Evidence dossier · candidate cand-covid-anaphylaxis · CICP program · · DRAFT — not a determination
This is a draft research-tracking dossier, not a determination that COVID-19 vaccine causes Anaphylaxis, and not an incidence or legal finding. All evidence is flagged needs_human_review and must be reviewed before any page is published or cited. Every value is grounded in retrieved citations (PMID + retrieval date); unsourced items read "no evidence found / not assessable". Symmetric search: every supporting query has a mirror/null query, and zeros are shown (negative dossiers report the absence of signal).
Claim matrix (C1–C6, computed)
Claim
Label
Status
Missing nodes
C1
Coherent clinical object exists
contested
C2
Consistent temporal window
contested
C3
Epidemiologic excess risk
supported
C4
Consistency / replication
supported
C5
Specificity (product / dose)
contested
C6
Biological mechanism
supported
Two evidentiary bars apply to the epi nodes/claims (C3, C4): · VICP — preponderance of the evidence. · CICP (off-Table) — compelling, reliable, valid medical and scientific evidence (higher bar).
Bradford Hill assessment (computed)
Each viewpoint is derived from the node statuses below (see the framework crosswalk in compensation-tables-schema.md §8). Hill's viewpoints are aids to judgement, not a scoring checklist that proves causation; temporality is the only strictly necessary criterion.
Viewpoint
What it asks
Status (from evidence)
Temporality(necessary)
cause precedes effect in a plausible window (necessary)
NASEM (formerly IOM), "Adverse Effects of Vaccines: Evidence and Causality" (2011, updated 2024). Independent grading of epidemiologic and mechanistic evidence, synthesized into one of four causal-conclusion categories. This is a computed approximation of that framework, not a NASEM determination. See compensation-tables-schema.md §8bis.
Case-definition standard: Brighton Collaboration (named in spec §1: anaphylaxis) — governs the case-certainty scale on A1/A2/A6/A8 below. See compensation-tables-schema.md §8ter.
Evidence matrix (68 nodes by workstream)
68 of 68 nodes evaluated · 136 PubMed queries logged (supporting + mirror, incl. zeros). Statuses are computed from retrieved citations; not hand-set.
Definition & attribution 24/24 evaluated
A1 · Case reportssupports
Measure: New definite object in risk window T Comparator: Pre-vaccination baseline Hit rule: Definite object present, onset in window, competing causes considered
Finding: Multiple case reports describe anaphylaxis occurring within minutes to hours after COVID-19 vaccination, with some cases considering alternative causes, such as cholinergic urticaria or idiopathic anaphylaxis, and one report of prolonged anaphylaxis.
supporting: COVID-19 vaccine Anaphylaxis case report OR case series Case reports pubmed · 66197 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis alternative diagnosis OR not vaccine-related pubmed · 4056 hits · run 2026-09-06
16 retrieved record(s)
supports_node 35226841 · Clinical practice and cases in emergency (2022) — A Case Report of Prolonged Anaphylaxis after COVID-19 Vaccine.
supports_node 34734159 · Therapeutic advances in vaccines and imm (2021) — Anaphylaxis after Moderna COVID-19 vaccine.
refutes_node 33851711 · Military medicine (2022) — Anaphylaxis After the Covid-19 Vaccine in a Patient With Cholinergic Urticaria.
supports_node 35677740 · Cureus (2022) — Hypertensive Anaphylaxis After Moderna COVID-19 Vaccination: A Case Report.
supports_node 39515796 · Allergologia et immunopathologia (2024) — A case with recurrent idiopathic anaphylaxis episodes starting soon after COVID-19 mRNA vaccination.
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
supports_node 39324928 · Singapore medical journal (2024) — Anaphylaxis post-COVID-19 vaccinations in Singapore.
A2 · Series with objective confirmationsupports
Measure: Definite object plus objective test Comparator: Reference range / diagnostic criteria Hit rule: Objective confirmation in >=1 case per the working definition
Finding: Multiple case reports describe anaphylaxis occurring after COVID-19 vaccination, with some cases including objective confirmation via clinical presentation and diagnostic testing, but the evidence is limited to individual case reports and does not provide systematic or population-level objective confirmation.
supporting: COVID-19 vaccine Anaphylaxis case report OR case series Series with objective confirmation pubmed · 5677 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis alternative diagnosis OR not vaccine-related pubmed · 4056 hits · run 2026-09-06
16 retrieved record(s)
supports_node 35226841 · Clinical practice and cases in emergency (2022) — A Case Report of Prolonged Anaphylaxis after COVID-19 Vaccine.
refutes_node 33851711 · Military medicine (2022) — Anaphylaxis After the Covid-19 Vaccine in a Patient With Cholinergic Urticaria.
supports_node 34734159 · Therapeutic advances in vaccines and imm (2021) — Anaphylaxis after Moderna COVID-19 vaccine.
supports_node 35677740 · Cureus (2022) — Hypertensive Anaphylaxis After Moderna COVID-19 Vaccination: A Case Report.
supports_node 39515796 · Allergologia et immunopathologia (2024) — A case with recurrent idiopathic anaphylaxis episodes starting soon after COVID-19 mRNA vaccination.
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
supports_node 39324928 · Singapore medical journal (2024) — Anaphylaxis post-COVID-19 vaccinations in Singapore.
A3 · Onset histogramno_data
Measure: Distribution of onset times after dose Comparator: Pre-specified risk window Hit rule: Onset clusters inside the pre-specified window (not uniform/flat)
Finding: Retrieved evidence consists exclusively of case reports describing anaphylaxis after COVID-19 vaccination, with onset times typically within minutes to hours post-dose (e.g., 30 minutes in PMID 35677740), but no systematic onset-interval histogram or cluster analysis is provided to assess whether onset times cluster within a pre-specified window versus being uniform/flat.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis case report OR case series Onset histogram pubmed · 39 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis alternative diagnosis OR not vaccine-related pubmed · 4056 hits · run 2026-09-06
20 retrieved record(s)
supports_node 35226841 · Clinical practice and cases in emergency (2022) — A Case Report of Prolonged Anaphylaxis after COVID-19 Vaccine.
refutes_node 33851711 · Military medicine (2022) — Anaphylaxis After the Covid-19 Vaccine in a Patient With Cholinergic Urticaria.
supports_node 34734159 · Therapeutic advances in vaccines and imm (2021) — Anaphylaxis after Moderna COVID-19 vaccine.
supports_node 35677740 · Cureus (2022) — Hypertensive Anaphylaxis After Moderna COVID-19 Vaccination: A Case Report.
supports_node 39515796 · Allergologia et immunopathologia (2024) — A case with recurrent idiopathic anaphylaxis episodes starting soon after COVID-19 mRNA vaccination.
supports_node 40386747 · HCA healthcare journal of medicine (2025) — Resolution of Patient's Anaphylaxis to the Moderna COVID-19 Vaccine by Desensitization.
supports_node 34675550 · Journal of asthma and allergy (2021) — CoronaVac COVID-19 Vaccine-Induced Anaphylaxis: Clinical Characteristics and Revaccination Outcomes.
does_not_resolve 35223425 · Respiratory medicine case reports (2022) — Interstitial lung disease after receiving the mRNA-based COVID-19 vaccine tozinameran.
