Safety Evaluation of 2nd Dose of mRNA COVID Vaccines in Patients With Immediate Reactions to 1st

 Matthew S. Krantz, MD¹; Jason H. Kwah, MD, MSCI²; Cosby A. Stone Jr, MD, MPH¹; et al

doi:10.1001/jamainternmed.2021.3779

PDF: https://scholar.google.com/scholar_url?url=https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/2782348/jamainternal_krantz_2021_ld_210043_1626713885.93287.pdf&hl=en&sa=T&oi=ucasa&ct=ufr&ei=uhsGYadkyqCZAYvjpoAD&scisig=AAGBfm1OhwAClDcB5-d4b1VOt864JV35SQ

Allergic reactions after messenger RNA (mRNA) COVID-19 vaccines have been reported to be as high as 2%, with anaphylaxis occurring in up to 2.5 per 10 000 individuals.¹ There is uncertainty as to whether to administer a second dose of mRNA COVID-19 vaccine after a first-dose reaction.^2,3 In this study, we examine the safety of the second dose of Pfizer-BioNTech or Moderna vaccine in those with a history of immediate and potentially allergic reactions to the first dose.

Methods

This multicenter, retrospective study conducted by Massachusetts General Hospital (Boston), Brigham and Women’s Hospital (Boston, Massachusetts), Vanderbilt University Medical Center (Nashville, Tennessee), Yale School of Medicine (New Haven, Connecticut), and University of Texas Southwestern Medical Center (Dallas) from January 1, 2021, to March 31, 2021, included patients with an immediate allergic reaction to the Pfizer-BioNTech or Moderna vaccine, which was defined as: (1) symptom onset within 4 hours of dose 1, (2) at least 1 allergic symptom, and (3) referral for an allergy/immunology consultation with in-clinic or telehealth assessment (eMethods in the Supplement). Anaphylaxis was scored using the Brighton and the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network criteria.^4,5 Confirmed anaphylaxis required meeting at least 1 of these 2 criteria.

The primary outcome was second dose tolerance, which was defined as either: (1) no immediate symptoms after second dose administration or (2) symptoms that were mild, self-limited, and/or resolved with antihistamines alone. For any individuals who did not have their second dose observed by allergy/immunology departments, phone calls elicited clinical details. This study was approved by the Mass General Brigham human research committee with waiver of informed consent.

Results

There were 189 patients who participated in this study (mean [SD] age, 43 (14) years; 163 women [86%]) (Table). Of the mRNA COVID-19 vaccine first-dose reactions evaluated, 130 (69%) were to Moderna and 59 (31%) to Pfizer-BioNTech. The most frequently reported first-dose reactions were flushing or erythema (53 [28%]), dizziness or lightheadedness (49 [26%]), tingling (46 [24%]), throat tightness (41 [22%]), hives (39 [21%]), and wheezing or shortness of breath (39 [21%]). Thirty-two (17%) met anaphylaxis criteria.

A total of 159 patients (84%) received a second dose. Antihistamine premedication before the second dose was given in 47 patients (30%). All 159 patients, including 19 individuals with first-dose anaphylaxis, tolerated the second dose. Thirty-two (20%) reported immediate and potentially allergic symptoms that were associated with the second dose that were self-limited, mild, and/or resolved with antihistamines alone.

Discussion

This multisite US study supports the safety of Pfizer-BioNTech or Moderna vaccine second dose administration in patients who report immediate and potentially allergic reactions after the first dose. Although mild symptoms were reported in 20% of patients with second dose administration, all patients who received a second dose safely completed their vaccination series and could use mRNA COVID-19 vaccines in the future when indicated. Second dose tolerance following reactions to the first dose argues that either many of these initial reactions are not all truly allergic reactions, or supports an allergic, but non–immunoglobulin E–mediated mechanism in which symptoms can typically be abated with premedications.⁶

Because the Janssen vaccine received emergency use authorization, the US Centers for Disease Control and Prevention recommended that individuals with an immediate and potentially allergic reaction to the first dose of the Pfizer-BioNTech or Moderna mRNA COVID-19 vaccine could receive a Janssen single dose subsequently.² However, our data suggest that most patients with immediate and potentially allergic reactions to mRNA COVID-19 vaccines tolerate a second dose. Therefore, it may not be necessary to consider this, to our knowledge, largely unstudied alternative mixed series approach. Although earlier work provided a shared framework for the clinical approach,³ our pooled study was limited by its retrospective study design, referral bias, and lack of a shared evaluation protocol among participating institutions.

