Side Effects of COVID Vaccine in the US 2026
COVID vaccine side effects in the United States have been studied through the most comprehensive vaccine safety monitoring program in American history. Since the first doses were administered in December 2020, the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) have tracked post-vaccination reactions through four complementary, real-time safety systems — VAERS, VSD (Vaccine Safety Datalink), V-safe, and the CISA Project — covering tens of millions of Americans simultaneously. As of June 2025, more than approximately 1 billion COVID-19 vaccine doses had been distributed in the United States, and the CDC’s Immunization Safety Office had evaluated at least 65 specific outcomes to fully characterize the safety profile of these vaccines. The body of evidence includes 17 VaST work group reports, 29 MMWR publications, 114 published manuscripts, and data from approximately 9.6 million V-safe participants who self-reported their health after vaccination.
The overwhelming finding from all of this surveillance is consistent: the vast majority of COVID vaccine side effects are local and systemic reactions that are mild to moderate in severity and resolve within 1 to 3 days of vaccination. These include well-understood post-vaccination responses — injection site pain, fatigue, headache, chills, muscle pain, and fever — that are part of the body’s normal immune response to vaccination. The 2025–2026 COVID-19 vaccine formulations authorized by the FDA in August 2025 continue to show the same established side effect profile as prior-season vaccines, with no new common adverse effects identified. The CDC’s updated guidance, last revised in November 2025, confirms that post-vaccination reactions are generally similar across all age groups, though frequency can vary by age, vaccine manufacturer, and dose number. This article presents only verified, confirmed data from official US government sources — CDC, FDA, and peer-reviewed CDC-authored publications — to give the clearest and most accurate picture of COVID vaccine side effects statistics in the US in 2026.
Key Interesting Facts: COVID Vaccine Side Effects in the US 2026
| Fact | Data / Figure |
|---|---|
| Total COVID-19 vaccine doses distributed in the US (Dec 2020–June 2025) | Approximately 1 billion doses |
| V-safe participants enrolled and monitored | Approximately 9.6 million participants |
| Specific safety outcomes evaluated by CDC | At least 65 distinct outcomes |
| Published manuscripts on COVID vaccine safety | 114 peer-reviewed manuscripts |
| Most common side effect after Dose 1 (V-safe data) | Injection site pain — reported by 66.3% of participants |
| Participants reporting any injection site reaction after Dose 1 | 68.5% |
| Participants reporting any injection site reaction after Dose 2 | 72.9% |
| Participants reporting any systemic reaction after Dose 1 | 50.6% |
| Participants reporting any systemic reaction after Dose 2 | 69.5% |
| Most common systemic side effects after Dose 2 | Fatigue (53.9%), headache (45.5%), myalgia (43.0%), chills (30.4%), fever (28.8%) |
| Typical onset of post-vaccination symptoms | 1–3 days after vaccination |
| Typical duration of post-vaccination symptoms | Resolve within 1–3 days |
| Adults reporting 2025–26 COVID vaccine as of February 7, 2026 | 17.3% of adults 18+ |
| Children up to date with 2025–26 COVID vaccine (Feb 7, 2026) | 8.6% of children |
| V-safe participants unable to do daily activities after any dose (2023–2024 season) | At least 10% reported a health impact event in 7 days after vaccination |
| Reactions greater after Dose 2 vs Dose 1 | Consistently confirmed — more reactogenicity after second dose across all groups |
| Groups with higher reported reactogenicity | Younger adults (under 45) and females |
Data Source: CDC Immunization Safety Office — ACIP Presentation, June 25, 2025 (Sarah Meyer, MD MPH, Director). CDC V-safe surveillance system — Chapin-Bardales J et al., Vaccine, November 2021; Shimabukuro TT et al., The Lancet Infectious Diseases, March 2022. CDC — Safety Considerations for COVID-19 Vaccines, updated November 4, 2025. CDC COVIDVaxView Weekly Dashboard, data as of February 7, 2026.
