The First Shot, The Haves and The Have-Nots

Barriers to healthcare Clinical Trials Disease Control Emerging Infectious Diseases Global Pandemic Herd immunity SARS-CoV-2 SARS-CoV-2 Vaccine

Interestingly, two pre-prints were released this week that looked at the same issue. These papers were a comparison of the immune response to the first shot of an mRNA vaccine between those who have had COVID-19 already and have IgG antibodies versus those who have not had the disease yet and thus have no antibodies. These papers answer a very important question; “What happens if I get a shot after having Covid-19 infection?”

The Saadat et al, 2021 Study

The first one is from the University of Maryland; Saman Saadat et al. Single Dose Vaccination in Healthcare Workers Previously Infected with SARS-CoV-2. medRxiv, Feb 1, 2021. They looked at 59 healthcare workers (HCW). Seventeen had no antibodies to SARS-CoV-2 (Group I). Out of the rest, 16 had had COVID-19 but were asymptomatic during the course (Group II). In contrast, 26 had symptomatic COVID-19 back in July – August 2020 (Group III).

All participants had antibody levels measured, and then they got the first shot of either the Pfizer-BNT or Moderna COVID-19 vaccine. Antibody titers were then measured on Days 0, 7, 10, and 14. On Days 7, 10, and 14, those in Groups II and III (participants who had already had COVID-19) had significantly higher titers of IgG antibodies to SARS-CoV-2 than those in Group I (those who had never had COVID-19). On Days 0 and 14, the sera in Groups II and III were able to neutralize live virus to a greater extent than Group I.

Anti-SARS-CoV-2 antibody responses after single dose of vaccination.
IgG spike trimer end-point titers. By 7 days and continuing to 14 days post vaccination HCW with prior COVID-19 who received a single vaccination developed higher peak IgG titers than HCW without COVID and COVID-19 infected patients – Source Saadat et al 2021
Take Home Summary From Saadat et al

After the first shot of either vaccine, antibody titers in Groups II and III were higher than the titers in patients with active disease and almost as the titer in those who had had both shots of an mRNA COVID-19 vaccine.

Results From Krammer F. et al

Florian Krammer led the second study from Mount Sinai in NY: Krammer F et al. Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine. medRxiv, Feb 1, 2021. They looked at 109 participants. Sixty-eight were seronegative (no antibodies), while 41 were seropositive (had SARS-CoV-2 antibodies).

They also found that after the first shot of either mRNA vaccine, the immune response in those who already had antibodies to SARS-CoV-2 due to a prior infection was more robust than in those who had had no previous infection at all. They found that the antibody titers in those with prior infections were 10-20 times higher after the first shot than those who were seronegative. The latter group even had titers ten times higher than those who had gotten both vaccine shots.

SARS-CoV-2 Vaccine Response In Those With and Without Prior Infection

This shows that after the first dose some of those with prior infection had antibody levels above those who had completed all two doses. Source: Krammer F et al 2021

The Mount Sinai group also looked at side effects in 231 participants after the first shot. They found that those who had had COVID-19 already and thus were seropositive before the first shot had more severe local and systemic side effects.

Take Home Summary

So what do these two studies tell us? We are looking at the phenomenon of the secondary response. It is the immune system’s reaction when it contacts an antigen for the second and subsequent times. The immune response is always more robust after the first time. That is the idea behind the two-shot regime used to administer the majority of the COVID-19 vaccines. Thus the first shot primes the immune system, whereas the second boosts the response (the booster).

In participants who have had prior COVID-19 infection, the insult acts like the first vaccine shot. The first vaccine shot becomes the booster. This phenomenon is illustrated quite well through the data from these two small studies. We see significant levels of antibody titers in participants who have had COVID-19 already. Unsurprisingly, these people also had more severe side effects.

Like my immunologist friend, Anthony Affum-Adjei Awuah, PhD, was pointing out a few hours ago on his Facebook page. The secondary response is also responsible for boosting the immune response if we are re-exposed to the disease-causing pathogen. These episodes of re-exposure can prolong immunity to the pathogen past the period it is estimated to last.

Primary and Secondary Immune Response

A depiction of the primary and secondary immune response

As we struggle to get all vaccinated, maybe those who’ve already had COVID-19 infection should only get one shot. It is even worth considering if such individuals should go to the back of the queue. This would allow more seronegative people to get vaccinated.

A beneficial tool would be a dependable and easy-to-perform antibody essay. This could be used to screen those with an unknown infection history and ascertain the antibody titer. Lastly, those who have had the infection should be aware that they would have more severe side effects from the first shot.

Stay safe!

The studies described in this post are preliminary articles. The papers have not yet been reviewed by experts and approved for publication.

By Nana Dadzie Ghansah an anesthesiologist who lives and works in Lexington Kentucky

Another contributor to this post is; Anthony Affum-Adjei Awuah an immunologist at the Kumasi Centre for Collaborative Research in Tropical Medi├žine


A physician providing primary medical care to patients across the lifespan

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