Coagulation and inflammatory response after intramuscular or intradermal mRNA-1273 SARS-CoV-2 vaccine: secondary analysis of a randomized trial.

Background: Fractional-dosed intradermal (i.d.) vaccination produces antibody concentrations above the proposed proxy for protection against severe disease as compared with intramuscular (i.m.) vaccination and may be associated with a decreased prothrombotic effect. Objectives: To assess changes in coagulation following standard dosed i.m. or fractional-dosed i.d. (one-fifth of i.m.) mRNA-1273 SARS-CoV-2 vaccine and to determine the association between the inflammatory response and coagulation. Methods: This study was embedded in a randomized controlled trial assessing the immunogenicity of an i.d. fractional-dosed mRNA-1273 vaccine. Healthy participants, aged 18 to 30 years, were randomized (2:1) to receive either 2 doses of i.d. or i.m. vaccine. Blood was drawn prior to first and second vaccination doses and 1 and 2 weeks after the second dose. The outcomes were changes in coagulation parameters (primary endpoint peak height of the thrombin generation curve) and inflammation (high-sensitivity C-reactive protein [hs-CRP]). Results: One hundred twenty-three participants were included (81 i.d.; 42 i.m.). Peak height increased after vaccination (i.m., 28.8 nmol; 95% CI, 6.3-63.8; i.d., 17.3 nmol; 95% CI, 12.5-47.2) and recovered back to baseline within 2 weeks. I.m. vaccination showed a higher inflammatory response compared with i.d. vaccination (extra increase hs-CRP, 0.92 mg/L; 95% CI, 0.2-1.7). Change in endogenous thrombin potential was associated with change in hs-CRP (beta, 28.0; 95% CI, 7.6-48.3). Conclusion: A transient increase in coagulability after mRNA-1273 SARS-CoV-2 vaccination occurred, which was associated with the inflammatory response. While i.d. administration showed antibody concentrations above the proposed proxy for protection against severe disease, it was associated with less systemic inflammation. Hence, i.d. vaccination may be safer.

Racial and ethnic disparities in COVID-19 booster vaccination among U.S. older adults differ by geographic region and Medicare enrollment.

Introduction: COVID-19 booster vaccines are highly effective at reducing severe illness and death from COVID-19. Research is needed to identify whether racial and ethnic disparities observed for the primary series of the COVID-19 vaccines persist for booster vaccinations and how those disparities may vary by other characteristics. We aimed to measure racial and ethnic differences in booster vaccine receipt among U.S. Medicare beneficiaries and characterize potential variation by demographic characteristics. Methods: We conducted a cohort study using CVS Health and Walgreens pharmacy data linked to Medicare claims. We included community-dwelling Medicare beneficiaries aged ≥66 years who received two mRNA vaccine doses (BNT162b2 and mRNA-1273) as of 8/1/2021. We followed beneficiaries from 8/1/2021 until booster vaccine receipt, death, Medicare disenrollment, or end of follow-up (12/31/2021). Adjusted Poisson regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) comparing vaccine uptake between groups. Results: We identified 11,339,103 eligible beneficiaries (mean age 76 years, 60% female, 78% White). Overall, 67% received a booster vaccine (White = 68.5%; Asian = 67.0%; Black = 57.0%; Hispanic = 53.3%). Compared to White individuals, Black (RR = 0.78 [95%CI = 0.78-0.78]) and Hispanic individuals (RR = 0.72 [95% = CI 0.72-0.72]) had lower rates of booster vaccination. Disparities varied by geographic region, urbanicity, and Medicare plan/Medicaid eligibility. The relative magnitude of disparities was lesser in areas where vaccine uptake was lower in White individuals. Discussion: Racial and ethnic disparities in COVID-19 vaccination have persisted for booster vaccines. These findings highlight that interventions to improve vaccine uptake should be designed at the intersection of race and ethnicity and geographic location.

Assessment of the Immune Response in Patients with Insulin Resistance, Obesity, and Diabetes to COVID-19 Vaccination.

