Real-World Effectiveness of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA Vaccines in Preventing Confirmed Infection in Patients on Chronic Hemodialysis.

BACKGROUND: Persons on chronic hemodialysis have a significantly diminished humoral immune response to SARS-CoV-2 vaccines. Whether this translates to reduced vaccine effectiveness (VE) is unknown. METHODS: We used the US Department of Veterans Affairs COVID-19 Shared Data Resource to identify all veterans who were tested for SARS-CoV-2 between 26 January and 31 August 2021. Using International Classification of Diseases, 10th edition, codes and attendance at a dialysis clinic/center, we identified those who were on chronic hemodialysis. We used a test-negative, case-control design using a doubly robust logistic regression model to determine the VE of the BNT-162b2 (Pfizer) or mRNA-1273 (Moderna) vaccines in preventing confirmed SARS-CoV-2 infection. RESULTS: Among 847 199 veterans tested for SARS-CoV-2 between 26 January and 31 August 2021, there were 6076 veterans on chronic hemodialysis. Among those, we identified 1270 cases (580 fully vaccinated) and 2959 controls (2120 fully vaccinated). The overall VE >14 days after the second dose in preventing documented infection was 68.2% (95% CI: 62.6-72.9%). VE was 68.9% (95% CI: 61.9-74.7%) for Pfizer BNT-162b2 and 66.7% (95% CI: 58.9-73.0%) for Moderna mRNA-1273 vaccine. There was no difference in VE by age (<70 vs >70 years), race, or sex. There were no events recorded in persons with a Charlson's comorbidity index score <2. CONCLUSIONS: VE of 2 doses of current mRNA vaccines in preventing SARS-CoV-2 infection in persons on chronic hemodialysis is lower than historic VE rates in the general population. Effects of additional doses in improving VE in this special population need further study.

Myocarditis following COVID-19 vaccination in adolescents and adults: a cumulative experience of 2021.

Clinical course and outcomes of myocarditis after COVID-19 vaccination remain variable. We retrospectively collected data on patients > 12 years old from 01/01/2021 to 12/30/2021 who received COVID-19 messenger RNA (mRNA) vaccination and were diagnosed with myocarditis within 60 days of vaccination. Myocarditis cases were based on case definitions by authors. We report on 238 patients of whom most were male (n = 208; 87.1%). The mean age was 27.4 ± 16 (range 12-80) years. Females presented at older ages (41.3 ± 21.5 years) than men 25.7 ± 14 years (p = 0.001). In patients > 20 years of age, the mean duration from vaccination to symptoms was 4.8 days ± 5.5 days, but in < 20, it was 3.0 ± 3.3 days (p = 0.04). Myocarditis occurred most commonly after the Pfizer-BioNTech mRNA vaccine (n = 183; 76.45) and after the second dose (n = 182; 80%). Symptoms started 3.95 ± 4.5 days after vaccination. The commonest symptom was chest pain (n = 221; 93%). Patients were treated with non-steroidal anti-inflammatory drugs (n = 105; 58.3%), colchicine (n = 38; 21.1%), or glucocorticoids (n = 23; 12.7%). About 30% of the patients had left ventricular ejection fraction but more than half recovered the on repeat imaging. Abnormal cardiac MRIs were common; 168 patients (96% of 175 patients that had MRI) had late gadolinium enhancement, while 120 patients (68.5%) had myocardial edema. Heart failure guideline-directed medical therapy use was common (n = 27; 15%). Eleven patients had cardiogenic shock; and 4 patients required mechanical circulatory support. Five patients (1.7%) died; of these, 3 patients had endomyocardial biopsy/autopsy-confirmed myocarditis. Most cases of COVID-19 vaccine myocarditis are mild. Females presented at older ages than men and duration from vaccination to symptoms was longer in patients > 20 years. Cardiogenic shock requiring mechanical circulatory support was seen and mortality was low. Future studies are needed to better evaluate risk factors, and long-term outcomes of COVID-19 mRNA vaccine myocarditis.

Applicability of probabilistic graphical models for early detection of SARS-CoV-2 reactive antibodies after SARS-CoV-2 vaccination in hematological patients.

Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3-6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.

