By Venice Servellita, et al. PREPrint ~ August 25, 2021 with Commentary from TrialSiteNews Below

Abstract

Associations between vaccine breakthrough cases and infection by SARS coronavirus 2 (SARS-CoV-2) variants have remained largely unexplored. Here we analyzed SARS-CoV-2 whole-genome sequences and viral loads from 1,373 persons with COVID-19 from the San Francisco Bay Area from February 1 to June 30, 2021, of which 125 (9.1%) were vaccine breakthrough infections. Fully vaccinated were more likely than unvaccinated persons to be infected by variants carrying mutations associated with decreased antibody neutralization (L452R, L452Q, E484K, and/or F490S) (78% versus 48%, p = 1.96e-08), but not by those associated with increased infectivity (L452R and/or N501Y) (85% versus 77%, p = 0.092). Differences in viral loads were non-significant between unvaccinated and fully vaccinated persons overall (p = 0.99) and according to lineage (p = 0.09 – 0.78). Viral loads were significantly higher in symptomatic as compared to asymptomatic vaccine breakthrough cases (p < 0.0001), and symptomatic vaccine breakthrough infections had similar viral loads to unvaccinated infections (p = 0.64). In 5 cases with available longitudinal samples for serologic analyses, vaccine breakthrough infections were found to be associated with low or undetectable neutralizing antibody levels attributable to immunocompromised state or infection by an antibody-resistant lineage. These findings suggest that vaccine breakthrough cases are preferentially caused by circulating antibody-resistant SARS-CoV-2 variants, and that symptomatic breakthrough infections may potentially transmit COVID-19 as efficiently as unvaccinated infections, regardless of the infecting lineage.

Read Full Article


UCSF Scientist-led Study Indicates Growing Occurrence of Breakthrough Infections

TrialSite Op-ed author Geert Vanden Bossche warned public health authorities that intervening in a mass pandemic with mass vaccination could have both “detrimental and beneficial effects,” which could vary depending on age, impacted by the unfolding of events. Suggesting that while mass intervention in the pandemic may lead to short-term benefits, the action may ultimately “lead to insufficient training of innate immune mechanisms,” fundamentally appearing “in those who primarily rely on innate immunity as the first line of immune defense (i.e., children). Vanden Bossche’s dire prediction centered on the premise that mass vaccination such as what is occurring in the world’s war against SARS-CoV-2 ultimately triggers the “propagation of more infectious variants.” A negative reinforcing cycle follows as “a resurgence of viral infectious pressure, thereby eroding the innate immune defense of the unvaccinated (i.e., mostly younger age groups), making them more susceptible to disease. Now a group of San Francisco Bay Area scientists probes the association between breakthrough cases and SARS-CoV-2 variants.  Recently publishing their study in the preprint server medXriv, the authors came to a surprising conclusion, perhaps for the mainstream but probably not for Vanden Bossche, that their findings “suggest that vaccine breakthrough cases are preferentially caused by circulating antibody-resistant SARS-CoV-2 variants and that those with symptomatic breakthrough infections may potentially transmit COVID-19 as efficiently as those with unvaccinated infections, regardless, of the infecting lineage.” While POTUS continuously declares this is a “pandemic of the unvaccinated,” a rethink of such inappropriate, divisive, and seemingly factual incorrect assessments is in order.

Northern California Teams

The scientific research team represented several institutions, including University of California, San Francisco, UCSF Abbott Viral Diagnostics and Discovery Center, SF Department of Public Health, Color Genomics, Inc., and others.

The Study

The study team looked at SARS-CoV-2 whole-genome sequences and viral loads during February 1, 2021, to June 30, 2021.  In this study, the team found that of the total subjects, 125 (9.1%) represented vaccine breakthrough infections.

Of note, the fully vaccinated in this study were more prone to succumbing to breakthrough infections. That is, as described by the authors, “Fully vaccinated were more likely than unvaccinated persons to be infected by variants carrying mutations associated with decreased antibody neutralization (L L452R, L452Q, E484K, and/or F490S) (78% versus 48%, p = 1.96e-08), however, not those variants with greater infectivity such as L452R and N501Y) (85% versus 77%, p = 0.092).

In what is becoming a common finding, the difference between viral loads in vaccinated versus the unvaccinated is nil. The Northern California-based scientists did find that “Viral loads were significantly higher in symptomatic as compared to asymptomatic vaccine breakthrough cases (p < 0.0001), and symptomatic vaccine breakthrough infections had similar loads to unvaccinated infections (p=0.64).

Noteworthy, the team drilled into five cases associated with longitudinal data, including serologic analyses, vaccine breakthrough infections finding links with “low or undetectable neutralizing antibody levels attributable to an immunocompromised state or infection by an antibody-resistant lineage.” The takeaway:  vaccine breakthrough cases are preferentially made possible by “circulating antibody-resistant SARS-CoV-2 variants, and those symptomatic breakthrough infections may potentially transmit COVID-19 as efficiently as unvaccinated infection” irrespective of variant. 

Limitations

Several limitations must be considered. They include:

  • Possibility of sampling bias in the testing of patients (mitigated by reporting of variant distributions and viral load comparisons across two different test cohorts)
  • A relatively small number of breakthrough infections (125)—clinical and epidemiologic metadata only available in 39 cases
  • Retrospective medical chart review
  • Absence of contact tracing metadata—couldn’t assess transmission and secondary attack rates from those vaccinated persons to exposed contacts.

Lead Research/Investigator         

Charles Y. Chiu, Department of Laboratory Medicine, University of California, San Francisco

Read Full Article

Comments

0 Comments

Submit a Comment