Time to optimize vaccination strategies in blood cancer patients.

Immune response to vaccinations is dampened in patients with indolent lymphomas due to disease and treatment-related factors. The study by Lim et al. demonstrated impaired humoral response but intact cellular response to the SARS-CoV2 vaccine in patients with follicular lymphoma receiving front-line therapy. The results highlight the importance of several factors in predicting immune response to vaccination and provide estimates of immune response for different clinical scenarios and treatment points. Commentary on: Lim et al. Immunogenicity of COVID-19 vaccines in patients with follicular lymphoma receiving frontline chemoimmunotherapy. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19562.

Serological Correlates of Protection Induced by COVID-19 Vaccination in the Working Age Population: A Systematic Review and Meta-Analysis.

COVID-19 vaccines represent effective public health measures in contrasting the pandemic worldwide. However, protection at the individual-level, which is of crucial importance from an occupational health perspective, is commonly assessed by a serological correlate of protection (CoP) for SARS-CoV-2, which has not yet been determined. The emergence of variants of concern (VOCs) that have shown high rates of breakthrough infections has further complicated the understanding of immune protection against infection. To define a potential serological correlate of protection induced by the COVID-19 vaccination, a systematic review and meta-analysis was performed to summarize the evidence concerning the binding antibody concentration corresponding to a protective effect. Eighteen and four studies were included in the qualitative and quantitative analyses, respectively. The protection against infection was shown for anti-receptor-binding domain (RBD) titers ranging from 154 to 168.2 binding antibody units (BAU)/mL during the pre-Omicron period, while ranging from 1235 to 3035 BAU/mL in the Omicron period. Pooling the results from the studies concerning anti-RBD and anti-Spike antibody titer, we found a mean of 1341.5 BAU/mL and 1400.1 BAU/mL, respectively. These findings suggest that although a fixed serological threshold corresponding to protection against different SARS-CoV-2 variants is not yet definable, higher binding antibody concentrations are associated with increased protective effects.

SARS-CoV-2 specific antibody response after an mRNA vaccine as the third dose: Homologous versus heterologous boost.

The aim of this study was to evaluate immunogenicity and longevity of the humoral immune response within six months after the homologous (BNT162b2/BNT162b2) or heterologous (BBIBP-CorV/BNT162b2) third dose, and to assess breakthrough infections among vaccinees during the Omicron wave in Serbia. Serum samples were analyzed at four timepoints: five months after the primary series; three weeks, three months, and six months after the boost. IgG antibodies against the receptor-binding domain of the spike protein were detected using enzyme-linked fluorescence assay. Both homologous (n = 55) and heterologous group (n = 36) showed a highly significant increase in antibody concentrations (p < 0.001) three weeks after the boost. A moderate inverse correlation between the age of recipients and the antibody levels at three weeks post-boost was observed in the homologous group (p = 0.02, r = -0.37), while the same correlation was not significant for heterologous group (p = 0.55, r = -0.15). Heterologous group had significantly higher antibody concentrations than homologous group at three weeks (Median 851.4(IQR 766.6-894.1); 784.3(676.9-847.4); p = 0.03) and three months post-boost (766.6(534.8-798.9); 496.8(361.6-664.0); p < 0.001). However, a significant decline in antibody response over time was noted for both strategies. The overall incidence of breakthrough cases was estimated at 36.36% (20/55) for homologous, and 16.67% (6/36) for heterologous group, but none of them required hospitalization. Although observed incidence in the homologous group was more than double when compared to the heterologous group, this difference was not statistically significant, most likely due to the small sample size. In conclusion, waning immunity after inactivated vaccine can be recovered by BNT162b2 heterologous boost regardless of the age of recipients, and both boost strategies induced potent humoral immune response and protection against severe COVID-19 during the Omicron wave. However, as the observed incidence of breakthrough infections was higher in the homologous group, although non-significant, this finding could indicate an advantage of heterologous approach.

Systemic lupus erythematosus following COVID-19 vaccination. A systematic review of case reports and case series.