These headline facts put COVID vaccine side effects in the United States in 2026 in proper scientific context. The 9.6 million V-safe participants who actively reported their health after vaccination represent one of the largest real-world vaccine safety datasets ever assembled in US history — and the signal from that data is remarkably clear. Injection site pain was the most commonly reported side effect after Dose 1, affecting 66.3% of participants, followed by fatigue at 31.7% and headache at 25.9%. After Dose 2, reactogenicity increased noticeably — 72.9% reported at least one injection site reaction and 69.5% reported at least one systemic reaction — a pattern that has been consistent across all mRNA vaccine seasons. Crucially, the CDC confirms these reactions typically begin within 1–3 days and resolve equally quickly, reflecting normal immune system activation rather than any sign of lasting harm.
The population-level context is equally important. As of February 7, 2026, 17.3% of US adults aged 18 and older had received the 2025–26 COVID-19 vaccine, and 8.6% of children were reported up to date. At the same time, the CDC’s ongoing safety surveillance — actively monitoring millions of Americans through the VSD, covering more than 15.5 million people per year across 13 integrated healthcare organizations — continues to confirm the established safety profile of mRNA COVID vaccines. The finding that at least 10% of vaccine recipients in V-safe reported a health impact event — such as being temporarily unable to complete daily activities in the 7 days after vaccination — during the 2023–2024 season reflects the real-world intensity of some post-vaccination reactions, particularly after second doses, while also confirming that these effects are transient and self-resolving for the vast majority of people.
Common Local Side Effects of COVID Vaccine in the US 2026
| Local Reaction | Reported Frequency |
|---|---|
| Injection site pain / tenderness (Dose 1, V-safe) | 66.3% of participants |
| Injection site pain (Dose 2, V-safe) | 69.7% of participants |
| Any injection site reaction (Dose 1, V-safe) | 68.5% |
| Any injection site reaction (Dose 2, V-safe) | 72.9% |
| Injection site swelling (Dose 2, V-safe) | 17.7% |
| Injection site pain — Pfizer younger adults (Dose 1) | 83.1% |
| Injection site pain — Pfizer older adults (Dose 1) | 71.1% |
| Injection site pain — Pfizer younger adults (Dose 2) | 77.8% |
| Injection site pain — Pfizer older adults (Dose 2) | 66.1% |
| Injection site pain — Moderna mRNA-1273 (Dose 2) | 75.4% |
| Injection site pain — Pfizer BNT162b2 (Dose 2) | 63.2% |
| Localized lymph node swelling (axillary/groin) | Less commonly reported; same side as vaccinated arm |
| Typical duration of local reactions | Median 1–2 days after either dose |
| Typical onset of local reactions | Day 0 (day of vaccination) to 2 days post-vaccination |
Data Source: CDC V-safe surveillance system data — Chapin-Bardales J et al., Vaccine, 2021; Shimabukuro TT et al., The Lancet Infectious Diseases, 2022. CDC — Pfizer-BioNTech COVID-19 Vaccine Reactions and Adverse Events (archived CDC product page). CDC — Safety Considerations for COVID-19 Vaccines, updated November 4, 2025.
Injection site pain is the single most commonly reported COVID vaccine side effect in the United States, and it has been consistently documented across every season’s formulation since December 2020. The V-safe data — drawn from millions of self-reported post-vaccination health surveys — shows that 66.3% of participants reported injection site pain after Dose 1, rising slightly to 69.7% after Dose 2. The CDC’s product-specific reactogenicity data for the Pfizer-BioNTech vaccine confirms a consistent age gradient: younger adults reported injection site pain more frequently than older adults — 83.1% vs. 71.1% after Dose 1, and 77.8% vs. 66.1% after Dose 2. This pattern holds across both mRNA vaccine manufacturers and reflects the more robust immune response typical of younger immune systems. Redness and swelling at the injection site are reported less frequently than pain, and localized lymph node swelling on the same side as the vaccinated arm — while noted — is uncommon.
The practical significance of these local reactions is well-documented. The median onset of local reactions is day 0 to day 2 post-vaccination, and they resolve within a median of 1 to 2 days — meaning the discomfort is real but brief for most people. The CDC also notes that new or worsening local reactions in the second week after vaccination are uncommon — in the V-safe study, fewer than 3 in 100 participants reported any reaction on Day 14 after either dose. This temporal pattern is an important clinical reference point: local reactions peaking in the first 48 hours and resolving by day 3 are expected and normal, while reactions that persist or worsen after the first week warrant medical attention. The data comparing Moderna (mRNA-1273) and Pfizer (BNT162b2) consistently shows that Moderna recipients report higher local and systemic reactogenicity than Pfizer recipients, particularly after Dose 2, with 75.4% of Moderna Dose 2 recipients reporting injection site pain compared to 63.2% of Pfizer Dose 2 recipients.