The SARS-CoV-19 pandemic overwhelmed multiple healthcare systems across the world. Patients with underlying medical conditions such as obesity or diabetes were particularly vulnerable, had more severe symptoms, and were more frequently hospitalized. To date, there have been many studies on the severity of SARS-CoV-2 in patients with metabolic disorders, but data on the efficiency of vaccines against COVID-19 are still limited. This paper aims to provide a comprehensive overview of the effectiveness of COVID-19 vaccines in individuals with diabetes, insulin resistance, and obesity. A comparison is made between the immune response after vaccination in patients with and without metabolic comorbidities. Additionally, an attempt is made to highlight the mechanisms of immune stimulation affected by SARS-CoV-2 vaccines and how metabolic comorbidities modulate these mechanisms. The focus is on the most common COVID-19 vaccines, which include mRNA vaccines such as Pfizer-BioNTech and Moderna, as well as viral vector vaccines such as AstraZeneca and Johnson & Johnson. Furthermore, an effort is made to clarify how the functional differences between these vaccines may impact the response in individuals with metabolic disorders, drawing from available experimental data. This review summarizes the current knowledge regarding the post-vaccination response to COVID-19 in the context of metabolic comorbidities such as diabetes, insulin resistance, and obesity.

A severe case of rhabdomyolysis after Moderna mRNA anti-COVID-19 vaccine with a literature review.

The identification of rhabdomyolysis as a potential fatal adverse reaction to recent COVID-19 vaccines is essential. As the symptoms of rhabdomyolysis are not specific, the threshold to actively search for this complication should be low.

Herpes zoster ophthalmicus after COVID-19 vaccine booster in healthy younger adult: a case report.

There were growing reports of herpes zoster reactivation after the coronavirus disease 2019 (COVID-19) vaccination, including a more severe form, herpes zoster ophthalmicus (HZO). A 35-year-old male presented HZO in his left V1 dermatome 10 days after his COVID-19 vaccine booster with Moderna (messenger RNA-1273). He had no history of chronic disease, immunocompromised, autoimmune, malignancy, or long-term immunosuppressive drug use. The rash improved without any further complications after being treated with oral valacyclovir for 7 days. This was a unique case of HZO after the COVID-19 vaccine in a booster setting in healthy younger adults. The association of herpes zoster after a COVID vaccine remained inconclusive and potentially coincidental, especially without the known risk factor. However, we would like to add a report to increase awareness among physicians and the general population, for early recognition and treatment with an antiviral.

Data resource profile: COVid VAXines effects on the aged (COVVAXAGE).

Background: To improve the assessment of COVID-19 vaccine use, safety, and effectiveness in older adults and persons with complex multimorbidity, the COVid VAXines Effects on the Aged (COVVAXAGE) database was established by linking CVS Health and Walgreens pharmacy customers to Medicare claims. Methods: We deterministically linked CVS Health and Walgreens customers who had a pharmacy dispensation/encounter paid for by Medicare to Medicare enrollment and claims records. Linked data include U.S. Medicare claims, Medicare enrollment files, and community pharmacy records. The data currently span 01/01/2016 to 08/31/2022. "Research-ready" files were created, with weekly indicators for vaccinations, censoring, death, enrollment, demographics, and comorbidities. Data are updated quarterly. Results: As of November 2022, records for 27,086,723 CVS Health and 23,510,025 Walgreens unique customer IDs were identified for potential linkage. Approximately 91% of customers were matched to a Medicare beneficiary ID (95% for those aged 65 years or older). In the final linked cohort, there were 38,250,873 unique beneficiaries representing ~60% of the Medicare population. Among those alive and enrolled in Medicare as of January 1, 2020 (n = 33,721,568; average age = 73 years, 74% White, 51% Medicare Fee-for-Service, and 11% dual-eligible for Medicaid), the average follow-up time was 130 weeks. The cohort contains 16,021,055 beneficiaries with evidence a first COVID-19 vaccine dose. Data are stored on the secure Medicare & Medicaid Resource Information Center Health & Aging Data Enclave. Data access: Investigators with funded or in-progress funding applications to the National Institute on Aging who are interested in learning more about the database should contact Dr Vincent Mor [Vincent_mor@brown.edu] and Dr Kaleen Hayes [kaley_hayes@brown.edu]. A data dictionary can be provided under reasonable request. Conclusions: The COVVAXAGE cohort is a large and diverse cohort that can be used for the ongoing evaluation of COVID-19 vaccine use and other research questions relevant to the Medicare population.