OBJECTIVE: Vaccination against SARS-CoV-2 reduced morbidity and mortality rates due to COVID-19 worldwide. However, several adverse effects have been documented and of great interest such as Systemic Lupus Erythematosus (SLE). The aim of the present study was to perform a systematic review of case reports and case series describing the development of SLE following COVID-19 against vaccination. METHODS: Case report and case series studies were included. Systematic reviews, narratives, letters to the editor, correspondence, etc. were excluded. A selective bibliographic search was performed in the PubMed, Scopus, and EMBASE databases. In addition, the Web of Science platform was consulted. The Joanna Brigs Institute (JBI) tool was used to assess the risk of bias and quality of the studies. The Statistical Package for the Social Sciences (SPSS) 23.0 was used for the formal analysis of the descriptive data. RESULTS: 12 studies met the eligibility criteria and reported a total of 16 patients. The mean age was 42.4 ± 18.69 years. A slight predominance of post-vaccination SLE was observed in females (females (n = 9) and males (n = 7). A higher association was found with Pfizer-BioNTech-162b2 vaccine (75%), followed by Sinopharm (12.5%), Moderna (6.25%). and AstraZeneca (6.25%) vaccines. Most cases were associated with the first dose (56.25%), followed by the second dose (37.5%) and only one case associated with the third dose. The number of days elapsed from vaccine administration to the appearance of the first clinical manifestations was between 1 and 30 days. Mainly there was involvement of the musculoskeletal and cutaneous system. All patients responded well to treatment with good evolution and there was no case of death. CONCLUSION: Cases of SLE associated with COVID-19 vaccination against are infrequent. However, clinical monitoring is recommended for persons receiving the SARS-CoV-2 vaccine, mainly those receiving the first dose and the Pfizer-BioNTech-162b2 vaccine.

Acute abdomen following COVID-19 vaccination: a systematic review.

Purpose: Conduct a systematic review of case reports and case series regarding the development of acute abdomen following coronavirus disease 2019 (COVID-19) vaccination, to describe the possible association and the clinical and demographic characteristics in detail. Materials and Methods: This study included case report studies and case series that focused on the development of acute abdomen following COVID-19 vaccination. Systematic review studies, literature, letters to the editor, brief comments, and so forth were excluded. PubMed, Scopus, EMBASE, and Web of Science databases were searched until June 15, 2023. The Joanna Briggs Institute tool was used to assess the risk of bias and the quality of the study. Descriptive data were presented as frequency, median, mean, and standard deviation. Results: Seventeen clinical case studies were identified, evaluating 17 patients with acute abdomen associated with COVID-19 vaccination, which included acute appendicitis (n=3), acute pancreatitis (n=9), diverticulitis (n=1), cholecystitis (n=2), and colitis (n=2). The COVID-19 vaccine most commonly linked to acute abdomen was Pfizer-BioNTech (messenger RNA), accounting for 64.71% of cases. Acute abdomen predominantly occurred after the first vaccine dose (52.94%). All patients responded objectively to medical (88.34%) and surgical (11.76%) treatment and were discharged within a few weeks. No cases of death were reported. Conclusion: Acute abdomen is a rare complication of great interest in the medical and surgical practice of COVID-19 vaccination. Our study is based on a small sample of patients; therefore, it is recommended to conduct future observational studies to fully elucidate the underlying mechanisms of this association.

SARS-CoV-2 mRNA Vaccines Induce Greater Complement Activation and Decreased Viremia and Nef Antibodies in Men With HIV-1.

BACKGROUND: Immune dysregulation in people with human immunodeficiency virus-1 (PWH) persists despite potent antiretroviral therapy and, consequently, PWH tend to have lower immune responses to licensed vaccines. However, limited information is available about the impact of mRNA vaccines in PWH. This study details the immunologic responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in PWH and their impact on HIV-1. METHODS: We quantified anti-S immunoglobulin G (IgG) binding and neutralization of 3 SARS-CoV-2 variants of concern and complement activation in blood from virally suppressed men with HIV-1 (MWH) and men without HIV-1 (MWOH), and the characteristics that may impact the vaccine immune responses. We also studied antibody levels against HIV-1 proteins and HIV-1 plasma RNA. RESULTS: MWH had lower anti-S IgG binding and neutralizing antibodies against the 3 variants compared to MWOH. MWH also produced anti-S1 antibodies with a 10-fold greater ability to activate complement and exhibited higher C3a blood levels than MWOH. MWH had decreased residual HIV-1 plasma viremia and anti-Nef IgG approximately 100 days after immunization. CONCLUSIONS: MWH respond to SARS-CoV-2 mRNA vaccines with lower antibody titers and with greater activation of complement, while exhibiting a decrease in HIV-1 viremia and anti-Nef antibodies. These results suggest an important role of complement activation mediating protection in MWH.

