COVID-19 vaccination

Are there clinically significant interactions between COVID-19 vaccination and post-COVID-19 condition (long COVID)?

Source: Emerging Science Group of the Public Health Agency of Canada. Evidence Brief on the associations and safety of COVID-19 vaccination and post-COVID-19 condition: January 13, 2022. Full report available from: ocsoevidence-bcscdonneesprobantes@phac-aspc.gc.ca

Background: "Long COVID" has been studied both as post-acute sequelae (PAS), defined as symptoms 4 to 12 weeks post diagnosis, and as post-COVID-19 condition (PCC), defined by the World Health Organization as persistent or recurring symptoms lasting for at least 8 weeks and occurring 12 or more weeks after an acute COVID-19 infection^{Footnote 1}. It is important to know if there are any beneficial or harmful effects of COVID-19 vaccination on PAS or PCC, or if PAS or PCC increases the risk of adverse events following vaccination. This report addresses three questions: Does COVID-19 vaccination before or after COVID-19 infection decrease the risk of developing PAS or PCC? Among those who already have PAS or PCC, does COVID-19 vaccination affect their symptoms? Is it safe to receive a COVID-19 vaccine after PAS or PCC?

Methods: Twenty databases and key websites were searched for relevant reviews, peer-reviewed publications and preprints up to January 13, 2022. Search terms included the following: immuniz*, immunis*, vaccin*, long covid, long-covid, post covid, post-covid, chronic covid, chronic-covid, long-term sequelae, long hauler and long-hauler. The search netted 97 citations, which were screened for relevance. Data were extracted from relevant studies into three evidence tables to address each of the questions.

Results: Fourteen relevant studies were identified: four prospective cohort studies; four retrospective cohort studies; and six cross-sectional studies. One was peer-reviewed, twelve were preprints and one was a letter to the editor. Twelve studies reported on vaccines authorized for use in Canada and are reported on here; the two others were on a vaccine authorized for use in India^{Footnote 2Footnote 3}.

COVID-19 vaccination prior to developing PAS or PCC

All studies in this area were on PCC. Four situations were assessed: four studies assessed one or two doses of COVID-19 vaccine before COVID-19 infection and the risk of developing PCC; and two studies assessed having one or two doses of a COVID-19 vaccine after COVID-19 infection, but before developing PCC.

COVID-19 vaccination before COVID-19 infection

No studies found an increased risk of developing PCC subsequent to infection. All studies were retrospective or cross-sectional studies; thus, the evidence of a protective effect from vaccination was not strong.

• Two studies assessed one dose of a vaccine prior to COVID-19 infection. One study identified a decreased risk of PCC (odds ratio [OR] 0.22)^{Footnote 4} and one study found no difference^{Footnote 5}.
• Two studies assessed two doses of a vaccine prior to COVID-19 infection. One study identified a decreased risk of PCC (hazard ratio [HR] 0.87)^{Footnote 6}, two studies reported a lower proportion of some PCC symptoms among vaccinated people^{Footnote 5Footnote 7} and one study found no difference^{Footnote 5}.

COVID-19 vaccination after infection and before post-COVID-19 condition

This was reported in two studies; both found a decreased risk of developing PCC.

• A prospective cohort described a temporary reduction in the risk of PCC (13%) post first dose and a 9% reduction post second dose followed by further decreases of 0.8% per week regardless of the vaccine received^{Footnote 8}. Timing of the vaccine post-infection did not appear to affect results.
• A retrospective cohort that assessed at least one dose of a vaccine received 0–20 weeks post-COVID-19 diagnosis found a reduced risk of PCC, and this was most protective when received closer to diagnosis (OR 0.38 at 0–4 weeks vs OR 0.75 at 8–12 weeks)^{Footnote 4}.

One study did not differentiate between vaccination before or after COVID-19 and reported no association with vaccination and development of PCC overall, however those vaccinated had a lower risk of certain symptoms^{Footnote 9}.

COVID-19 vaccination after developing PAS or PCC

Five studies examined the effect of COVID-19 vaccination after developing PAS or PCC. Three studies showed a small beneficial effect and two studies showed no difference.

• A large prospective cohort study found that the PCC remission rate in vaccinated individuals was 16.6% vs 7.5% in unvaccinated individuals^{Footnote 10}.
• A smaller prospective cohort study found that the PCC remission rate in vaccinated individuals was higher than the unvaccinated (23.2% vs 15.4%), the proportion with worsening symptoms was lower (5.6% vs 14.3%) and in the majority of vaccinated and unvaccinated people PCC symptoms were the same (71.1% vs 70.3%)^{Footnote 11}.
• A third prospective cohort study found that there were fewer general practitioner consultations among individuals with PAS after vaccination compared with before vaccination^{Footnote 12}.
• A retrospective cohort on PCC^{Footnote 13} and a cross-sectional study on PAS^{Footnote 14} found that there was no change in symptoms with vaccination status.

Safety of COVID-19 vaccination in those with PAS or PCC

Two studies reported on vaccine adverse events after one dose of a COVID-19 vaccine in individuals with PCC.

• A cross-sectional study of one dose of an mRNA vaccine found that there was no significant difference in the number or duration of vaccine adverse events in those with PCC (n=30) vs those without (n=944)^{Footnote 15}.
• A large prospective cohort study of individuals with PCC concluded vaccination was safe with fewer than 1% reporting a serious adverse event (0.88%)^{Footnote 10}.

Conclusion: Preliminary research findings suggest COVID-19 vaccination may decrease the risk of developing PCC and, in those who already have PCC or PAS, receiving a COVID-19 vaccination was not associated with an increase in adverse events and was associated with remission of PAS or PCC symptoms in some people. There is low confidence in these findings as the evidence was limited by the number of studies, lack of peer review and risk of bias in the retrospective studies. Peer-reviewed longer-term prospective studies are needed.

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