Tuesday, October 03, 2023

Preprint: Covid-19 Vaccine Side Effects and Long-Term Neutralizing Antibody Response



As one of the `lucky' ones who never seems to suffer any discernible side effects from vaccines (flu, COVID, even a Tdap last May) - no sore arm, headache, fever, or tiredness - I've always wondered if that meant my immune system wasn't mounting as robust of a response to the shot as other people.

Anecdotally, I can report that I haven't had a `flu-like illness' since the summer of 2009 (before the pandemic H1N1 vaccine became available), and I've not had COVID since Feb 2021, just prior to my first COVID jab. 

But I've also worn a face mask in public for most of the past 42 months, use copious amounts of hand sanitizer, and have avoided crowds whenever possible. Parsing out how much of my protection stems from the COVID vaccines I've taken, and how much comes from NPIs (non-pharmaceutical interventions) is difficult to quantify. 

Nevertheless, I'm scheduled to get the fall COVID shot tomorrow morning. I figure, every ounce of protection I can get is worthwhile. 

But today we've got a preprint which looks at people (like me) who don't experience the mild side-effects from COVID-19 vaccines that many others do, and measures their immune response.  

They suggest that while mild side effects may put some people off getting the shot, it is actually a good sign, and should be `re-framed' as desirable.  

Due to its length (24-pages) I've only reproduced the Abstract and a small excerpt from the discussion. Follow the link to read it in its entirety. 

The more symptoms the better? Covid-19 vaccine side effects and long-term neutralizing antibody response

Ethan G. Dutcher, Elissa S. Epel, Ashley E. Mason, Frederick M. Hecht, James E. Robinson, Stacy S. Drury, Aric A. Prather+

doi: https://doi.org/10.1101/2023.09.26.23296186
Preview PDF


Protection against SARS-CoV-2 wanes over time, and booster uptake has been low. This study explores the link between post-vaccination symptoms, biometric changes, and neutralizing antibodies (nAB) after mRNA vaccination.

 Data were collected from adults (n = 363) who received two doses of either BNT162b2 or mRNA-1273, with serum nAB concentration measured at 1 and 6 months post-vaccination. Daily symptom surveys were completed for six days starting on the day of each dose. Concurrently, objective biometric measurements, including skin temperature, heart rate, heart rate variability, and respiratory rate, were collected. 

We found that certain symptoms (chills, tiredness, feeling unwell, and headache) after the second dose were associated with increases in nAB at 1 and 6 months post-vaccination, to roughly 140-160% the level of individuals without each symptom. Each additional symptom predicted a 1.1-fold nAB increase. Greater changes in skin temperature and heart rate after the second dose predicted higher nAB levels. Skin temperature had a stronger predictive relationship for 6-month than 1-month nAB level. 

In the context of low ongoing vaccine uptake, our findings suggest that public health messaging could seek to reframe systemic symptoms after vaccination as desirable.



We show here that individuals who reported experiencing chills, tiredness, feeling unwell, or headache following the second dose of a SARS-CoV-2 vaccine subsequently had 140-160% of the neutralizing antibody level of people who did not report these symptoms, at both 1 and 6 months later. We also show that each additional symptom experienced following dose two predicted a 1.1 fold increase in subsequent nAB.

This means that, on average, individuals reporting 7 distinct symptoms subsequently had nearly 200% the nAB level of individuals reporting 0 symptoms. Using objective biometric data, we present convergent findings showing that greater vaccination-induced change in body temperature and heart rate, specifically at dose two, predicts greater nAB, especially at 6-month follow-up. Effect sizes were again large, with a difference between individuals of 1 degree Celsius in vaccination-induced change in skin temperature predicting 300% of the nAB level six months later. 


In sum, we show here in a large community sample that systemic symptoms and increases in skin temperature and heart rate following SARS-CoV-2 mRNA vaccination predict higher subsequent nAB level. We show that these relationships are stronger when predicting longer-term rather than short-term nAB outcome.

Our results suggest that the presence or absence of symptoms might be able to be used as an approximate proxy for likely protection against Covid-19, by individuals or their healthcare providers. In the context of low rates of booster uptake, our findings have particular relevance for individuals with a degree of ambivalence regarding receiving a booster vaccination.

          (Continue . . . . )

As with all studies, this one has some limitations, which the authors list as including:
  • results are from individuals who received only the initial Covid-19 vaccine series
  • results are from individuals with no serological evidence of prior SARS-CoV-2 infection
  • the pseudovirus assay used the spike protein from the original Wuhan/D614G strain of SARS-CoV-2 
  • It only measures neutralizing antibodies (nABs)
Still, this is a fascinating report, and it reinforces what I've suspected all along. 

Convincing the public that a day or two of feeling lousy following COVID vaccination is a `good thing' may prove to be a hard sell, even though it is little different from urging people to endure a mild fever rather than immediately treat it with antipyretics like acetaminophen, aspirin, and other NSAIDs.

In the past we've looked at some of the potential disadvantages of fever reduction following vaccination, including in Two Studies On Impact Of Fever & Antipyretics On Flu Vaccine Immune Response In Children

Although I find my lack of a side effects following vaccination a little concerning, my avoidance of COVID illness since receiving my first COVID vaccine in March of 2021 is encouraging. 

While my luck may not last forever, for now, I figure whatever I'm doing is working.