage post-COVID-19.

Development and characterization of a multimeric recombinant protein using the spike protein receptor binding domain as an antigen to induce SARS-CoV-2 neutralization.

BACKGROUND: SARS-CoV2 virus, responsible for the COVID-19 pandemic, has four structural proteins and 16 nonstructural proteins. S-protein is one of the structural proteins exposed on the virus surface and is the main target for producing neutralizing antibodies and vaccines. The S-protein forms a trimer that can bind the angiotensin-converting enzyme 2 (ACE2) through its receptor binding domain (RBD) for cell entry. AIMS: The goal of this study was to express in HEK293 cells a new RBD recombinant protein in a constitutive and stable manner in order to use it as an alternative immunogen and diagnostic tool for COVID-19. MATERIALS & METHODS: The protein was designed to contain an immunoglobulin signal sequence, an explanded C-terminal section of the RBD, a region responsible for the bacteriophage T4 trimerization inducer, and six histidines in the pCDNA-3.1 plasmid. Following transformation, the cells were selected with geneticin-G418 and purified from serum-fre culture supernatants using Ni2+-agarand size exclusion chromatography. The protein was structurally identified by cross-linking and circular dichroism experiments, and utilized to immunize mice in conjuction with AS03 or alum adjuvants. The mice sera were examined for antibody recognition, receptor-binding inhibition, and virus neutralization, while spleens were evaluated for γ-interferon production in the presence of RBD. RESULTS: The protein released in the culture supernatant of cells, and exhibited a molecular mass of 135 kDa with a secondary structure like the monomeric and trimeric RBD. After purification, it formed a multimeric structure comprising trimers and hexamers, which were able to bind the ACE2 receptor. It generated high antibody titers in mice when combined with AS03 adjuvant (up to 1:50,000). The sera were capable of inhibiting binding of biotin-labeled ACE2 to the virus S1 subunit and could neutralize the entry of the Wuhan virus strain into cells at dilutions up to 1:2000. It produced specific IFN-γ producing cells in immunized mouse splenocytes. DISCUSSION: Our data describe a new RBD containing protein, forming trimers and hexamers, which are able to induce a protective humoral and cellular response against SARS-CoV2. CONCLUSION: These results add a new arsenal to combat COVID-19, as an alternative immunogen or antigen for diagnosis.

Assessment of the COVID-19 pandemic progression in Ecuador through seroprevalence analysis of anti-SARS-CoV-2 IgG/IgM antibodies in blood donors.

Introduction: Coronavirus Disease 2019 (COVID-19) is a severe respiratory illness caused by the RNA virus SARS-CoV-2. Globally, there have been over 759.4 million cases and 6.74 million deaths, while Ecuador has reported more than 1.06 million cases and 35.9 thousand deaths. To describe the COVID-19 pandemic impact and the vaccinations effectiveness in a low-income country like Ecuador, we aim to assess the seroprevalence of IgG and IgM antibodies against SARS-CoV-2 in a sample from healthy blood donors at the Cruz Roja Ecuatoriana. Methods: The present seroprevalence study used a lateral flow immunoassay (LFIA) to detect anti-SARS-CoV-2 IgG and IgM antibodies in months with the highest confirmed case rates (May 2020; January, April 2021; January, February, June, July 2022) and months with the highest vaccination rates (May, June, July, August, December 2021) in Quito, Ecuador. The IgG and IgM seroprevalence were also assessed based on sex, age range, blood type and RhD antigen type. The sample size was 8,159, and sampling was performed based on the availability of each blood type. Results: The results showed an overall IgG and IgM seroprevalence of 47.76% and 3.44%, respectively. There were no differences in IgG and IgM seroprevalences between blood groups and sex, whereas statistical differences were found based on months, age range groups, and RhD antigen type. For instance, the highest IgG seroprevalence was observed in February 2022 and within the 17-26 years age range group, while the highest IgM seroprevalence was in April 2021 and within the 47-56 years age range group. Lastly, only IgG seroprevalence was higher in RhD+ individuals while IgM seroprevalence was similar across RhD types. Discussion: This project contributes to limited data on IgG and IgM antibodies against SARS-CoV-2 in Ecuador. It suggests that herd immunity may have been achieved in the last evaluated months, and highlights a potential link between the RhD antigen type and COVID-19 susceptibility. These findings have implications for public health strategies and vaccine distribution not only in Ecuador but also in regions with similar characteristics.

Analysis of the immune response using FTIR spectroscopy in mothers and their newborns with different vaccination schemes for COVID-19.

