Unvaccinated Subjects Research Articles

Detección de anticuerpos anti-SARS-CoV-2 en lágrimas: inmunidad de la superficie ocular frente a COVID-19

PurposeTo evaluate the presence of SARS-CoV-2 specific IgA and IgG antibodies in tears of unvaccinated and anti-COVID-19 vaccinated subjects with previous history of SARS-CoV-2 infection. To compare results in tears with those in saliva and serum and correlate with clinical data and vaccination regimens. MethodsCross-sectional study including subjects with a previous history of SARS-CoV-2 infection, both unvaccinated and vaccinated against COVID-19. Three samples were collected: tears, saliva and serum. IgA and IgG antibodies against S-1 protein of SARS-CoV-2 were analyzed with a semi-quantitative ELISA. ResultsThirty subjects, mean age 36.4±10, males 13/30 (43.3%) with history of mild SARS-CoV-2 infection were included. 13/30 (43.3%) subjects had received a 2-dose regimen and 13/30 (43.3%) a 3-dose regimen of anti-COVID-19 vaccine, 4/30 (13.3%) subjects were unvaccinated. All the participants with full anti-COVID-19 vaccination (2-or 3-doses) presented detectable anti-S1 specific IgA in all 3biofluids, tears, saliva and serum. Among unvaccinated subjects, specific IgA was detected in 3/4 subjects in tears and saliva, whereas IgG was not detected. Considering IgA and IgG antibodies titers, no differences were observed between the 2- and 3-dose vaccination regimen. ConclusionsSARS-CoV-2-specific IgA and IgG antibodies were detected in tears after mild COVID-19, highlighting the role of the ocular surface as a first line of defense against infection. Most naturally infected unvaccinated individuals exhibit long-term specific IgA in tears and saliva. Hybrid immunization (natural infection plus vaccination) appears to enhance mucosal and systemic IgG responses. However, no differences were observed between the 2- and 3-dose vaccination schedule.

COVID-19 Exposure in Urban and Rural Areas

The COVID-19 pandemic has majorly impacted the lives of people living in different living environments, such as large cities or small towns. However, there is limited knowledge about the difference in infection prevalence between urban and rural populations. To examine these differences, this study examined SARS-CoV-2 antibody levels in blood serum from 36 unvaccinated subjects of urban and rural backgrounds with no self-reported history of COVID-19 infection. Enzyme Linked Immunosorbent Assays (ELISA) detected the presence of SARS-CoV-2 antibodies in the subjects’ blood. IgG and IgM assays were used to distinguish between prior (recovered) and more recent infections, respectively. A t-test was conducted to identify a statistically significant difference, or lack thereof, between the antibody levels detected in urban and rural participants. The results indicated that there was no significant difference between the two experimental groups for both IgG and IgM (p = 0.09, 0.93, respectively), although the p-value for IgG was low enough to be notable. Overall, this study suggests that there is no major difference between urban and rural environments that impact susceptibility to SARS-CoV-2 infection, although more research with a greater sample size should be conducted.

The quantity and quality of anti-SARS-CoV-2 antibodies show contrariwise association with COVID-19 severity: lessons learned from IgG avidity.

Gaining more appreciation on the protective/damaging aspects of anti-SARS-CoV-2 immunity associated with disease severity is of great importance. This study aimed to evaluate the avidity of serum IgG antibodies against SARS-CoV-2 spike (S) and nucleocapsid (N) in hospitalized symptomatic COVID-19 patients and asymptomatic RT-PCR-confirmed SARS-CoV-2 carriers as well as to compare antibody avidities with respect to vaccination status, vaccination dose and reinfection status. Serum levels of anti-S and anti-N IgG were determined using specific ELISA kits. Antibody avidity was determined by urea dissociation assay and expressed as avidity index (AI) value. Despite higher IgG levels in the symptomatic group, AI values of both anti-S and anti-N IgG were significantly lower in this group compared to asymptomatic individuals. In both groups, anti-S AI values were elevated in one-dose and two-dose vaccinees versus unvaccinated subjects, although significant differences were only detected in the symptomatic group. However, anti-N avidity showed no significant difference between the vaccinated and unvaccinated subgroups. Almost all vaccinated patients of different subgroups (based on vaccine type) had higher anti-S IgG avidity, while the statistical significance was detected only between those receiving Sinopharm compared to the unvaccinated subgroup. Also, statistically significant differences in antibody AIs were only found between primarily infected individuals of the two groups. Our findings indicate a key role for anti-SARS-CoV-2 IgG avidity in protection from symptomatic COVID-19 and calls for the incorporation of antibody avidity measurement into the current diagnostic tests to predict effective immunity toward SARS-CoV-2 infection or even for prognostic purposes.