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2782348

COVID-19 Vaccine Safety in Adolescents 12–17 Years — US, Dec 14, 2020–July 16, 2021

 Anne M. Hause, PhD1; Julianne Gee, MPH1; James Baggs, PhD1; Winston E. Abara, MD1; Paige Marquez, MSPH1; Deborah Thompson, MD2; John R. Su, MD, PhD1; Charles Licata, PhD1; Hannah G. Rosenblum, MD1,3; Tanya R. Myers, PhD1; Tom T. Shimabukuro, MD1; David K. Shay, MD

DOI:

http://dx.doi.org/10.15585/mmwr.mm7031e1external icon

PDF: https://www.cdc.gov/mmwr/volumes/70/wr/pdfs/mm7031e1-H.pdf

Summary

What is already known about this topic?

In preauthorization trials of the Pfizer-BioNTech COVID-19 vaccine, adolescents aged 12–17 years reported local and systemic mild and moderate reactions. Myocarditis has been observed after vaccination with mRNA vaccines in postauthorization monitoring.

What is added by this report?

Local and systemic reactions after vaccination with Pfizer-BioNTech vaccine were commonly reported by adolescents aged 12–17 years to U.S. vaccine safety monitoring systems, especially after dose 2. A small proportion of these reactions are consistent with myocarditis.

What are the implications for public health practice?

Mild local and systemic reactions are common among adolescents following Pfizer-BioNTech vaccine, and serious adverse events are rare. The Advisory Committee on Immunization Practices conducted a risk-benefit assessment and continues to recommend the Pfizer-BioNTech COVID-19 vaccine for all persons aged ≥12 years.

https://www.cdc.gov/mmwr/volumes/70/wr/mm7031e1.htm

Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine-breakthrough infections

  

View ORCID ProfilePo Ying Chia,  View ORCID ProfileSean Ong, Calvin J Chiew, Li Wei Ang, Jean-marc Gilbert Chavatte, Tze Minn Mak, Lin Cui, Shirin Kalimuddin, Wan Ni Chia, Chee Wah Tan, Louis Yi Ann Chai, Seow Yen Tan, Shuwei Zheng, Raymong Tzer Pin Lin, Linfa Wang, Yee-Sin Leo, Vernon J Lee, David .Chien Lye, Barnaby Edward Young

doi: https://doi.org/10.1101/2021.07.28.21261295

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.07.28.21261295v1.full.pdf

Abstract

Objectives Highly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns (VOCs) with mutations in the spike protein are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections. Methods We conducted a multi-centre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared the clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals. Results Of 218 individuals with B.1.617.2 infection, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). PCR cycle threshold (Ct) values were similar between both vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients, however, these titers were significantly lower against B.1.617.2 as compared with the wildtype vaccine strain. Conclusion The mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of COVID-19 pandemic.

Competing Interest Statement

BEY reports personal fees from Roche and Sanofi, outside the submitted work. All other authors declare no competing interests.

Funding Statement

This study was funded by grants from the Singapore National Medical Research Council (COVID19RF-001, COVID19RF-008). The funders had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

https://www.medrxiv.org/content/10.1101/2021.07.28.21261295v1

Interferon-inducer antivirals: Potential candidates to combat COVID-19

 Ashkan Bagheri a,b,c,d,1 , Seyed Mohammad Iman Moezzi a,b,c,d,1 , Pouria Mosaddeghi a,b,c,d , Sadra Nadimi Parashkouhi a,b,c,d , Seyed Mostafa Fazel Hoseini a,b,c,d , Fatemeh Badakhshan a,b,c,d , Manica Negahdaripour a,b,*