Common Systemic Side Effects of COVID Vaccine in the US 2026
| Systemic Reaction | Dose 1 Frequency | Dose 2 Frequency |
|---|---|---|
| Any systemic reaction (V-safe) | 50.6% | 69.5% |
| Fatigue | 31.7% | 53.9% |
| Headache | 25.9% | 45.5% |
| Myalgia (muscle pain) | 19.5% | 43.0% |
| Chills | Not separately listed Dose 1 | 30.4% |
| Fever | Less common Dose 1 | 28.8% |
| Joint pain (arthralgia) | Not separately listed Dose 1 | 25.1% |
| Nausea | Not separately listed Dose 1 | 15.6% |
| Moderna Dose 2 fatigue vs. Pfizer Dose 2 | — | 59.6% (Moderna) vs. 47.3% (Pfizer) |
| Moderna Dose 2 headache vs. Pfizer Dose 2 | — | 51.3% (Moderna) vs. 38.9% (Pfizer) |
| Typical onset of systemic reactions | 1–3 days after vaccination | 1–3 days after vaccination |
| Typical duration of systemic reactions | Median 1 day | Median 1–2 days |
Data Source: CDC V-safe surveillance system data — Chapin-Bardales J et al., Vaccine, 2021. Shimabukuro TT et al., The Lancet Infectious Diseases, 2022. CDC — Safety Considerations for COVID-19 Vaccines, updated November 4, 2025 (CDC.gov/covid/hcp/vaccine-considerations/safety-considerations.html).
The systemic side effects of COVID vaccines in the US — fatigue, headache, muscle pain, chills, and fever — are among the best-documented vaccine reactions in American public health history, and the data is unambiguous: these effects are common, predictable, and temporary. After Dose 1, 50.6% of V-safe participants reported at least one systemic reaction, with fatigue (31.7%), headache (25.9%), and myalgia (19.5%) leading the list. After Dose 2, those numbers climbed significantly — 69.5% reported any systemic reaction, with fatigue reaching 53.9% and headache 45.5%. The increase in reactogenicity from Dose 1 to Dose 2 is a consistent and expected finding across all mRNA COVID vaccine studies, attributed to a primed immune system mounting a stronger and faster response upon second antigen exposure. The CDC notes that the majority of systemic events were mild or moderate in severity after both doses.
The comparison between vaccine manufacturers is clinically meaningful and consistently documented. Moderna (mRNA-1273) recipients report notably higher systemic reactogenicity than Pfizer (BNT162b2) recipients after Dose 2 — with fatigue affecting 59.6% of Moderna vs. 47.3% of Pfizer recipients, and headache affecting 51.3% vs. 38.9% respectively. Two demographic patterns are also firmly established in the surveillance data: younger adults (under 45 years) and females consistently report higher rates of reactogenicity than older adults and males across both vaccine types and all doses. This pattern is well understood from immunology — younger immune systems and female immune biology are associated with more vigorous inflammatory responses to vaccination. The median onset of systemic reactions is 1 to 3 days after vaccination, and they last a median of 1 to 2 days, which aligns with the normal kinetics of an immune response to a vaccine antigen.