Association between history of SARS-CoV-2 infection and severe systemic adverse events after mRNA COVID-19 vaccination among U.S. adults.

BACKGROUND: Risk of experiencing a systemic adverse event (AE) after mRNA coronavirus disease 2019 (COVID-19) vaccination may be greater among persons with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; data on serious events are limited. We assessed if adults reporting systemic AEs resulting in emergency department visits or hospitalizations during days 0-7 after mRNA COVID-19 vaccine dose 1 were more likely to have a history of prior SARS-CoV-2 infection compared with persons who reported no or non-severe systemic AEs. METHODS: We conducted a nested case-control study using v-safe surveillance data. Participants were ≥ 18 years and received dose 1 during December 14, 2020─May 9, 2021. Cases reported severe systemic AEs 0-7 days after vaccination. Three controls were frequency matched per case by age, vaccination date, and days since vaccination. Follow-up surveys collected SARS-CoV-2 histories. RESULTS: Follow-up survey response rates were 38.6 % (potential cases) and 56.8 % (potential controls). In multivariable analyses including 3,862 case-patients and 11,586 controls, the odds of experiencing a severe systemic AE were 2.4 (Moderna, mRNA-1273; 95 % confidence interval [CI]: 1.89, 3.09) and 1.5 (Pfizer-BioNTech, BNT162b2; 95 % CI: 1.17, 2.02) times higher among participants with pre-vaccination SARS-CoV-2 histories compared with those without. Medical attention of any kind for symptoms during days 0-7 following dose 2 was not common among case-patients or controls. CONCLUSIONS: History of SARS-CoV-2 infection was significantly associated with severe systemic AEs following dose 1 of mRNA COVID-19 vaccine; the effect varied by vaccine received. Most participants who experienced severe systemic AEs following dose 1 did not require medical attention of any kind for symptoms following dose 2. Vaccine providers can use these findings to counsel patients who had pre-vaccination SARS-CoV-2 infection histories, experienced severe systemic AEs following dose 1, and are considering not receiving additional mRNA COVID-19 vaccine doses.

Effectiveness of Booster and Influenza Vaccines against COVID-19 among Healthcare Workers, Taiwan.

Among previously uninfected healthcare workers in Taiwan, mRNA COVID-19 booster vaccine was associated with lower odds of COVID-19 after primary recombinant vaccine. Symptom-triggered testing revealed that tetravalent influenza vaccine was associated with higher odds of SARS-CoV-2 infection. COVID-19 vaccination continues to be most effective against SARS-CoV-2.

Risk of Myocarditis After Sequential Doses of COVID-19 Vaccine and SARS-CoV-2 Infection by Age and Sex.

BACKGROUND: Myocarditis is more common after severe acute respiratory syndrome coronavirus 2 infection than after COVID-19 vaccination, but the risks in younger people and after sequential vaccine doses are less certain. METHODS: A self-controlled case series study of people ages 13 years or older vaccinated for COVID-19 in England between December 1, 2020, and December 15, 2021, evaluated the association between vaccination and myocarditis, stratified by age and sex. The incidence rate ratio and excess number of hospital admissions or deaths from myocarditis per million people were estimated for the 1 to 28 days after sequential doses of adenovirus (ChAdOx1) or mRNA-based (BNT162b2, mRNA-1273) vaccines, or after a positive SARS-CoV-2 test. RESULTS: In 42 842 345 people receiving at least 1 dose of vaccine, 21 242 629 received 3 doses, and 5 934 153 had SARS-CoV-2 infection before or after vaccination. Myocarditis occurred in 2861 (0.007%) people, with 617 events 1 to 28 days after vaccination. Risk of myocarditis was increased in the 1 to 28 days after a first dose of ChAdOx1 (incidence rate ratio, 1.33 [95% CI, 1.09-1.62]) and a first, second, and booster dose of BNT162b2 (1.52 [95% CI, 1.24-1.85]; 1.57 [95% CI, 1.28-1.92], and 1.72 [95% CI, 1.33-2.22], respectively) but was lower than the risks after a positive SARS-CoV-2 test before or after vaccination (11.14 [95% CI, 8.64-14.36] and 5.97 [95% CI, 4.54-7.87], respectively). The risk of myocarditis was higher 1 to 28 days after a second dose of mRNA-1273 (11.76 [95% CI, 7.25-19.08]) and persisted after a booster dose (2.64 [95% CI, 1.25-5.58]). Associations were stronger in men younger than 40 years for all vaccines. In men younger than 40 years old, the number of excess myocarditis events per million people was higher after a second dose of mRNA-1273 than after a positive SARS-CoV-2 test (97 [95% CI, 91-99] versus 16 [95% CI, 12-18]). In women younger than 40 years, the number of excess events per million was similar after a second dose of mRNA-1273 and a positive test (7 [95% CI, 1-9] versus 8 [95% CI, 6-8]). CONCLUSIONS: Overall, the risk of myocarditis is greater after SARS-CoV-2 infection than after COVID-19 vaccination and remains modest after sequential doses including a booster dose of BNT162b2 mRNA vaccine. However, the risk of myocarditis after vaccination is higher in younger men, particularly after a second dose of the mRNA-1273 vaccine.

