COVID Reference

The COVID Textbook

Vaccines 29 May

28 May 2021

CDC COVID-19 Vaccine Breakthrough Case Investigations Team. COVID-19 Vaccine Breakthrough Infections Reported to CDC – United States, January 1-April 30, 2021. MMWR Morb Mortal Wkly Rep. 2021 May 28;70(21):792-793. PubMed: https://pubmed.gov/34043615. Full-text: https://doi.org/10.15585/mmwr.mm7021e3

As of 30 April, 10,262 SARS-CoV-2 vaccine breakthrough infections had been reported in the US (median age: 58 years; 63% females):

  • 2,725 (27%) vaccine breakthrough infections were asymptomatic
  • 995 (10%) patients were hospitalized
    • 289 (29%) of these were asymptomatic or hospitalized for a reason unrelated to COVID-19
  • 160 (2%) patients died

The authors caution that the number of reported breakthrough cases is likely a substantial underestimate of all SARS-CoV-2 infections (especially asymptomatic infections or mild illness) among fully vaccinated persons.

 

EMA 20210528. First COVID-19 vaccine approved for children aged 12 to 15 in EU. European Medicines Agency 2021, published 28 May (accessed 30 May). Full text: https://www.ema.europa.eu/en/news/first-covid-19-vaccine-approved-children-aged-12-15-eu

EMA’s human medicines committee (CHMP) has recommended the approval of the BioNTech/Pfizer vaccine for children aged 12 to 15 (EMA 20210528).

 

27 May

Frenck RW Jr, Klein NP, Kitchin N, et al. Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents. N Engl J Med. 2021 May 27. PubMed: https://pubmed.gov/34043894. Full-text: https://doi.org/10.1056/NEJMoa2107456

The data that led to the approval of the BioNTech/Pfizer vaccine for adolescents 12 to 15 years old. The vaccine produced a greater immune response than in young adults and had a favorable safety profile.

 

Sahin U, Muik A, Vogler I, et al. BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans. Nature. 2021 May 27. PubMed: https://pubmed.gov/34044428. Full-text: https://doi.org/10.1038/s41586-021-03653-6

Data from a second BioNTech/Pfizer Phase I/II trial showing that one week after the second vaccine dose neutralizing antibody titers were up to 3.3-fold above those observed in COVID-19 human convalescent samples. Most participants had a strong IFNγ- or IL-2-positive CD8+ and CD4+ T helper type 1 (TH1) T cell response (Sahin 2021).

 

Kowarz E, Krutzke L, Reis J, Bracharz S, Kochanek S, Marschalek R. “Vaccine-Induced Covid-19 Mimicry” Syndrome: Splice reactions within the SARS-CoV-2 Spike open reading frame result in Spike protein variants that may cause thromboembolic events in patients immunized with vector-based vaccines. Research Square 2021, posted 26 May, accessed 30 May. Full text: https://www.researchsquare.com/article/rs-558954/v1

Cerebral venous sinus thromboses (CVST) and splanchnic vein thromboses (SVT) have been reported after first vaccinations with vector-based vaccines (AstraZeneca, Johnson & Johnson). The authors explain that these serious complications might be due to alternative splice events producing soluble Spike protein variants which bind to ACE2-expressing endothelial cells in blood vessels (Kowarz 2021). They also suggest how to optimize vector-based vaccines to increase their safety.

 

Chen Y, Shen H, Huang R, Tong X, Wu C. Serum neutralising activity against SARS-CoV-2 variants elicited by CoronaVac. Lancet Infect Dis 2021, published 27 May. Full text: https://doi.org/10.1016/S1473-3099(21)00287-5

In this in vitro study of sera from 93 healthy health-care professionals from Nanjing, China, the Sinovac vaccine was equally effective in neutralizing D614G, B.1.1.7, and B.1.429. However, only a small proportion of post-vaccine sera were capable of neutralizing B.1.526 (26%), P.1 (34%), and B.1.351 (5%) (Chen Y 2021).