COVID Vaccine Side Effects After Booster and Additional Doses in the US 2026
| Indicator | Data |
|---|---|
| Local reactions reported after additional/booster dose (V-safe) | 74.9% reported a local reaction |
| Systemic reactions after additional/booster dose | 69.9% |
| Injection site pain after additional dose | 71.0% |
| Fatigue after additional dose | 56.0% |
| Headache after additional dose | 43.4% |
| Unable to perform normal daily activities after additional dose | 28.3% — most commonly on the day after vaccination |
| Medical care sought after additional dose (V-safe) | 1.8% of registrants |
| Hospitalized after additional dose (V-safe) | 0.1% (13 of 22,191 additional dose recipients) |
| Reactogenicity after booster vs. initial series | Generally lower than after the initial primary series doses |
| Reactogenicity in older adults after booster (65+) | Milder and less frequent than in adolescents and younger adults |
| 2024–25 COVID-19 vaccine health impact rate (V-safe) | At least 10% reported being unable to complete daily activities in the 7 days post-vaccination |
Data Source: CDC MMWR — Hause AM et al., “Safety Monitoring of an Additional Dose of COVID-19 Vaccine — United States, August 12–September 19, 2021,” MMWR, September 30, 2021. ACIP Recommendations — Roper LE et al., “Use of Additional Doses of 2024–2025 COVID-19 Vaccine,” MMWR, December 12, 2024. CDC Immunization Safety Office ACIP Presentation, June 25, 2025.
COVID vaccine booster and additional dose side effects in the US show a well-documented and largely reassuring pattern: reactogenicity after additional doses is generally lower than after the initial primary series doses, and older adults — who are at greatest risk from COVID-19 and most likely to receive additional doses — experience milder and less frequent reactions than younger vaccinees. The CDC MMWR study of V-safe data covering additional dose recipients between August and September 2021 found that 74.9% reported a local reaction and 69.9% reported a systemic reaction in the 7 days following their additional dose — with injection site pain (71.0%), fatigue (56.0%), and headache (43.4%) remaining the most common complaints. These numbers are broadly consistent with Dose 2 reactogenicity, which is expected given that boosters similarly re-engage the primed immune system.
What stands out most meaningfully in the booster data is the daily activity impact figure: 28.3% of additional dose recipients reported being temporarily unable to perform normal daily activities, most commonly on the day after vaccination. This is a real-world side effect burden that affects more than 1 in 4 people receiving additional doses — worth knowing for individuals planning around vaccination. At the same time, the data frames this impact clearly: only 1.8% of registrants sought medical care, and only 0.1% — 13 individuals out of 22,191 additional dose recipients — were hospitalized, with no causality determination specified in the surveillance data. The 2024–25 season V-safe data extends this picture, confirming that at least 10% of COVID vaccine recipients reported health impact events in the 7 days after vaccination during the most recent completed season — a figure that reflects the real experience of vaccination in a large, diverse US population.
COVID Vaccine Side Effects by Age Group in the US 2026
| Age Group | Key Side Effect Patterns |
|---|---|
| Adults under 45 years | Higher reactogenicity — more frequent and intense local and systemic reactions than older adults |
| Adults 65 years and older | Lower reactogenicity — less frequent and milder reactions; 10.9% fever after Pfizer Dose 2 |
| Adults 18–54 years (Pfizer Dose 2 fever rate) | 15.8% fever — notably higher than older adults |
| Adolescents aged 12–15 years (Pfizer trials) | Injection site pain (90.5%), fatigue (77.5%), headache (75.5%), chills (49.2%), muscle pain (42.2%) |
| Adolescents aged 12–15 — fever | 24.3% |
| Adolescents aged 12–15 — joint pain | 20.2% |
| Children aged 6–23 months (Moderna trials) | Irritability/crying, sleepiness, loss of appetite as primary systemic reactions |
| Children under 3 years | Systemic reactions include irritability/crying, sleepiness, and decreased appetite |
| Children 5–11 years | Systemic reactions consistent with other age groups; fatigue, headache, muscle pain most common |
| Females across all ages | Consistently report higher reactogenicity than males across all doses and vaccine types |
| Reactogenicity trend across all ages | Decreases with older age — consistent finding across all vaccine manufacturers and dose numbers |
Data Source: CDC — Pfizer-BioNTech COVID-19 Vaccine Reactions and Adverse Events (archived CDC clinical page). CDC — Safety Considerations for COVID-19 Vaccines, updated November 4, 2025. FDA Pfizer-BioNTech EUI Recipient Fact Sheet (2024–2025 Formula). Shimabukuro TT et al., The Lancet Infectious Diseases, 2022. CDC MMWR — Safety of COVID-19 Vaccination in United States Children Ages 5–11 Years, Pediatrics, AAP.