Synergistic Effect between SARS-CoV-2 Wave and COVID-19 Vaccination on the Occurrence of Mild Symptoms in Healthcare Workers.

Since the beginning of the pandemic, five variants of epidemiological interest have been identified, each of them with its pattern of symptomology and disease severity. The aim of this study is to analyze the role of vaccination status in modulating the pattern of symptomatology associated with COVID-19 infection during four waves. Data from the surveillance activity of healthcare workers were used to carry out descriptive analysis, association analyses and multivariable analysis. A synergism analysis between vaccination status and symptomatology during the waves was performed. Females were found at a higher risk of developing symptoms. Four SARS-CoV-2 waves were identified. Pharyngitis and rhinitis were more frequent during the fourth wave and among vaccinated subjects while cough, fever, flu syndrome, headache, anosmia, ageusia, arthralgia/arthritis and myalgia were more frequent during the first three waves and among unvaccinated subjects. A correlation was found between vaccination and the different waves in terms of developing pharyngitis and rhinitis. Vaccination status and viruses' mutations had a synergic effect in the mitigation of the symptomatology caused by SARS-CoV-2 in healthcare workers.

Human papillomavirus-specific antibody status among unvaccinated subjects in the region of Vojvodina, Serbia.

The aim of the study was to evaluate the immune status of young people from the Vojvodina province, Serbia, through the detection of IgG antibodies specific for the L1 protein of HPV types 6, 11, 16, and 18 contained in quadrivalent vaccine. The study enrolled 514 healthy persons of both genders, aged between 18 and 30 years. All potential participants were informed about the project's aims by trained interviewers before venous blood collection. Also, participants completed a specially designed anonymous questionnaire to identify socio-demographic characteristics and individual behaviours associated with HPV seroprevalence. VPL HPV L1-specific IgG antibodies were measured using a semi-quantitative HPV IgG ELISA kit (Dia.Pro, Italy). A total of 472 (91.8%) young subjects had no detectable antibodies against high- and low-risk HPV types covered by the quadrivalent vaccine. A slightly higher number of seropositive individuals were detected in the age group of 26-30 years compared to younger than 25. Multivariate analysis showed that the number of lifetime sexual partners was the most powerful predictor of HPV seropositivity (OR = 3.483, 95% CI: 1.294-9.379). Obtained data point out low levels of naturally induced HPV-specific serum antibodies among the target population in the Vojvodina province. The present work highlights the significance and potential benefits of HPV vaccination. Routine HPV vaccination should be the public health priority in our country and should be included in the national immunization programme as soon as possible.

Pfizer-BioNTech vaccine induces the production of cross-reactive antibodies against Trypanosoma cruzi proteins: A preliminary study.

To evaluate the presence of cross-reactivity by anti-SARS-CoV-2 antibodies induced by the Pfizer-BioNTech vaccine against T. cruzi proteins in a screening test. Forty-three serum samples were obtained from personnel at the Hospital General Naval de Alta Especialidad in Mexico City who received one or two doses of the vaccine and were tested for T. cruzi infection using four tests: two "in house" ELISAs, a commercial ELISA diagnostic kit and an immunoblot test. IgG antibodies against the T. cruzi proteins were present in the serum of unvaccinated subjects and subjects who had received one or two doses of the vaccine. The positivity of the samples against T. cruzi was ruled out by means of a Western Blot assay, where all samples were negative for T. cruzi. The data suggest that people convalescing from COVID-19 and those who received the Pfizer-BioNTech vaccine exhibit cross-reactive antibodies against T. cruzi antigens in ELISA assays.