A4 · Temporal plausibilitysupports
Measure: Onset latency vs object pathophysiology Comparator: Object's known natural latency Hit rule: Onset latency consistent with the object's pathophysiology
Finding: Multiple case reports document anaphylaxis onset within minutes to hours after COVID-19 vaccination, with onset latencies (e.g., 30 minutes, 45 minutes) consistent with the typical pathophysiology of immediate hypersensitivity reactions. However, evidence is limited to individual case reports and small case series, lacking controlled epidemiological data.
supporting: COVID-19 vaccine Anaphylaxis case report OR case series Temporal plausibility pubmed · 68 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis alternative diagnosis OR not vaccine-related pubmed · 4056 hits · run 2026-09-06
18 retrieved record(s)
supports_node 35226841 · Clinical practice and cases in emergency (2022) — A Case Report of Prolonged Anaphylaxis after COVID-19 Vaccine.
refutes_node 33851711 · Military medicine (2022) — Anaphylaxis After the Covid-19 Vaccine in a Patient With Cholinergic Urticaria.
supports_node 34734159 · Therapeutic advances in vaccines and imm (2021) — Anaphylaxis after Moderna COVID-19 vaccine.
supports_node 35677740 · Cureus (2022) — Hypertensive Anaphylaxis After Moderna COVID-19 Vaccination: A Case Report.
supports_node 39515796 · Allergologia et immunopathologia (2024) — A case with recurrent idiopathic anaphylaxis episodes starting soon after COVID-19 mRNA vaccination.
supports_node 40386747 · HCA healthcare journal of medicine (2025) — Resolution of Patient's Anaphylaxis to the Moderna COVID-19 Vaccine by Desensitization.
supports_node 34675550 · Journal of asthma and allergy (2021) — CoronaVac COVID-19 Vaccine-Induced Anaphylaxis: Clinical Characteristics and Revaccination Outcomes.
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
A5 · Onset-interval documentationno_data
Measure: Onset interval documented in source Comparator: Dose date Hit rule: Onset interval is recorded (not imputed) in a primary source
Finding: Several case reports document anaphylaxis after COVID-19 vaccination with specific onset intervals recorded (e.g., 30 minutes post-vaccination in PMID 35677740, immediate onset in PMID 33851711), but the retrieved evidence consists entirely of case reports and does not provide systematic documentation of onset intervals from primary sources for population-level evidence screening.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis case report OR case series Onset-interval documentation pubmed · 37 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis alternative diagnosis OR not vaccine-related pubmed · 4056 hits · run 2026-09-06
20 retrieved record(s)
supports_node 35226841 · Clinical practice and cases in emergency (2022) — A Case Report of Prolonged Anaphylaxis after COVID-19 Vaccine.
refutes_node 33851711 · Military medicine (2022) — Anaphylaxis After the Covid-19 Vaccine in a Patient With Cholinergic Urticaria.
supports_node 34734159 · Therapeutic advances in vaccines and imm (2021) — Anaphylaxis after Moderna COVID-19 vaccine.
supports_node 35677740 · Cureus (2022) — Hypertensive Anaphylaxis After Moderna COVID-19 Vaccination: A Case Report.
supports_node 39515796 · Allergologia et immunopathologia (2024) — A case with recurrent idiopathic anaphylaxis episodes starting soon after COVID-19 mRNA vaccination.
supports_node 40386747 · HCA healthcare journal of medicine (2025) — Resolution of Patient's Anaphylaxis to the Moderna COVID-19 Vaccine by Desensitization.
supports_node 34675550 · Journal of asthma and allergy (2021) — CoronaVac COVID-19 Vaccine-Induced Anaphylaxis: Clinical Characteristics and Revaccination Outcomes.
does_not_resolve 35223425 · Respiratory medicine case reports (2022) — Interstitial lung disease after receiving the mRNA-based COVID-19 vaccine tozinameran.
A6 · Differential diagnosis excludedno_data
Measure: Competing causes assessed and excluded Comparator: Likely alternative diagnoses Hit rule: Pre-specified competing causes ruled out per the working definition
Finding: Multiple case reports describe anaphylaxis after COVID-19 vaccination, but none explicitly document that pre-specified competing causes were ruled out per a working definition; the report in PMID 33851711 mentions evaluation for cholinergic urticaria but does not confirm exclusion of all competing causes for the anaphylaxis episode.
supporting: COVID-19 vaccine Anaphylaxis case report OR case series Differential diagnosis excluded pubmed · 464 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis alternative diagnosis OR not vaccine-related pubmed · 4056 hits · run 2026-09-06
14 retrieved record(s)
supports_node 35226841 · Clinical practice and cases in emergency (2022) — A Case Report of Prolonged Anaphylaxis after COVID-19 Vaccine.
refutes_node 33851711 · Military medicine (2022) — Anaphylaxis After the Covid-19 Vaccine in a Patient With Cholinergic Urticaria.
supports_node 34734159 · Therapeutic advances in vaccines and imm (2021) — Anaphylaxis after Moderna COVID-19 vaccine.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
supports_node 39324928 · Singapore medical journal (2024) — Anaphylaxis post-COVID-19 vaccinations in Singapore.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
does_not_resolve 30000765 · (2006) — Human Papillomavirus Vaccines.
A7 · Rechallenge / re-exposureno_data
Measure: Object recurs on a further dose Comparator: First-dose response Hit rule: Object recurs after a subsequent dose (re-exposure)
Finding: No retrieved evidence describes a case where anaphylaxis clearly recurs after a subsequent dose (re-exposure) from the same vaccine type; the reports describe anaphylaxis after the first dose, and only one case described resolution via desensitization but did not confirm recurrence of anaphylaxis on rechallenge.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis case report OR case series Rechallenge / re-exposure pubmed · 39 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis alternative diagnosis OR not vaccine-related pubmed · 4056 hits · run 2026-09-06
20 retrieved record(s)
supports_node 35226841 · Clinical practice and cases in emergency (2022) — A Case Report of Prolonged Anaphylaxis after COVID-19 Vaccine.
refutes_node 33851711 · Military medicine (2022) — Anaphylaxis After the Covid-19 Vaccine in a Patient With Cholinergic Urticaria.
supports_node 34734159 · Therapeutic advances in vaccines and imm (2021) — Anaphylaxis after Moderna COVID-19 vaccine.
supports_node 35677740 · Cureus (2022) — Hypertensive Anaphylaxis After Moderna COVID-19 Vaccination: A Case Report.
supports_node 39515796 · Allergologia et immunopathologia (2024) — A case with recurrent idiopathic anaphylaxis episodes starting soon after COVID-19 mRNA vaccination.
supports_node 40386747 · HCA healthcare journal of medicine (2025) — Resolution of Patient's Anaphylaxis to the Moderna COVID-19 Vaccine by Desensitization.
supports_node 34675550 · Journal of asthma and allergy (2021) — CoronaVac COVID-19 Vaccine-Induced Anaphylaxis: Clinical Characteristics and Revaccination Outcomes.
does_not_resolve 35223425 · Respiratory medicine case reports (2022) — Interstitial lung disease after receiving the mRNA-based COVID-19 vaccine tozinameran.
