BNT162b2 vaccine breakthrough: clinical characteristics of 152 fully vaccinated hospitalized COVID-19 patients in Israel

Abstract

Objectives mRNA COVID-19 vaccines have shown high effectiveness in the prevention of symptomatic COVID-19, hospitalization, severe disease, and death. Nevertheless, a minority of vaccinated individuals might get infected and suffer significant morbidity. Characteristics of vaccine breakthrough infections have not been studied. We sought to portray the population of Israeli patients, who were hospitalized with COVID-19 despite full vaccination. Methods A retrospective multicenter cohort study of 17 hospitals included Pfizer/BioNTech's BNT162b2 fully-vaccinated patients who developed COVID-19 more than 7 days after the second vaccine dose and required hospitalization. The risk for poor outcome, defined as a composite of mechanical ventilation or death, was assessed. Results 152 patients were included, accounting for half of hospitalized fully-vaccinated patients in Israel. Poor outcome was noted in 38 patients and mortality rate reached 22% (34/152). Notable, the cohort was characterized by a high rate of comorbidities predisposing to severe COVID-19, including hypertension (108, 71%), diabetes (73, 48%), CHF (41, 27%), chronic kidney and lung diseases (37, 24% each), dementia (29, 19%), and cancer (36, 24%), and only 6 (%) had no comorbidities. Sixty (40%) of the patients were immunocompromised. Higher SARS-CoV-2 viral-load was associated with a significant risk for poor outcome. Risk also appeared higher in patients receiving anti-CD20 treatment and in patients with low titers of anti-spike IgG, but these differences did not reach statistical significance. Conclusions We found that severe COVID-19 infection, associated with a high mortality rate, might develop in a minority of fully-vaccinated individuals with multiple comorbidities. Our patients had a higher rate of comorbidities and immunosuppression compared to previously reported non-vaccinated hospitalized COVID-19 patients. Further characterization of this vulnerable population may help to develop guidance to augment their protection, either by continued social-distancing, or by additional active or passive vaccinations.

Breakthrough Infections with Multiple Lineages of SARS-CoV-2 Variants Reveals Continued Risk of Severe Disease in Immunosuppressed Patients

“…Breakthrough infection in vaccinated asymptomatic subjects, such as those described here, may contribute to the spread of SARS-CoV-2 in the population. Our study is in agreement with several recent reports documenting high viral loads in breakthrough infections in both symptomatic and asymptomatic individuals [7,12,39]. More studies are needed to determine the contribution of breakthrough infections in the spread of SARS-CoV-2 variants of concern.…”

“…Our results are in agreement with the recent study of Brosh-Nissimov et al that reported the characteristics of breakthrough infections in 152 vaccinated individuals identified from January to April 2021. They reported that 40% of the patients with breakthrough infections were immunocompromised (11% SOT patients), and that co-morbidities including hypertension and diabetes predisposed to severe COVID-19 [7]. Additional studies are needed to determine if SOT patients are vulnerable to specific variants, and if a subset of variants are associated with more severe disease.…”

“…COVID-19 vaccine deployment has dramatically reduced the number of infections, hospitalizations, and deaths caused by SARS-CoV-2 [1,2]. However, there are reports of SARS-CoV-2 infections in fully vaccinated individuals [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. In the majority of individuals, these infections are presumed to be breakthrough infections associated with SARS-CoV-2 variants that escape vaccine-induced immunity.…”

Protective mucosal immunity against SARS-CoV-2 after heterologous systemic RNA-mucosal adenoviral vector immunization

“…To further investigate potential advantages of mucosal immune responses, upcoming studies must mimic the settings more closely that likely contribute to breakthrough infections in vaccinated individuals: age 71 , comorbidities 72,73 , waning immunity, and infection with less neutralization-sensitive variants like B.1.617.2 [12][13][14][15][16][17][18] . However, experimental human challenge studies with a small number of participants might also illuminate this topic similar to challenge studies previously performed in the context of RSV 45,46 or Influenza 74,75 .…”

“…Humoral as well as cellular immune responses against the spike (S) surface protein were successfully induced by both types of vaccines [7][8][9][10][11] . However, breakthrough infections of fully vaccinated individuals have been reported and the numbers might increase in the phase of waning immunity [12][13][14][15][16][17][18] . The impact of immune escape and newly emerging virus variants (i.e.…”