A multifaceted approach for identification, validation, and immunogenicity of naturally processed and in silico-predicted highly conserved SARS-CoV-2 peptides.

SARS-CoV-2 remains a major global public health concern. Antibody waning and immune escape variant emergence necessitate the development of next generation vaccines that induce cross-reactive durable immune responses. T cell responses to SARS-CoV-2 demonstrate higher conservation, antigenic breadth, and longevity than antibody responses. Therefore, we sought to identify pathogen-derived T cell epitopes for a potential peptide-based vaccine. We pursued an approach leveraging: 1) liquid chromatography and tandem mass spectrometry (LC-MS/MS)-based identification of peptides from ancestral SARS-CoV-2-infected cell lines, 2) epitope prediction algorithms, and 3) overlapping peptide libraries. From this strategy, we identified 380 unique SARS-CoV-2-derived peptide sequences, including 53 antigenic HLA class I and class II peptides from multiple structural and non-structural/accessory viral proteins. These peptide sequences were highly conserved across variants of concern/interest (VoC/VoIs), and are estimated to achieve coverage of >96% of the world population. Our findings validate this discovery pipeline for peptide identification and immunogenicity testing, and are a crucial step toward the development of a next-generation multi-epitope SARS-CoV-2 peptide vaccine, and a novel vaccine platform methodology.

A third (booster) dose of the inactivated SARS-CoV-2 vaccine elicits immunogenicity and T follicular helper cell responses in people living with HIV.

Introduction: This study sought to explore the immunogenicity of a booster dose of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in people living with human immunodeficiency virus (HIV) and identify the factors affecting the magnitude of anti-SARS-CoV-2 antibody levels. Materials and methods: A total of 34 people living with HIV (PLWH) and 34 healthy donors (HD) were administered a booster dose of the same SARS-CoV-2 vaccine. Anti-SARS-CoV-2 antibody and immunoglobulin G (IgG) levels were measured using the SARS-CoV-2 S protein neutralizing antibody Enzyme-Linked Immunosorbent Assay (ELISA) and 2019-nCov IgG Chemiluminescent Immunoassay Microparticles, respectively. Spearman correlation analysis was used to measure the correlation between laboratory markers and neutralizing antibody and IgG levels. Peripheral blood mononuclear cells (PBMCs) were extracted from each subject using density gradient centrifugation and the numbers of memory T and T follicular helper (Tfh) cells were determined using flow cytometry. Results: PLWH had a marked reduction in CD4 and B cell levels that was accompanied by a lower CD4/CD8 T cell ratio. However, those who received a supplementary dose of inactivated SARS-CoV-2 vaccines exhibited antibody positivity rates that were analogous to levels previously observed. The booster vaccine led to a reduction in IgG and neutralizing antibody levels and the amplitude of this decline was substantially higher in the PLWH than HD group. Correlation analyses revealed a strong correlation between neutralizing antibody levels and the count and proportion of CD4 cells. Anti-SARS-CoV-2 IgG antibody levels followed a similar trend. The expression of memory T and Tfh cells was considerably lower in the PLWH than in the HD group. Discussion: PLWH had an attenuated immune response to a third (booster) administration of an inactivated SARS-CoV-2 vaccine, as shown by lower neutralizing antibody and IgG levels. This could be attributed to the reduced responsiveness of CD4 cells, particularly memory T and cTfh subsets. CD4 and cTfh cells may serve as pivotal markers of enduring and protective antibody levels. Vaccination dose recalibration may be critical for HIV-positive individuals, particularly those with a lower proportion of CD4 and Tfh cells.