A8 · Adjudicated by criteria (Brighton Collaboration)supports
Measure: Object adjudicated by published criteria Comparator: Published clinical / Brighton criteria Hit rule: Cases adjudicated to 'definite' by a published criterion set
Finding: Multiple case reports describe anaphylaxis after COVID-19 vaccination, including cases adjudicated using Brighton Collaboration criteria, supporting the occurrence of definite anaphylaxis by published criteria.
supporting: COVID-19 vaccine Anaphylaxis case report OR case series Adjudicated by criteria pubmed · 76 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis alternative diagnosis OR not vaccine-related pubmed · 4056 hits · run 2026-09-06
18 retrieved record(s)
supports_node 35226841 · Clinical practice and cases in emergency (2022) — A Case Report of Prolonged Anaphylaxis after COVID-19 Vaccine.
refutes_node 33851711 · Military medicine (2022) — Anaphylaxis After the Covid-19 Vaccine in a Patient With Cholinergic Urticaria.
supports_node 34734159 · Therapeutic advances in vaccines and imm (2021) — Anaphylaxis after Moderna COVID-19 vaccine.
supports_node 35677740 · Cureus (2022) — Hypertensive Anaphylaxis After Moderna COVID-19 Vaccination: A Case Report.
supports_node 40386747 · HCA healthcare journal of medicine (2025) — Resolution of Patient's Anaphylaxis to the Moderna COVID-19 Vaccine by Desensitization.
supports_node 39515796 · Allergologia et immunopathologia (2024) — A case with recurrent idiopathic anaphylaxis episodes starting soon after COVID-19 mRNA vaccination.
supports_node 34675550 · Journal of asthma and allergy (2021) — CoronaVac COVID-19 Vaccine-Induced Anaphylaxis: Clinical Characteristics and Revaccination Outcomes.
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
A9 · Natural-history consistencyno_data
Measure: Course matches the object's natural history Comparator: Known natural history of the object Hit rule: Clinical course (onset, peak, recovery) matches the object's natural history
Finding: Case reports describe anaphylaxis after COVID-19 vaccination, but none detail the full clinical course (onset, peak, recovery) compared to the natural history of anaphylaxis in a systematic or epidemiologically robust manner.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis case report OR case series Natural-history consistency pubmed · 140 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis alternative diagnosis OR not vaccine-related pubmed · 4056 hits · run 2026-09-06
16 retrieved record(s)
supports_node 35226841 · Clinical practice and cases in emergency (2022) — A Case Report of Prolonged Anaphylaxis after COVID-19 Vaccine.
refutes_node 33851711 · Military medicine (2022) — Anaphylaxis After the Covid-19 Vaccine in a Patient With Cholinergic Urticaria.
supports_node 34734159 · Therapeutic advances in vaccines and imm (2021) — Anaphylaxis after Moderna COVID-19 vaccine.
supports_node 35677740 · Cureus (2022) — Hypertensive Anaphylaxis After Moderna COVID-19 Vaccination: A Case Report.
supports_node 39515796 · Allergologia et immunopathologia (2024) — A case with recurrent idiopathic anaphylaxis episodes starting soon after COVID-19 mRNA vaccination.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
supports_node 39324928 · Singapore medical journal (2024) — Anaphylaxis post-COVID-19 vaccinations in Singapore.
A10 · No confounding objectmixed
Measure: Not attributable to a co-occurring condition Comparator: Co-occurring illness that could produce the object Hit rule: Object not better explained by a co-occurring condition (infection, etc.)
Finding: Several case reports describe anaphylaxis occurring after COVID-19 vaccination, including cases where co-occurring conditions such as cholinergic urticaria or idiopathic anaphylaxis were present, but the evidence does not systematically assess whether anaphylaxis was attributable to the vaccine after ruling out co-occurring conditions or competing causes.
supporting: COVID-19 vaccine Anaphylaxis case report OR case series No confounding object pubmed · 56 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis alternative diagnosis OR not vaccine-related pubmed · 4056 hits · run 2026-09-06
18 retrieved record(s)
supports_node 35226841 · Clinical practice and cases in emergency (2022) — A Case Report of Prolonged Anaphylaxis after COVID-19 Vaccine.
refutes_node 33851711 · Military medicine (2022) — Anaphylaxis After the Covid-19 Vaccine in a Patient With Cholinergic Urticaria.
supports_node 34734159 · Therapeutic advances in vaccines and imm (2021) — Anaphylaxis after Moderna COVID-19 vaccine.
supports_node 35677740 · Cureus (2022) — Hypertensive Anaphylaxis After Moderna COVID-19 Vaccination: A Case Report.
supports_node 39515796 · Allergologia et immunopathologia (2024) — A case with recurrent idiopathic anaphylaxis episodes starting soon after COVID-19 mRNA vaccination.
supports_node 40386747 · HCA healthcare journal of medicine (2025) — Resolution of Patient's Anaphylaxis to the Moderna COVID-19 Vaccine by Desensitization.
supports_node 34675550 · Journal of asthma and allergy (2021) — CoronaVac COVID-19 Vaccine-Induced Anaphylaxis: Clinical Characteristics and Revaccination Outcomes.
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
D1 · Predicted site of injuryno_data
Measure: Object at the site the mechanism predicts Comparator: Predicted anatomic site from the mechanism Hit rule: Object localizes to the anatomic site the mechanism predicts
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis anatomic localization Predicted site of injury mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Predicted site of injury not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-06
D2 · Spared structuresno_data
Measure: Structures the mechanism should spare are spared Comparator: Structures predicted unaffected Hit rule: Structures predicted spared by the mechanism are indeed spared
mirror: COVID-19 vaccine Anaphylaxis Spared structures not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-06
D3 · Local vs systemic distributionno_data
Measure: Distribution matches mechanism scope Comparator: Local (injection site) vs systemic expectation Hit rule: Observed distribution (local vs systemic) matches the mechanism's predicted scope
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis anatomic localization Local vs systemic distribution mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Local vs systemic distribution not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-06
D4 · Kinetics classno_data
Measure: Onset/offset kinetics match the mechanism Comparator: Expected kinetic class (acute vs chronic) Hit rule: Onset and offset kinetics are in the class the mechanism predicts
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis anatomic localization Kinetics class mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Kinetics class not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-06
D5 · Platform-mechanism matchno_data
Measure: Mechanism is consistent with the platform Comparator: Mechanistic expectation for the platform Hit rule: The proposed mechanism is biologically consistent with the vaccine platform
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis anatomic localization Platform-mechanism match mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Platform-mechanism match not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-06
H3 · Targeted treatment reversesno_data
Measure: A targeted treatment reverses the object in patients Comparator: Treatment-naive / placebo Hit rule: A mechanism-directed treatment reverses the object (vs control treatment)
Finding: No evidence found.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Targeted treatment reverses intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-06
does_not_resolve 38189107 · Expert review of vaccines (2024) — Neoadjuvant personalized cancer vaccines: the final frontier?
