Discussion
As mentioned above, this case report documents a strong reactivation of
a pulmonary pathology beginning some hours after the administration of a
first dose of a mRNA vaccine in a patient having presented a symptomatic
pulmonary form of covid-19 one month before. It confirms previous
reports of stronger adverse effects of mRNA vaccine in patients
previously infected and sero-positive for SARS-CoV-2 (1-3). However, the
clinical history, by contrast with the previous reports, highlights an
unexpected renewal of the same severe pulmonary symptomatology in the
post vaccination episode as during the initial covid-19 infection.
The main information brought by this clinical observation is the need to
delay much more the first inoculation of anti-covid-19 mRNA vaccine in
patients having suffered from a symptomatic pulmonary form of covid-19.
In order to avoid such unpleasant and painful episode in vaccinated
subjects, it would be wise to postpone to some months the first dose of
mRNA vaccine to apply in these patients. In such cases, 3 months should
be a minimum delay, as already recommended by the health authorities in
USA and France for SARS-CoV-2-seropositive individuals.
Otherwise, this case report raises the question of the need to apply or
not a second dose of vaccine, since the first one seems plainly wake up
the immunological memory of the previous infection with SARS-CoV-2.
Indeed, it was shown that: i) stable levels of neutralizing antibodies
and T-cells responses are observed until at least 6 months after mild or
severe COVID-19 episodes (5, 6), and, ii) the immune responses to a
first vaccine dose in patients having previously suffered covid-19 are
strongly stimulated and much more important (up to 10 to 45 times) than
in previously uninfected subjects having received 2 vaccine doses (up to
3 times) (1, 3, 7-9). Changing the policy to give to these individuals
only one dose of vaccine would not negatively impact on their antibody
titers, spare them from unnecessary pain and free up many urgently
needed vaccine doses.
Another speculative question concerns why this vaccine injection induced
symptoms mimicking the severe pulmonary covid-19 clinical form appeared
one month before? A potential role of an antibody dependent enhancement
(ADE) of SARS-CoV-2 infection (10) with the newly synthesized antibodies
in response to vaccine is unlikely, since: i) circulating antibodies are
already present following the past natural infection; ii) the timing of
symptoms appearance after vaccine inoculation is too short for allowing
a significant antibody synthesis. Nevertheless, the presence of living
circulating viruses necessary to the ADE of infection in the observed
patient remains questionable since the performed SARS-Cov-2 antigen
positive test is not sufficient enough to confirm their presence and a
PCR test was not performed after vaccination. A reinfection with another
SARS-CoV-2 variant at the vaccination time can not be excluded, but
remains unlikely since no other cases were observed in the area. The
short time occurring between the vaccine inoculation and the symptoms
onset is compatible with a strong non-specific inflammatory reaction to
the mRNA vaccine. Although reactivity to mRNA vaccines is known to be
higher than for more classical protein-based vaccines (11), generally
they lead to mild local (at the inoculation site) or systemic symptoms.
Such a non-specific inflammatory reaction can hardly explain why the
vaccinated patient felt symptoms and presented pulmonary signs mimicking
those occurring during its running covid-19 infection one month before.
So, we raise the working hypothesis of an initial release in blood flow
of the SARS-Cov-2 S protein antigen synthetized at the vaccine IM
inoculation site. Indeed, the initiation of protein synthesis and its
running production needs few hours in cells (12, 13). Such circulating
antigen might be recognized and captured by still activated specific
T-cells, which, with dendritic cells and monocytes/macrophages, are
particularly present and concentrated at the pulmonary bases, where lung
lesions were objectified in chest CT during the covid-19 episode. This
specific recognizing by T-cell receptors might induce again an important
release of inflammatory cytokines reinitiating the lung pathology of the
first clinical episode, through a viral antigen-specific mechanism not
needing the presence of viruses. Another non-exclusive possibility,
besides the specific recognition of components of the S protein, relates
to the concept of “trained immunity”, by which cells of the innate
immune system, such as macrophages, monocytes and natural killer cells,
show enhanced responsiveness and some capacity to remember (driven by
epigenetic changes) when they reencounter pathogen elements (14). Such
considerations deserve further investigations.
In conclusion, the case report presented herein confirms the occurrence
of strong adverse effects of anti-covid-19 mRNA vaccine in patients
having suffering previously a pulmonary form of covid-19, and the need
to delay for some months the first inoculation of such vaccine in these
patients. Among different possible mechanisms, it puts forward a
prospective antigen-specific inducible inflammatory mechanism needing
further investigations.