Immune mediated support of metastasis: Implication for bone invasion.

Bone is a common organ affected by metastasis in various advanced cancers, including lung, breast, prostate, colorectal, and melanoma. Once a patient is diagnosed with bone metastasis, the patient's quality of life and overall survival are significantly reduced owing to a wide range of morbidities and the increasing difficulty of treatment. Many studies have shown that bone metastasis is closely related to bone microenvironment, especially bone immune microenvironment. However, the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear. Here, we described the changes in various immune cells during bone metastasis and discussed their related mechanisms. Osteoblasts, adipocytes, and other non-immune cells closely related to bone metastasis were also included. This review also summarized the existing treatment methods and potential therapeutic targets, and provided insights for future studies of cancer bone metastasis.

Trends in the administration of COVID-19 vaccines with other vaccines in the United States reported to V-safe during December 14, 2020-May 19, 2023.

Introduction COVID-19 vaccines may be administered with other vaccines during the same healthcare visit. COVID-19 monovalent (Fall 2021) and bivalent (Fall 2022) vaccine recommendations coincided with annual seasonal influenza vaccination. Data describing the frequency of the co-administration of COVID-19 vaccines with other vaccines are limited. Methods We used V-safe, a voluntary smartphone-based U.S. safety surveillance system established by the CDC, to describe trends in the administration of COVID-19 vaccines with other vaccines reported to V-safe during December 14, 2020 - May 19, 2023. Results Of the 21 million COVID-19 vaccinations reported to V-safe, 2.2% (459,817) were administered with at least 1 other vaccine. Co-administration most frequently occurred during the first week of October 2023 (27,092; 44.1%). Most reports of co-administration included influenza vaccine (393,003; 85.5%). Co-administration was most frequently reported for registrants aged 6 months-6 years (4,872; 4.4%). Conclusion Reports of co-administration to V-safe peaked during October 2023, when influenza vaccination most often occurs, possibly reflecting increased opportunities for multiple vaccinations and greater acceptability of the co-administration of COVID-19 vaccine with other vaccines, especially influenza vaccine.

Increasing serum complement component 1q is associated with worse prognosis in advanced non-small cell lung cancer treated with immune checkpoint inhibitors: a single-center, retrospective study.

Background: There is a lack of readily available clinical markers of non-small cell lung cancer (NSCLC) immunotherapy efficacy. Previous studies have found that overexpressed complement component 1q (C1q) promotes macrophage M2 polarization and an immunosuppressive tumor microenvironment. This study aimed to evaluate the association between serum C1q and the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced NSCLC. Methods: A total of 168 patients with advanced NSCLC who received ICIs in the Renmin Hospital of Wuhan University were included in this study. Serum C1q levels were collected before and 3 weeks after immunotherapy treatment, together with other data on clinical and demographic characteristics. The primary outcome was overall survival (OS) (months from first dose of ICIs to death, censored at date of last follow-up). Secondary outcome was progression-free survival (PFS) [defined as months from first dose of ICIs to clinical or radiographic progression by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death, censored at date of last follow-up] and objective response rate (ORR) which was defined as rate of complete response (CR) or partial response (PR) at best response by RECIST 1.1. Results: A total of 168 patients were included in this study, including 127 males (75.60%) and 41 females (24.40%). Thirty-nine patients achieved objective response (2 CR, 37 PR), and 111 patients (66.07%) had stable disease (SD) as best response. The ORR was 23.21% and the disease control rate was 89.28%. The upward trends of serum C1q levels between baseline and post-treatment were strongly associated with the shorter PFS [hazard ratio (HR) =1.554, 95% confidence interval (CI): 1.07-2.10, P=0.01] and OS (HR =1.444, 95% CI: 1.01-1.98, P=0.03). Moreover, taking the median OS 18.9 months as the cut-off of prognosis, receiver operating characteristic (ROC) analysis showed that serum baseline C1q yielded an area under the ROC curve of 0.785 (95% CI: 0.711-0.869). The optimal serum baseline C1q cut-off point to predict immunotherapy prognosis was 216.2 mg/L. Conclusions: These findings suggested that elevated serum C1q after ICIs treatment was related to a worse prognosis in NSCLC. Monitoring the baseline and dynamic data of C1q during hospitalization showed the potential to predict the prognosis of NSCLC patients.

Occult Breast Cancer Presenting as Sternum Pain.

