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The Journal of Allergy and Clinical... May 2022Previous reports suggested that food proteins present in human milk (HM) may trigger symptoms in allergic children during breastfeeding, but existing evidence has never...
BACKGROUND
Previous reports suggested that food proteins present in human milk (HM) may trigger symptoms in allergic children during breastfeeding, but existing evidence has never been reviewed systematically.
OBJECTIVE
To assess the probability of food proteins in HM to trigger allergic reactions in infants with IgE-mediated food allergy.
METHODS
Electronic bibliographic databases (MEDLINE, EMBASE) were systematically searched from inception to November 3, 2021. The data regarding the levels of food proteins detected in HM were extracted and compared with data from the Voluntary Incidental Trace Allergen Labelling (VITAL 3.0) guide to assess the probability of food-allergic individuals to experience immediate type allergic reactions on ingesting HM.
RESULTS
A total of 32 studies were identified. Fourteen studies assessed excretion of cow's milk proteins into HM, 9 egg, 4 peanut, and 2 wheat; 3 measured levels of cow's milk and egg proteins simultaneously. We found that levels of all food proteins across the studies were much lower than the eliciting dose for 1% of allergic individuals (ED01) in most of the samples. The probability of an IgE-mediated allergic reaction in a food-allergic infant breastfed by a woman consuming the relevant food can be estimated as ≤1:1000 for cow's milk, egg, peanut, and wheat.
CONCLUSIONS
To our knowledge, this is the first systematic review that assesses and summarizes evidence on food proteins in HM and potential for IgE-mediated allergic reactions. Our data suggest that the probability of IgE-mediated allergic reactions to food proteins in HM is low.
Topics: Allergens; Animals; Arachis; Breast Feeding; Cattle; Female; Food Hypersensitivity; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Infant; Milk Hypersensitivity; Milk Proteins; Milk, Human; Probability
PubMed: 35123103
DOI: 10.1016/j.jaip.2022.01.028 -
The Journal of Allergy and Clinical... Apr 2020Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need... (Meta-Analysis)
Meta-Analysis
Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need for repeated doses of epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis. Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy. Evidence is lacking to support the role of antihistamines and/or glucocorticoid routine premedication in patients receiving low- or iso-osmolar contrast material to prevent recurrent radiocontrast media anaphylaxis. Epinephrine is the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis. After diagnosis and treatment of anaphylaxis, all patients should be kept under observation until symptoms have fully resolved. All patients with anaphylaxis should receive education on anaphylaxis and risk of recurrence, trigger avoidance, self-injectable epinephrine education, referral to an allergist, and be educated about thresholds for further care.
Topics: Anaphylaxis; Desensitization, Immunologic; Epinephrine; Evidence-Based Medicine; Glucocorticoids; Histamine Antagonists; Humans; Hypersensitivity; Practice Guidelines as Topic; Risk Factors
PubMed: 32001253
DOI: 10.1016/j.jaci.2020.01.017 -
European Respiratory Review : An... Dec 2023We aim to assess the impact of montelukast on paediatric patients with asthma/allergic rhinitis, measured using patient-reported outcome measures, compared with other... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We aim to assess the impact of montelukast on paediatric patients with asthma/allergic rhinitis, measured using patient-reported outcome measures, compared with other treatments or placebo.
METHODS
Protocol registration CRD42020216098 (www.crd.york.ac.uk/PROSPERO). MEDLINE and Embase databases were used to conduct the search. Two authors independently selected studies and extracted data, and a third reviewer resolved discrepancies. Meta-analyses were constructed to estimate the standardised mean difference (SMD) using a random-effects model.
RESULTS
Out of 3937 articles identified, 49 studies met the inclusion criteria, mostly randomised clinical trials (sample sizes: 21-689 patients). The SMD of change pooled estimators for the global, mental and physical domains of health-related quality of life were not statistically significant. For daytime and night-time symptoms scores, the SMD (95% CI) was in favour of inhaled corticosteroids (-0.12, -0.20- -0.05 and -0.23, -0.41- -0.06, respectively). The pooled estimator for global asthma symptoms was better for montelukast when compared with placebo (0.90, 0.44-1.36).
