Durability of humoral and cellular immunity six months after the BNT162b2 bivalent booster.

Studies about the duration of the humoral and cellular response following the bivalent booster administration are still scarce. We aimed at assessing the humoral and cellular response in a cohort of healthcare workers that received this booster. Blood samples were collected before the administration of the bivalent booster from Pfizer-BioNTech and after 14, 28, 90, and 180 days. Neutralizing antibodies against either the D614G strain, the delta variant, the BA.5 variant, or the XBB.1.5 subvariant were measured. The cellular response was assessed by measurement of the release of interferon gamma from T cells in response to an in vitro SARS-CoV-2 stimulation. A substantial waning of neutralizing antibodies was observed after 6 months (23.1-fold decrease), especially considering the XBB.1.5 subvariant. The estimated T1/2 of neutralizing antibodies was 16.1 days (95% CI = 10.2-38.4 days). Although most participants still present a robust cellular response after 6 months (i.e., 95%), a significant decrease was also observed compared to the peak response (0.95 vs. 0.41 UI/L, p = 0.0083). A significant waning of the humoral and cellular response was observed after 6 months. These data can also help competent national authorities in their recommendation regarding the administration of an additional booster.

Effect of biologic therapy on the humoral immune response to the BNT162b2 vaccine in patients with asthma.

The effect of inhaled corticosteroids (ICS) and biologics on the humoral immune response following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination in patients with asthma is unknown. We prospectively evaluated the humoral immune response 3 weeks (T1) and 6 months (T2) after the second dose of BNT162b2 in 30 SARS-CoV-2-naïve patients with asthma. We measured anti-spike immunoglobulin G (IgG) titers and serum-neutralizing activity against the ancestral SARS-CoV-2 strain. The anti-spike IgG titer and neutralizing activity did not differ significantly between the biologics and non-biologics groups at T1 (P = 0.708 and P = 0.417, respectively) or T2 (P = 0.299 and P = 0.492, respectively). In the multivariate analysis, age and sex were significantly associated with the magnitude of the humoral immune response; however, the use of biologics and ICS dose were not, suggesting that these would not affect BNT162b2 immunogenicity in patients with asthma. Larger studies are needed to validate these findings.

Association of systemic adverse reaction patterns with long-term dynamics of humoral and cellular immunity after coronavirus disease 2019 third vaccination.

The objective of this study was to clarify the impact of adverse reactions on immune dynamics. We investigated the pattern of systemic adverse reactions after the second and third coronavirus disease 2019 (COVID-19) vaccinations and their relationship with immunoglobulin G against severe acute respiratory syndrome coronavirus 2 spike 1 protein titers, neutralizing antibody levels, peak cellular responses, and the rate of decrease after the third vaccination in a large-scale community-based cohort in Japan. Participants who received a third vaccination with BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna), had two blood samples, had not had COVID-19, and had information on adverse reactions after the second and third vaccinations (n = 2198) were enrolled. We collected data on sex, age, adverse reactions, comorbidities, and daily medicine using a questionnaire survey. Participants with many systemic adverse reactions after the second and third vaccinations had significantly higher humoral and cellular immunity in the peak phase. Participants with multiple systemic adverse reactions after the third vaccination had small changes in the geometric values of humoral immunity and had the largest geometric mean of cellar immunity in the decay phase. Systemic adverse reactions after the third vaccination helped achieve high peak values and maintain humoral and cellular immunity. This information may help promote uptake of a third vaccination, even among those who hesitate due to adverse reactions.

Reactions following Pfizer-BioNTech COVID-19 mRNA vaccination and related healthcare encounters among 7,077 children aged 5-11 years within an integrated healthcare system.