Bone metastasis has been reported in up to 70% of patients with advanced breast cancer. A total of 55.76% of skeletal metastases in women were derived from breast cancer. However, patients with bone metastasis from an occult primary breast cancer are a rare subset of patients. Here, we present the case of a 38-year-old woman who had sternum pain for 4 months. A whole-body PET-CT scan revealed that the FDG uptake of both the sternum and internal mammary node was significantly increased. The final diagnosis of occult breast cancer was established by immunohistochemical (IHC) staining, which is of great significance for identifying the origin of a metastatic tumor despite no visualized lesions of mammary glands.

Impact of grassland degradation on soil multifunctionality: Linking to protozoan network complexity and stability.

Soil protozoa, as predators of microbial communities, profoundly influence multifunctionality of soils. Understanding the relationship between soil protozoa and soil multifunctionality (SMF) is crucial to unraveling the driving mechanisms of SMF. However, this relationship remains unclear, particularly in grassland ecosystems that are experiencing degradation. By employing 18S rRNA gene sequencing and network analysis, we examined the diversity, composition, and network patterns of the soil protozoan community along a well-characterized gradient of grassland degradation at four alpine sites, including two alpine meadows (Cuona and Jiuzhi) and two alpine steppes (Shuanghu and Gonghe) on the Qinghai-Tibetan Plateau. Our findings showed that grassland degradation decreased SMF for 1-2 times in all four sites but increased soil protozoan diversity (Shannon index) for 13.82-298.01 % in alpine steppes. Grassland degradation-induced changes in soil protozoan composition, particularly to the Intramacronucleata with a large body size, were consistently observed across all four sites. The enhancing network complexity (average degree), stability (robustness), and cooperative relationships (positive correlation) are the responses of protozoa to grassland degradation. Further analyses revealed that the increased network complexity and stability led to a decrease in SMF by affecting microbial biomass. Overall, protozoa increase their diversity and strengthen their cooperative relationships to resist grassland degradation, and emphasize the critical role of protozoan network complexity and stability in regulating SMF. Therefore, not only protozoan diversity and composition but also their interactions should be considered in evaluating SMF responses to grassland degradation, which has important implications for predicting changes in soil function under future scenarios of anthropogenic change.

JYNNEOS Vaccine Safety Surveillance During the 2022 Mpox Outbreak Using the Vaccine Adverse Event Reporting System and V-safe, United States, 2022 to 2023.

BACKGROUND: In response to the 2022 mpox outbreak in the United States, people with higher potential for exposure to mpox were recommended to receive 2 doses of the JYNNEOS vaccine. Vaccine safety was monitored using 2 complementary systems. METHODS: The Vaccine Adverse Event Reporting System (VAERS) is a passive surveillance system that accepts reports of adverse events after vaccination. VAERS is capable of rapidly identifying rare adverse events and unusual reporting patterns. Medical records were requested and reviewed for adverse events of special interest, including myocarditis. Adverse event reporting rates were calculated as the number of verified adverse event cases divided by the number of JYNNEOS doses administered. V-safe for mpox was a voluntary smartphone-based vaccine safety surveillance system that sent enrolled persons text messages linked to health surveys asking about reactions and health impact events occurring after vaccination. RESULTS: There were 1,207,056 JYNNEOS doses administered in the United States. VAERS received 1927 reports for JYNNEOS. The myocarditis reporting rate per million doses was 2.69 after dose 1 and 8.64 after dose 2. V-safe had 213 participants complete at least one health survey. Rates of injection site and systemic reactions were similar in the first week after dose 1 and dose 2. CONCLUSIONS: JYNNEOS vaccine safety surveillance findings from VAERS and v-safe did not identify any unexpected safety concerns. The VAERS reporting rate for myocarditis was similar to previously published population background rates.

Safety monitoring of bivalent mRNA COVID-19 vaccine among pregnant persons in the vaccine adverse event reporting System - United States, September 1, 2022 - March 31, 2023.