Adjustment of Immunosuppressants to Facilitate Anti-COVID-19 Antibody Production after mRNA Vaccination in Liver Transplant Recipients.

Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for 2 weeks during both the 1st and 2nd doses of Moderna mRNA-1273 vaccine. A total of 183 recipients receiving two doses of Moderna mRNA-1273 vaccine were enrolled and grouped into tacrolimus monotherapy (MT, n = 41), and dual therapy with non-adjustment (NA, n = 23), single suspension (SS, n = 19) and double suspension (DS, n = 100) of MMF/EVR in two-dose mRNA vaccination. A total of 155 (84.7%) patients had a humoral response to vaccines in this study. The humoral response rates were 60.9%, 89.5%, 91.0% and 80.5% in NA, SS, DS, and MT group patients, respectively (p = 0.003). Multivariate analysis showed that favorable factors for humoral response were temporary suspension of MMF/EVR and monotherapy, and unfavorable factors were deceased donor liver transplantation, WBC count < 4000/uL, lymphocyte < 20% and tacrolimus trough level ≥ 6.8 ng/mL. In conclusion, temporary two-week suspension of anti-proliferation immunosuppressants could create a window to facilitate antibody production during anti-COVID-19 mRNA vaccination. This concept may be applied to other vaccinations in liver transplant recipients.

Spike-specific humoral and cellular immune responses after COVID-19 mRNA vaccination in patients with cirrhosis: A prospective single center study.

BACKGROUND AND AIMS: COVID-19 mRNA vaccines were approved to prevent severe forms of the disease, but their immunogenicity and safety in cirrhosis is poorly known. METHOD: In this prospective single-center study enrolling patients with cirrhosis undergoing COVID-19 vaccination (BNT162b2 and mRNA-1273), we assessed humoral and cellular responses vs healthy controls, the incidence of breakthrough infections and adverse events (AEs). Antibodies against spike- and nucleocapsid-protein (anti-S and anti-N) and Spike-specific T-cells responses were quantified at baseline, 21 days after the first and second doses and during follow-up. RESULTS: 182 cirrhotics (85% SARS-CoV-2-naïve) and 38 controls were enrolled. After 2 doses of vaccine, anti-S titres were significantly lower in cirrhotics vs controls [1,751 (0.4-25,000) U/mL vs 4,523 (259-25,000) U/mL, p=0.012] and in SARS-CoV-2-naïve vs previously infected cirrhotics [999 (0.4-17,329) U/mL vs 7,500 (12.5-25,000) U/mL, (p<0.001)]. T-cell responses in cirrhotics were similar to controls, although with different kinetics. In SARS-CoV-2-naïve cirrhotics, HCC, Child-Pugh B/C and BNT162b2 were independent predictors of low response. Neither unexpected nor severe AEs emerged. During follow-up, 2% turned SARS-CoV-2 positive, all asymptomatic. CONCLUSION: Humoral response to COVID-19 vaccines appeared suboptimal in patients with cirrhosis, particularly in SARS-CoV-2-naïve decompensated cirrhotics, although cellular response appeared preserved, and low breakthrough infections rate was registered.

Evaluation of Short-Term Symptoms Associated With COVID-19 Vaccines Used Among Adolescents in Saudi Arabia.

OBJECTIVES: Several government-sponsored reporting systems have stated mild to moderate side effects of COVID-19 vaccines. However, patient-reported data on COVID-19 vaccine-associated adverse effects in adolescents are lacking. Our objective was to assess the short-term side effects of Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 vaccinations among teenagers in Saudi Arabia. METHODS: A retrospective, cross-sectional study was conducted among individuals aged 12-18 years old who received one of the two mentioned vaccines between July 2021 and March 2022 in Riyadh, Saudi Arabia. RESULTS: The most common short-term side effects reported for COVID-19 vaccines among teenagers in our study were fatigue, pain at the site of injection, fever, chills, headache, nausea, and vomiting. Female participants, individuals who had a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and those who received two doses of the vaccine are at higher risk to develop side effects after getting the vaccine. Importantly, asthmatic participants have a higher incidence of COVID-19 vaccine side effects when compared to those with no history of chronic diseases. CONCLUSION: Our findings might enhance public trust in the COVID-19 vaccine, which could speed up the immunization procedure.