Investigation of SARS-CoV-2 seroprevalence in relation to natural infection and vaccination between October 2020 and September 2021 in the Czech Republic: a prospective national cohort study

ObjectiveExamine changes in SARS-CoV-2 seropositivity before and during the national vaccination campaign in the Czech Republic.DesignProspective national population-based cohort study.SettingMasaryk University, RECETOX, Brno.Participants22 130 persons provided blood samples at two...

Autopsies Revealed Pathological Features of COVID-19 in Unvaccinated vs. Vaccinated Patients.

Background: In Italy, by the end of 2021, a new pandemic wave led to increased hospitalizations and death, even in some vaccinated people. We aimed to investigate the death of COVID-19-vaccinated patients who acquired infection and developed severe disease, and to assess differences with fatal COVID-19 in unvaccinated subjects by studying the pathological events triggered by SARS-CoV-2. Methods: Detailed autoptic examination was performed on five fully vaccinated compared to five unvaccinated patients. Histopathological analysis focused on the lung and heart, the two major affected organs. Results: COVID-19 caused, or contributed to death, in all the unvaccinated cases. By contrast, in vaccinated group, pre-existing pathologies played a major role, and death was not COVID-19-related in four out of five patients. These patients did not show the histological features of SARS-CoV-2 lung damage. Diffuse inflammatory macrophages infiltration recently emerged as the main feature of COVID-19 cardiac injury. Interestingly, the most striking difference between the two groups was the absence of increased macrophage infiltration in the heart of vaccinated patients. Conclusions: Results of this study confirm the efficacy of anti-SARS-CoV-2 vaccination in protecting organs from injury and support the need to maintain an adequate immune response by booster dose administration.

A Presentation of Analyses of COVID-19 Vaccine Samples, Blood Samples, Urine Samples, Foot Bath Samples, Sitz Bath Samples, and Skin-Extract Samples

Some members of Korea Veritas Doctors of COVID-19 analyzed COVID-19 vaccines samples, blood samples, urine samples, foot bath samples, sitz bath samples, and skin extract samples from COVID-19 vaccinated and unvaccinated subjects. Among the objects analyzed were self-assembling micro-sized particles, probable Graphene Oxide (GO), and strands of micro-sized materials of diverse structures (probably small GO particles). Intermittently self-vibrating objects (probable GO particles) in the blood of the injected were presented. Slowly moving synthetic parasite-like objects in the blood of the injected and another object of a water ski-like fast moving object in the foot bath water were also presented. COVID-19 vaccines were known to contain programmable mRNA, GO and synthetic parasite-like objects. The effect of these materials in the blood is a widespread damage to everything inside the body including multiple organs. Those damaging effects are linked to endotheliitis, mitochondrial damage, microthrombosis, myocarditis, Sudden Adult Death Syndrome (SADS), human DNA changes and Genetically Modified Organism (GMO), prion disease and dementia, infertility and depopulation, Vaccine Aided Immune Deficiency Syndrome (VAIDS), reprogramming of innate immunity, cancer, RNA Replicons (i.e., replicating spike proteins forever as far as the host lives), and shedding by vaccinated people. Moreover, these materials may cause Vaccine-Induced Thrombotic Thrombocytopenia (VITT), and cytokine storms which is claimed to be typical COVID-19 symptoms. It can be easily argued that there is no other reason for the presence of these main components of COVID-19 vaccines including programmable mRNA, GO, and synthetic parasite-like objects, but to produce slow and painful death in people and to depopulate the world. Considering the hazardous effects of those GOs and other synthetic materials in the human body, human beings need to be detoxified from those hazardous materials and those extracted structures came out of human body need to be carefully treated and detoxified.

Heterogeneous evolution of SARS-CoV-2 seroprevalence in school-age children: Results from the school-based cohort study Ciao Corona in November-December 2021 in the canton of Zurich.