BACKGROUND: Pregnant persons are at increased risk of severe COVID-19 illness. Bivalent mRNA COVID-19 vaccination is recommended for everyone, including pregnant persons. However, data are limited on the safety of bivalent mRNA COVID-19 vaccination during pregnancy. OBJECTIVE: To evaluate and summarize reports to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system, among pregnant persons who received bivalent mRNA COVID-19 vaccine. METHODS: VAERS U.S. reports of adverse events (AEs) in pregnant persons who received the bivalent mRNA COVID-19 vaccine from 9/1/2022-03/31/2023 were identified. Clinicians reviewed all reports and available medical records. AEs of these reports were compared with AEs reported to VAERS following monovalent mRNA COVID-19 booster vaccination in pregnancy. RESULTS: VAERS received 136 reports for pregnant persons who received bivalent mRNA COVID-19 vaccine; 87 (64 %) after BNT162b2 (Pfizer-BioNTech), and 48 (35 %) after mRNA-1273 (Moderna); 28 (20.6 %) reports were classified as serious. The most common pregnancy-specific outcomes reported included 12 (8.8 %) spontaneous abortions (<20 weeks gestation), 6 (4.4 %) episodes of preterm delivery, and 5 (3.7 %) reports of preeclampsia. One stillbirth (≥20 weeks gestation) was reported. No maternal or infant deaths were reported. There were 6 reports of AEs in infants, which included 3 reports of admissions to the neonatal intensive care unit: two infants with low birth weight, and one infant with a patent ductus arteriosus and patent foramen ovale. Non-pregnancy-specific adverse events were mostly COVID-19 infection and systemic reactions (e.g., headache, fatigue). Pregnancy-specific conditions were reported less frequently after bivalent mRNA COVID-19 vaccination compared to monovalent mRNA COVID-19 booster vaccination (3rd and 4th dose). CONCLUSIONS: Based on this review of reports to VAERS, the safety profile of bivalent mRNA COVID-19 vaccination in pregnant persons was comparable to that observed for monovalent mRNA COVID-19 booster vaccination (3rd and 4th dose) in pregnant persons.

Administration of the GSK Respiratory Syncytial Virus Vaccine to Pregnant Persons in Error.

The GSK and Pfizer respiratory syncytial virus (RSV) vaccines are both indicated for adults aged 60 years and older, but only the Pfizer product is approved for use in pregnancy to prevent RSV-associated lower respiratory tract disease in infants aged younger than 6 months. To assess for vaccine administration errors (ie, administration of the GSK RSV vaccine to pregnant persons) VAERS (Vaccine Adverse Event Reporting System), a U.S. passive reporting system, was searched for the time period from August 2023 to January 2024. A total of 113 reports of these administration errors were identified. Most reports (103, 91.2%) did not describe an adverse event. These administration errors are preventable with proper education and training and other preventive measures.

Safety of Simultaneous Administration of Bivalent mRNA COVID-19 and Influenza Vaccines in the Vaccine Adverse Event Reporting System (VAERS).

INTRODUCTION: Bivalent mRNA coronavirus disease 2019 (COVID-19) vaccines may be simultaneously administered with other recommended vaccines, including seasonal influenza vaccines. However, few studies have evaluated the safety of co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines. OBJECTIVE: The aim was to describe reports to the Vaccine Adverse Event Reporting System (VAERS) after co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines. METHODS: We searched the VAERS database for reports of adverse events (AEs) following co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines during the period of September 1, 2022-March 31, 2023. We assessed the characteristics of these reports and described the most frequently reported AEs. Clinicians reviewed available medical records for reports of serious AEs and adverse events of special interest (AESI). RESULTS: During the period of 1 September 2022 through 31 March 2023, VAERS received 3689 reports of AEs following co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines. The median age of vaccinees was 59 years (interquartile range 39, 70 years); 342 reports (9.3%) were classified as serious. The most common AEs among non-serious reports were severe-acute-respiratory-syndrome-related coronavirus (SARS-CoV-2) infection (785, 23.5%), cough (592, 17.7%), and fatigue (568, 17.0%). The most common AEs among serious reports were Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (88, 25.7%), dyspnea (81, 23.7%), and condition aggravated (55, 16.1%). DISCUSSION: Reports of AEs following co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines did not reveal any unusual or unexpected patterns of AEs. Increased reporting of certain events (e.g., COVID-19) was expected due to Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) reporting requirements. CDC and FDA will continue to monitor the safety of co-administration of mRNA COVID-19 and seasonal influenza vaccines.

The efficacy of immune checkpoint inhibitors is limited in elderly NSCLC: a retrospective efficacy study and meta-analysis.