BACKGROUND: Studies combining data from digital surveys and electronic health records (EHR) can be used to conduct comprehensive assessments on COVID-19 vaccine safety. METHODS: We conducted an observational study using data from a digital survey and EHR of children aged 5-11 years vaccinated with Pfizer-BioNTech COVID-19 mRNA vaccine across Kaiser Permanente Southern California during November 4, 2021-February 28, 2022. Parents/guardians who enrolled their children were sent a 14-day survey on reactions. Survey results were combined with EHR, and medical encounters were described for children whose parents or guardians indicated seeking medical care for vaccine-related symptoms. This study describes self-reported reactions (local and systemic) and additional symptoms (chest pain, tachycardia, and pre-syncope). RESULTS: The study recruited 7,077 participants aged 5-11 years who received the Pfizer-BioNTech COVID-19 mRNA vaccine. Of 6,247 participants with survey responses after dose 1, 2,176 (35 %) reported at least one systemic reaction, and 1,076 (32 %) of 3,401 respondents following dose 2 reported at least one systemic reaction. Local reactions were reported less frequently following dose 2 (1,113, 33 %) than dose 1 (3,140, 50 %). The most frequently reported reactions after dose 1 were pain at the injection site (48 %), fatigue (20 %), headache (12 %), myalgia (9 %) and fever (5 %). The most frequently reported symptoms after dose 2 were also pain at the injection site (30 %), fatigue (19 %), headache (13 %), myalgia (10 %) and fever (9 %). Post-vaccination reactions occurred most frequently-one day following vaccination. Chest pain or tachycardia were reported infrequently (1 %). EHR demonstrated that parents rarely sought care for post-vaccination symptoms, and among those seeking care, the most common symptoms documented in EHR were fever and nausea, comprising <0.5 % of children. No encounters were related to myocarditis. CONCLUSION: While post-vaccination reactions to the Pfizer-BioNTech COVID-19 mRNA vaccine were common in children aged 5-11 years, our data showed that in most cases they were transient and did not require medical care.

Serological response after anti-SARS-CoV-2 BNT162b2 vaccine in IBD patients on biological therapy: a monocentric case-control study.

BACKGROUND: Inflammatory bowel disease (IBD) patients on biological therapy are receiving vaccines against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). However, it is unclear if IBD therapy could influence the response to this vaccine. In a case-control study, we assessed the antibody profiling after anti-SARS-CoV-2 BNT162b2 vaccine in IBD patients on biological therapy. METHODS: We analyzed seroprevalence and antibody titer, after 14 weeks from the first BNT162b2 vaccine dose, in IBD patients on biological therapy and health care workers (HCWs). In IBD patients, medical history and disease data were recorded. RESULTS: Eighty-two subjects were enrolled in this study. Among them, 40 were IBD patients on biological therapy and 42 were HCWs. All subjects developed an IgG anti-Spike antibody titer above the cut-off. IBD patients on biological therapy developed a lower antibody titer than HCWs (P<0.00001). No differences were reported in patients who received at least one dose of the vaccine within a period of 7 days from the last biological drug administration, compared to all other IBD patients. A difference was found between patients who were on concomitant immunosuppressive therapy and patients on sole biological therapy (P=0.0287). Patients with presence of any sign of disease activity (clinical, endoscopic or laboratory) showed a higher development of antibody titer compared to those in complete disease remission (P=0.0468). CONCLUSIONS: Our data indicate that in IBD patients, treatment with biological therapies do not affect the seroprevalence but leads to a lower antibody titer development after anti-SARS-CoV-2 BNT162b2 vaccine.

Vitamin D Supplementation Does Not Influence SARS-CoV-2 Vaccine Efficacy or Immunogenicity: Sub-Studies Nested within the CORONAVIT Randomised Controlled Trial.

Vitamin D deficiency has been reported to associate with the impaired development of antigen-specific responses following vaccination. We aimed to determine whether vitamin D supplements might boost the immunogenicity and efficacy of SARS-CoV-2 vaccination by conducting three sub-studies nested within the CORONAVIT randomised controlled trial, which investigated the effects of offering vitamin D supplements at a dose of 800 IU/day or 3200 IU/day vs. no offer on risk of acute respiratory infections in UK adults with circulating 25-hydroxyvitamin D concentrations <75 nmol/L. Sub-study 1 (n = 2808) investigated the effects of vitamin D supplementation on the risk of breakthrough SARS-CoV-2 infection following two doses of SARS-CoV-2 vaccine. Sub-study 2 (n = 1853) investigated the effects of vitamin D supplementation on titres of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies in eluates of dried blood spots collected after SARS-CoV-2 vaccination. Sub-study 3 (n = 100) investigated the effects of vitamin D supplementation on neutralising antibody and cellular responses in venous blood samples collected after SARS-CoV-2 vaccination. In total, 1945/2808 (69.3%) sub-study 1 participants received two doses of ChAdOx1 nCoV-19 (Oxford−AstraZeneca); the remainder received two doses of BNT162b2 (Pfizer). Mean follow-up 25(OH)D concentrations were significantly elevated in the 800 IU/day vs. no-offer group (82.5 vs. 53.6 nmol/L; mean difference 28.8 nmol/L, 95% CI 22.8−34.8) and in the 3200 IU/day vs. no offer group (105.4 vs. 53.6 nmol/L; mean difference 51.7 nmol/L, 45.1−58.4). Vitamin D supplementation did not influence the risk of breakthrough SARS-CoV-2 infection in vaccinated participants (800 IU/day vs. no offer: adjusted hazard ratio 1.28, 95% CI 0.89 to 1.84; 3200 IU/day vs. no offer: 1.17, 0.81 to 1.70). Neither did it influence IgGAM anti-Spike titres, neutralising antibody titres or IFN-γ concentrations in the supernatants of S peptide-stimulated whole blood. In conclusion, vitamin D replacement at a dose of 800 or 3200 IU/day effectively elevated 25(OH)D concentrations, but it did not influence the protective efficacy or immunogenicity of SARS-CoV-2 vaccination when given to adults who had a sub-optimal vitamin D status at baseline.