The age-stratified COVID vaccine side effect data in the US tells a consistent, well-supported story: younger people experience more intense and frequent reactions than older people, and females report higher reactogenicity than males across all age groups. Among adolescents aged 12–15 years in the Pfizer clinical trials, the reaction profile was notably more pronounced than in adults — 90.5% reported injection site pain, 77.5% reported fatigue, and 75.5% reported headache after vaccination. Fever affected 24.3% of this age group, and the company noted that chills and fever were more common in adolescents than adults. These reactions generally subsided within 1 to 2 days. For context, the adult Pfizer Dose 2 systemic reaction rate was 66.6% for any systemic reaction — lower across every specific symptom than the adolescent 12–15 figures, confirming the age pattern clearly.
On the older end of the age spectrum, the CDC data is equally consistent. Among Pfizer Dose 2 recipients, fever was reported by 15.8% of the younger adult group compared to only 10.9% of the older adult group — a difference that reflects the well-established immunosenescence pattern in vaccine response. Adults aged 65 and older also showed lower injection site pain rates after both doses (71.1% vs. 83.1% after Dose 1; 66.1% vs. 77.8% after Dose 2) compared to younger adults. For young children — those aged 6–23 months and under 3 years — the systemic reaction picture shifts from the standard adult profile to age-appropriate presentations including irritability/crying, sleepiness, and loss of appetite, as these children cannot communicate headache or fatigue in the same way. The CDC’s active surveillance through the VSD has confirmed no increased risks for 22 pre-specified outcomes in children following COVID-19 vaccination, providing an important safety baseline for the youngest age groups.
COVID Vaccine Safety Monitoring Systems and Surveillance in the US 2026
| System | Key Details and Scale |
|---|---|
| VAERS (Vaccine Adverse Event Reporting System) | Co-managed by CDC and FDA; nationwide spontaneous reporting; established 1990; healthcare providers mandated to report |
| V-safe | Active smartphone-based self-reporting; launched December 2020; approx. 9.6 million participants enrolled as of June 2025 |
| VSD (Vaccine Safety Datalink) | 13 integrated healthcare organizations; covers more than 15.5 million people per year; active weekly monitoring using electronic medical records |
| CISA Project | 8 medical research centers with vaccine safety experts; provides expert clinical consultation and conducts clinical research |
| VaST work group reports produced | 17 reports produced December 2020–June 2025 |
| ACIP/VRBPAC advisory meeting presentations | 28 presentations between December 2020–June 2025 |
| MMWR publications on COVID vaccine safety | 29 published between December 2020–June 2025 |
| Published scientific manuscripts on COVID vaccine safety | 114 peer-reviewed manuscripts as of June 2025 |
| VSD rapid cycle analyses (RCAs) | Conducted weekly since December 2020 on up to 23 pre-specified outcomes among over 12 million people |
| Specific outcomes assessed by CDC using all systems | At least 65 distinct clinical outcomes |
Data Source: CDC Immunization Safety Office — ACIP Presentation by Sarah Meyer, MD MPH, Director, CDC Immunization Safety Office, June 25, 2025. CDC — Safety Considerations for COVID-19 Vaccines, updated November 4, 2025.
The COVID-19 vaccine safety monitoring infrastructure in the United States is, by any metric, the most comprehensive post-authorization surveillance system ever assembled for a vaccine program in American history. The combination of four overlapping, complementary systems — VAERS, V-safe, VSD, and the CISA Project — ensures that both common expected reactions and rare, unexpected signals can be detected quickly and rigorously investigated. The VSD alone covers more than 15.5 million people per year through 13 integrated healthcare organizations, using active electronic medical record monitoring and chart reviews to detect safety signals week by week. The scale of V-safe — approximately 9.6 million enrolled participants self-reporting their health after every dose — means that even very uncommon events occurring in 1 in 100,000 vaccinees would be statistically detectable in this dataset. This is not passive surveillance; it is active, continuous, real-time monitoring at a scale that dwarfs any previous vaccine safety program in the US.