CONCLUSIONS
The synthesis of the available evidence suggests that, in children and adolescents, montelukast was effective in controlling asthma symptoms when compared with placebo, but inhaled corticosteroids were superior in controlling symptoms, especially at night-time. These findings of our systematic review concur with current guidelines for asthma treatment.
Topics: Adolescent; Humans; Child; Quality of Life; Asthma; Rhinitis, Allergic; Adrenal Cortex Hormones
PubMed: 37852659
DOI: 10.1183/16000617.0124-2023 -
The American Journal of Clinical... Mar 2019Nutrition during infancy and toddlerhood may influence health and disease prevention across the life span. Complementary feeding (CF) starts when human milk or infant...
BACKGROUND
Nutrition during infancy and toddlerhood may influence health and disease prevention across the life span. Complementary feeding (CF) starts when human milk or infant formula is complemented by other foods and beverages, beginning during infancy and continuing to age 24 mo.
OBJECTIVES
The aim of this study was to describe systematic reviews conducted for the USDA and the Department of Health and Human Services Pregnancy and Birth to 24 Months Project to answer the following question: What is the relationship between the timing of the introduction of complementary foods and beverages (CFBs), or types and amounts of CFBs consumed, and the development of food allergy, atopic dermatitis/eczema, asthma, and allergic rhinitis?
METHODS
The literature was searched using 4 databases (CINAHL, Cochrane, Embase, PubMed) to identify articles published from January 1980 to February 2017 that met predetermined inclusion criteria. For each study, data were extracted and risk of bias was assessed. The evidence was qualitatively synthesized to develop a conclusion statement, and the strength of the evidence was graded.
RESULTS
Thirty-one included articles addressed the timing of CFB introduction, and 47 articles addressed the types and amounts of CFBs consumed.
CONCLUSIONS
Moderate evidence suggests that there is no relationship between the age at which CF first begins and the risk of developing food allergy, atopic dermatitis/eczema, or childhood asthma. Limited to strong evidence, depending on the specific food, suggests that introducing allergenic foods in the first year of life (after 4 mo) does not increase the risk of food allergy and atopic dermatitis/eczema but may prevent peanut and egg allergy. There is not enough evidence to determine a relationship between diet diversity or dietary patterns and atopic disease. Research is needed to address gaps and limitations in the evidence on CF and atopic disease, including research that uses valid and reliable diagnostic measures and accounts for key confounders and potential reverse causality.
Topics: Asthma; Breast Feeding; Dermatitis, Atopic; Diet; Eczema; Feeding Behavior; Food Hypersensitivity; Humans; Hypersensitivity, Immediate; Infant; Infant Food; Infant Nutritional Physiological Phenomena; Rhinitis, Allergic
PubMed: 30982864
DOI: 10.1093/ajcn/nqy220 -
PLoS Medicine Feb 2018There is uncertainty about the influence of diet during pregnancy and infancy on a child's immune development. We assessed whether variations in maternal or infant diet... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is uncertainty about the influence of diet during pregnancy and infancy on a child's immune development. We assessed whether variations in maternal or infant diet can influence risk of allergic or autoimmune disease.
METHODS AND FINDINGS
Two authors selected studies, extracted data, and assessed risk of bias. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess certainty of findings. We searched Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), Web of Science, Central Register of Controlled Trials (CENTRAL), and Literatura Latino Americana em Ciências da Saúde (LILACS) between January 1946 and July 2013 for observational studies and until December 2017 for intervention studies that evaluated the relationship between diet during pregnancy, lactation, or the first year of life and future risk of allergic or autoimmune disease. We identified 260 original studies (964,143 participants) of milk feeding, including 1 intervention trial of breastfeeding promotion, and 173 original studies (542,672 participants) of other maternal or infant dietary exposures, including 80 trials of maternal (n = 26), infant (n = 32), or combined (n = 22) interventions. Risk of bias was high in 125 (48%) milk feeding studies and 44 (25%) studies of other dietary exposures. Evidence from 19 intervention trials suggests that oral supplementation with nonpathogenic micro-organisms (probiotics) during late pregnancy and lactation may reduce risk of eczema (Risk Ratio [RR] 0.78; 95% CI 0.68-0.90; I2 = 61%; Absolute Risk Reduction 44 cases per 1,000; 95% CI 20-64), and 6 trials suggest that fish oil supplementation during pregnancy and lactation may reduce risk of allergic sensitisation to egg (RR 0.69, 95% CI 0.53-0.90; I2 = 15%; Absolute Risk Reduction 31 cases per 1,000; 95% CI 10-47). GRADE certainty of these findings was moderate. We found weaker support for the hypotheses that breastfeeding promotion reduces risk of eczema during infancy (1 intervention trial), that longer exclusive breastfeeding is associated with reduced type 1 diabetes mellitus (28 observational studies), and that probiotics reduce risk of allergic sensitisation to cow's milk (9 intervention trials), where GRADE certainty of findings was low. We did not find that other dietary exposures-including prebiotic supplements, maternal allergenic food avoidance, and vitamin, mineral, fruit, and vegetable intake-influence risk of allergic or autoimmune disease. For many dietary exposures, data were inconclusive or inconsistent, such that we were unable to exclude the possibility of important beneficial or harmful effects. In this comprehensive systematic review, we were not able to include more recent observational studies or verify data via direct contact with authors, and we did not evaluate measures of food diversity during infancy.