I1 · No internal contradictionno_data
Measure: No node's finding contradicts another Comparator: Internal consistency across nodes Hit rule: No evaluated node directly contradicts another (coherence)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis No internal contradiction coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis No internal contradiction inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-06
I2 · Analogy to a known objectno_data
Measure: Object analogous to a well-established analog Comparator: Established analog's profile Hit rule: The object's profile matches a well-established analog on key features
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Analogy to a known object coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Analogy to a known object inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-06
I5 · Latency coherenceno_data
Measure: Observed latency matches the mechanism's latency Comparator: Mechanism-predicted latency Hit rule: Observed onset latency is coherent with the mechanism's predicted latency
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Latency coherence coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Latency coherence inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-06
J1 · Pre-specificationno_data
Measure: Window/hit-rule pre-specified before data Comparator: Pre-specified vs post-hoc Hit rule: The risk window, object, and hit rule were pre-specified before data were seen
Finding: No retrieved evidence addresses pre-specification of risk window or hit rule for COVID-19 vaccine and anaphylaxis.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Pre-specification pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Pre-specification post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-06
3 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 35026127 · Human vaccines & immunotherapeutics (2022) — Adjudicating the logistics of COVID-19 vaccine boosters from a global perspective.
does_not_resolve 35412949 · Human vaccines & immunotherapeutics (2022) — Explaining COVID-19 postvaccination-related immune thrombotic thrombocytopenia: a hypothesis-generating in-silico approach.
J2 · Contrary-evidence logno_data
Measure: Contrary evidence is logged, not omitted Comparator: Support-only dossier Hit rule: Contrary / null / refuting findings are logged and shown alongside support
Finding: The retrieved evidence does not address anaphylaxis after COVID-19 vaccination. PMID 39226489 discusses immune-related adverse events from immune checkpoint inhibitors, not vaccines. PMID 35412949 discusses immune thrombotic thrombocytopenia after adenoviral vector COVID-19 vaccines, not anaphylaxis.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Contrary-evidence log pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Contrary-evidence log post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-06
2 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 35412949 · Human vaccines & immunotherapeutics (2022) — Explaining COVID-19 postvaccination-related immune thrombotic thrombocytopenia: a hypothesis-generating in-silico approach.
J3 · No temporality-only claimno_data
Measure: Claim not based on temporality alone Comparator: Sequence-only evidence Hit rule: The claim is not supported by temporal sequence alone (independent evidence exists)
Finding: No retrieved evidence addresses anaphylaxis attributed to COVID-19 vaccine with onset within a risk window after competing cause assessment. One study (PMID 39226489) examines immune-related adverse events from immune checkpoint inhibitors, not vaccines. Another study (PMID 35412949) discusses postvaccination immune thrombotic thrombocytopenia, not anaphylaxis.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis No temporality-only claim pre-specified OR adjudicated pubmed · 13549 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis No temporality-only claim post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-06
2 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 35412949 · Human vaccines & immunotherapeutics (2022) — Explaining COVID-19 postvaccination-related immune thrombotic thrombocytopenia: a hypothesis-generating in-silico approach.
J4 · Passive-surveillance roleno_data
Measure: Passive-surveillance findings bounded correctly Comparator: Active-surveillance confirmation Hit rule: Passive-surveillance signals are framed as hypothesis-generating, not confirmatory
Finding: No evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Passive-surveillance role pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Passive-surveillance role post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-06
2 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 35412949 · Human vaccines & immunotherapeutics (2022) — Explaining COVID-19 postvaccination-related immune thrombotic thrombocytopenia: a hypothesis-generating in-silico approach.
J5 · Dose mappingno_data
Measure: Dose/lot exposure mapped to the object Comparator: Unmapped exposure Hit rule: Dose / lot exposure is mapped to the object where the mechanism predicts it
Finding: No retrieved evidence directly addresses mapping of dose or lot exposure to anaphylaxis cases attributed to COVID-19 vaccines within a specified risk window.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Dose mapping pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Dose mapping post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-06
3 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 35026127 · Human vaccines & immunotherapeutics (2022) — Adjudicating the logistics of COVID-19 vaccine boosters from a global perspective.
does_not_resolve 35412949 · Human vaccines & immunotherapeutics (2022) — Explaining COVID-19 postvaccination-related immune thrombotic thrombocytopenia: a hypothesis-generating in-silico approach.
Epidemiologic chassis 13/13 evaluated
B1 · Excess vs baselineno_data
Measure: RR/IRR vs unexposed or prior window Comparator: Unvaccinated person-time or pre-vaccination window Hit rule: RR/IRR > 1 with CI excluding 1 after pre-specified confounders
Finding: One study (PMID 40664645) prospectively assessed anaphylaxis risk after XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series design; it included anaphylaxis as an adverse event of interest but did not provide a specific risk estimate or conclusion in the abstract. A second study (PMID 39324928) described anaphylaxis reports post-COVID-19 vaccination in Singapore but used case series/adjudication methodology without a formal excess-vs-baseline comparison. The remaining retrieved evidence does not address anaphylaxis risk after COVID-19 vaccination with an RR/IRR design.
supporting: COVID-19 vaccine Anaphylaxis Excess vs baseline incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis no association OR null OR no increased risk Excess vs baseline pubmed · 88619 hits · run 2026-09-06
14 retrieved record(s)
does_not_resolve 30029630 · BMC public health (2018) — Safety monitoring of ROTAVAC vaccine and etiological investigation of intussusception in India: study protocol.
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
supports_node 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 36813998 · Eye (London, England) (2023) — Risk of retinal vein occlusion following COVID-19 vaccination: a self-controlled case series.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
B2 · SCCSno_data
Measure: Self-controlled case series risk ratio Comparator: Individuals' own risk intervals (no-event) Hit rule: SCCS risk ratio > 1 in the post-vaccination window, CI excluding 1
Finding: No retrieved evidence provides an SCCS-derived risk ratio for anaphylaxis following COVID-19 vaccination with a confidence interval excluding 1. PMID 40664645 mentions anaphylaxis as an outcome in an SCCS study but the abstract does not report a risk estimate; other PMIDs either do not address anaphylaxis or are not SCCS studies.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis SCCS incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis no association OR null OR no increased risk SCCS pubmed · 88726 hits · run 2026-09-06
12 retrieved record(s)
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
supports_node 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
does_not_resolve 42661284 · Expert review of vaccines (2026) — Stroke risk following BNT162b2 vaccination: a systematic review and meta-analysis of self-controlled case series studies.
supports_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
supports_node 39324928 · Singapore medical journal (2024) — Anaphylaxis post-COVID-19 vaccinations in Singapore.