Much remains unknown regarding the evolution of SARS-CoV-2 seroprevalence and variability in seropositive children in districts, schools and classes as only a few school-based cohort studies exist. Vaccination of children, initiated at different times for different age groups, adds additional complexity to the understanding of how seroprevalence developed in the school aged population. We investigated the evolution of SARS-CoV-2 seroprevalence in children and its variability in districts, schools and classes in Switzerland from June/July 2020 to November/December 2021. In this school-based cohort study, SARS-CoV-2 antibodies were measured in primary and secondary school children from randomly selected schools in the canton of Zurich in October/November 2020, March/April 2021 and November/December 2021. Seroprevalence was estimated using Bayesian logistic regression to adjust for test sensitivity and specificity. Variability of seroprevalence between school classes was expressed as maximum minus minimum seroprevalence in a class and summarised as median (interquartile range). 1875 children from 287 classes in 43 schools were tested, with median age 12 years (range 6-17), 51% 12+ vaccinated. Seroprevalence increased from 5.6% (95% credible interval [CrI] 3.5-7.6%) to 31.1% (95% CrI 27.0-36.1%) in unvaccinated children, and 46.4% (95% CrI 42.6-50.9%) in all children (including vaccinated). Earlier in the pandemic, seropositivity rates in primary schools were similar to or slightly higher (<5%) than those in secondary schools, but by late 2021, primary schools had 12.3% (44.3%) lower seroprevalence for unvaccinated (all) subjects. Variability in seroprevalence among districts and schools increased more than two-fold over time, and in classes from 11% (95% CrI 7-17%) to 40% (95% CrI 22-49%). Seroprevalence in children increased greatly, especially in 2021 following introduction of vaccines. Variability in seroprevalence was high and increased substantially over time, suggesting complex transmission chains.

Hospitalisation outcomes in pneumococcal-vaccinated versus -unvaccinated patients with exacerbation of COPD: results from the HOPE COPD Study.

Infectious exacerbations are crucial events that dictate the natural course of COPD patients. Pneumococcal vaccination has been shown to decrease incidence of community-acquired pneumonia in COPD patients. There is a paucity of data on outcomes of hospitalisation in pneumococcal-vaccinated COPD patients in comparison with unvaccinated subjects. The objectives of the present study were to evaluate the difference in hospitalisation outcomes in pneumococcal-vaccinated versus -unvaccinated COPD subjects hospitalised with acute exacerbation. This was a prospective analytical study on 120 subjects hospitalised with acute COPD exacerbation. 60 patients with prior pneumococcal vaccination and 60 unvaccinated patients were recruited. Outcomes of hospitalisation such as mortality rate, need for assisted ventilation, length of hospital stay, need for intensive care unit (ICU) care and length of ICU stay were collected and compared between two groups with appropriate statistical tools. 60% of unvaccinated patients (36 out of 60) required assisted ventilation, whereas only 43.3% of vaccinated subjects (26 out of 60) needed assisted ventilation (p-value of 0.04). Most of the secondary outcomes were better in the vaccinated group. The mean±SD length of ICU stay in the vaccinated group was 0.67±1.11 days compared to 1.77±1.89 days in the unvaccinated group. The mean±SD length of hospital stay was 4.50±1.64 days and 5.47±2.03 days in the vaccinated and unvaccinated group, respectively (p-value of 0.005). COPD patients who have received prior pneumococcal vaccination have better outcomes when they are hospitalised for an acute exacerbation. Pneumococcal vaccination may be recommended for all patients with COPD who are at risk of hospitalisation with acute exacerbation.

Effectiveness of Live Attenuated Varicella-Zoster Vaccine in Adults Older than 50 Years in Japan: A Retrospective Cohort Study.