The output of this system speaks for itself: 114 peer-reviewed manuscripts, 29 MMWR publications, 17 VaST work group reports, and 28 presentations to the ACIP and VRBPAC — all generated between December 2020 and June 2025 alone. The rapid cycle analyses (RCAs) conducted weekly in the VSD on up to 23 pre-specified outcomes among over 12 million people allow the CDC to detect even modest elevations in risk within weeks of a new vaccine rollout, not months or years. As of June 2025, these weekly analyses had produced 8 statistical signals for mRNA COVID-19 vaccines across the 2020–2025 period, all of which underwent further investigation through chart reviews, trend analyses, and additional epidemiologic studies — demonstrating not that the system missed things, but that it found and rigorously investigated everything worth examining. The 2025–26 COVID-19 vaccine formulations authorized in August 2025 continue to be actively monitored through all of these systems, and the CDC’s guidance and safety summaries are updated publicly as new data emerges.
COVID Vaccine Side Effects in Special Populations in the US 2026
| Population | Side Effect / Safety Data |
|---|---|
| Pregnant women | V-safe and the COVID-19 Vaccine Pregnancy Registry used to monitor maternal and infant outcomes; no increased risk of adverse pregnancy outcomes identified in CDC safety reviews |
| Breastfeeding women | 2024–25 COVID-19 vaccine recommended; no CDC-identified safety concerns for breastfeeding women |
| Immunocompromised persons (ages 6 months–64 years) | 2 or more doses of 2024–25 COVID-19 vaccine recommended; reactogenicity generally consistent with immunocompetent individuals |
| Adults aged 65 and older | Recommended 2 doses of 2024–25 COVID-19 vaccine (6 months apart); lower reactogenicity than younger adults; Medicare FFS coverage rate 13.9% (through Nov 29, 2025) |
| Infants and toddlers (6 months–2 years) | Systemic reactions include irritability, crying, sleepiness, loss of appetite; no confirmed myocarditis in children under 5 in VAERS or VSD |
| Children 5–11 years | No increased risks for 22 pre-specified outcomes found in VSD rapid cycle analyses following COVID-19 vaccination |
| Adolescents 12–17 years | Higher reactogenicity than adults; reactions (fatigue, headache, injection site pain) most pronounced and generally subside within 1–2 days |
| People with prior COVID-19 infection | May experience stronger systemic reactions after first dose due to existing immune memory |
| People with severe allergies | Monitored onsite for 30 minutes after vaccination (vs. standard 15 minutes for others); severe allergic reactions are rare |
| People with history of myocarditis/pericarditis | Should generally avoid subsequent COVID vaccine dose within 3 weeks of the episode; individualized clinical assessment recommended |
Data Source: CDC — Safety Considerations for COVID-19 Vaccines, updated November 4, 2025. CDC — COVID-19 Vaccine Safety (last updated June 6, 2025). ACIP Recommendations — Roper LE et al., MMWR, December 12, 2024. CDC COVIDVaxView Weekly Dashboard, data as of February 7, 2026.
The CDC’s guidance on COVID vaccine side effects in special populations in the US in 2026 reflects more than four years of accumulated safety data and clinical experience across the full diversity of the American population. For pregnant women, V-safe and a dedicated COVID-19 Vaccine Pregnancy Registry were established at launch specifically to track maternal and infant outcomes — and the CDC’s safety reviews have not identified increased risks of adverse pregnancy outcomes from mRNA COVID-19 vaccines. For adults aged 65 and older, the ACIP in October 2024 updated its recommendations to reflect that this group should receive two doses of the 2024–25 COVID-19 vaccine, spaced 6 months apart, to maintain protection throughout the year — and the safety data confirms that older adults experience milder and less frequent reactions than younger populations. As of November 29, 2025, 13.9% of Medicare fee-for-service beneficiaries aged 65 and older had received their updated seasonal COVID vaccine, with the highest coverage among non-Hispanic White beneficiaries (14.4%) and lowest among Hispanic beneficiaries (5.1%).
For the youngest children — infants and toddlers aged 6 months to 2 years — the side effect profile is age-appropriate and distinct from the adult experience. The CDC notes that no confirmed myocarditis cases have been identified in children under 5 in either VAERS or the VSD, and rapid cycle analyses in the VSD have found no increased risks for 22 pre-specified outcomes following COVID-19 vaccination in children aged 5–11 years. For people with severe allergies, the standard precaution is onsite monitoring for 30 minutes after vaccination, compared to the standard 15-minute observation period for all other recipients. This extended monitoring protocol reflects the CDC’s response to the small number of anaphylaxis cases identified in the early months of the vaccine rollout — demonstrating the responsive, practical nature of how post-authorization safety findings translate into updated clinical guidance. Overall, the CDC’s current safety profile for COVID vaccine side effects across all populations in the US in 2026 is: common reactions are expected, mild, brief, and manageable; rare serious events are actively monitored and clinically addressed through individualized medical guidance.