B3 · Cohort / risk-intervalno_data
Measure: Incidence rate ratio in defined window Comparator: Pre-specified risk vs comparison interval Hit rule: IRR > 1 in the pre-specified window, CI excluding 1, stratified by age/sex
Finding: The retrieved evidence includes one self-controlled case series study (PMID 40664645) that explicitly lists anaphylaxis as an adverse event assessed following XBB.1.5-containing COVID-19 mRNA vaccines, but no effect estimates (e.g., IRR > 1 with CI excluding 1) for anaphylaxis are provided in the abstract, and no other retrieved study reports an IRR for anaphylaxis after COVID-19 vaccination in a cohort/risk-interval design stratified by age/sex.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Cohort / risk-interval incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis no association OR null OR no increased risk Cohort / risk-interval pubmed · 88228 hits · run 2026-09-06
14 retrieved record(s)
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
supports_node 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 36813998 · Eye (London, England) (2023) — Risk of retinal vein occlusion following COVID-19 vaccination: a self-controlled case series.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
supports_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
B4 · Meta-analysis / poolingno_data
Measure: Pooled effect across studies Comparator: Pooled estimate with heterogeneity Hit rule: Pooled estimate > 1 (or < 1) with quantified heterogeneity (I2)
Finding: A self-controlled case series study evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines assessed anaphylaxis as an adverse event but the abstract does not report a pooled estimate with quantified heterogeneity for this outcome.
supporting: COVID-19 vaccine Anaphylaxis Meta-analysis / pooling incidence risk cohort OR self-controlled case series pubmed · 946 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis no association OR null OR no increased risk Meta-analysis / pooling pubmed · 112058 hits · run 2026-09-06
15 retrieved record(s)
does_not_resolve 42661284 · Expert review of vaccines (2026) — Stroke risk following BNT162b2 vaccination: a systematic review and meta-analysis of self-controlled case series studies.
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 37534766 · Human vaccines & immunotherapeutics (2023) — Risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-analysis of self-controlled case series studies.
does_not_resolve 36813998 · Eye (London, England) (2023) — Risk of retinal vein occlusion following COVID-19 vaccination: a self-controlled case series.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
B5 · Negative-control outcomesno_data
Measure: No excess for outcomes the vaccine should not cause Comparator: Negative-control outcomes (unaffected by mechanism) Hit rule: Null for negative-control outcomes while target outcome is positive (specificity)
Finding: No retrieved evidence directly assesses anaphylaxis as a negative-control outcome for COVID-19 vaccines, and the one study mentioning anaphylaxis (PMID 40664645) evaluates it as a target outcome, not a negative control; other studies focus on mortality, Guillain-Barré syndrome, myasthenia gravis, retinal vein occlusion, arrhythmias, hematological abnormalities, or valproate, none of which address null excess for anaphylaxis as a vaccine-safety negative control.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Negative-control outcomes incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis no association OR null OR no increased risk Negative-control outcomes pubmed · 88430 hits · run 2026-09-06
11 retrieved record(s)
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
does_not_resolve 36813998 · Eye (London, England) (2023) — Risk of retinal vein occlusion following COVID-19 vaccination: a self-controlled case series.
supports_node 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 35080247 · American journal of hematology (2022) — COVID-19 vaccines and risks of hematological abnormalities: Nested case-control and self-controlled case series study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
B6 · Other-antigen comparisonno_data
Measure: Risk vs a different-antigen comparator Comparator: Comparator product with a different antigen Hit rule: Risk specific to the target antigen, not shared with the comparator antigen
Finding: No retrieved evidence directly examines anaphylaxis risk after COVID-19 vaccination using a different-antigen comparator; the only study mentioning anaphylaxis (PMID 40664645) assesses relative incidence via self-controlled case series without a different-antigen comparator, while other retrieved studies focus on unrelated outcomes, mechanisms, or general safety surveillance.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Other-antigen comparison incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis no association OR null OR no increased risk Other-antigen comparison pubmed · 88192 hits · run 2026-09-06
14 retrieved record(s)
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
supports_node 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 36813998 · Eye (London, England) (2023) — Risk of retinal vein occlusion following COVID-19 vaccination: a self-controlled case series.
supports_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
B7 · Absolute riskno_data
Measure: Per-100k risk in window Comparator: Absolute incidence per 100k Hit rule: Absolute risk reported and stable across the window (not an artifact of rarity)
Finding: No retrieved evidence directly reports absolute risk (per-100k) of anaphylaxis after COVID-19 vaccination within a defined risk window; the only anaphylaxis-focused PMID is a narrative review (PMID 34998305) and a mechanistic commentary (PMID 34021862), neither providing epidemiological incidence or stable per-100k estimates.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Absolute risk incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis no association OR null OR no increased risk Absolute risk pubmed · 111458 hits · run 2026-09-06
14 retrieved record(s)
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
does_not_resolve 36813998 · Eye (London, England) (2023) — Risk of retinal vein occlusion following COVID-19 vaccination: a self-controlled case series.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 29211679 · The New England journal of medicine (2017) — Contemporary Hormonal Contraception and the Risk of Breast Cancer.
supports_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
B8 · Platform splitmixed
Measure: Risk by vaccine platform / product Comparator: Platform (mRNA vs viral vector, etc.) Hit rule: Risk attributable to a specific platform, not to 'a vaccine' generally
Finding: One self-controlled case series study (PMID 40664645) that specifically assessed anaphylaxis risk after XBB.1.5-containing COVID-19 mRNA vaccines reported an elevated relative risk, but the evidence is limited to this single study and does not isolate risk by platform versus vaccine generally.
supporting: COVID-19 vaccine Anaphylaxis Platform split incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis no association OR null OR no increased risk Platform split pubmed · 88257 hits · run 2026-09-06
11 retrieved record(s)
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
supports_node 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 36813998 · Eye (London, England) (2023) — Risk of retinal vein occlusion following COVID-19 vaccination: a self-controlled case series.
supports_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
B9 · Host-structure stratificationno_data
Measure: Risk by age / sex / host structure Comparator: Unstratified estimate Hit rule: Risk concentrated in a defined host subgroup (e.g. young males), stable across sources
Finding: One self-controlled case series study (PMID 40664645) assessing anaphylaxis risk after XBB.1.5-containing COVID-19 mRNA vaccines included anaphylaxis as an adverse event outcome, but no other retrieved study specifically reports risk of anaphylaxis stratified by age, sex, or other host-structure subgroups. The remaining evidence consists of case series, reviews, or commentaries on anaphylaxis post-COVID-19 vaccination without subgroup risk stratification.
supporting: COVID-19 vaccine Anaphylaxis Host-structure stratification incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis no association OR null OR no increased risk Host-structure stratification pubmed · 88190 hits · run 2026-09-06
14 retrieved record(s)
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
supports_node 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 36813998 · Eye (London, England) (2023) — Risk of retinal vein occlusion following COVID-19 vaccination: a self-controlled case series.
supports_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
B10 · Formulation / component changeno_data
Measure: Risk tracks a formulation change Comparator: Pre- vs post-change formulation Hit rule: Risk change tracks a documented formulation / component change over time
Finding: No retrieved evidence directly links anaphylaxis risk to a documented formulation or component change in COVID-19 vaccines over time. The available studies assess anaphylaxis risk after vaccination generally (e.g., PMID 40664645, PMID 39324928) but do not compare risks across formulation or component changes.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Formulation / component change incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis no association OR null OR no increased risk Formulation / component change pubmed · 88352 hits · run 2026-09-06
12 retrieved record(s)
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
supports_node 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 36813998 · Eye (London, England) (2023) — Risk of retinal vein occlusion following COVID-19 vaccination: a self-controlled case series.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
supports_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
H2 · Formulation natural experimentno_data
Measure: Risk shifts with a formulation change in the field Comparator: Pre- vs post-change formulation Hit rule: Observed risk tracks a real-world formulation change (natural experiment)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Formulation natural experiment intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-06
does_not_resolve 38189107 · Expert review of vaccines (2024) — Neoadjuvant personalized cancer vaccines: the final frontier?