Heterologous prime-boost with the mRNA-1273 vaccine among CoronaVac-vaccinated healthcare workers in Indonesia.

Purpose: This study was performed to investigate humoral immune response and adverse events upon the heterologous prime-boost with a single dose of the mRNA-1273 vaccine among fully CoronaVac-vaccinated, infection-naïve healthcare workers in Indonesia. Materials and Methods: One hundred twenty-five eligible healthcare workers were recruited from one hospital for this prospective cohort study. Blood collection was conducted twice, i.e., on 7 days before and 28 days after the booster vaccination. The titer of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies was quantified accordingly. The post-vaccination adverse event was recorded for both CoronaVac and mRNA-1273 vaccinations. Any breakthrough infection was monitored during the follow-up period. Wilcoxon matched-pairs signed rank test was used to test differences between groups. Results: A significant increase was observed in the titer of anti-SARS-CoV-2 RBD antibodies upon receiving the mRNA-1273 booster (geometric mean titers of 65.57 and 47,445 U/mL in pre- and post-booster, respectively), supporting the argument to use heterologous prime-boost vaccination to improve the protection against COVID-19 in a high-risk population. The mRNA-1273 vaccine, however, caused a higher frequency of adverse events than the CoronaVac vaccine. Nonetheless, the adverse events were considered minor medical events and temporary as all subjects were not hospitalized and fully recovered. Of note, no breakthrough infection was observed during the follow-up to 12 weeks post-booster. Conclusion: The heterologous prime-boost vaccination of healthcare workers with a single dose of the mRNA-1273 vaccine generated a significant elevation in humoral immune response towards RBD of SARS-CoV-2 and was associated with a higher frequency, but minor and transient, adverse events.

Factors Associated with Delayed or Missed Second-Dose mRNA COVID-19 Vaccination among Persons >12 Years of Age, United States.

To identify demographic factors associated with delaying or not receiving a second dose of the 2-dose primary mRNA COVID-19 vaccine series, we matched 323 million single Pfizer-BioNTech (https://www.pfizer.com) and Moderna (https://www.modernatx.com) COVID-19 vaccine administration records from 2021 and determined whether second doses were delayed or missed. We used 2 sets of logistic regression models to examine associated factors. Overall, 87.3% of recipients received a timely second dose (≤42 days between first and second dose), 3.4% received a delayed second dose (>42 days between first and second dose), and 9.4% missed the second dose. Persons more likely to have delayed or missed the second dose belonged to several racial/ethnic minority groups, were 18-39 years of age, lived in more socially vulnerable areas, and lived in regions other than the northeastern United States. Logistic regression models identified specific subgroups for providing outreach and encouragement to receive subsequent doses on time.

Safety and Adverse Events Related to COVID-19 mRNA Vaccines; a Systematic Review.

