Scientists identify breakthrough cases of SARS-CoV-2’s delta variant in fully vaccinated individuals

In a recent study conducted at the Baylor College of Medicine, Houston, USA, scientists have identified six vaccine breakthrough cases caused by the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

A vaccine breakthrough case is defined as the detection of SARS-CoV-2 infection in individuals who are fully vaccinated against coronavirus disease 2019 (COVID-19). The study is currently available on the medRxiv* preprint server.


Recently, India has seen a significant rise in new COVID-19 cases predominantly caused by the delta variant (B.1.617.2) of SARS-CoV-2. Similar to the alpha (B.1.1.7), beta (B.1.351), and gamma (P.1) variants, the delta variant has gained beneficial mutations in the spike protein, which make it more infectious and pathogenic than previously circulating variants.

The delta variant belongs to the B.1.617 lineage that is currently circulating in more than 50 countries. Because of its significant threat to public health, the delta variant has been designated as the Variant of Concern (VOC) by the World Health Organization.  

Studies investigating vaccine efficacy against emerging SARS-CoV-2 variants have indicated that the delta variant is partially resistant to vaccine-induced antibodies. A study conducted in the UK has indicated that the Pfizer/BioNTech COVID-19 vaccines is 88% effective in preventing symptomatic disease caused by the delta variant.

In the current study, the scientists have described the transmission of delta variants among family members who were attending a wedding ceremony with 92 guests. The wedding events were held outside in a large open-air tent, and all guests were fully vaccinated.  

Important observations

The scientists identified a total of six individuals at the wedding ceremony who tested positive for SARS-CoV-2 and were symptomatic. Of them, one developed severe COVID-19 requiring monoclonal antibody infusion and one died eventually. Based on encounter timings and viral sequence similarities, the scientists suggested that two persons traveling from India probably have transmitted the delta variant to other guests during the wedding events.

Of two guests from India, one was a man without any comorbidities, and one was a woman with diabetes. They both received the 2nd dose of Covaxin (BBV152) 10 days before traveling to the wedding venue. Moreover, they tested negative for SARS-CoV-2 before boarding the flight.

Soon after developing symptoms including fatigue, cough, and fever, both guests from India tested positive for SARS-CoV-2 infection. At day 6 post-wedding, the man without comorbidity was admitted to a hospital because of worsening symptoms. One month after the wedding, he died due to COVID-19 related complications.

Four other guests who also tested positive for SARS-CoV-2 had confirmed interactions with the guests from India. Of 4 guests who were fully immunized with the Pfizer/BioNTech or Moderna COVID-19 vaccine, one developed severe COVID-19 that required infusion of monoclonal antibodies.

Testing of viral variant

Nasopharyngeal swab samples were collected from all six guests and analyzed by reverse transcription-polymerase chain reaction (RT-PCR) to detect viral variants. All samples tested positive for the original Wuhan strain of SARS-CoV-2 and negative for the alpha variant. All positive samples were subsequently sequenced by Swift Normalase Amplicon Panels with multiple overlapping amplicons to identify the causative variant. The findings revealed that all six guests were infected with the delta variant of SARS-CoV-2 (B.1.617.2).

Study significance

Six vaccine breakthrough cases identified in the study highlight the notion that antibodies elicited by Pfizer/BioNTech BNT162b2, Moderna mRNA-1273, and Covaxin BBV152 may not be sufficient to provide full protection against the delta variant. Although some people fail to develop adequate immunity in response to vaccination, none of the patients identified in the study had a history of vaccine failure.  

As mentioned by the scientists, mutations in three antigenic regions of the spike receptor-binding domain (450–469 IDf, 480–499 IDg, and 522–646 IDh) could potentially reduce the susceptibility of delta variant to antibody-mediated neutralization.

Taken together, the study suggests that vaccine breakthrough cases by highly transmissible viral variants can potentially disrupt the management of the COVID-19 pandemic. Thus, it is necessary to continuously generate viral genomic sequences from positive samples to identify potential vaccine breakthrough mutations.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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