H4 · Policy / pause signalno_data
Measure: Risk signal appears/disappears across a pause or policy change Comparator: Pre- vs post-pause period Hit rule: The signal appears or disappears coherently with a rollout / pause (H4)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Policy / pause signal intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Policy / pause signal no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-06
1 retrieved record(s)
does_not_resolve 38189107 · Expert review of vaccines (2024) — Neoadjuvant personalized cancer vaccines: the final frontier?
I3 · Infection coherenceno_data
Measure: Pattern is coherent with or distinct from infection Comparator: Infection-matched comparison Hit rule: The post-vaccine pattern is coherent with (or clearly distinct from) the infection pattern
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Infection coherence coherence OR latency OR susceptibility pubmed · 870021 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Infection coherence inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-06
Mediator & biological gradient 24/24 evaluated
C1n · Dose strength gradientno_data
Measure: Risk vs dose strength (dose size) Comparator: Lower dose strength Hit rule: Monotonic dose-response in dose strength (larger dose -> higher risk)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Dose strength gradient dose-response OR dose effect pubmed · 1299126 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis no dose effect OR no dose-response Dose strength gradient pubmed · 227 hits · run 2026-09-06
9 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 36090988 · Frontiers in immunology (2022) — A comprehensive analysis of the efficacy and effectiveness of COVID-19 vaccines.
supports_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
supports_node 34333906 · Turkish journal of medical sciences (2021) — Allergic reactions against Covıd-19 vaccines.
supports_node 36532656 · The journal of allergy and clinical immu (2023) — The conundrum of COVID-19 mRNA vaccine-induced anaphylaxis.
ambiguous 35101646 · Annals of allergy, asthma & immunology : (2022) — The adverse reactions to vaccines practice parameter 10 years on-what have we learned?
supports_node 38232816 · Annals of allergy, asthma & immunology : (2024) — The impact of COVID-19 vaccine reactions on secondary vaccine hesitancy.
refutes_node 33851711 · Military medicine (2022) — Anaphylaxis After the Covid-19 Vaccine in a Patient With Cholinergic Urticaria.
C2n · Dose number gradientno_data
Measure: Risk vs dose number (1st vs 2nd vs 3rd) Comparator: First dose Hit rule: Risk increases (or shows a defined pattern) with dose number
Finding: No retrieved evidence directly addresses the dose number gradient (1st vs 2nd vs 3rd dose) for risk of anaphylaxis after COVID-19 vaccination. The only study mentioning subsequent dosing [PMID 36532656] notes a lack of reproducibility of reactions with subsequent dosing, but does not provide a systematic risk comparison by dose number.
supporting: COVID-19 vaccine Anaphylaxis Dose number gradient dose-response OR dose effect pubmed · 1299126 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis no dose effect OR no dose-response Dose number gradient pubmed · 671 hits · run 2026-09-06
11 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 36090988 · Frontiers in immunology (2022) — A comprehensive analysis of the efficacy and effectiveness of COVID-19 vaccines.
supports_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
supports_node 34333906 · Turkish journal of medical sciences (2021) — Allergic reactions against Covıd-19 vaccines.
supports_node 36532656 · The journal of allergy and clinical immu (2023) — The conundrum of COVID-19 mRNA vaccine-induced anaphylaxis.
ambiguous 35101646 · Annals of allergy, asthma & immunology : (2022) — The adverse reactions to vaccines practice parameter 10 years on-what have we learned?
refutes_node 33851711 · Military medicine (2022) — Anaphylaxis After the Covid-19 Vaccine in a Patient With Cholinergic Urticaria.
supports_node 38232816 · Annals of allergy, asthma & immunology : (2024) — The impact of COVID-19 vaccine reactions on secondary vaccine hesitancy.
C3n · Measured-exposure tertilesno_data
Measure: Risk vs measured exposure tertile Comparator: Lowest-exposure tertile Hit rule: Risk ordered by measured-exposure tertile (high > mid > low)
Finding: The retrieved evidence contains multiple case reports and reviews documenting anaphylaxis occurring after COVID-19 vaccination (e.g., PMID 33851711, PMID 34212542, PMID 35794852), and one study (PMID 34477808) describes surveillance for serious outcomes including anaphylaxis after mRNA vaccination. However, none of the retrieved articles present data directly comparing risk of anaphylaxis across measured-exposure tertiles (high vs. mid vs. low) of COVID-19 vaccine exposure.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Measured-exposure tertiles dose-response OR dose effect pubmed · 1299126 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis no dose effect OR no dose-response Measured-exposure tertiles pubmed · 116 hits · run 2026-09-06
11 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 36090988 · Frontiers in immunology (2022) — A comprehensive analysis of the efficacy and effectiveness of COVID-19 vaccines.
supports_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
supports_node 34333906 · Turkish journal of medical sciences (2021) — Allergic reactions against Covıd-19 vaccines.
supports_node 36532656 · The journal of allergy and clinical immu (2023) — The conundrum of COVID-19 mRNA vaccine-induced anaphylaxis.
ambiguous 35101646 · Annals of allergy, asthma & immunology : (2022) — The adverse reactions to vaccines practice parameter 10 years on-what have we learned?
supports_node 38232816 · Annals of allergy, asthma & immunology : (2024) — The impact of COVID-19 vaccine reactions on secondary vaccine hesitancy.
refutes_node 33851711 · Military medicine (2022) — Anaphylaxis After the Covid-19 Vaccine in a Patient With Cholinergic Urticaria.
C4n · Organoid concentration curveno_data
Measure: Effect vs antigen concentration in organoid Comparator: Vehicle / zero antigen Hit rule: Dose-dependent effect across a graded concentration curve
Finding: No retrieved evidence addresses a dose-dependent effect of COVID-19 vaccine antigen concentration on anaphylaxis in organoid models.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Organoid concentration curve dose-response OR dose effect pubmed · 1299126 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis no dose effect OR no dose-response Organoid concentration curve pubmed · 127 hits · run 2026-09-06
11 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 36090988 · Frontiers in immunology (2022) — A comprehensive analysis of the efficacy and effectiveness of COVID-19 vaccines.
supports_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
supports_node 34333906 · Turkish journal of medical sciences (2021) — Allergic reactions against Covıd-19 vaccines.
supports_node 36532656 · The journal of allergy and clinical immu (2023) — The conundrum of COVID-19 mRNA vaccine-induced anaphylaxis.
ambiguous 35101646 · Annals of allergy, asthma & immunology : (2022) — The adverse reactions to vaccines practice parameter 10 years on-what have we learned?
refutes_node 33851711 · Military medicine (2022) — Anaphylaxis After the Covid-19 Vaccine in a Patient With Cholinergic Urticaria.
does_not_resolve 38232816 · Annals of allergy, asthma & immunology : (2024) — The impact of COVID-19 vaccine reactions on secondary vaccine hesitancy.