Introduction: Knowledge of vaccine-related adverse events is crucial as they are among the most important factors that cause hesitation in receiving vaccines. Therefore, we aimed to systematically review the adverse events related to the mRNA vaccines reported in the literature. . Method: A systematic literature search was carried out in the databases of Scopus, PubMed, Cochrane, and Web of Science. We selected original studies that explored the side effects of mRNA COVID-19 vaccines using a two-phase (title/abstract and full-text) screening process. . Results: Cardiac complications were the most commonly reported severe adverse events. It appeared that systemic adverse reactions are more common after the second dose of vaccines. The number of adverse effects reported after the Pfizer vaccine was higher than other vaccines, mostly due to its earlier approval and more widespread use throughout the world. Cardiac adverse events had a higher prevalence but no significant association has been found between COVID-19 mRNA vaccines and cardiac adverse events except for myopericarditis. . Conclusion: Vaccines play a crucial role in controlling the COVID-19 pandemic and decreasing mortalities and the results of the present review acknowledge the fact that the benefits outweigh the adverse events of these vaccines. .

Expert recommendations on booster immunization strategies of 2019-nCoV vaccines / 中华临床感染病杂志

Since the end of 2019, the COVID-19 caused by 2019-nCoV has emerged and the pandemic ravaged the world, which seriously threatens global public health security and economic development. 2019-nCoV vaccine is an effective weapon to combat the viral infection, however, studies have shown that vaccine-induced immune protection decreases over time, coupled with some novel and immune escape variants continual emerging. Therefore, it is urgent to complete booster immunization to improve protection. At present, 2019-nCoV vaccines based on a variety of technical platforms have been approved and available in China. Therefore, we developed this sequential vaccination strategy guide to provide documentation guidance for the prevention and control of the epidemic caused by 2019-nCoV and its variant strains.

Clinical characteristics of patients infected with 2019-nCoV Omicron variants BA.1 and BA.2 in Zhuhai city / 中华临床感染病杂志

Objective:To analyze the clinical characteristics of patients infected with 2019-nCoV Omicron variants BA.1 and BA.2 in Zhuhai city.Methods:A retrospective study was conducted to compare clinical characteristics of patients infected with 2019-nCoV Omicron variants BA.1 and BA.2, who were admitted in the Fifth Affiliated Hospital of Sun Yat-sen University during January 13 to March 8 2022. The Mann-Whitney U-test or Kruskal-Wallis H test was used for quantitative data, and the χ2 test or Fisher’s exact test was used for qualitative data. Results:Among 122 patients infected with the Omicron variant, there was 79 adults (BA.1 23 cases, BA.2 56 cases) and 43 children (BA.1 19 cases, BA.2 24 cases). In adults, patients infected with BA.2 sub-variant had a higher baseline viral loads at admission than BA.1 infected patients [7.64(6.92, 8.55) lg copies/mL vs. 6.64(6.04, 7.34) lg copies/mL; Z=-3.022, P=0.003]; compared to BA.1 patients, BA.2 patients had a higher proportion of mild and asymptomatic cases and a lower proportion of common infection cases ( χ2=8.052, P=0.012); the proportion of patients with pneumonia imaging changes in BA.1 patients was higher than that in BA.2 infected patients [(6/23, 26.1%) vs. (2/56, 3.6%); χ2=6.776, P=0.009). In children, the rate of fever in BA.2 group was higher than that in BA.1 group [(16/24, 66.7%) vs. ( 5/19, 26.3%); χ2=6.910, P=0.009); the proportion of patients with reduced lymphocyte counts in BA.2 group was higher than that in BA.1 group [(17/24, 70.8%) vs.(1/19, 5.3%); χ2=18.734, P<0.001). Compared with adult cases, children with BA.2 sub-variant infection had higher fever rate [(16/24, 66.7%) vs. (19/56, 33.9%); χ2=7.317, P=0.007). The viral loads of daily nasal swabs in BA.2 infected patients increased first and then decreased in both adults and children, with a greater decrease than BA.1 during the first two weeks. Conclusions:Compare with 2019-nCoV Omicron variant BA.1, BA.2 has a higher baseline viral loads in adults, which means much more contagious in the early stages. But the viral load drops faster in BA.2 infected patients. In children, BA.2 patients are more likely to have fever and reduced lymphocyte counts, which indicates that the prevention and control of 2019-nCoV Omicron sub-variant BA.2 is more difficult.