BNT162b2 mRNA COVID-19 vaccine is safe in a setting of patients on biologic therapy with inflammatory bowel diseases: a monocentric real-life study.

OBJECTIVES: Patients with inflammatory bowel disease were excluded from trials that led to the approval of anti-COVID-19 vaccines and are worthy of real-life studies providing information on the safety of these vaccines in this clinical setting. METHODS: A prospective observational study was performed to estimate BNT162b2 mRNA COVID-19 Vaccine local and systemic adverse events (AEs) incidence related to administration in patients with inflammatory bowel disease through a questionnaire administered at the first, second, and third doses. Disease activity by Mayo Partial Score and Harvey-Bradshaw Index was also evaluated. RESULTS: Eighty patients with a median age of 47.5 years were initially enrolled. The local AEs rate was 26.25%, 58.75%, and 28.37% at the first, second, and third doses of the vaccine, respectively. In contrast, the systemic AEs rate was 52.2%, 48.75%, and 43.24%. Clinic-demographic predictor variables for AEs were not identified. Vaccination did not affect disease activity and no statistically significant difference in disease activity index scores was observed between the three doses. No serious adverse events were observed. CONCLUSION: This vaccine was safe in a population of patients with inflammatory bowel disease and, therefore, could be safely administered in this clinical setting.

Effectiveness Associated With BNT162b2 Vaccine Against Emergency Department and Urgent Care Encounters for Delta and Omicron SARS-CoV-2 Infection Among Adolescents Aged 12 to 17 Years.

Importance: Data about the duration of protection of 2 and 3 doses of BNT162b2 in children and adolescents are needed to help inform recommendations for boosters in this age group. Objective: To evaluate vaccine effectiveness (VE) and durability associated with 2 doses of BNT162b2 against Delta- and Omicron-related emergency department (ED) and urgent care (UC) encounters among adolescents aged 12 to 17 years and to estimate VE associated with 3 doses against these same outcomes. Design, Setting, and Participants: This test-negative case-control study was conducted at Kaiser Permanente Southern California, an integrated health care system using electronic health records in the US. Participants included Kaiser Permanente Southern California members ages 12 to 17 years with an ED or UC encounter from November 1, 2021, through March 18, 2022, for acute respiratory infection who were tested for SARS-CoV-2 via a reverse transction-polymerase chain reaction test. Analyses were conducted from March 21 to June 22, 2022. Exposures: BNT162b2 vaccination status ascertained from electronic health records and state registry data. Main Outcomes and Measures: The main outcome was VE associated with BNT162b2 against ED and UC encounters related to Delta or Omicron variant SARS-CoV-2 infection. Results: Analyses were conducted among 3168 adolescents, including 1004 with ED visits and 2164 with UC visits. Median (IQR) age was 15 (13-16) years, and 1461 (46.1%) were boys. In adjusted analyses, VE associated with 2 doses of BNT162b2 against ED or UC encounters was highest within the first 2 months for both Delta (89% [95% CI, 69% to 96%]) and Omicron (73% [95% CI, 54% to 84%]) variants but waned to 49% (95% CI, 27% to 65%) for the Delta variant and 16% (95% CI, -7% to 34%) for the Omicron variant at 6 months and beyond. A third dose of BNT162b2 was associated with improved protection against the Omicron variant (87% [95% CI, 72% to 94%]) after a median (IQR) of 19 (9-32) days after dose 3. Conclusions and Relevance: These findings suggest that 2 doses of the BNT162b2 COVID-19 vaccine were associated with high levels of protection against ED and UC encounters related to the Delta and Omicron variants of SARS-CoV-2 in the first few months after vaccination. However, effectiveness waned over time, especially against Omicron. A third dose of BNT162b2 was associated with improved protection against Omicron beyond that seen initially after 2 doses, underscoring the importance of boosters for adolescents aged 12 to 17 years.