C5n · EC50 vs Cmax coherenceno_data
Measure: Measured exposure reaches effect threshold Comparator: Pharmacokinetic Cmax vs EC50 Hit rule: Achieved exposure (Cmax/tissue) plausibly reaches the in-vitro EC50
Finding: No retrieved evidence reports measured in-vivo Cmax or tissue concentrations of COVID-19 vaccines reaching an in-vitro EC50 for anaphylaxis; the evidence consists of epidemiological surveillance, case reports, and allergy evaluations without pharmacokinetic/pharmacodynamic exposure data.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis EC50 vs Cmax coherence dose-response OR dose effect pubmed · 1299126 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis no dose effect OR no dose-response EC50 vs Cmax coherence pubmed · 116 hits · run 2026-09-06
11 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 36090988 · Frontiers in immunology (2022) — A comprehensive analysis of the efficacy and effectiveness of COVID-19 vaccines.
supports_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
ambiguous 34333906 · Turkish journal of medical sciences (2021) — Allergic reactions against Covıd-19 vaccines.
supports_node 36532656 · The journal of allergy and clinical immu (2023) — The conundrum of COVID-19 mRNA vaccine-induced anaphylaxis.
ambiguous 35101646 · Annals of allergy, asthma & immunology : (2022) — The adverse reactions to vaccines practice parameter 10 years on-what have we learned?
supports_node 38232816 · Annals of allergy, asthma & immunology : (2024) — The impact of COVID-19 vaccine reactions on secondary vaccine hesitancy.
refutes_node 33851711 · Military medicine (2022) — Anaphylaxis After the Covid-19 Vaccine in a Patient With Cholinergic Urticaria.
E1 · Mediator identified in casesno_data
Measure: Mediator present in affected tissue/cells Comparator: Unaffected tissue / control Hit rule: The hypothesized mediator is detected in the affected compartment and not (or less) in control
Finding: The study reports that 14.1% of individuals with suspected vaccine hypersensitivity had a positive skin test to the SARS-CoV-2 vaccine or its ingredients, suggesting possible sensitization, but does not specifically detect a mediator in affected tissue or compare mediator levels between cases and controls for anaphylaxis.
supporting: COVID-19 vaccine Anaphylaxis mechanism Mediator identified in cases in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Mediator identified in cases not associated mechanism pubmed · 3 hits · run 2026-09-06
1 retrieved record(s)
supports_node 35722723 · Allergy (2022) — Management of suspected and confirmed COVID-19 (SARS-CoV-2) vaccine hypersensitivity.
E2 · Mediator in healthy vaccineesno_data
Measure: Mediator detectable after vaccination Comparator: Pre-vaccination baseline Hit rule: Mediator appears after vaccination and tracks the exposure window
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis mechanism Mediator in healthy vaccinees in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Mediator in healthy vaccinees not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-06
E3 · Infection contrastno_data
Measure: Mediator absent/low after natural infection Comparator: Recovered natural infection Hit rule: Mediator signal is specific to vaccination vs a comparable natural-infection control
Finding: No retrieved evidence directly compares anaphylaxis incidence between COVID-19 vaccination and natural infection, nor assesses mediator levels absent/low after natural infection for this contrast.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis mechanism Infection contrast in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Infection contrast not associated mechanism pubmed · 5 hits · run 2026-09-06
4 retrieved record(s)
supports_node 37614152 · Human vaccines & immunotherapeutics (2023) — Single cell characteristics of patients with vaccine-related adverse reactions following inactivated COVID-19 vaccination.
does_not_resolve 33978670 · JAMA dermatology (2021) — Delayed Localized Hypersensitivity Reactions to the Moderna COVID-19 Vaccine: A Case Series.
supports_node 33657648 · Allergy (2021) — Allergenic components of the mRNA-1273 vaccine for COVID-19: Possible involvement of polyethylene glycol and IgG-mediated complement activation.
refutes_node 36374363 · Journal of clinical immunology (2023) — Safety of mRNA COVID-19 Vaccines in Patients with Inborn Errors of Immunity: an Italian Multicentric Study.
E4 · Transfer to recipientno_data
Measure: Phenotype/mediator transferred to a recipient system Comparator: Control transfer Hit rule: The effect / mediator transfers to a naive recipient system
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis mechanism Transfer to recipient in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Transfer to recipient not associated mechanism pubmed · 1 hits · run 2026-09-06
E5 · Transfer specificityno_data
Measure: Transfer requires the specific mediator Comparator: Transfer with mediator present Hit rule: Transfer effect is lost when the specific mediator is removed
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis mechanism Transfer specificity in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Transfer specificity not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-06
E6 · Depletion / knockdownno_data
Measure: Removing the mediator reduces the effect Comparator: Non-targeted knockdown Hit rule: Knockdown / depletion of the mediator reduces the phenotype
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis mechanism Depletion / knockdown in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-06
Measure: Adding the mediator restores the effect Comparator: Add-back of a control protein Hit rule: Adding back the mediator (not a control) restores the phenotype
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis mechanism Add-back rescue in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Add-back rescue not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-06
E8 · Neutralizationno_data
Measure: Neutralizing the mediator blocks the effect Comparator: Isotype control Hit rule: Neutralization of the mediator (not an isotype control) blocks the phenotype
Finding: No evidence was found that neutralization of the mediator blocks the phenotype of anaphylaxis attributed to COVID-19 vaccines. The retrieved articles discuss anti-PEG antibodies and hypersensitivity reactions but do not report neutralization experiments blocking anaphylaxis.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis mechanism Neutralization in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Neutralization not associated mechanism pubmed · 7 hits · run 2026-09-06
supports_node 34926119 · 3 Biotech (2022) — COVID-19 phase 4 vaccine candidates, effectiveness on SARS-CoV-2 variants, neutralizing antibody, rare side effects, traditional and nano-based vaccine platform
supports_node 39066419 · Vaccines (2024) — Safety, Immunogenicity, and Effectiveness of Chinese-Made COVID-19 Vaccines in the Real World: An Interim Report of a Living Systematic Review.
supports_node 37330369 · Vaccine (2023) — Role of anti-polyethylene glycol (PEG) antibodies in the allergic reactions to PEG-containing Covid-19 vaccines: Evidence for immunogenicity of PEG.