Immune checkpoint inhibitors (ICIs) have improved the long-term survival of NSCLC patients. However, the efficacy of ICIs in elderly NSCLC patients remains controversial. We conducted a retrospective study and meta-analysis exploring the efficacy of ICIs in those patients using public databases and RCTs. NSCLC patients were identified into elderly and non-elderly groups by age 75 years. The retrospective study showed significant differences in OS and PFS between non-elderly and elderly patients treated with ICIs (P= 0.029 and 0.027), with reduced efficacy in elderly NSCLC patients. ECOG PS also negatively affected OS in elderly NSCLC patients (P= 0.007). In meta-analysis, the HR for OS in the non-elderly and elderly groups were 0.74 and 0.90, respectively, and the difference between the two age groups was statistically significant (P= 0.025). ICIs resulted in a lower incidence of all-grade (OR= 0.47) and high-grade TRAEs (OR= 0.38) than chemotherapy. Our findings revealed that the survival benefit of ICIs in elderly patients (≥ 75 years) may be lower than in non-elderly patients. In addition, the incidence of TRAEs induced by ICIs was lower than chemotherapy.

Radiomics Signature Based on Support Vector Machines for the Prediction of Pathological Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

The objective of this study was to evaluate the discriminative capabilities of radiomics signatures derived from three distinct machine learning algorithms and to identify a robust radiomics signature capable of predicting pathological complete response (pCR) after neoadjuvant chemoradiotherapy in patients diagnosed with locally advanced rectal cancer (LARC). In a retrospective study, 211 LARC patients were consecutively enrolled and divided into a training cohort (n = 148) and a validation cohort (n = 63). From pretreatment contrast-enhanced planning CT images, a total of 851 radiomics features were extracted. Feature selection and radiomics score (Radscore) construction were performed using three different machine learning methods: least absolute shrinkage and selection operator (LASSO), random forest (RF) and support vector machine (SVM). The SVM-derived Radscore demonstrated a strong correlation with the pCR status, yielding area under the receiver operating characteristic curves (AUCs) of 0.880 and 0.830 in the training and validation cohorts, respectively, outperforming the RF and LASSO methods. Based on this, a nomogram was developed by combining the SVM-based Radscore with clinical indicators to predict pCR after neoadjuvant chemoradiotherapy. The nomogram exhibited superior predictive power, achieving AUCs of 0.910 and 0.866 in the training and validation cohorts, respectively. Calibration curves and decision curve analyses confirmed its appropriateness. The SVM-based Radscore demonstrated promising performance in predicting pCR for LARC patients. The machine learning-driven nomogram, which integrates the Radscore and clinical indicators, represents a valuable tool for predicting pCR in LARC patients.

Chinese expert consensus recommendations for the administration of immune checkpoint inhibitors to special cancer patient populations.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1, programmed cell death ligand 1, and cytotoxic T lymphocyte-associated antigen-4 have shown significantly durable clinical benefits and tolerable toxicities and have improved the survival of patients with various types of cancer. Since 2018, the National Medical Products Administration of China has approved 17 ICIs as the standard treatment for certain advanced or metastatic solid tumors. As ICIs represent a broad-spectrum antitumor strategy, the populations eligible for cancer immunotherapy are rapidly expanding. However, the clinical applications of ICIs in cancer patient populations with special issues, a term that refers to complex subgroups of patients with comorbidities, special clinical conditions, or concomitant medications who are routinely excluded from prospective clinical trials of ICIs or are underrepresented in these trials, represent a great real-world challenge. Although the Chinese Society of Clinical Oncology (CSCO) has provided recommendations for screening before the use of ICIs in special populations, the recommendations for full-course management remain insufficient. The CSCO Expert Committee on Immunotherapy organized leading medical oncology and multidisciplinary experts to develop a consensus that will serve as an important reference for clinicians to guide the proper application of ICIs in special patient populations. This article is a translation of a study first published in Chinese in The Chinese Clinical Oncology (ISSN 1009-0460, CN 32-1577/R) in May 2022 (27(5):442-454). The publisher of the original paper has provided written confirmation of permission to publish this translation in Therapeutic Advances in Medical Oncology.

Postmarketing Safety Surveillance of a Hexavalent Vaccine in the Vaccine Adverse Event Reporting System.

We assessed the safety of hexavalent vaccine diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus, hepatitis b, and haemophilus influenzae b conjugate vaccine in the Vaccine Adverse Event Reporting System. Five hundred-one reports of adverse events (AEs) were identified; 21 (4.2%) were serious. Most frequently reported AEs were fever (10.2%) and injection site erythema (5.4%). AEs reported were consistent with findings from prelicensure studies.