ABSTRACT 

Coronavirus disease 2019 (COVID-19) is an infective disease generated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the pandemic urgency and lack of an effective cure for this disease, drug repurposing could open the way for finding a solution. Lots of investigations are ongoing to test the compounds already identified as antivirals. On the other hand, induction of type I interferons are found to play an important role in the generation of immune responses against SARS-CoV-2. Therefore, it was opined that the antivirals capable of triggering the interferons and their signaling pathway, could rationally be beneficial for treating COVID-19. On this basis, using a database of antivirals, called drugvirus, some antiviral agents were derived, followed by searches on their relevance to interferon induction. The examined list included drugs from different categories such as antibiotics, immunosuppressants, anti-cancers, non-steroidal anti-inflammatory drugs (NSAID), calcium channel blocker compounds, and some others. The results as briefed here, could help in finding potential drug candidates for COVID-19 treatment. However, their advantages and risks should be taken into account through precise studies, considering a systemic approach. Even though the adverse effects of some of these drugs may overweight their benefits, considering their mechanisms and structures may give a clue for designing novel drugs in the future. Furthermore, the antiviral effect and IFN-modifying mechanisms possessed by some of these drugs might lead to a synergistic effect against SARS-CoV-2, which deserve to be evaluated in further investigations. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705326/pdf/main.pdf

Correlation of SARS-CoV-2 Breakthrough Infections to Time-from-vaccine; Prelim Study

 Roni Lotan, Sivan Gazit, Gabriel Chodik, Tal Patalon, Galit Perez, Amir Ben Tov, barak mizrahi, Nir Kalkstein, Asaf Peretz

doi: https://doi.org/10.1101/2021.07.29.21261317

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.07.29.21261317v1.full.pdf

Abstract

The short-term effectiveness of a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine was widely demonstrated. However, long term effectiveness is still unknown. A nationwide vaccination campaign was initiated early in Israel, allowing for a real-world evaluation of the interaction between protection and time-from-vaccine. The Delta (B.1.617.2) variant became the dominant strain in Israel in June 2021, as Israel is currently experiencing a new surge of cases. Leveraging the centralized computerized database of Maccabi Healthcare Services (MHS), we assessed the correlation between time-from-vaccine and incidence of breakthrough infection. We found that the risk for infection was significantly higher for early vaccinees compared to those vaccinated later. This preliminary finding should prompt further investigagions into long-term protection against different strains, and prospective clinical trials to examine the effect of a booster vaccine against breakthrough infection.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

This is a retrospective study

Funding Statement

Funded by Maccabi health care

https://www.medrxiv.org/content/10.1101/2021.07.29.21261317v1

Vaccinated, unvaccinated individuals have similar viral loads in communities with high prevalence of delta variant

 Kasen K Riemersma, Brittany E Grogan, Amanda Kita-Yarbro, Gunnar E Jeppson, David H O'Connor,  

View ORCID ProfileThomas C Friedrich, Katarina M Grande

doi: https://doi.org/10.1101/2021.07.31.21261387

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.07.31.21261387v1.full.pdf

Abstract

SARS-CoV-2 variant B.1.617.2 (delta) is associated with higher viral loads [1] and increased transmissibility relative to other variants, as well as partial escape from polyclonal and monoclonal antibodies [2]. The emergence of the delta variant has been associated with increasing case counts and test-positivity rates, indicative of rapid community spread. Since early July 2021, SARS-CoV-2 cases in the United States have increased coincident with delta SARS-CoV-2 becoming the predominant lineage nationwide [3]. Understanding how and why the virus is spreading in settings where there is high vaccine coverage has important public health implications. It is particularly important to assess whether vaccinated individuals who become infected can transmit SARS-CoV-2 to others. In Wisconsin, a large local contract laboratory provides SARS-CoV-2 testing for multiple local health departments, providing a single standard source of data using the same assay to measure virus burdens in test-positive cases. This includes providing high-volume testing in Dane County, a county with extremely high vaccine coverage. These PCR-based tests provide semi-quantitative information about the viral load, or amount of SARS-CoV-2 RNA, in respiratory specimens. Here we use this viral load data to compare the amount of SARS-CoV-2 present in test-positive specimens from people who self-report their vaccine status and date of final immunization, during a period in which the delta variant became the predominant circulating variant in Wisconsin. We find no difference in viral loads when comparing unvaccinated individuals to those who have vaccine "breakthrough" infections. Furthermore, individuals with vaccine breakthrough infections frequently test positive with viral loads consistent with the ability to shed infectious viruses. Our results, while preliminary, suggest that if vaccinated individuals become infected with the delta variant, they may be sources of SARS-CoV-2 transmission to others.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was supported by Centers for Disease Control and Prevention contracts 75D30120C09870 and 75D30121C11060 to D.H.O and T.C.F. The authors are also members of the Upper Midwest Regional Accelerator for Genomic Surveillance funded by the Rockefeller Foundation.

https://www.medrxiv.org/content/10.1101/2021.07.31.21261387v1