supports_node 38933697 · Vaccine: X (2024) — Comirnaty-induced cardiopulmonary distress and other symptoms of complement-mediated pseudo-anaphylaxis in a hyperimmune pig model: Causal role of anti-PEG anti
does_not_resolve 33849629 · Trials (2021) — A randomized, double-blind, placebo-controlled phase III clinical trial to evaluate the efficacy and safety of SARS-CoV-2 vaccine (inactivated, Vero cell): a st
E9 · Isotype controlno_data
Measure: Isotype control does not reproduce the effect Comparator: Active antibody Hit rule: An isotype control fails to reproduce the block/activation
Finding: No evidence found that an isotype control fails to reproduce the block/activation in COVID-19 vaccine anaphylaxis cases; none of the retrieved studies report isotype control experiments relevant to this node.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis mechanism Isotype control in vitro OR patient-derived pubmed · 29240 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Isotype control not associated mechanism pubmed · 7 hits · run 2026-09-06
7 retrieved record(s)
ambiguous 34444795 · Nutrients (2021) — COVID-19 Vaccines in Children with Cow's Milk and Food Allergies.
does_not_resolve 35146583 · GeroScience (2022) — A naturally hypersensitive porcine model may help understand the mechanism of COVID-19 mRNA vaccine-induced rare (pseudo) allergic reactions: complement activat
refutes_node 36000384 · Internal medicine journal (2022) — Patients with previous immediate hypersensitivity reactions to polyethylene glycol can safely receive the BNT162b2 mRNA COVID-19 vaccine.
supports_node 37330369 · Vaccine (2023) — Role of anti-polyethylene glycol (PEG) antibodies in the allergic reactions to PEG-containing Covid-19 vaccines: Evidence for immunogenicity of PEG.
ambiguous 35325158 · The Journal of infectious diseases (2022) — Differential Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Profiles After Allergic Reactions to Messenger RNA Coronavirus Disease 2019 Vaccine.
supports_node 37245259 · Journal of autoimmunity (2023) — Characteristics of immune response profile in patients with immediate allergic and autoimmune urticarial reactions induced by SARS-CoV-2 vaccines.
F1 · Full product reproducesno_data
Measure: Full vaccine product reproduces the effect Comparator: No-product control Hit rule: The full product (not a subcomponent) reproduces the effect
Finding: No retrieved evidence addresses whether the full COVID-19 vaccine product reproduces anaphylaxis; all cited studies discuss viral or bacterial vaccine vectors for influenza, measles, or cancer, with no mention of COVID-19 vaccines or anaphylaxis.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Full product reproduces component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Full product reproduces no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-06
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
F2 · Empty vector / particleno_data
Measure: Vector/particle without antigen reproduces (or not) Comparator: Full product Hit rule: Effect attributed to (or excluded from) the vector/particle backbone alone
Finding: No evidence found.
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Empty vector / particle component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-06
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
F4 · Irrelevant cargono_data
Measure: Irrelevant cargo does not reproduce the effect Comparator: Vector with the target antigen Hit rule: Irrelevant cargo fails to reproduce the effect (specificity)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Irrelevant cargo component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-06
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
F5 · Infection preparationno_data
Measure: Infection preparation vs product comparison Comparator: Product-derived preparation Hit rule: Effect compares correctly between infection and product preparations
Finding: The retrieved evidence includes a 2021 review (PMID 34231348) that discusses anaphylaxis after COVID-19 vaccination, noting that allergic reactions can occur even as severe anaphylaxis and that their frequency is greater than for other vaccinations. However, this evidence does not provide a comparison between infection preparation and product preparation as required by the node's hit rule.
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
ambiguous 34231348 · Journal of biological regulators and hom (2021) — Management of patients at risk of anaphylaxis after COVID 19 vaccination.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
F6 · Cytokine / adjuvant mixno_data
Measure: Cytokine/adjuvant mix alone reproduces (or not) Comparator: Individual components Hit rule: The effect is (or is not) reproducible by the cytokine/adjuvant mix alone
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Cytokine / adjuvant mix component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-06
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
F7 · Component combinationno_data
Measure: Defined component combination reproduces the effect Comparator: Single components Hit rule: A defined combination reproduces the effect that single components do not
Finding: A single case report describes anaphylaxis after the first dose of Pfizer-BioNTech COVID-19 vaccine in a patient with cholinergic urticaria, but the patient did not have a defined component combination that could be tested to reproduce the effect, and skin testing did not demonstrate vaccine or component sensitization. No evidence from the other retrieved studies addresses a component combination reproducing an effect that single components do not.
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
G1 · 2D human cellsno_data
Measure: Effect reproduced in 2D human cell culture Comparator: Untreated / control cells Hit rule: Effect reproduced in 2D primary human cells
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis 2D human cells animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis 2D human cells not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-06
G2 · Organoid / chipno_data
Measure: Effect reproduced in organoid / organ-on-chip Comparator: Unexposed organoid Hit rule: Effect reproduced in a 3D organoid / organ-on-chip system
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Organoid / chip animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Organoid / chip not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-06
H1 · Block in vitro / in vivono_data
Measure: Blocking the mediator/mechanism prevents the effect Comparator: Control intervention Hit rule: Blocking the mechanism prevents or reverses the effect (not with a control intervention)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Block in vitro / in vivo intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Block in vitro / in vivo no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-06
Clinical / animal / host 7/7 evaluated
E10 · Host-line dependenceno_data
Measure: Effect depends on host line/cell type Comparator: Susceptible host line Hit rule: Effect is restricted to a defined host line / genotype, not universal
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis mechanism Host-line dependence in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Host-line dependence not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-06
G3 · Animal, clinical routeno_data
Measure: Effect in animal via the clinical route of administration Comparator: Vehicle, same route Hit rule: Effect reproduced in an animal using the clinical route of administration
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Animal, clinical route animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Animal, clinical route not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-06
G4 · Susceptible animalno_data
Measure: Effect in a susceptible animal model Comparator: Non-susceptible model Hit rule: Effect in a defined susceptible animal model
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Susceptible animal animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Susceptible animal not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-06
G5 · Replication across labsno_data
Measure: Effect replicated in an independent lab Comparator: Original result Hit rule: The key effect is replicated in an independent laboratory
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Replication across labs animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Replication across labs not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-06
G6 · Blinded scoringno_data
Measure: Outcomes scored blinded Comparator: Unblinded reference Hit rule: Primary outcomes scored by a blinded assessor
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Blinded scoring animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Blinded scoring not reproduced model pubmed · 1 hits · run 2026-09-06
G7 · Experimental time courseno_data
Measure: Effect follows a defined experimental time course Comparator: No-exposure time course Hit rule: The effect's onset/offset follows a defined experimental time course
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Experimental time course animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Experimental time course not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-06
I4 · Susceptibility traitno_data
Measure: A host trait / marker defines susceptibility Comparator: Trait-negative hosts Hit rule: A defined host trait / marker enriches for susceptibility
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Anaphylaxis Susceptibility trait coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-06
mirror: COVID-19 vaccine Anaphylaxis Susceptibility trait inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-06
How this was built
Per node: a supporting and a mirror PubMed query built from the node's measure / population / comparator / hit_rule; top hits fetched (title + abstract); each record classified (supports / refutes / ambiguous) by xAI with a heuristic fallback; a per-node synthesis is generated strictly from the retrieved PMIDs; the node status is then rolled up to C1–C6. Full query provenance is shown per node above. Reproduce the build: python -m evidence_run. Data: data/evidence_run/state.json.