 

26 May

Académie nationale de médecine. « Obligation » n’est pas un gros mot quand il s’agit de vacciner contre la Covid-19. French national academy of medicine 2021, published 25 May. Full text: https://www.academie-medecine.fr/obligation-nest-pas-un-gros-mot-quand-il-sagit-de-vacciner-contre-la-covid-19

The French Académie nationale de médecine has issued a statement calling for a progressive introduction of mandatory COVID-19 vaccination (Académe national de médecine 2021) because individual and collective mitigation measures (barrier gestures and curfews) might not be sufficient to control the epidemic if a sizable proportion of the population refuses to be vaccinated. In the past, mandatory vaccination has been used in France for smallpox (1902-1984), diphtheria (since 1938), tetanus (since 1940), tuberculosis (1950-2007) and polio (since 1964). Since 2017, 11 vaccines are required for infants.

The Académie recommends that obligations should be introduced gradually. For a start, vaccination should be mandatory for

  • People working in “essential categories” (teachers, health professions; army personnel, police and civil service in general; supply services for food, water, energy, cash and computer equipment); and other public services
  • People who have a professional contact with the public in bars, shops, restaurants, hotels, cultural and sports sectors
  • Travelers
  • People involved in associative events
  • Blood, tissue and organ donors
  • Students before the start of the 2021 academic year

 

McEwen AE, Cohen S, Bryson-Cahn C, et al. Variants of concern are overrepresented among post-vaccination breakthrough infections of SARS-CoV-2 in Washington State. medRxiv 2021, posted 25 May. Full text: https://doi.org/10.1101/2021.05.23.21257679

So-called variants of concern (VOCs, i.e., B.1.1.7, B.1.351, P.1., B.1.427/B.1.429) may be significantly enriched among breakthrough infections. Across 20 vaccine breakthrough cases detected at University of Washington, all 20 infections (100%) were due to VOCs and had a median Ct of 20.2 (IQR=17.1-23.3) (McEwen 2021).

 

Volpp KG, Cannuscio CC. Incentives for Immunity – Strategies for Increasing Covid-19 Vaccine Uptake. N Engl J Med. 2021 May 26. PubMed: https://pubmed.gov/34038633. Full-text: https://doi.org/10.1056/NEJMp2107719

A $5 million vaccination grand prize in New York? And a $1 million award in Ohio to a vaccinated adult or a full ride, college scholarship to a vaccinated child? The authors are convinced that the money could be spent better.

 

25 May

Botton J, Dray-Spira R, Baricault B, et al. Estimation de l’impact de la vaccination chez les personnes âgées de 75 ans et plus sur le risque de formes graves de Covid-19 en France à partir des données du Système National des Données de Santé (SNDS) – Premiers résultats. Epi-Phare 2021, published 21 May.  Full text: https://www.epi-phare.fr/app/uploads/2021/05/epi-phare_premiers_resultats_impact_vaccination_covid_20210521.pdf

The first real-life COVID-19 vaccine study in France including 1,422,461 people vaccinated between 27 December 2020 and 24 February 2021 and 2,631,108 controls. Vaccination reduced the risk of severe forms of Covid-19 by 87% in those over 75 years old as early as seven days after the injection of the second dose (Botton 2021).

 

24 May

Solforosi L, Kuipers H, Jongeneelen M, et al. Immunogenicity and efficacy of one and two doses of Ad26.COV2.S COVID vaccine in adult and aged NHP. J Exp Med April 28 2021. https://rupress.org/jem/article/218/7/e20202756/212032/Immunogenicity-and-efficacy-of-one-and-two-doses

In both adult and aged rhesus macaques, two doses of the Johnson & Johnson vaccine administered 8 weeks apart induced higher peak binding and neutralizing antibody responses compared with a single dose. In humans, a two-dose regimen is currently evaluated in a Phase 3 study (ENSEMBLE 2).

 

Bernal JL, Andrews N, Gower C, et al. Effectiveness of COVID-19 vaccines against the B.1.617.2 variant. medRxiv 2021, posted 24 May. Full text: https://doi.org/10.1101/2021.05.22.21257658

The BioNTech/Pfizer and AstraZeneca vaccines seem to be only slightly less effective against B.1.617.2, the variant first identified in India:

 

Table xxx – Effectiveness of the BioNTech/Pfizer and AstraZeneca vaccines against B.1.1.7 (first identified in England) and B.1.617.2 (fdi India)
Effectiveness against
  B.1.1.7 B.1.617.2
First dose
BioNTech/Pfizer 51.1%* 33.5%*
AstraZeneca
Second dose
BioNTech/Pfizer 93.4% 87.9%
AstraZeneca 66.1% 59.8%

* Results were similar for both vaccines