Safety Monitoring of mRNA COVID-19 Vaccine Third Doses Among Children Aged 6 Months-5 Years - United States, June 17, 2022-May 7, 2023.

As of May 7, 2023, CDC's Advisory Committee on Immunization Practices (ACIP) recommends that all children aged 6 months-5 years receive at least 1 age-appropriate bivalent mRNA COVID-19 vaccine dose. Depending on their COVID-19 vaccination history and history of immunocompromise, these children might also need additional doses* (1-3). Initial vaccine safety findings after primary series vaccination among children aged 6 months-5 years showed that transient local and systemic reactions were common whereas serious adverse events were rare (4). To characterize the safety of a third mRNA COVID-19 vaccine dose among children aged 6 months-5 years, CDC reviewed adverse events and health surveys reported to v-safe, a voluntary smartphone-based U.S. safety surveillance system established by CDC to monitor health after COVID-19 vaccination (https://vsafe.cdc.gov/en/) and the Vaccine Adverse Event Reporting System (VAERS), a U.S. passive vaccine safety surveillance system co-managed by CDC and the Food and Drug Administration (FDA) (https://vaers.hhs.gov/) (5). During June 17, 2022-May 7, 2023, approximately 495,576 children aged 6 months-4 years received a third dose (monovalent or bivalent) of Pfizer-BioNTech vaccine and 63,919 children aged 6 months-5 years received a third dose of Moderna vaccine.† A third mRNA COVID-19 vaccination was recorded for 2,969 children in v-safe; approximately 37.7% had no reported reactions, and among those for whom reactions were reported, most reactions were mild and transient. VAERS received 536 reports after a third dose of mRNA COVID-19 vaccine for children in these age groups; 98.5% of reports were nonserious and most (78.4%) were classified as a vaccination error.§ No new safety concerns were identified. Preliminary safety findings after a third dose of COVID-19 vaccine for children aged 6 months-5 years are similar to those after other doses. Health care providers can counsel parents and guardians of young children that most reactions reported after vaccination with Pfizer-BioNTech or Moderna vaccine were mild and transient and that serious adverse events are rare.

COVID-19 Vaccine Safety First Year Findings in Adolescents.

BACKGROUND AND OBJECTIVES: The Food and Drug Administration expanded Emergency Use Authorization for use of Pfizer-BioNTech (BNT-162b2) coronavirus disease 2019 vaccine to include people ages 12 years and older on May 10, 2021. We describe adverse events observed during the first full year of the US coronavirus disease 2019 vaccination program for adolescents ages 12 to 17 years. METHODS: We conducted descriptive analyses using data from 2 complementary US vaccine safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health impacts, and the Vaccine Adverse Event Reporting System (VAERS), the national spontaneous reporting system. We reviewed reports and calculated adverse event reporting rates using vaccine administration data. RESULTS: Among 172 032 adolescents ages 12 to 17 years enrolled in v-safe, most reported reactions following BNT-162b2 were mild to moderate, most frequently reported on the day after vaccination, and more common after dose 2. VAERS received 20 240 adverse event reports; 91.5% were nonserious. Among adverse events of interest, we verified 40 cases of multisystem inflammation syndrome in children (1.2 cases per million vaccinations), 34 (85%) of which had evidence of prior severe acute respiratory syndrome coronavirus 2 infection; and 570 cases of myocarditis (17.7 cases per million vaccinations), most of whom (77%) reported symptom resolution at the time of report. CONCLUSIONS: During the first year BNT-162b2 was administered to adolescents ages 12 to 17 years, most reported adverse events were mild and appeared self-limited. Rates of myocarditis were lower than earlier reports. No new serious safety concerns were identified.

Safety Monitoring of Bivalent COVID-19 mRNA Vaccine Booster Doses Among Children Aged 5-11 Years - United States, October 12-January 1, 2023.