Background: In Japan, freeze-dried live attenuated varicella-zoster vaccine BIKEN is available for adults aged ≥50 years to prevent herpes zoster (HZ). A prospective cohort study of 1200 healthy adults and 300 patients with underlying illness confirmed vaccine safety between 2016 and 2017. However, evidence of vaccine effectiveness (VE) is limited. Methods: VE against HZ and postherpetic neuralgia (PHN) was evaluated in the vaccinated cohort of the previous safety study in a follow-up study between 2021 and 2022 and compared with unvaccinated family members. Self-administered questionnaires determined retrospective experiences of HZ and PHN diagnosis. Logistic regression estimated the VE by calculating the outcome odds ratio (OR) in vaccinated vs. unvaccinated groups: VE = (1 - OR) × 100(%). Results: Overall, 1098 vaccinated and 518 unvaccinated subjects were analysed. Between 2016 and 2022, 26 vaccinated (2.4%) and 22 unvaccinated (4.2%) subjects reported HZ diagnosis, and 3 vaccinated (0.3%) and 2 unvaccinated (0.4%) subjects reported PHN. Adjusted VE against a clinical diagnosis was 41% for HZ [-6% to 67%], with marginal significance, and 16% [-408% to 86%] for PHN. Stratification by age, sex, or comorbidities had an adjusted VE against HZ of ~40%, which was similar between strata. Conclusion: Freeze-dried live attenuated varicella-zoster vaccine reduces the risk of HZ regardless of age, sex, or comorbidities.

The Outcome of BNT162b2, ChAdOx1-Sand mRNA-1273 Vaccines and Two Boosters: A Prospective Longitudinal Real-World Study.

To date, the effectiveness of COVID-19 vaccines and booster doses has yet to be evaluated in longitudinal head-to-head studies. This single-center longitudinal study assessed the effectiveness of ChAdOx1 nCoV-19, BNT162b2, and mRNA-1273 vaccines and assessed two BNT162b2 boosters in 1550 participants, of whom 26% had comorbidities. In addition, the SARS-CoV-2 antibody dynamics was monitored. A group of 1500 unvaccinated subjects was included as the controls. The study's endpoint was the development of virologically-proven COVID-19 cases after vaccine completion, while the secondary endpoint was hospitalizations due to severe COVID-19. Overall, 23 (4.6%), 16 (3%), and 18 (3.8%) participants vaccinated with ChAdOx1 nCoV-19, BNT162b2, and mRNA-1273, respectively, developed COVID-19 after vaccine completion, with an effectiveness of 89%, 92%, and 90%. Ten COVID-19 cases were reported in participants with comorbidities, three of whom were hospitalized. No hospitalizations occurred after boosters. SARS-CoV-2 antibody levels peaked 2-4 weeks after the second vaccine dose but declined after a mean of 28.50 ± 3.48 weeks. Booster doses significantly enhanced antibody responses. Antibody titers ≤ 154 U/mL were associated with a higher risk of COVID-19 emergence. Thus, COVID-19 vaccines effectively reduced COVID-19 and prevented severe disease. The vaccine-induced SARS-CoV-2 antibody responses declined after 28-32 weeks. Booster doses induced significant maintained responses. SARS-CoV-2 antibody levels may help determine the timing and need for vaccine booster doses.

COVID-19 Vaccination Status and Pregnant Women’s Perceptions of Pandemic Omicron COVID-19 Wave in Indonesia

Pregnant women are susceptible to COVID-19 infection. COVID-19 vaccination protects pregnant women. This study aims to determine their perception of COVID-19 vaccination and its relation to the Omicron Variant wave of the COVID-19 pandemic in Indonesia. This cross-sectional study took time from February to March 2022. Subjects were asked to sign an informed consent and fill out a questionnaire. Demographic data, vaccination status, and perception of the pandemic were collected and statistically analyzed. Of the 361 study subjects, 219 (60%) are vaccinated, and 142 (40%) are unvaccinated. The vaccinated pregnant women were less anxious about the COVID-19 pandemic (p0.001, OR 2.24). Pregnant women with higher education or those who work were also less anxious about the COVID-19 pandemic (p0.05; OR 1.58 and OR 1.6). Most unvaccinated subjects were afraid of the vaccine’s effects on the fetus (62%). The emergence of the Omicron variant is the most cause of anxiety (38%). The most reason for pregnant women who were not anxious is because they had received vaccination (55%). The COVID-19 vaccination can provide a sense of security for pregnant women facing the COVID-19 pandemic.

