Team at Prominent German Academic Medical Center Find Risk Factors for Severe Breakthrough Infection Among Pfizer-Vaccinated Patients

by | Mar 21, 2022 | Featured, Vaccines

A group of researchers at the  University Medical Center Mannheim affiliated with prominent German academic medical centers, including Heidelberg University, have analyzed COVID-19 breakthrough vaccines since July 13, 2021, as part of an extended reporting period required by German law. During the first weeks of this study, the group of investigators analyzed a group of 67 hospitalized patients with vaccine breakthrough infection. They found that several factors raised the risks for breakthrough infections.


By mid-July 2021, the German Federal Ministry of Health promulgated an ordinance requiring extended reporting based on a law called the Infection Protection Act (IfSF) for hospitalized COVID-19 patients experiencing severe breakthrough vaccination. In other words, this means they have become seriously infected with COVID-19 despite being fully vaccinated.

With the Delta variant dominating circulation by then, cases increased across Germany despite a vaccination rate of 66.7% of all adults at that time. 

Study Question

The study team sought to better understand what individuals faced the most risk for severe breakthrough COVID-19 infection.Subscribe to the Trialsitenews “COVID-19” ChannelNo spam – we promise

The Study

Within the University Hospital Mannheim, all patient data records are managed by the Department of Hygiene. During the study period, the investigators organized a subgroup of patients with vaccination breakthroughs for investigation via prospective analysis from July 13, 2021, to September 6, 2021. The study team classified breakthrough vaccines in accordance with the national standard via the Public Health Institute for Germany [Robert Koch Institute]. That is, “a vaccination breakthrough was defined as SARS-CoV-2 infection confirmed by PCR with clinical symptoms of COVID-19 disease that occurred in fully vaccinated persons, i.e., at least 14 days after completion of a vaccination series.”


The German team reports that nine of 67 patients or 13.4% hospitalized for COVID-19 were fully vaccinated at this time. They found the median age at 75 years. Furthermore, they report that five of the vaccinated patients required intensive care and two of the inoculated patients unfortunately died.

The report a median of 99 days between complete vaccination and symptom onset demonstrating the waning vaccine effectiveness identified with mRNA-based vaccines that summer. All the patients received the mRNA-based Pfizer-BioNTech vaccine called BNT162b2. 

Interestingly, all of the patients were afflicted with 3 or more comorbidities while six patients (66.7%) showed negative Anti-SARS-CoV-2 titer at the time of vaccine breakthrough while five of the patients had Anti-SARS-CoV-2-S titers < 100 U/ml. The Delta variant was identified in all of the breakthrough infections.


The German team reports that a number of risk factors boost the probability of breakthrough serious infections, meaning that the risk of symptomatic COVID-19, hospitalization, and death remains higher for certain individuals despite being fully vaccinated with an mRNA-based vaccine.

For example, the elderly face more risk, which isn’t a surprise based on other studies, but so is underlying cardiorespiratory disease as well as the Delta variant of SARS-CoV-2.

Moreover, select environmental or behavioral conditions can raise risks from avoidance of wearing a face mask to a lack of immunization of close contacts as well as travel in high-risk areas could be factors attributed to “modifiable behavioral circumstances.”

The study authors propose extra vigilance with stronger pathogens such as Delta from more consistent use of personal protective measures to vaccination of close caregivers to greater awareness of the public health threat as well as a COVID-19 booster vaccination for patients in the high-risk category.  

Corresponding Author

Bettina Lang, Medical Faculty Mannheim, Department of Hygiene, Heidelberg University, University Medical Center Mannheim

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