Assessment of the Neutralizing Antibody Response of BNT162b2 and mRNA-1273 SARS-CoV-2 Vaccines in Naïve and Previously Infected Individuals: A Comparative Study.

The currently authorized mRNA COVID-19 vaccines, Pfizer-BNT162b2 and Moderna-mRNA-1273, offer great promise for reducing the spread of the COVID-19 by generating protective immunity against SARS-CoV-2. Recently, it was shown that the magnitude of the neutralizing antibody (NAbs) response correlates with the degree of protection. However, the difference between the immune response in naïve mRNA-vaccinated and previously infected (PI) individuals is not well studied. We investigated the level of NAbs in naïve and PI individuals after 1 to 26 (median = 6) weeks of the second dose of BNT162b2 or mRNA-1273 vaccination. The naïve mRNA-1273 vaccinated group (n = 68) generated significantly higher (~2-fold, p ≤ 0.001) NAbs than the naïve BNT162b2 (n = 358) group. The P -vaccinated group (n = 42) generated significantly higher (~3-fold; p ≤ 0.001) NAbs levels than the naïve-BNT162b2 (n = 426). Additionally, the older age groups produced a significantly higher levels of antibodies than the young age group (<30) (p = 0.0007). Our results showed that mRNA-1273 generated a higher NAbs response than the BNT162b2 vaccine, and the PI group generated the highest level of NAbs response regardless of the type of vaccine.

Bullous Pemphigoid Following the Moderna mRNA-1273 Vaccine.

As the onset of novel variants of the severe acute respiratory syndrome coronavirus 2 virus pushes policy-makers to push widespread vaccination efforts, it is likely that an increased number of severe cutaneous adverse reactions (SCARs) will present. Therefore, it is important to understand the presentation of possible SCARs. However, data are limited regarding which SCARs are most likely to be found following vaccination, and specific presentations in certain demographic groups, such as postmenopausal women, remain widely unknown. Here, we present the case of a 73-year-old female with no medical history or allergies presenting with a unique reaction of systemic bullous pemphigoid following the Moderna mRNA-1273 vaccine. To our knowledge at the time of this writing, based on a thorough review of the literature using PubMed, no such cases exist following the Moderna vaccine in the United States in elderly, postmenopausal women. We present a brief discussion on the presentation and management to hopefully alleviate future morbidity from similar reactions with increased distribution of the vaccine.

Chronic Inflammatory Demyelinating Polyneuropathy Post-mRNA-1273 Vaccination.

Massive efforts are being made to develop coronavirus disease 2019 (COVID-19) vaccines at an unprecedented rate. The vaccinations' adverse impact profile, on the other hand, has not been well established. Neurological complications are increasingly reported as a result of these vaccines. One such complication identified is immune-mediated inflammatory polyneuropathy, which affects peripheral nerves and neurons. We report a case of chronic inflammatory demyelinating polyneuropathy (CIDP) post-mRNA-1273 (Moderna) COVID-19 vaccine. Recognizing this complication and distinguishing it from Guillain-Barré syndrome enables timely initiation of treatment. Additionally, our report highlights a possible link between vaccination and subsequent development of CIDP, but conclusive evidence of a causal relationship requires more extensive studies.

Erythema Migrans-like COVID Vaccine Arm: A Literature Review.

COVID Vaccine Arm (CVA) is an adverse drug reaction from mRNA vaccine for SARS-CoV-2. CVA is characterized by erythema and edema on the vaccination site (usually deltoid area) that appears from 5 to 10 days after vaccination and is sometimes associated with itching or pain. The exact etiology of CVA is still unclear, but delayed hypersensitivity against an excipient seems to play an essential role in the pathogenesis of the disease. This work performs a systematic literature review on CVA using three different databases containing articles published until 10 November 2021. The literature review includes eight papers reporting single cases or case series of CVA. Moreover, it also addresses, other cutaneous reactions following COVID 19 vaccinations as well as possible differential diagnosis. CVA migrans-like erythema is characterized by a ring-shaped rash in the injection area, which appears some days after the injection and disappears in about 10 days. This reaction may appear more rapidly in subsequent doses.