2025–2026 COVID Vaccine Formulation and Side Effect Profile in the US 2026
| Indicator | Data |
|---|---|
| 2025–26 COVID vaccine FDA authorization date | August 2025 |
| 2025–26 vaccines recommended for | All persons aged 6 months and older |
| Vaccines fully FDA-approved (ages 12+) | Comirnaty (Pfizer) and Spikevax (Moderna) — both single-dose injection for 2025–26 |
| Vaccine authorized under Emergency Use (ages 6 months–11 years) | Pfizer-BioNTech and Moderna mRNA vaccines |
| Novavax | Authorized under Emergency Use for ages 12+; protein subunit vaccine |
| New common side effects identified for 2025–26 formulations | None — same established profile of injection site pain, fatigue, headache, muscle pain, chills, fever |
| 2025–26 vaccine recommendation basis (ACIP) | Shared clinical decision-making for persons under 65; benefits most clearly outweigh risks in those at high risk for severe COVID-19 |
| 2024–25 vaccine effectiveness (adults, ED/UC visits) | 33% overall — 30% for ages 18–64, 36% for adults 65+ (VISION network, Sept 2024–Jan 2025) |
| 2024–25 vaccine effectiveness against hospitalization (adults 65+) | 45% in immunocompetent and 40% in immunocompromised persons |
| Observation period post-vaccination (all recipients) | Minimum 15 minutes onsite |
| Observation period (prior allergic reaction) | 30 minutes onsite |
Data Source: CDC — Safety Considerations for COVID-19 Vaccines, updated November 4, 2025. CDC — COVID-19 Vaccine VIS (Vaccine Information Statement), updated June 3, 2025. The Medical Letter — COVID-19 Update: 2025–2026 Vaccine Formulations and Recommendations, September 2025. CDC MMWR — Link-Gelles R et al., “Interim Estimates of 2024–2025 COVID-19 Vaccine Effectiveness Among Adults Aged ≥18 Years,” MMWR, 2025;74:73.
The 2025–26 COVID-19 vaccine formulations represent the fifth generation of updated mRNA vaccines since the original 2020 approvals, and the safety data is consistent: no new common side effects have been identified in any of the updated formulations compared to prior seasons. The same well-characterized profile — local arm pain, fatigue, headache, muscle aches, chills, and fever — applies to the 2025–26 KP.2-lineage-targeted formulations authorized in August 2025 for Pfizer and Moderna, both of which are FDA-fully approved for persons aged 12 and older as a single-dose annual injection. Novavax’s protein subunit vaccine continues to be available for those who prefer a non-mRNA option, also authorized under Emergency Use for ages 12 and older. The ACIP’s 2025–26 guidance, reflecting a shift toward shared clinical decision-making for persons under 65, emphasizes that the benefits of vaccination most clearly outweigh the risks in those at high risk for severe COVID-19.
The effectiveness data for the 2024–25 season provides important context for the overall benefit-risk assessment of COVID vaccination. Interim estimates from the VISION network covering September 2024–January 2025 found that receipt of the 2024–25 COVID-19 vaccine was associated with a 33% reduction in COVID-19-associated emergency department and urgent care visits (30% in adults 18–64, 36% in adults 65+), and a 45% reduction in COVID-19-associated hospitalization in immunocompetent adults aged 65 and older. These effectiveness figures, set against a side effect profile dominated by mild, transient, self-resolving reactions in the first 1–3 days after vaccination, form the foundation of the CDC’s public health guidance on COVID vaccine side effects and safety in the US in 2026: the reactions are real, the data is transparent, and the monitoring continues without pause.
Disclaimer: The data reports published on The Global Files are sourced from publicly available materials considered reliable. While efforts are made to ensure accuracy, no guarantees are provided regarding completeness or reliability. The Global Files is not liable for any errors, omissions, or damages resulting from the use of these reports.