Efficacy of Antibody Cocktail Drug in COVID-19 Positive Patients: A Retrospective Single-centered Study

Introduction: Neutralising monoclonal antibodies (mABs) have been proposed and developed for the treatment of Coronavirus Disease-2019 (COVID-19) patients with mild to moderate diseases and to prevent further progression. The combination of Casirivimab and Imdevimab blocks the entry of virus into cells by attaching to receptor binding domain of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) spike glycoprotein. The mABs are utilised as a pre-emptive strategy in certain high-risk groups such as those suffering from chronic liver, kidney and respiratory disease, malignancies and other immunocompromised states where efficacy of vaccines may be suboptimal. Aim: To evaluate the clinical outcomes in COVID-19 patients who were treated with Antibody Cocktail drug (casirivimab and imdevimab). Materials and Methods: A retrospective observational study was conducted in patients confirmed positive for SARS-CoV-2 from June 2021 to January 2022 and subsequently, the collected data was analysed from May 2022 to June 2022. The study was conducted in a tertiary care referral hospital in eastern India. All eligible patient subsequently received casirivimab and imdevimab at COVID-19 facility. Monitoring of patients was done upto 12 hour postinfusion. Demographic parameters, routine investigations and clinical outcomes were assessed. Data entry was done using Microsoft Excel. Data was entered, coded and analysed using International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) version 21.0. All analysis was done at a preset alpha error of 5% and results expressed at confidence levels of 95%. Results: Total 104 eligible cases were taken in present study. Nearly, 93% of those patients who had not been vaccinated were at higher risk for having severely elevated levels of C-Reactive Protein (CRP) as compared to 48% of those with COVID-19 vaccination. Nearly, 9 out of 10 patients with moderate-severe CRP levels were at nine times more risk for longer duration of hospitalisation as compared to normal levels of CRP. All patients having moderate-severe CRP levels required mechanical ventilation in comparison to mild CRP levels. Patients with comorbidities were more likely to get severe COVID-19 infections (p-value ≤0.05). Unvaccinated subjects were more likely to have severe infections than vaccinated subjects. (p-value ≤0.05). Prolonged hospitalisation (&gt;7 days) was statistically significant in severe COVID-19. Unvaccinated subjects had a statistically significant rise in CRP over vaccinated subjects. The majority of the patients receiving antibody cocktail did not require prolonged hospitalisation while a minor fraction required invasive ventilation. Antibody cocktail was safe, well tolerated and had good efficacy and low mortality rate as compared to other modalities of treatment in this study. Conclusion: The duration of hospitalisation and outcomes were superior in patients having mild to moderate COVID-19 who received antibody cocktail without any serious side-effects.

Abstract 12057: Absence of Pericarditis Recurrence in Rilonacept-Treated Patients With COVID-19 and mRNA Vaccinations: Experience From Phase 3 Rhapsody Long-Term Extension

Introduction: Rare cardiac complications of COVID-19 and COVID-19 mRNA vaccination include pericarditis and myocarditis. Patients with recurrent pericarditis may be at increased risk of triggered recurrence. The known efficacy of the interleukin (IL)-1 antagonist rilonacept in treating and preventing recurrence could inform COVID-19 disease and vaccination management. Methods: The Phase 3 trial RHAPSODY was a global, double-blind, placebo-controlled, randomized-withdrawal study. A long-term extension (LTE) enabled up to 24 months further open-label treatment from May 2020 until June 2022. Concomitant vaccination data and adverse events, including COVID-19, were collected. Results: No COVID-19 cases were reported during the run-in and randomized withdrawal periods (n=86). As of the 6 May 2022 data cutoff, a COVID-19 AE was reported in 19% (14/74) of LTE subjects, of whom 12 were on rilonacept: 5 of 44 fully-vaccinated (≥14 days beyond second serial dose) subjects (11.4%) and 9 of 30 unvaccinated or partially-vaccinated subjects (30.0%). Of the fully-vaccinated subjects, 1 case occurred ~11 months post primary vaccination cycle (no booster). COVID-19 severity was mild (n= 11), moderate (n=2), or severe (n=1). All cases resolved except the severe AE complicated by comorbidities; the subject discontinued. Of 12 subjects receiving rilonacept at the time of COVID-19 diagnosis, 10 maintained dosing with rilonacept, 1 interrupted rilonacept for ~4 weeks, and 1 discontinued rilonacept permanently; none experienced a pericarditis recurrence (PR) after the AE. The remaining 2 subjects had previously interrupted rilonacept for off-treatment observation: one had a PR &gt;4.5 months after suspending rilonacept and 18 days after COVID-19 resolution; no PR in the other (&gt;6 months). There were no PR AEs associated with COVID-19 vaccination (all subjects were receiving rilonacept). Conclusions: In patients on rilonacept in this study, although numbers are small, vaccination reduced COVID-19 events, pericarditis recurrence was not increased by vaccination or disease, and no pericarditis recurrences occurred during rilonacept treatment. One pericarditis recurrence occurred remotely after rilonacept suspension in the peri-COVID-19 period.