High-titer neutralization of Mu and C.1.2 SARS-CoV-2 variants by vaccine-elicited antibodies of previously infected individuals.

Recently identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants Mu and C.1.2 have spike proteins with mutations that may confer resistance to natural and vaccine-elicited antibodies. Analysis of neutralizing antibody titers in the sera of vaccinated individuals without previous history of infection and from convalescent individuals show partial resistance of the viruses. In contrast, sera from individuals with a previous history of SARS-CoV-2 infection who were subsequently vaccinated neutralize variants with titers 4- to 11-fold higher, providing a rationale for vaccination of individuals with previous infection. The heavily mutated C.1.2 spike is the most antibody neutralization-resistant spike to date; however, the avidity of C.1.2 spike protein for angiotensin-converting enzyme 2 (ACE2) is low. This finding suggests that the virus evolved to escape the humoral response but has a decrease in fitness, suggesting that it may cause milder disease or be less transmissible. It may be difficult for the spike protein to evolve to escape neutralizing antibodies while maintaining high affinity for ACE2.

Safety Profile of COVID-19 Vaccines among Healthcare Workers in Poland.

The aim of the study was to compare the safety profiles (prevalence of both local and systemic side effects) of COVID-19 vaccines (Pfizer−BioNTech, Moderna, Oxford−AstraZeneca) among healthcare workers (doctors, nurses, and pharmacists) administered with a first and a second dose of the vaccines. Another goal of the research was to evaluate potential demographic and clinical risk factors for the frequency and intensity of side effects. A post-marketing, cross-sectional survey-based study was carried out on a sample of 971 respondents (323 doctors, 324 nurses, and 324 pharmacists), all more than 18 years old, who have taken two doses of the following SARS-CoV-2 vaccines: BNT162b2 (Pfizer−BioNTech) (group 1), mRNA-1273 (Moderna) (group 2), and ChAdOx1 nCoV-19 (Oxford−AstraZeneca) (group 3). A validated, self-administered questionnaire was developed and delivered online to the target population group of healthcare workers. The survey was conducted during the third wave of the COVID-19 (1 February 2021−1 July 2021) pandemic. It was based on the CAWI (computer-assisted web interview) method. Questionnaires were disseminated using selected social media. The BNT162b2 (Pfizer−BioNTech) vaccine was the most commonly administered COVID-19 vaccine among healthcare professionals in Poland (69.61%). Side effects following a SARS-CoV-2 vaccine were reported by 53.11% of respondents in group 1, 72% in group 2, and 67.59% in group 3. The following were the most common side effects regardless of the type of vaccine administered: pain at the injection site, headache, muscle pain, fever, chills, and fatigue. The number and intensity of reported side effects following administration of a BNT162b2 (Pfizer−BioNTech) vaccine were significantly lower than in the other two study groups (p < 0.00001). Risk factors for side effects following administration of one of the SARS-CoV-2 vaccines subject to the analysis included being female, young, and suffering from a diagnosed allergy. Our results clearly show that the short-term safety profiles of the eligible COVID-19 vaccines (Pfizer−BioNTech, Moderna, Oxford−AstraZeneca) are acceptable. Nevertheless, the two-dose COVID-19 vaccines available in Poland differ significantly in the frequency of both local and systemic side effects and their intensity. Women, young people, and patients diagnosed with allergies are particularly exposed to the risk of side effects. Further studies are needed to determine the long-term safety profile of COVID-19 vaccines.

SARS-CoV-2 vaccine response and rate of breakthrough infection in patients with hematological disorders.