Risk of myocarditis and pericarditis following BNT162b2 and mRNA-1273 COVID-19 vaccination.

BACKGROUND: Evidence indicates that mRNA COVID-19 vaccination is associated with risk of myocarditis and possibly pericarditis, especially in young males. It is not clear if risk differs between mRNA-1273 versus BNT162b2. We assessed if risk differs using comprehensive health records on a diverse population. METHODS: Members 18-39 years of age at eight integrated healthcare-delivery systems were monitored using data updated weekly and supplemented with medical record review of myocarditis and pericarditis cases. Incidence of myocarditis and pericarditis events that occurred among vaccine recipients 0 to 7 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by conditional Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. Head-to-head comparison directly assessed risk following mRNA-1273 versus BNT162b2 during 0-7 days post-vaccination. RESULTS: From December 14, 2020 - January 15, 2022 there were 41 cases after 2,891,498 doses of BNT162b2 and 38 cases after 1,803,267 doses of mRNA-1273. Cases had similar demographic and clinical characteristics. Most were hospitalized for ≤1 day; none required intensive care. During days 0-7 after dose 2 of BNT162b2, the incidence was 14.3 (CI: 6.5-34.9) times higher than the comparison interval, amounting to 22.4 excess cases per million doses; after mRNA-1273 the incidence was 18.8 (CI: 6.7-64.9) times higher than the comparison interval, amounting to 31.2 excess cases per million doses. In head-to-head comparisons 0-7 days after either dose, risk was moderately higher after mRNA-1273 than after BNT162b2 (RR: 1.61, CI 1.02-2.54). CONCLUSIONS: Both vaccines were associated with increased risk of myocarditis and pericarditis in 18-39-year-olds. Risk estimates were modestly higher after mRNA-1273 than after BNT162b2.

Serum Free Zinc Is Associated With Vaccination Response to SARS-CoV-2.

Background: Zinc (Zn) is an essential trace element with high relevance for the immune system, and its deficiency is associated with elevated infection risk and severe disease course. The association of Zn status with the immune response to SARS-CoV-2 vaccination is unknown. Methods: A cohort of adult health care workers (n=126) received two doses of BNT162B2, and provided up to four serum samples over a time course of 6 months. Total SARS-CoV-2 IgG and neutralizing antibody potency was determined, along with total as well as free Zn concentrations. Results: The SARS-CoV-2 antibodies showed the expected rise in response to vaccination, and decreased toward the last sampling point, with highest levels measured three weeks after the second dose. Total serum Zn concentrations were relatively stable over time, and showed no significant association with SARS-CoV-2 antibodies. Baseline total serum Zn concentration and supplemental intake of Zn were both unrelated to the antibody response to SARS-CoV-2 vaccination. Time resolved analysis of free Zn indicated a similar dynamic as the humoral response. A positive correlation was observed between free Zn concentrations and both the induced antibodies and neutralizing antibody potency. Conclusion: While the biomarkers of Zn status and supplemental Zn intake appeared unrelated to the humoral immune response to SARS-CoV-2 vaccination, the observed correlation of free Zn to the induced antibodies indicates a diagnostic value of this novel biomarker for the immune system.

Comparative Safety of BNT162b2 and mRNA-1273 Vaccines in a Nationwide Cohort of US Veterans.