The SARS-CoV-2 outbreak has provoked more than 6 million deaths worldwide. The scarcity of effective treatments and its virulence converted the vaccines into an essential tool to face it. The most used vaccines were the mRNA, adenovirus vector, and inactivated whole-virus. However, nowadays, infants aged < 6 months are not eligible for any vaccines against COVID-19, and their immunization relies on passive immunity. In this research, we investigated the humoral and cellular immune response generated on newborns of SARS-CoV-2 vaccinated mothers with mRNA or viral vector (VV) vaccine employing Fourier transformed infrared (FTIR) spectroscopy in saliva samples. For this purpose, saliva samples of newborns and their mothers were collected; the population was divided into two groups, VV and mRNA, which were subdivided into three subgroups: before pregnancy (BP), at the first (FTP) and second (STP) trimesters of pregnancy. The samples were analyzed using FTIR spectroscopy, and the bands associated with the humoral and cellular immune responses, such as IgG, IgA, and IFN-γ were analyzed. The integrated areas were calculated and compared to elucidate the quantity of those immunoglobins and the cytokine. Likewise, the correlation of the humoral and cellular immune response between the newborns and their mothers and the correlation between cellular and humoral immune response was also evaluated. The VV vaccine produced a significant humoral and cellular immune response in newborns and their mothers when they received it at the STP compared with the mRNA vaccine, evidencing statistical significance. However, no correlation was observed between newborns and their mothers when the vaccine was applied in this trimester of pregnancy. When administered BP, the mRNA vaccine generated more humoral immunity in newborns and their mothers. Nevertheless, compared with the VV vaccine, it only showed statistical significance in the mothers, highlighting that IgG showed a moderate positive correlation between the newborns and their mothers.

The seroconversion history to SARS-CoV-2 in Indigenous people from Brazil - the interplay between exposure, vaccination, and tuberculosis.

The COVID-19 pandemic caused a significant loss of human lives and a worldwide decline in quality of life. Although our understanding of the pandemic has improved significantly since the beginning, the natural history of COVID-19 and its impacts on under-represented populations, such as Indigenous people from America, remain largely unknown. We performed a retrospective serological survey with two Brazilian Indigenous populations (n=624), Tupiniquim and Guarani-Mbyá. Samples were collected between September 2020 and July 2021: a period comprising the dissemination of SARS-CoV-2 variants and the beginning of COVID-19 vaccination in Brazil. Seroconversions against S and N antigens were assessed using three different commercially available ELISA kits. Samples were also used to assess the prevalence of tuberculosis (TB) in the same population (n=529). Seroconversion against SARS-CoV-2 antigens was considered positive if at least one of the three ELISA kits detected levels of specific antibodies above the threshold specified by the manufacturer. In this sense, we report 56.0% (n=349/623) of seroconverted individuals. Relative seroconversion peaked after introduction of the Coronavac vaccine in February 2021. Vaccination increased the production of anti-S IgG from 3.9% to 48.6%. Our results also indicated that 11.0% (n=46/417) of all individuals were positive for TB. Seroconversion to SARS-CoV-2 was similar between individuals with positive tuberculosis test results to those with negative test results. Most vaccinated individuals seroconverted to SARS-CoV-2, indicating that Coronavac may be as protective in individuals from these indigenous groups as observed in the general Brazilian population. COVID-19 severity was minimal regardless of incomplete vaccine coverage, suggesting that vaccination may not be the only factor protecting individuals from severe COVID-19. Tuberculosis is highly prevalent and not associated with increased seroconversion to SARS-CoV-2.

Genomic surveillance and vaccine response to the dominant SARS-CoV-2 XBB lineage in Rio Grande do Sul.

The COVID-19 pandemic has been marked by novel viral variants, posing challenges to global public health. Recombination, a viral evolution mechanism, is implicated in SARS-CoV-2's ongoing evolution. The XBB recombinant lineage, known for evading antibody-mediated immunity, exhibits higher transmissibility without increased disease severity. We investigated the prevalence and genomic features of XBB in SARS-CoV-2-positive cases in Rio Grande do Sul (RS), Brazil. We sequenced 357 samples from epidemiological weeks (EW) 47/2022 to 17/2023, and included 389 publicly available sequences. Clinical and epidemiological data were obtained from DATASUS, e-SUS, and SIVEP GRIPE (data recording systems of the Brazilian Ministry of Health). Of these, 143 were classified as XBB and 586 were other Omicron lineages. In March 2023 (EW 10), XBB became dominant, accounting for 83.3% of cases. 97.7% of XBB-infected patients successfully recovered from the infection, with a low mortality rate (2.3%). Even after receiving three vaccine doses and having been previously infected, 59.5% of the patients experienced reinfection with XBB. However, for 54% of the individuals, the interval between their XBB infection and the last vaccine dose exceeded one year, potentially leading to a decline in antibody levels. In addition, we identified 90 mutations in RS circulating XBB, spread throughout the genome, notably in the Spike protein region associated with immune resistance. This study provides insights into the dynamics and impact of a recombinant variant becoming predominant for the first time in the state. Continued surveillance of SARS-CoV-2 genomic evolution is crucial for effective public health management.