Fatal breakthroughs in the alpha, delta and omicron eras

As Coronavirus is evolving breakthrough infections are not breakthroughs anymore. 

The first Israeli who died from Omicron was a fully vaccinated and boosted woman. The first Australian was a fully vaccinated man in his 80s with an underlying health condition. The first US case was a reinfection in an unvaccinated man in his 50s. The first India death from Omicron was a fully vaccinated 74-year-old man with diabetes. The first Brazilian was a triple-vaccinated 68-year-old man with chronic obstructive pulmonary disease and arterial hypertension.

According to today's technical briefing from UK Health Security Agency, a total of 57 people has been reported to have died within 28 days of an Omicron COVID-19 diagnosis up to 29 December 2021. The median time from Omicron specimen date to death was 5 days (range 0 to 14). The age of those dying ranged from 41 to 99 years.

23% of Omicron cases were vaccinated with 3 doses, over 50% with two doses, while 25% where not vaccinated at all. No information about vaccination status of most Omicron deaths is available yet. No additional details on Omicron deaths have been released by Germany (4 people aged from 35 to 79), Iran, and we don't know much about the latest US cases. 

Pre-Omicron data yielded the following statistics:

A total of 10,262 SARS-CoV-2 vaccine breakthrough infections had been reported from 46 U.S. states and territories by April 30, 2021. 2,725 (27%) vaccine breakthrough infections were asymptomatic, 995 (10%) patients were known to be hospitalized, and 160 (2%) patients died. The median age of patients who died in US from breakthrough infections before April 30 was 82 years (interquartile range = 71–89 years). Sequence data were available from 555 (5%) reported cases, 356 (64%) of which were identified as SARS-CoV-2 variants of concern including alpha variant B.1.1.7 (199; 56%), Epsilon variants B.1.429 (88; 25%) and B.1.427 (28; 8%), Gamma variant known as lineage P.1 (28; 8%), and beta variant B.1.351 (13; 4%).

From March 1 to June 30, 2021, 21 Wisconsinites have died from breakthrough COVID-19 cases. Their median age was 82 years old. A third were in long-term care facilities. 

The median age of the people who died from breakthrough infections in Oregon before the end of October was 81 (range: 34-103).

This picture changed in the Delta era as larger proportion of severe breakthroughs and younger breakthrough deaths started to happen.  The figure is for patients with SARS-CoV-2 infection confirmed by PCR test, who were hospitalized at the Yale New Haven Health System (New Haven, CT, USA) between Aug 4 and Oct 12, 2021, during which time the SARS-CoV-2 delta (B.1.617.2) variant accounted for over 95% of COVID-19 cases in the region. In Oregon, the median age of those who died from breakthrough cases in 2021 was 81 (range: 29-103). In Washington state, the median age was 78 (range: 14-105).  In Erie county, Pennsylvania, the fully vaccinated deaths from October 1 to Dec.15 were 60 to 78 years old. The vaccinated and boosted fatal breakthroughs happened mostly in those aged over 75. A fully vaccinated younger individual, US service member, died from COVID-19 despite being vaccinated with one shot Johnson & Johnson vaccine. No details have been released.  On December 14th, a fully vaccinated child died from COVID-19 (under 18) in Mendocino county. It was mentioned that he had comorbidities. 

By July 26, 1,263 vaccinated people died from the virus, according to the CDC. As of August 2, 2021, 1,507 deaths with vaccine breakthrough were reported to passive surveillance. 74% of these cases were people ages 65 and older. 987 fully vaccinated Virginians and 1090 fully vaccinated Indiana residents died from COVID-19 in 2021. Of the six vaccinated individuals who died in December in Peterborough, Ontario, Canada, two had received three doses while four had two doses, the age ranged from 40s to 90s. Seven of the 10 individuals died in hospital while three were in a long-term care setting. By the end of 2021, 730 fully vaccinated Missourians,  761 Ohioans and  660 Oregonians died from breakthrough infections. Dozens of them (~2%) were younger than 50. 

More than 1,000 fully vaccinated people in England have died from the Delta variant between 1 February and 29 August, according to the latest data from Public Health England. In this time period, 37 people under the age of 50 who had been double jabbed and 1,054 over-50s have died after testing positive for the Delta variant. In Israel, 65 people 50 or older died from COVID-19 in delta era despite being triple vaccinated. 

In a recent Morocco study of 30 severe breakthrough infections during the Delta wave, the average time between the last vaccine dose and the onset of clinical symptoms was roughly four months Eighteen patients, 60%, needed invasive ventilation, six patients, 20%, required non-invasive ventilation, one patient was put under high-flow nasal oxygen therapy, and five patients, about 16.66%, responded well to non-rebreather mask and nasal oxygen cannula. 67% died. 

No significant difference in severe COVID-19 between immunized and non-immunized was found for Beta variant of SARS-CoV-2. 


Public Health England. SARS-CoV-2 variants of concern and variants under investigation in England. technical briefing 12. 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. doi: 10.15585/mmwr.mm7021e3. PMID: 34043615; PMCID: PMC8158893.

Wang SY, Juthani PV, Borges KA, et al. Severe breakthrough COVID-19 cases in the SARS-CoV-2 delta (B.1.617.2) variant era. Lancet Microbe 2021; published online Dec 3. https://doi.org/10.1016/S2666-5247(21)00306-2


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