Vaccination Against SARS-CoV-2 Protects from COVID-19-induced Endothelial Dysfunction.

Coronavirus Disease-19 (COVID-19) is implicated in endotheliitis, which adversely affects cardiovascular events. The impact of vaccination with COVID-19 on the clinical outcome of patients is documented. To evaluate the impact of vaccination with COVID-19 on the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) infection-related endothelial impairment. We enrolled 45 patients hospitalized for COVID-19 (either vaccinated or not against SARS-CoV-2). Clinical and laboratory data were collected, and brachial artery flow-mediated dilation (FMD) was evaluated. Subjects without COVID-19 were used as the control group. There was no difference in age (64.7 ± 7.5 years vs. 61.2 ± 11.1 years vs. 62.4 ± 9.5, p = 0.28), male sex (49% vs. 60% vs. 52%, p = 0.71), control subjects, vaccinated, and unvaccinated subjects with COVID-19, respectively. Of the patients with COVID-19, 44% were vaccinated against SARS-CoV-2. Unvaccinated COVID-19 patients had significantly impaired FMD compared to vaccinated COVID-19 patients and Control subjects (2.05 ± 2.41 % vs. 7.24 ± 2.52% vs. 7.36 ± 2.94 %, p <0.001). Importantly, post hoc tests revealed that unvaccinated COVID-19 patients had significantly impaired FMD from both Vaccinated COVID-19 subjects (p <0.001) and from Control subjects (p <0.001). There was no difference in FMD between the control group and the vaccinated COVID-19 group (p = 0.99). Hospitalized patients with COVID-19 present endothelial dysfunction in the acute phase of the disease. Endothelial function in unvaccinated patients with COVID-19 is impaired compared to control subjects as well compared to vaccinated patients with COVID-19. Vaccinated hospitalized subjects with COVID-19 do not show endothelial dysfunction, strengthening the protective role of vaccination against SARS-CoV-2.

Effectiveness of mRNA COVID-19 Vaccines in Adolescents Over 6 Months.

On June 4, 2021, Italy launched the coronavirus disease 2019 (COVID-19) vaccination of adolescents to slow down the COVID-19 spread. Although clinical trials have evaluated messenger ribonucleic acid (mRNA) vaccine effectiveness in adolescents, there is limited literature on its real-world effectiveness. Accordingly, this study aimed to estimate the effectiveness of mRNA COVID-19 vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mild or severe COVID-19 in a cohort of Sicilian adolescents within a 6 month observation period. A retrospective cohort study was conducted with adolescents aged 12 to 18 years, residents of Sicily, who were followed from July 15 to December 31, 2021. SARS-CoV-2 infections, mild and severe COVID-19, and COVID-19-related intubation or deaths during the study period were compared between subjects vaccinated with 2 doses of mRNA vaccines and unvaccinated individuals. The Cox regression analysis, adjusted for age and sex, was performed to compare the 2 groups. Overall, the study included a total at-risk population of 274 782 adolescents with 61.4% of them having completed the vaccination cycle by the end of the study. Unvaccinated subjects had higher incidence rates of SARS-CoV-2 (1043 × 10 000 vs 158.7 × 10 000 subjects), mild COVID-19 (27.7 × 10 000 vs 1.8 × 10 000 subjects) and severe COVID-19 (1.41 × 10 000 vs 0 subjects) compared with the vaccinated population. The estimated adjusted vaccine effectiveness against SARS-CoV-2 infection was 71.2%, reaching 92.1% and 97.9% against mild and severe COVID-19, respectively. This study provides rigorous evidence of mRNA COVID-19 vaccines' effectiveness in protecting adolescents from both SARS-CoV-2 infection and COVID-19.