Importance: The risk of adverse events has been found to be low for participants receiving the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna Inc) vaccines in randomized trials. However, a head-to-head comparison of their safety for a broader range of potential adverse events over longer follow-up and in larger and more diverse populations is lacking, to our knowledge. Objective: To compare the head-to-head safety in terms of risk of adverse events of the BNT162b2 and mRNA-1273 vaccines in the national health care databases of the US Department of Veterans Affairs, the largest integrated health care system in the US. Design, Setting, and Participants: In this cohort study, the electronic health records of US veterans who received a first dose of the BNT162b2 or mRNA-1273 vaccine between January 4 and September 20, 2021, were used. Recipients of each vaccine were matched in a 1:1 ratio according to their risk factors. Exposures: Vaccination with either the BNT162b2 vaccine, with a second dose scheduled 21 days later, or the mRNA-1273 vaccine, with a second dose scheduled 28 days later. Main Outcomes and Measures: A large panel of potential adverse events was evaluated; the panel included neurologic events, hematologic events, hemorrhagic stroke, ischemic stroke, myocardial infarction, other thromboembolic events, myocarditis or pericarditis, arrhythmia, kidney injury, appendicitis, autoimmune events, herpes zoster or simplex, arthritis or arthropathy, and pneumonia. Risks over 38 weeks were estimated using the Kaplan-Meier estimator. Results: Among 433 672 persons included in the matched vaccine groups, the median age was 69 years (IQR, 60-74 years), 93% of individuals were male, and 20% were Black. Estimated 38-week risks of adverse events were generally low after administration of either the BNT162b2 or the mRNA-1273 vaccine. Compared with the mRNA-1273 group, the BNT162b2 group had an excess per 10 000 persons of 10.9 events (95% CI, 1.9-17.4 events) of ischemic stroke, 14.8 events (95% CI, 7.9-21.8 events) of myocardial infarction, 11.3 events (95% CI, 3.4-17.7 events) of other thromboembolic events, and 17.1 events (95% CI, 8.8-30.2 events) of kidney injury. Estimates were largely similar among subgroups defined by age (<40, 40-69, and ≥70 years) and race (Black, White), but there were higher magnitudes of risk differences of ischemic stroke among older persons and White persons, kidney injury among older persons, and other thromboembolic events among Black persons. Small-magnitude differences between the 2 vaccines were seen within 42 days of the first dose, and few differences were seen within 14 days of the first dose. Conclusions and Relevance: The findings of this cohort study suggest that there were few differences in risk of adverse events within 14 days of the first dose of either the BNT162b2 or the mRNA-1273 vaccine and small-magnitude differences within 42 days of the first dose. The 38-week risks of adverse events were low in both vaccine groups, although risks were lower for recipients of the mRNA-1273 vaccine than for recipients of the BNT162b2 vaccine. Although the primary analysis was designed to detect safety events unrelated to SARS-CoV-2 infection, the possibility that these differences may partially be explained by a lower effectiveness of the BNT162b2 vaccine in preventing the sequelae of SARS-CoV-2 infection compared with the mRNA-1273 vaccine could not be ruled out. These findings may help inform decision-making in future vaccination campaigns.

Safety of COVID-19 Vaccine in Patients with Cancer in a High-Volume Comprehensive Cancer Center.

BACKGROUND: Few data are available on the safety of COVID-19 vaccines in cancer patients undergoing active cancer-directed treatment. PATIENTS AND METHODS: This case series analyzes outcomes in terms of adverse events in 5297 patients undergoing anti-cancer treatment who were vaccinated with anti-SARS-CoV-2 Pfizer-BioNTech vaccine at a single cancer center from March 6, 2021 to May 9, 2021. Adverse events were retrieved from the national Italian pharmacovigilance platform (http://www.vigicovid.it). RESULTS: Of the 5297 patients treated for either solid tumors (87%) or onco-hematologic malignancies (13%) who were vaccinated, 8 adverse drug reactions (ADRs) were reported. One was a severe ADR and 7 were non-severe ADRs. Non-severe ADRs resolved within 48 hours. CONCLUSION: BNT162b2 Pfizer-BioNTech vaccine was safely administered in the largest cohort of cancer patients reported to date.

Age and vitamin D affect the magnitude of the antibody response to the first dose of the SARS-CoV-2 BNT162b2 vaccine.