CONCLUSIONS
Our findings support a relationship between maternal diet and risk of immune-mediated diseases in the child. Maternal probiotic and fish oil supplementation may reduce risk of eczema and allergic sensitisation to food, respectively.
Topics: Autoimmune Diseases; Diet; Female; Humans; Hypersensitivity; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Maternal Nutritional Physiological Phenomena; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors
PubMed: 29489823
DOI: 10.1371/journal.pmed.1002507 -
The American Journal of Clinical... Mar 2019During the Pregnancy and Birth to 24 Months Project, the USDA and Department of Health and Human Services initiated a review of evidence on diet and health in these...
BACKGROUND
During the Pregnancy and Birth to 24 Months Project, the USDA and Department of Health and Human Services initiated a review of evidence on diet and health in these populations.
OBJECTIVES
The aim of these systematic reviews was to examine the relation of 1) never versus ever feeding human milk, 2) shorter versus longer durations of any human milk feeding, 3) shorter versus longer durations of exclusive human milk feeding prior to infant formula introduction, 4) feeding a lower versus higher intensity of human milk to mixed-fed infants, and 5) feeding a higher intensity of human milk by bottle versus breast with food allergies, allergic rhinitis, atopic dermatitis, and asthma.
METHODS
The Nutrition Evidence Systematic Review team conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published between January 1980 and March 2016, dual-screened the results according to predetermined criteria, extracted data from and assessed the risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence.
RESULTS
The systematic reviews numbered 1-5 above included 44, 35, 1, 0, and 0 articles, respectively. Moderate, mostly observational, evidence suggests that 1) never versus ever being fed human milk is associated with higher risk of childhood asthma, and 2) among children and adolescents who were fed human milk as infants, shorter versus longer durations of any human milk feeding are associated with higher risk of asthma. Limited evidence does not suggest associations between 1) never versus ever being fed human milk and atopic dermatitis in childhood or 2) the duration of any human milk feeding and allergic rhinitis and atopic dermatitis in childhood.
CONCLUSIONS
Moderate evidence suggests that feeding human milk for short durations or not at all is associated with higher childhood asthma risk. Evidence on food allergies, allergic rhinitis, and atopic dermatitis is limited.
Topics: Adolescent; Asthma; Breast Feeding; Child; Dermatitis, Atopic; Diet; Feeding Behavior; Food Hypersensitivity; Humans; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Infant, Newborn; Milk, Human; Rhinitis, Allergic
PubMed: 30982870
DOI: 10.1093/ajcn/nqy283 -
The Journal of Allergy and Clinical... Jan 2023Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear.
OBJECTIVE
We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD.
METHODS
As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence.
RESULTS
Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings.
CONCLUSIONS
SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.
Topics: Adult; Animals; Humans; Child; Dermatitis, Atopic; Quality of Life; Bayes Theorem; Desensitization, Immunologic; Pyroglyphidae; Hypersensitivity; Asthma; Allergens; Sublingual Immunotherapy; Dermatophagoides pteronyssinus; Eczema
PubMed: 36191689
DOI: 10.1016/j.jaci.2022.09.020 -
JAMA Pediatrics May 2023Earlier egg and peanut introduction probably reduces risk of egg and peanut allergy, respectively, but it is uncertain whether food allergy as a whole can be prevented... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Earlier egg and peanut introduction probably reduces risk of egg and peanut allergy, respectively, but it is uncertain whether food allergy as a whole can be prevented using earlier allergenic food introduction.