SARS-CoV-2 Vaccine Effectiveness in Hospitalized Patients: A Multicenter Test-Negative Case-Control Study.

BACKGROUND: Phase III clinical trials have documented the efficacy of the SARS-CoV-2 vaccines in preventing symptomatic COVID-19. Nonetheless, it is imperative to continue analyzing the clinical response to different vaccines in real-life studies. Our objective was to evaluate the effectiveness of five different vaccines in hospitalized patients with COVID-19 during the third COVID-19 outbreak in Mexico dominated by the Delta variant. METHODS: A test-negative case-control study was performed in nine tertiary-care hospitals for COVID-19. We estimated odds ratios (OR) adjusted by variables related a priori with the likelihood of SARS-CoV-2 infection and its severity. RESULTS: We studied 761 subjects, 371 cases, and 390 controls with a mean age of 53 years (SD, 17 years). Overall, 51% had a complete vaccination scheme, and an incomplete scheme (one dose from a scheme of two), 14%. After adjustment for age, gender, obesity, and diabetes mellitus, we found that the effectiveness of avoiding a SARS-CoV-2 infection when hospitalized with at least one vaccination dose was 71% (OR 0.29, 95% CI 0.19-0.45), that of an incomplete vaccination scheme, 67% (OR 0.33, 95% CI 0.18-0.62), and that of any complete vaccination scheme, 73% (OR 0.27, 95% CI 0.17-0.43). CONCLUSIONS: The SARS-CoV-2 vaccination program showed effectiveness in preventing SARS-CoV-2 infection in hospitalized patients during a Delta variant outbreak.

COVID-19 Incidence Proportion as a Function of Regional Testing Strategy, Vaccination Coverage, and Vaccine Type.

Introduction: The COVID-19 pandemic has become a serious challenge for humanity almost everywhere globally. Despite active vaccination around the world, the incidence proportion in different countries varies significantly as of May 2022. The reason may be a combination of demographic, immunological, and epidemiological factors. The purpose of this study was to analyze possible relationships between COVID-19 incidence proportion in the population and the types of SARS-CoV-2 vaccines used in different countries globally, taking into account demographic and epidemiological factors. Materials and methods: An initial database was created of demographic and immunoepidemiological information about the COVID-19 situation in 104 countries collected from published official sources and repository data. The baseline included, for each country, population size and density; SARS-CoV-2 testing coverage; vaccination coverage; incidence proportion; and a list of vaccines that were used, including their relative share among all vaccinations. Subsequently, the initial data set was stratified by population and vaccination coverage. The final data set was subjected to statistical processing both in general and taking into account population testing coverage. Results: After formation of the final data set (including 53 countries), it turned out that reported COVID-19 case numbers correlated most strongly with testing coverage and the proportions of vaccine types used, specifically, mRNA (V1); vector (V2); peptide/protein (V3); and whole-virion/inactivated (V4). Due to the fact that an inverse correlation was found between 'reported COVID-19 case numbers' with V2, V3, and V4, these three vaccine types were also combined into one analytic group, 'non-mRNA group' vaccines (Vnmg). When the relationship between vaccine type and incidence proportion was examined, minimum incidence proportion was noted at V1:Vnmg ratios (%:%) from 0:100 to 30:70. Maximum incidence proportion was seen with V1:Vnmg from 80:20 to 100:0. On the other hand, we have shown that the number of reported COVID-19 cases in different countries largely depends on testing coverage. To offset this factor, countries with low and extremely high levels of testing were excluded from the data set; it was then confirmed that the largest number of reported COVID-19 cases occurred in countries with a dominance of V1 vaccines. The fewest reported cases were seen in countries with a dominance of Vnmg vaccines. Conclusion: In this paper, we have shown for the first time that the level of reported COVID-19 incidence proportion depends not only on SARS-CoV-2 testing and vaccination coverage, which is quite logical, but probably also on the vaccine types used. With the same vaccination level and testing coverage, those countries that predominantly use vector and whole-virion vaccines feature incidence proportion that is significantly lower than countries that predominantly use mRNA vaccines.