BACKGROUND: Most approved vaccines utilise a two-dose strategy. To enable larger groups of patients to receive the first dose, the UK government increased the gap between the two doses from three to twelve weeks. Here we report on the immunogenicity of the first dose, including effect of age and vitamin D status on these levels over an 8 week-period. METHODS: Blood samples were collected from healthcare workers (HCW) receiving their first BNT162b2 vaccine dose between January and February 2021. Antibody (Ab) production was measured, prior to and weekly for 4 weeks post immunization, and a final measurement was performed at 8 weeks. Serum vitamin D concentrations were also measured at baseline. FINDINGS: Immunization of 97 HCW induced an Ab response that peaked 3•2 weeks post immunization to decrease thereafter. Ab levels remained positive at 8 weeks. IgG peak concentration was negatively associated with age (ß=-0•440, p<0.001). Response to immunization was also significantly affected by vitamin D status (p=0•022), on average 29•3% greater peak value in individuals with 25(OH)D>50nmol/L. No other variable showed significant effect. INTERPRETATION: The first dose of BNT162b2 produced Ab levels that remained positive after 8 weeks. Peak was greater in younger subjects and 25(OH)D>50nmol/L was beneficial. Booster campaigns should take into consideration vitamin D status which is at its highest following a period of sunshine exposure or following oral supplementation (400-1000IU daily). FUNDING: Abbott Diagnostics Ltd supplied the kits used to quantify the anti-SARS -CoV-2 Spike IgG and technical support as well as provided financial support for sample collections.

Incidence of Guillain-Barré Syndrome After COVID-19 Vaccination in the Vaccine Safety Datalink.

Importance: Postauthorization monitoring of vaccines in a large population may detect rare adverse events not identified in clinical trials such as Guillain-Barré syndrome (GBS), which has a background rate of 1 to 2 per 100 000 person-years. Objective: To describe cases and incidence of GBS following COVID-19 vaccination and assess the risk of GBS after vaccination for Ad.26.COV2.S (Janssen) and mRNA vaccines. Design, Setting, and Participants: This cohort study used surveillance data from the Vaccine Safety Datalink at 8 participating integrated health care systems in the United States. There were 10 158 003 participants aged at least 12 years. Data analysis was performed from November 2021 to February 2022. Exposures: Ad.26.COV2.S, BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccine, including mRNA vaccine doses 1 and 2, December 13, 2020, to November 13, 2021. Main Outcomes and Measures: GBS with symptom onset in the 1 to 84 days after vaccination, confirmed by medical record review and adjudication. Descriptive characteristics of confirmed cases, GBS incidence rates during postvaccination risk intervals after each type of vaccine compared with the background rate, rate ratios (RRs) comparing GBS incidence in the 1 to 21 vs 22 to 42 days postvaccination, and RRs directly comparing risk of GBS after Ad.26.COV2.S vs mRNA vaccination, using Poisson regression adjusted for age, sex, race and ethnicity, site, and calendar day. Results: From December 13, 2020, through November 13, 2021, 15 120 073 doses of COVID-19 vaccines were administered to 7 894 989 individuals (mean [SE] age, 46.5 [0.02] years; 8 138 318 doses received [53.8%] by female individuals; 3 671 199 doses received [24.3%] by Hispanic or Latino individuals, 2 215 064 doses received [14.7%] by Asian individuals, 6 266 424 doses received [41.4%] by White individuals), including 483 053 Ad.26.COV2.S doses, 8 806 595 BNT162b2 doses, and 5 830 425 mRNA-1273 doses. Eleven cases of GBS after Ad.26.COV2.S were confirmed. The unadjusted incidence rate of GBS per 100 000 person-years in the 1 to 21 days after Ad.26.COV2.S was 32.4 (95% CI, 14.8-61.5), significantly higher than the background rate, and the adjusted RR in the 1 to 21 vs 22 to 42 days following Ad.26.COV2.S was 6.03 (95% CI, 0.79-147.79). Thirty-six cases of GBS after mRNA vaccines were confirmed. The unadjusted incidence rate per 100 000 person-years in the 1 to 21 days after mRNA vaccines was 1.3 (95% CI, 0.7-2.4) and the adjusted RR in the 1 to 21 vs 22 to 42 days following mRNA vaccines was 0.56 (95% CI, 0.21-1.48). In a head-to-head comparison of Ad.26.COV2.S vs mRNA vaccines, the adjusted RR was 20.56 (95% CI, 6.94-64.66). Conclusions and Relevance: In this cohort study of COVID-19 vaccines, the incidence of GBS was elevated after receiving the Ad.26.COV2.S vaccine. Surveillance is ongoing.