OBJECTIVE
To investigate associations between timing of allergenic food introduction to the infant diet and risk of food allergy.
DATA SOURCES
In this systematic review and meta-analysis, Medline, Embase, and CENTRAL databases were searched for articles from database inception to December 29, 2022. Search terms included infant, randomized controlled trial, and terms for common allergenic foods and allergic outcomes.
STUDY SELECTION
Randomized clinical trials evaluating age at allergenic food introduction (milk, egg, fish, shellfish, tree nuts, wheat, peanuts, and soya) during infancy and immunoglobulin E (IgE)-mediated food allergy from 1 to 5 years of age were included. Screening was conducted independently by multiple authors.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used. Data were extracted in duplicate and synthesized using a random-effects model. The Grading of Recommendations, Assessment, Development, and Evaluation framework was used to assess certainty of evidence.
MAIN OUTCOMES AND MEASURES
Primary outcomes were risk of IgE-mediated allergy to any food from 1 to 5 years of age and withdrawal from the intervention. Secondary outcomes included allergy to specific foods.
RESULTS
Of 9283 titles screened, data were extracted from 23 eligible trials (56 articles, 13 794 randomized participants). There was moderate-certainty evidence from 4 trials (3295 participants) that introduction of multiple allergenic foods from 2 to 12 months of age (median age, 3-4 months) was associated with reduced risk of food allergy (risk ratio [RR], 0.49; 95% CI, 0.33-0.74; I2 = 49%). Absolute risk difference for a population with 5% incidence of food allergy was -26 cases (95% CI, -34 to -13 cases) per 1000 population. There was moderate-certainty evidence from 5 trials (4703 participants) that introduction of multiple allergenic foods from 2 to 12 months of age was associated with increased withdrawal from the intervention (RR, 2.29; 95% CI, 1.45-3.63; I2 = 89%). Absolute risk difference for a population with 20% withdrawal from the intervention was 258 cases (95% CI, 90-526 cases) per 1000 population. There was high-certainty evidence from 9 trials (4811 participants) that introduction of egg from 3 to 6 months of age was associated with reduced risk of egg allergy (RR, 0.60; 95% CI, 0.46-0.77; I2 = 0%) and high-certainty evidence from 4 trials (3796 participants) that introduction of peanut from 3 to 10 months of age was associated with reduced risk of peanut allergy (RR, 0.31; 95% CI, 0.19-0.51; I2 = 21%). Evidence for timing of introduction of cow's milk and risk of cow's milk allergy was very low certainty.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, earlier introduction of multiple allergenic foods in the first year of life was associated with lower risk of developing food allergy but a high rate of withdrawal from the intervention. Further work is needed to develop allergenic food interventions that are safe and acceptable for infants and their families.
Topics: Female; Animals; Cattle; Humans; Peanut Hypersensitivity; Food Hypersensitivity; Milk Hypersensitivity; Egg Hypersensitivity; Milk; Allergens; Arachis
PubMed: 36972063
DOI: 10.1001/jamapediatrics.2023.0142 -
Allergy May 2021This systematic review used the GRADE approach to compile evidence to inform the European Academy of Allergy and Clinical Immunology's (EAACI) anaphylaxis guideline.
BACKGROUND
This systematic review used the GRADE approach to compile evidence to inform the European Academy of Allergy and Clinical Immunology's (EAACI) anaphylaxis guideline.
METHODS
We searched five bibliographic databases from 1946 to 20 April 2020 for studies about the diagnosis, management and prevention of anaphylaxis. We included 50 studies with 18 449 participants: 29 randomized controlled trials, seven controlled clinical trials, seven consecutive case series and seven case-control studies. Findings were summarized narratively because studies were too heterogeneous to conduct meta-analysis.
RESULTS
It is unclear whether the NIAID/FAAN criteria or Brighton case definition are valid for immediately diagnosing anaphylaxis due to the very low certainty of evidence. There was also insufficient evidence about the impact of most anaphylaxis management and prevention strategies. Adrenaline is regularly used for first-line emergency management of anaphylaxis but little robust research has assessed its effectiveness. Newer models of adrenaline autoinjectors may slightly increase the proportion of people correctly using the devices and reduce time to administration. Face-to-face training for laypeople may slightly improve anaphylaxis knowledge and competence in using autoinjectors. We searched for but found little or no comparative effectiveness evidence about strategies such as fluid replacement, oxygen, glucocorticosteroids, methylxanthines, bronchodilators, management plans, food labels, drug labels and similar.