Age and Comorbidities as Risk Factors for Severe COVID-19 in Mexico, before, during and after Massive Vaccination.

During 2020-2023, Mexico had a large COVID-19 emergency with >331,000 adult deaths and one of the highest excess mortalities worldwide. Age at COVID-19 death has been lower in Mexico than in high-income countries, presumably because of the young demographics and high prevalence of chronic metabolic diseases in young and middle-aged adults. SARS-CoV-2 vaccination covered 85% of adults with at least one dose and 50% with booster(s) up to April 2022. No new vaccination efforts or updated boosters were introduced until October 2023; thus, we explored the public health impact of massive SARS-CoV-2 vaccination against ancestral strains and asked whether their real-world protection has persisted through time. We compared three periods with respect to vaccine roll-outs: before, during and after vaccine introduction in a national retrospective cohort of >7.5 million COVID-19 cases. The main findings were that after vaccination, COVID-19 mortality decreased, age at COVID-19 death increased by 5-10 years, both in populations with and without comorbidities; obesity stopped being a significant risk factor for COVID-19 death and protection against severe disease persisted for a year after boosters, including at ages 60-79 and 80+. Middle-aged adults had the highest protection from vaccines/hybrid immunity and they more than halved their proportions in COVID-19 deaths.

Remdesivir or Nirmatrelvir/Ritonavir Therapy for Omicron SARS-CoV-2 Infection in Hematological Patients and Cell Therapy Recipients.

BACKGROUND: Scarce data exist that analyze the outcomes of hematological patients with SARS-CoV-2 infection during the Omicron variant period who received treatment with remdesivir or nirmatrelvir/ritonavir. METHODS: This study aims to address this issue by using a retrospective observational registry, created by the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group, spanning from 27 December 2021 to 30 April 2023. RESULTS: This study included 466 patients, 243 (52%) who were treated with remdesivir and 223 (48%) with nirmatrelvir/ritonavir. Nirmatrelvir/ritonavir was primarily used for mild cases, resulting in a lower COVID-19-related mortality rate (1.3%), while remdesivir was preferred for moderate to severe cases (40%), exhibiting a higher mortality rate (9%). A multivariate analysis in the remdesivir cohort showed that male gender (odds ratio (OR) 0.35, p = 0.042) correlated with a lower mortality risk, while corticosteroid use (OR 9.4, p < 0.001) and co-infection (OR 2.8, p = 0.047) were linked to a higher mortality risk. Prolonged virus shedding was common, with 52% of patients shedding the virus for more than 25 days. In patients treated with remdesivir, factors associated with prolonged shedding included B-cell malignancy as well as underlying disease, severe disease, a later onset of and shorter duration of remdesivir treatment and a higher baseline viral load. Nirmatrelvir/ritonavir demonstrated a comparable safety profile to remdesivir, despite a higher risk of drug interactions. CONCLUSIONS: Nirmatrelvir/ritonavir proved to be a safe and effective option for treating mild cases in the outpatient setting, while remdesivir was preferred for severe cases, where corticosteroids and co-infection significantly predicted worse outcomes. Despite antiviral therapy, prolonged shedding remains a matter of concern.

Influence of Disease Modifying Treatment, Severe Acute Respiratory Syndrome Coronavirus 2 Variants and Vaccination on Coronavirus Disease 2019 Risk and Outcome in Multiple Sclerosis and Neuromyelitis Optica.