Durability of BNT162b2 vaccine against hospital and emergency department admissions due to the omicron and delta variants in a large health system in the USA: a test-negative case-control study.

BACKGROUND: The duration of protection against the omicron (B.1.1.529) variant for current COVID-19 vaccines is not well characterised. Vaccine-specific estimates are especially needed. We aimed to evaluate the effectiveness and durability of two and three doses of the BNT162b2 (Pfizer-BioNTech) mRNA vaccine against hospital and emergency department admissions due to the delta (B.1.617.2) and omicron variants. METHODS: In this case-control study with a test-negative design, we analysed electronic health records of members of Kaiser Permanente Southern California (KPSC), a large integrated health system in California, USA, from Dec 1, 2021, to Feb 6, 2022. Vaccine effectiveness was calculated in KPSC patients aged 18 years and older admitted to hospital or an emergency department (without a subsequent hospital admission) with a diagnosis of acute respiratory infection and tested for SARS-CoV-2 via PCR. Adjusted vaccine effectiveness was estimated with odds ratios from adjusted logistic regression models. This study is registered with ClinicalTrials.gov (NCT04848584). FINDINGS: Analyses were done for 11 123 hospital or emergency department admissions. In adjusted analyses, effectiveness of two doses of the BNT162b2 vaccine against the omicron variant was 41% (95% CI 21-55) against hospital admission and 31% (16-43) against emergency department admission at 9 months or longer after the second dose. After three doses, effectiveness of BNT162b2 against hospital admission due to the omicron variant was 85% (95% CI 80-89) at less than 3 months but fell to 55% (28-71) at 3 months or longer, although confidence intervals were wide for the latter estimate. Against emergency department admission, the effectiveness of three doses of BNT162b2 against the omicron variant was 77% (72-81) at less than 3 months but fell to 53% (36-66) at 3 months or longer. Trends in waning against SARS-CoV-2 outcomes due to the delta variant were generally similar, but with higher effectiveness estimates at each timepoint than those seen for the omicron variant. INTERPRETATION: Three doses of BNT162b2 conferred high protection against hospital and emergency department admission due to both the delta and omicron variants in the first 3 months after vaccination. However, 3 months after receipt of a third dose, waning was apparent against SARS-CoV-2 outcomes due to the omicron variant, including hospital admission. Additional doses of current, adapted, or novel COVD-19 vaccines might be needed to maintain high levels of protection against subsequent waves of SARS-CoV-2 caused by the omicron variant or future variants with similar escape potential. FUNDING: Pfizer.

Humoral immune response to COVID-19 mRNA vaccination in relation to selenium status.

The essential trace element selenium (Se) is of central importance for human health and particularly for a regular functioning of the immune system. In the context of the current pandemic, Se deficiency in patients with COVID-19 correlated with disease severity and mortality risk. Selenium has been reported to be associated with the immune response following vaccination, but it is unknown whether this also applies to SARS-CoV-2 vaccines. In this observational study, adult health care workers (n = 126) who received two consecutive anti-SARS-CoV-2 vaccinations by BNT162b2 were followed for up to 24 weeks, with blood samples collected at the first and second dose and at three and 21 weeks after the second dose. Serum SARS-CoV-2 IgG titres, neutralising antibody potency, total Se and selenoprotein P concentrations, and glutathione peroxidase 3 activity were quantified. All three biomarkers of Se status were significantly correlated at all the time points, and participants who reported supplemental Se intake displayed higher Se concentrations. SARS-CoV-2 IgG titres and neutralising potency were highest three weeks after the second dose and decreased towards the last sampling point. The humoral immune response was not related to any of the three Se status biomarkers. Supplemental Se intake had no effect at any time point on the vaccination response as measured by serum SARS-CoV-2 IgG levels or neutralising potency. Overall, no association was found between Se status or supplemental Se intake and humoral immune response to COVID-19 mRNA vaccination.

Adverse Events Reported by Patients With Cancer After Administration of a 2-Dose mRNA COVID-19 Vaccine.