Risk of SARS-CoV-2 reinfection 18 months after first infection: population-level observational study

Abstract Background Current data suggest that SARS-CoV-2 reinfections are rare. Uncertainties remain, however, on the duration of the natural immunity, its protection against Omicron variant, and on the impact of vaccination to reduce reinfection rates. Methods In this retrospective cohort analysis of the entire population of an Italian Region, we followed 1,293,941 subjects from the beginning of the pandemic to the current scenario of Omicron predominance (up to mid-February 2022). We assessed the proportion of reinfections overall, and by demographic and clinical characteristics, time after primary infection, and predominant circulating variant. Cox proportional hazard analysis was used to compute the relative hazards of reinfection. Results After an average of 277 days, we recorded 729 reinfections among 119,266 previously infected subjects (overall rate: 6.1‰), eight COVID-19-related hospitalizations (7/100,000), and two deaths. Importantly, the incidence of reinfection did not vary substantially over time: after 18-22 months from the primary infection, the reinfection rate was still 6.7‰, suggesting that protection conferred by natural immunity may last beyond 12 months. The risk of reinfection was significantly higher among females, unvaccinated subjects, and during the Omicron wave. Conclusions This study confirms and expands previous findings reporting a low risk of SARS-CoV-2 reinfection, and a very low risk of severe or lethal COVID-19 for those who recovered from primary infection, suggesting that the protection conferred by the natural immunity lasts beyond 12 months. Although the marked increase of the reinfection rates during the Omicron wave is concerning, the risk of a secondary severe disease or death remained close to zero. Vaccines were able to significantly reduce the likelihood of reinfection in both pre-Omicron and Omicron waves, although the risk-benefit profile of multiple vaccine doses for this population should be carefully evaluated. Key messages • After primary infection, the risk of SARS-CoV-2 reinfection and of severe/lethal COVID-19 was low, suggesting that natural immunity lasts beyond 12 months. • Despite increasing reinfection rates with Omicron, the risk of a secondary severe/lethal disease was close to zero, and vaccines reduced the likelihood of reinfection before and during Omicron waves.

Evaluation of the analytical performance of three chemiluminescence serological assays for detecting anti-SARS-CoV-2 antibodies.

The serology surveillance of SARS-CoV-2 antibodies represents a useful tool for monitoring protective immunity in the population. We compared the performance of three SARS-CoV-2 antibody serological immunoassays in 600 vaccinated subjects after the BNT162b2 mRNA COVID-19 vaccine. All serum samples were evaluated by three different immunoassays for detecting anti-SARS-COV-2 antibodies. All SARS-CoV-2 antibody serological immunoassays could detect, when present, a post-vaccine humoral immune response. Median (interquartile range, IQR) anti-S-RBD IgG, Access SARS-CoV-2 IgG (1st IS) and Access SARS-CoV-2 IgG II levels of the subjects investigated were, respectively, 687 BAU/mL (131–2325), 419 IU/mL (58–1091) and 104 AU/mL (14–274). By studying a cohort of unvaccinated subjects, without previous COVID-19 infection, we found a high specificity for all methods. A high correlation was found between IgG titres. Considering the kinetics of subjects with multiple doses, we observed that percentage decreasing gradients were comparable across methods. Our results suggest that all the SARS-CoV-2 antibody serological immunoassays evaluated in this study are suitable for monitoring IgG titers over time. This study contributes to a better understanding of antibody response in vaccinated subjects using some currently available assays.