BACKGROUND: The clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has not yet been established. PATIENTS AND METHODS: A prospective multicenter registry-based cohort study conducted from December 2020 to December 2021 by the Spanish transplant and cell therapy group was used to analyze the relationship of antibody response at 3-6 weeks after full vaccination (2 doses) with breakthrough SARS-CoV-2 infection in 1394 patients with hematological disorders. RESULTS: At a median follow-up of 165 days after complete immunization, 37 out of 1394 (2.6%) developed breakthrough SARS-CoV-2 infection at median of 77 days (range 7-195) after full vaccination. The incidence rate was 6.39 per 100 persons-year. Most patients were asymptomatic (19/37, 51.4%), whereas only 19% developed pneumonia. The mortality rate was 8%. Lack of detectable antibodies at 3-6 weeks after full vaccination was the only variable associated with breakthrough infection in multivariate logistic regression analysis (Odds Ratio 2.35, 95% confidence interval 1.2-4.6, p = 0.012). Median antibody titers were lower in cases than in non-cases [1.83 binding antibody units (BAU)/mL (range 0-4854.93) vs 730.81 BAU/mL (range 0-56,800), respectively (p = 0.007)]. We identified 250 BAU/mL as a cutoff above which incidence and severity of the infection were significantly lower. CONCLUSIONS: Our study highlights the benefit of developing an antibody response in these highly immunosuppressed patients. Level of antibody titers at 3 to 6 weeks after 2-dose vaccination links with protection against both breakthrough infection and severe disease for non-Omicron SARS-CoV-2 variants.

B.1.526 SARS-CoV-2 Variants Identified in New York City are Neutralized by Vaccine-Elicited and Therapeutic Monoclonal Antibodies.

DNA sequence analysis recently identified the novel SARS-CoV-2 variant B.1.526 that is spreading at an alarming rate in the New York City area. Two versions of the variant were identified, both with the prevalent D614G mutation in the spike protein, together with four novel point mutations and with an E484K or S477N mutation in the receptor-binding domain, raising concerns of possible resistance to vaccine-elicited and therapeutic antibodies. We report that convalescent-phase sera and vaccine-elicited antibodies retain full neutralizing titer against the S477N B.1.526 variant and neutralize the E484K version with a modest 3.5-fold decrease in titer compared to D614G. The E484K version was neutralized with a 12-fold decrease in titer by the REGN10933 monoclonal antibody, but the combination cocktail with REGN10987 was fully active. The findings suggest that current vaccines and Regeneron therapeutic monoclonal antibodies will remain protective against the B.1.526 variants. The findings further support the value of widespread vaccination. IMPORTANCE A novel SARS-CoV-2 variant termed B.1.526 was recently identified in New York City and has been found to be spreading at an alarming rate. The variant has mutations in its spike protein that might allow it to escape neutralization by vaccine-elicited antibodies and might cause monoclonal antibody therapy for COVID-19 to be less successful. We report here that these fears are not substantiated; convalescent-phase sera and vaccine-elicited antibodies neutralized the B.1.526 variant. One of the Regeneron therapeutic monoclonal antibodies was less effective against the B.1.526 (E484K) variant but the two-antibody combination cocktail was fully active. The findings should assuage concerns that current vaccines will be ineffective against the B.1.526 (E484K) variant and suggest the importance of continued widespread vaccination.

Comparison of antibody immune responses between BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines in naïve and previously infected individuals.

BACKGROUND: Two mRNA vaccines, Pfizer-BNT162b2 and Moderna-mRNA-1273, obtained the Emergency Use Listing by WHO for preventing COVID-19. However, little is known about the difference in antibody responses induced by these two mRNA vaccines in naïve and previously infected (PI) individuals. METHOD: We investigated the levels of anti-S-RBD (total, IgG and IgA) levels in naïve and PI individuals, 1-13 (median = 6) weeks following the second dose of either vaccine. Results in the naïve-vaccinated group, the mRNA-1273 vaccine induced significantly higher levels of anti-S-RBD total antibodies (3.5-fold; P < 0.001), IgG (2-fold, P < 0.01) and IgA (2.1-fold, P < 0.001) as compared with the BNT162b2 vaccine. In addition, both vaccines produced significantly higher anti-S-RBD total antibody levels in the PI-group compared with naïve-vaccinated group. The PI group elicited a higher level of anti-S-RBD IgG than the naïve-BNT162b2 (P = 0.05), but not more than the naïve-mRNA-1273 (P = 0.9) group. Interestingly, the PI vaccinated group elicited a comparable level of IgA ratio to the naïve-mRNA-1273 group but significantly higher than the naïve-BNT162b2 group (1.6-fold, P < 0.001). CONCLUSION: Our results showed that the PI-vaccinated group produces a higher level of antibodies than the naïve vaccinated group, particularly for those vaccinated with BNT162b2.