CONCLUSIONS
Anaphylaxis is a potentially life-threatening condition but, due to practical and ethical challenges, there is a paucity of robust evidence about how to diagnose and manage it.
Topics: Anaphylaxis; Bronchodilator Agents; Case-Control Studies; Epinephrine; Humans; Pharmaceutical Preparations
PubMed: 32880997
DOI: 10.1111/all.14580 -
JAMA Internal Medicine Apr 2022Vaccination against SARS-CoV-2 is a highly effective strategy to prevent infection and severe COVID-19 outcomes. The best strategy for a second dose of vaccine among... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Vaccination against SARS-CoV-2 is a highly effective strategy to prevent infection and severe COVID-19 outcomes. The best strategy for a second dose of vaccine among persons who had an immediate allergic reaction to their first SARS CoV-2 vaccination is unclear.
OBJECTIVE
To assess the risk of severe immediate allergic reactions (eg, anaphylaxis) to a second dose of SARS-CoV-2 mRNA vaccine among persons with immediate allergic reactions to their first vaccine dose.
DATA SOURCES
MEDLINE, Embase, Web of Science, and the World Health Organization Global Coronavirus database were searched from inception through October 4, 2021.
STUDY SELECTION
Included studies addressed immediate allergic reactions of any severity to a second SARS-CoV-2 vaccine dose in persons with a known or suspected immediate allergic reaction (<4 hours after vaccination) after their first SARS-CoV-2 vaccine dose. Studies describing a second vaccine dose among persons reporting delayed reactions (>4 hours after vaccination) were excluded.
DATA EXTRACTION AND SYNTHESIS
Paired reviewers independently selected studies, extracted data, and assessed risk of bias. Random-effects models were used for meta-analysis. The GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach evaluated certainty of the evidence.
MAIN OUTCOMES AND MEASURES
Risk of severe immediate allergic reaction and repeated severe immediate allergic reactions with a second vaccine dose. Reaction severity was defined by the reporting investigator, using Brighton Collaboration Criteria, Ring and Messmer criteria, World Allergy Organization criteria, or National Institute of Allergy and Infectious Diseases criteria.
RESULTS
Among 22 studies of SARS-CoV-2 mRNA vaccines, 1366 individuals (87.8% women; mean age, 46.1 years) had immediate allergic reactions to their first vaccination. Analysis using the pooled random-effects model found that 6 patients developed severe immediate allergic reactions after their second vaccination (absolute risk, 0.16% [95% CI, 0.01%-2.94%]), 232 developed mild symptoms (13.65% [95% CI, 7.76%-22.9%]), and, conversely, 1360 tolerated the dose (99.84% [95% CI, 97.09%-99.99%]). Among 78 persons with severe immediate allergic reactions to their first SARS-CoV-2 mRNA vaccination, 4 people (4.94% [95% CI, 0.93%-22.28%]) had a second severe immediate reaction, and 15 had nonsevere symptoms (9.54% [95% CI, 2.18%-33.34%]). There were no deaths. Graded vaccine dosing, skin testing, and premedication as risk-stratification strategies did not alter the findings. Certainty of evidence was moderate for those with any allergic reaction to the first dose and low for those with severe allergic reactions to the first dose.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis of case studies and case reports, the risk of immediate allergic reactions and severe immediate reactions or anaphylaxis associated with a second dose of an SARS-CoV-2 mRNA vaccine was low among persons who experienced an immediate allergic reaction to their first dose. These findings suggest that revaccination of individuals with an immediate allergic reaction to a first SARS-CoV-2 mRNA vaccine dose in a supervised setting equipped to manage severe allergic reactions can be safe.
Topics: Anaphylaxis; COVID-19; COVID-19 Vaccines; Female; Humans; Male; Middle Aged; SARS-CoV-2; Vaccines, Synthetic; mRNA Vaccines
PubMed: 35188528
DOI: 10.1001/jamainternmed.2021.8515