BACKGROUND: Most safety and efficacy trials of the SARS-CoV-2 vaccines excluded patients with cancer, yet these patients are more likely than healthy individuals to contract SARS-CoV-2 and more likely to become seriously ill after infection. Our objective was to record short-term adverse reactions to the COVID-19 vaccine in patients with cancer, to compare the magnitude and duration of these reactions with those of patients without cancer, and to determine whether adverse reactions are related to active cancer therapy. PATIENTS AND METHODS: A prospective, single-institution observational study was performed at an NCI-designated Comprehensive Cancer Center. All study participants received 2 doses of the Pfizer BNT162b2 vaccine separated by approximately 3 weeks. A report of adverse reactions to dose 1 of the vaccine was completed upon return to the clinic for dose 2. Participants completed an identical survey either online or by telephone 2 weeks after the second vaccine dose. RESULTS: The cohort of 1,753 patients included 67.5% who had a history of cancer and 12.0% who were receiving active cancer treatment. Local pain at the injection site was the most frequently reported symptom for all respondents and did not distinguish patients with cancer from those without cancer after either dose 1 (39.3% vs 43.9%; P=.07) or dose 2 (42.5% vs 40.3%; P=.45). Among patients with cancer, those receiving active treatment were less likely to report pain at the injection site after dose 1 compared with those not receiving active treatment (30.0% vs 41.4%; P=.002). The onset and duration of adverse events was otherwise unrelated to active cancer treatment. CONCLUSIONS: When patients with cancer were compared with those without cancer, few differences in reported adverse events were noted. Active cancer treatment had little impact on adverse event profiles.

Lymphatic osteopathic manipulative treatment reduces duration of deltoid soreness after Pfizer/BioNTech COVID-19 vaccine.

Pfizer-BioNTech BNT162b2 is one of the three U.S. Food and Drug Administration (FDA)-approved vaccines for the prevention of COVID-19. Its most common side effect, injection site pain, occurs because of locally recruited inflammatory mediators and is mitigated by the lymphatic system. Side effects may discourage individuals from receiving vaccines; therefore, reducing the duration of injection site pain can promote vaccination compliance. Osteopathic manipulative treatments (OMT) can directly affect the physiology underlying muscle soreness; however, there is currently no literature that supports the use of OMT in this scenario. In this case report, an otherwise healthy male presented with acute left deltoid soreness after receiving the Pfizer COVID-19 vaccine. The pain began 5 h prior to the visit. Three hours after being treated with lymphatic OMT, the severity of the pain was significantly reduced and was alleviated 8h after onset in comparison to the median duration of 24-48 h. He received his second dose 3 weeks later. This case report can provide future studies with the groundwork for further investigating the role of OMT in treating postvaccination muscle soreness, which can improve patient satisfaction and potentially promote vaccination compliance.

Ferric carboxymaltose and SARS-CoV-2 vaccination-induced immunogenicity in kidney transplant recipients with iron deficiency: The COVAC-EFFECT randomized controlled trial.

Background: Kidney transplant recipients (KTRs) have an impaired immune response after vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Iron deficiency (ID) may adversely affect immunity and vaccine efficacy. We aimed to investigate whether ferric carboxymaltose (FCM) treatment improves humoral and cellular responses after SARS-CoV-2 vaccination in iron-deficient KTRs. Methods: We randomly assigned 48 iron-deficient KTRs to intravenous FCM (1-4 doses of 500mg with six-week intervals) or placebo. Co-primary endpoints were SARS-CoV-2-specific anti-Receptor Binding Domain (RBD) Immunoglobulin G (IgG) titers and T-lymphocyte reactivity against SARS-CoV-2 at four weeks after the second vaccination with mRNA-1273 or mRNA-BNT162b2. Results: At four weeks after the second vaccination, patients receiving FCM had higher plasma ferritin and transferrin saturation (P<0.001 vs. placebo) and iron (P=0.02). However, SARS-CoV-2-specific anti-RBD IgG titers (FCM: 66.51 [12.02-517.59] BAU/mL; placebo: 115.97 [68.86-974.67] BAU/mL, P=0.07) and SARS-CoV-2-specific T-lymphocyte activation (FCM: 93.3 [0.85-342.5] IFN-É£ spots per 106 peripheral blood mononuclear cells (PBMCs), placebo: 138.3 [0.0-391.7] IFN-É£ spots per 106 PBMCs, P=0.83) were not significantly different among both arms. After the third vaccination, SARS-CoV-2-specific anti-RBD IgG titers remained similar between treatment groups (P=0.99). Conclusions: Intravenous iron supplementation efficiently restored iron status but did not improve the humoral or cellular immune response against SARS-CoV-2 after three vaccinations.