Patients suffering from neuro-inflammatory diseases such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) remain vulnerable to COVID-19. We investigated the risk of COVID-19 in MS and NMOSD patients over time, considering the impact of disease-modifying treatments (DMTs), vaccinations, and the spread of new SARS-CoV-2 variants. We retrospectively collected clinical information regarding all MS and NMOSD consecutive patients seen at the Neurocenter of Southern Switzerland. Logistic regression was used to test variables (age, sex, vaccination status, DMT at vaccination, DMT at infection, disease course, disability scores, prevalent SARS-CoV-2 variant) for association with COVID-19 risk and severe outcome (hospitalization or death). We included 352 individuals in this study; 315 (89.5%) received ≥1 dose of SARS-CoV-2 mRNA-vaccine, and 134 (38.1%) experienced COVID-19 between March 2020 and August 2022. COVID-19 risk decreased in vaccinated patients (OR = 0.10, 95% CI = 0.05-0.20, p < 0.001) and increased in anti-CD20 therapies (OR = 2.26, 95% CI = 1.28-4.00, p = 0.005). Anti-CD20 treatment was associated with severe COVID-19 (OR = 27.41, 95% CI = 3.68-204.25, p = 0.001), whereas Omicron infections were milder compared to Alpha infections (OR = 0.03, 95% CI = 0.01-0.35, p = 0.006). We confirmed a protective effect of mRNA vaccines on COVID-19 risk, which is impaired by anti-CD20 treatment. We provided evidence for milder COVID-19 with the Omicron SARS-CoV-2 variant, which should not, however, discourage vaccinations.

Self-reported side effects following COVID-19 vaccination in athletes: A retrospective study.

Billions of coronavirus disease 19 (COVID-19) vaccines have been administered worldwide. However, limited data on side effects have been reported in athletes. This study aimed to describe the incidence of side effects following COVID-19 vaccination in athletes and to identify the factors associated with the main side effects in this population. Information on COVID-19 vaccination, side effects, and overall symptom duration was retrospectively collected from recreational and competitive athletes. A total of 460 participants were included in this study. Fever and arm pain were more frequently reported after the first-dose vaccination, 9.6% vs 4.6%, p = .007 and 81.3% vs 24.9%, p ≤ .001. Myalgia was more common after the second-dose vaccination, 0.65% vs. 7.1% p ≤ .001. Males were more likely to present with arm pain after the first and second vaccinations. Those with SARS-CoV-2 infection before vaccination were less likely to present with arm pain after the first dose of vaccination (OR: 0.162, p ≤ .001) and more likely to present with fever after the second dose of vaccination (OR: 3.442, p = .046). First-dose vaccination with the BNT162b2 vaccine compared to other brands was characterized by lower odds of fever (OR: 0.394, p = .017). Our results indicated mild adverse effects and a short duration of symptoms in athletes following COVID-19 vaccination.

Effects of Sinovac-Coronavac and Pfizer-BioNTech mRNA vaccines on choroidal and retinal vascular system.

PURPOSE: To evaluate the effects of Sinovac-Coronavac and Pfizer-BioNTech mRNA vaccines on choroidal and retinal vascular system using enhanced depth imaging optical coherence tomography (EDI-OCT) and optical coherence tomography angiography (OCTA). METHODS: In this prospective cross-sectional study, 63 healthy participants (29 with Pfizer-BioNTech, 34 with Sinovac-CoronaVac) were evaluated after the first dose of vaccination. Vessel density (VD) of the superficial (SCP), deep capillary plexus (DCP) and choriocapillaris (CC) were measured with OCTA. Choroidal thickness (CT) were measured with EDI-OCT. Measurements were performed at the 2nd week and the 4th week after vaccinations and compared to pre-vaccination values. RESULTS: Regarding Pfizer-BioNTech vaccination, CT in the subfoveal and nasal region significantly increased between the pre-vaccination and post-vaccination 2nd week and then significantly decreased to pre-vaccine values at 4th week. The SCP-VD (whole image, fovea, parafovea, perifovea temporal) variables showed a significant decrease at 2nd week. The DCP-VD inferior hemi, parafovea inferior hemi, parafovea inferior variables demonstrated a significant decrease at 2nd week. The perifovea DCP-VD variables also showed a significant decrease at 2nd week, and these variables returned to pre-vaccination values after 4 weeks. The CC-VD variables showed a significant decrease between pre-vaccine and 2nd week post-vaccination. Regarding the Sinovac-CoronaVac vaccination, there was no statistically significant difference in CT and VD values before and after vaccination (p> 0.05). CONCLUSION: Our study showed significant alterations in retinal vascular density and CT for the Pfizer-BioNTech vaccine at the 2nd week, and these parameters became compatible with pre-vaccination values at the 4th week. In contrast, no differences were observed after the Sinovac-Coronovac vaccination.