On October 12, 2022, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for bivalent (mRNA encoding the spike protein from the SARS-CoV-2 ancestral strain and BA.4/BA.5 Omicron variants) formulations of Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines for use as a single booster dose ≥2 months after completion of primary series or monovalent booster vaccination for children aged 5-11 years (Pfizer-BioNTech) and 6-17 years (Moderna); on December 8, 2022, FDA amended the EUAs to include children aged ≥6 months (1,2). The Advisory Committee on Immunization Practices (ACIP) recommends that all persons aged ≥6 months receive an age-appropriate bivalent mRNA booster dose (3). The safety of bivalent mRNA booster doses among persons aged ≥12 years has previously been described (4). To characterize the safety of bivalent mRNA booster doses among children aged 5-11 years after receipt of bivalent Pfizer-BioNTech and Moderna booster doses, CDC reviewed adverse events and health impacts reported to v-safe,* a voluntary, smartphone-based U.S. safety surveillance system established by CDC to monitor adverse events after COVID-19 vaccination, and to the Vaccine Adverse Event Reporting System (VAERS), a U.S. passive vaccine safety surveillance system co-managed by CDC and FDA† (5). During October 12-January 1, 2023, a total of 861,251 children aged 5-11 years received a bivalent Pfizer-BioNTech booster, and 92,108 children aged 6-11 years received a bivalent Moderna booster.§ Among 3,259 children aged 5-11 years registered in v-safe who received a bivalent booster dose, local (68.7%) and systemic reactions (49.5%) were commonly reported in the week after vaccination. Approximately 99.8% of reports to VAERS for children aged 5-11 years after bivalent booster vaccination were nonserious. There were no reports of myocarditis or death after bivalent booster vaccination. Eighty-four percent of VAERS reports were related to vaccination errors, 90.5% of which did not list an adverse health event. Local and systemic reactions reported after receipt of a bivalent booster dose are consistent with those reported after a monovalent booster dose; serious adverse events are rare. Vaccine providers should provide this information when counseling parents or guardians about bivalent booster vaccination. Preliminary safety findings from the first 11 weeks of bivalent booster vaccination among children aged 5-11 years are reassuring. Compared with the low risk of serious health effects after mRNA COVID-19 vaccination, the health effects of SARS-CoV-2 infection include death and serious long-term sequalae (6). ACIP recommends that all persons aged ≥6 months receive an age-appropriate bivalent mRNA booster dose ≥2 months after completion of a COVID-19 primary series or receipt of a monovalent booster dose.¶.

Safety of co-administration of mRNA COVID-19 and seasonal inactivated influenza vaccines in the vaccine adverse event reporting system (VAERS) during July 1, 2021-June 30, 2022.

BACKGROUND: COVID-19 vaccines may be co-administered with other recommended vaccines, including seasonal influenza vaccines. However, few studies have evaluated the safety of co-administration of mRNA COVID-19 and seasonal influenza vaccines. OBJECTIVE: To describe reports to the Vaccine Adverse Event Reporting System (VAERS) after co-administration of mRNA COVID-19 and seasonal influenza vaccines. METHODS: We searched the VAERS database for reports of adverse events (AEs) following co-administration of mRNA COVID-19 and seasonal influenza vaccines and following a first booster dose mRNA COVID-19 vaccine alone, during July 1, 2021-June 30, 2022. We assessed the characteristics of these reports and described the most frequently reported MedDRA preferred terms (PTs). Clinicians reviewed available medical records for serious reports and reports of adverse events of special interest (AESI) and categorized the main diagnosis by system organ class. RESULTS: From July 1, 2021 through June 30, 2022, VAERS received 2,449 reports of adverse events following co-administration of mRNA COVID-19 and seasonal influenza vaccines. Median age of vaccinees was 48 years (IQR: 31, 66); 387 (15.8%) were classified as serious. Most reports (1,713; 69.3%) described co-administration of a first booster dose of an mRNA COVID-19 vaccine with seasonal influenza vaccine. The most common AEs among non-serious reports were injection site reactions (193; 14.5%), headache (181; 13.6%), and pain (171; 12.8%). The most common AEs among reports classified as serious were dyspnea (38; 14.9%), COVID-19 infection (32; 12.6%), and chest pain (27; 10.6%). DISCUSSION: This review of reports to VAERS following co-administration of mRNA COVID-19 and seasonal influenza vaccines did not reveal any unusual or unexpected patterns of AEs. Increased reporting of certain events (e.g., COVID-19 disease) was expected. CDC will continue to monitor the safety of co-administration of mRNA COVID-19 and seasonal influenza vaccines, including co-administration involving bivalent mRNA COVID-19 booster vaccines that have been recommended for people ages ≥ 6 months in the United States.