Lack of symptoms doesn't mean COVID-19 vaccine not working, USUHS and partners find

Lack of symptoms doesn't mean COVID-19 vaccine not working, USUHS and partners find

July 12, 2021

A study conducted by researchers from the Uniformed Services University of the Health Sciences in Bethesda, the Naval Medical Research Center in Silver Spring, and the Frederick National Laboratory for Cancer Research has found no correlation between the symptoms that develop following vaccination against coronavirus disease 2019 (COVID-19) and the antibody responses that are generated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The team’s analysis of 206 adults who received the Pfizer-BioNTech BNT162b2 vaccine found no correlation between vaccine-associated symptom severity scores and the magnitude of vaccine-induced antibody responses to SARS-CoV-2.

The researchers say that some media outlets and medical professionals have frequently referred to the presence of post-immunization symptoms as a sign that a COVID-19 vaccine is “working.” This incorrectly implies that a lack of symptoms means that a vaccine has not induced the appropriate antibody responses. However, Edward Mitre and colleagues say the current study findings suggest that individuals who do not develop symptoms can be reassured that this does not mean the vaccine “did not work.”

The team also reports that symptoms were inversely correlated with age and weight, were more common among women, and occurred more frequently following a second vaccine dose.

A pre-print version of the research paper is available on the medRxiv server, while the article undergoes peer review.

The mass rollout of vaccines that protect against SARS-CoV-2 infection currently represents the most promising approach to bringing the COVID-19 pandemic under control. One feature shared by both the Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273 vaccines is the high level of reactogenicity. The majority of participants from phase 1 to 3 studies reported both local and systemic reactions.

Coggins and his team say it has become commonplace for media outlets and medical professionals to state that the development of symptoms indicates that a vaccine is “working.”

“Although this statement is fundamentally true because vaccines ‘work’ by inducing inflammatory responses, it also implies incorrectly that a lack of symptoms post-vaccination may indicate an absence of appropriate antiviral antibody responses,” according to the researchers. “Notably, there is little data demonstrating correlations between vaccine-induced symptoms and antibody titers with any vaccine platforms.”

The team assessed whether adverse effects induced by first and second doses of the Pfizer-BioNTech BNT162b2 vaccine were associated with the magnitude of the anti-SARS-CoV-2 antibody response among participants enrolled in the Prospective Assessment of SARS-CoV-2 Study (PASS). PASS is an observational, longitudinal cohort study of healthcare workers that was initiated in August 2020 to assess clinical and immunologic responses to SARS-CoV-2 infection and vaccination.

Participants completed a vaccine-associated symptom questionnaire one month after receiving each vaccination. In addition, Immunoglobulin G (IgG) antibodies against the SARS-CoV-2 spike protein and spike receptor-binding domain (RBD) were measured using microsphere-based multiplex immunoassays. The spike protein mediates the initial stage of the infection process when its RBD binds to the host cell receptor angiotensin-converting enzyme 2 (ACE2). This spike RBD is the primary target of antibodies following SARS-CoV-2 infection or vaccination.

Among 206 of 271 PASS participants (aged a median of 41.5 years) who were seronegative for SARS-CoV-2 prior to vaccination, no correlations between vaccine-associated symptom severity scores and vaccine-induced IgG titers were identified one month after the first or second vaccine dose. Individuals with either high or low symptom scores had similar levels of both spike-specific and RBD-specific IgG antibodies. Coggins and colleagues say this lack of correlation was maintained even following adjustment for age, weight and sex.

“Lack of post-vaccination symptoms following receipt of the BNT162b2 vaccine does not equate to a lack of vaccine-induced antibodies one month after vaccination,” the authors wrote. “These findings suggest that patients receiving the BNT162b2 vaccine should be reassured that a lack of symptoms does not necessarily equate to a lack of desired vaccine function.”

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