El enigma del coronavirus - La variante BA.2.86 del SARS-CoV-2 - Lo nuevo sobre el COVID prolongado - Vacunas - Premios Nobel

El coronavirus ha continuado paseándose por el mundo con nuevas variantes, algunas consideradas de preocupación. Las hospitalizaciones aumentaron en algunas partes con la variante BA.2.86, especialmente en personas mayores obesas o con morbilidad, pero han disminuido, así como los fallecimientos. Las mujeres que gestaron mediante técnicas de reproducción asistida tuvieron similar morbilidad que quienes gestaron espontáneamente, pero con más resultados maternoperinatales adversos en aquellas de mayor edad, con embarazos múltiples, nuliparidad, índice de masa corporal >30. Los niños que nacieron al inicio de la pandemia mostraron un microbioma de diferente composición que quienes nacieron antes de la pandemia, lo que pudiera afectar su salud más adelante en la vida. Las personas que presentan COVID prolongado, un cuarto de ellas sufre secuelas en órganos y sistemas, con limitación y años perdidos de actividades, así como posibilidad de muerte prematura. El COVID prolongado ocurre más en mujeres entre 35 y 49 años y en quienes tienen menos ingresos económicos. Podrían desarrollar diabetes tipo 2. Habría interacciones directas entre el SARS-CoV-2 y proteínas mitocondriales esenciales en la producción de energía. El ARN viral ha sido detectado en lesiones ateroescleróticas coronarias y la espiga ha sido hallada en huesos del cráneo, meninges y cerebro. Las vacunas contra el coronavirus protegen a las gestantes y sus recién nacidos a través de transferencia placentaria y la lactancia. En la población, la inmunidad protectora de la infección y de las vacunas declina con el tiempo y se requerirá nueva vacunación con una regularidad aún no determinada.

The coronavirus has continued to move around the world with new variants, some of which are of concern. Hospitalizations increased in some places with the BA.2.86 variant, especially in obese or morbid elderly people, but have decreased, as have deaths. Women who gestated by assisted reproductive techniques had similar morbidity as those who gestated spontaneously, but with more adverse maternal-perinatal outcomes in those older, with multiple pregnancies, nulliparity, body mass index >30. Children born at the beginning of the pandemic showed a different microbiome composition than those born before the pandemic, which could affect their health later in life. Among people with long COVID, a quarter of them suffer organ and system sequelae, with limitation and lost years of activity, as well as the possibility of premature death. Long COVID occurs more in women between 35-49 years of age and in those with lower income. They could develop type 2 diabetes. There would be direct interactions between SARS-CoV-2 and mitochondrial proteins essential in energy production. Viral RNA has been detected in coronary atherosclerotic lesions and the spike has been found in skull bones, meninges and brain. Coronavirus vaccines protect pregnant women and their newborns through placental transfer and lactation. In the population, protective immunity from infection and vaccines declines over time and new vaccination will be required at an as yet undetermined regularity.

Jerne's "immune network theory", of interacting anti-idiotypic antibodies applied to immune responses during COVID-19 infection and after COVID-19 vaccination.

Niels Kaj Jerne has proposed the "immune network theory" of interactions among anti-idiotypic antibodies, able to interfere with humoral responses to certain antigens. After the occurrence of the primary generation of antibodies, against an antigenic epitope, idiotypes of these antibodies induce anti-idiotypic antibodies that modulate the intensity of the first response, and so on. Adverse effects following SARS-COV-2 COVID-19 vaccines are occasionally similar to the symptoms of COVID-19 infection. Rare events linked to SARS-CoV-2 vaccines also resemble some rarely reported COVID-19 complications. Safety data from product information by European Medicines Agency suggest that spectra do overlap for four main vaccines. The proposition is that vaccine events and COVID-19 complications are related to anti-idiotypic antibodies whose spatial shape can lead to interactions with ACE2 molecules, in individuals with a prolonged Spike protein synthesis. The vaccines target cells by their affinity to the vaccine vector, or to engulf lipid nanoparticles. Anti-idiotypic antibodies shaped similarly to the Spike protein possibly interact with ACE2 molecules and cause diverse signs and symptoms.

COVID-19 Vaccines and Myocarditis: An Overview of Current Evidence.

COVID-19 vaccines have been widely used to reduce the incidence and disease severity of COVID-19. Questions have lately been raised about the possibility of an association between COVID-19 vaccines and myocarditis, an inflammatory condition affecting the myocardium, or the middle layer of the heart. Myocarditis can be caused by infections, immune reactions, or toxic exposure. The incidence rate of myocarditis and pericarditis was calculated to be 5.98 instances per million COVID-19 vaccine doses delivered, which is less than half of the incidences after SARS-CoV-2 infection. Myocarditis rates in people aged 12 to 39 years are around 12.6 cases per million doses following the second dose of mRNA vaccination. Adolescent men are more likely than women to develop myocarditis after receiving mRNA vaccines. The objectives of this systematic review and meta-analysis are to find out how often myocarditis occurs after receiving the COVID-19 vaccine, as well as the risk factors and clinical repercussions of this condition. Nevertheless, the causal relationship between vaccination and myocarditis has been difficult to establish, and further research is required. It is also essential to distinguish between suggested cases of myocarditis and those confirmed by endomyocardial biopsy.

Robust Vaccine-Induced as Well as Hybrid B- and T-Cell Immunity across SARS-CoV-2 Vaccine Platforms in People with HIV.

Few studies have comprehensively compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced and hybrid B- and T-cell responses in people with HIV (PWH) to those in comparable controls without HIV. We included 195 PWH and 246 comparable controls from the AGEhIV COVID-19 substudy. A positive nucleocapsid antibody (INgezim IgA/IgM/IgG) or self-reported PCR test defined prior SARS-CoV-2 infection. SARS-CoV-2 anti-spike (anti-S) IgG titers and anti-S IgG production by memory B cells were assessed. Neutralizing antibody titers were determined in a subset of participants. T-cell responses were assessed by gamma interferon (IFN-γ) release and activation-induced marker assay. We estimated mean differences in postvaccination immune responses (ß) between levels of determinants. Anti-S IgG titers and anti-S IgG production by memory B cells were not different between PWH and controls. Prior SARS-CoV-2 infection (ß = 0.77), receiving mRNA vaccine (ß = 0.56), female sex (ß = 0.24), fewer days between last vaccination and sampling (ß = 0.07), and a CD4/CD8 ratio of <1.0 (ß = -0.39) were independently associated with anti-S IgG titers, but HIV status was not. Neutralization titers against the ancestral and Delta and Omicron SARS-CoV-2 variants were not different between PWH and controls. IFN-γ release was higher in PWH. Prior SARS-CoV-2 infection (ß = 2.39), HIV-positive status (ß = 1.61), and fewer days between last vaccination and sampling (ß = 0.23) were independently associated with higher IFN-γ release. The percentages of SARS-CoV-2-reactive CD4+ and CD8+ T cells, however, were not different between PWH and controls. Individuals with well-controlled HIV generally mount robust vaccine-induced as well as hybrid B- and T-cell immunity across SARS-CoV-2 vaccine platforms similar to controls. Determinants of a reduced vaccine response were likewise largely similar in both groups and included a lower CD4/CD8 ratio. IMPORTANCE Some studies have suggested that people with HIV may respond less well to vaccines against SARS-CoV-2. We comprehensively compared B- and T-cell responses to different COVID-19 vaccines in middle-aged persons with well-treated HIV and individuals of the same age without HIV, who were also highly comparable in terms of demographics and lifestyle, including those with prior SARS-CoV-2 infection. Individuals with HIV generally mounted equally robust immunity to the different vaccines. Even stronger immunity was observed in both groups after prior SARS-CoV-2 infection. These findings are reassuring with respect to the efficacy of SARS-Cov-2 vaccines for the sizable and increasing global population of people with HIV with access and a good response to HIV treatment.