Changes in trajectory of long COVID symptoms before vaccination

Almost as soon as the gravity of the coronavirus disease 2019 (COVID-19) pandemic was known, vaccine development went on apace over the next year to prevent the hundreds of thousands of deaths that would eventually be recorded as the result of this outbreak. The approval of the first few vaccines was followed by their widespread deployment in developed countries and some Asian countries as well.

Study: Changes in the trajectory of Long Covid symptoms following COVID-19 vaccination: community-based cohort study. Image Credit: Dmitry Demidovich/ShutterstockStudy: Changes in the trajectory of Long Covid symptoms following COVID-19 vaccination: community-based cohort study. Image Credit: Dmitry Demidovich/Shutterstock

Early findings showed that vaccination with two doses led to a rapid decline in the rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, spread, and hospitalization/mortality statistics. However, long COVID is recorded to be a significant contributor to the disease burden and the acute infection.

Long COVID is less frequent in individuals who have breakthrough infections, but not much is known on how vaccination affects individuals who already have long COVID symptoms. A new preprint describes the results of a study examining this aspect of the disease.

A preprint version of the study is available on the medRxiv* server while the article undergoes peer review.


Symptoms may exist for several weeks or months after infection with SARS-CoV-2) and are defined as long COVID when they are present beyond 12 weeks from the onset of symptomatic illness. Some common presentations include fatigue, shortness of breath, and cognitive defects.

It is estimated that in October 2021, almost 2% of the UK population in private households reported such symptoms. Over two in three of them said this was hampering their daily functioning.

Vaccinations against symptomatic disease following SARS-CoV-2 infection began in December 2020, using adenovirus vectored vaccines or messenger ribonucleic acid (mRNA) vaccines. This rollout was followed by reduced infection numbers, a fall in viral transmission, and declining hospitalizations and deaths.

Breakthrough infections have been rising for about six months following the primary series of vaccination, but early results seem to suggest that they are much less likely to lead to long COVID. The researchers looked at data from the Office for National Statistics (ONS) COVID-19 Infection Survey (CIS) to further examine this association. This covers longitudinally acquired data from people aged 2 years or more, living in private households.

What did the study show?

There were over 28,000 participants in the final analysis who had been infected with the virus 12 or more weeks before the last visit, following which they had been vaccinated. Most of them had received both vaccine doses by September 5, 2021, and over 70% by February 3, 2021. The mean age was 46 years. Participants who received mRNA vaccines were typically younger, at a mean of 40 years, and more likely to be non-Whites.

The researchers found that about a quarter of participants said they had some symptoms of long COVID at some point during the study period. The odds were lower by 0.3% per week after the infection, went down by ~13% after the first dose of the vaccine, and then again declined by 0.3% per week until the second dose.

At this point, there was a fall of ~9% per week, and then the decrease continued at 0.8% per week.

One in seven said their long COVID symptoms limited some aspect of daily life. This went down by ~13% after the first dose but then went up by ~1% per week until the second dose. At this point, it went down by 9%, and then by 0.5% per week.

Individual symptoms also decreased after each vaccine dose, especially for anosmia, ageusia, insomnia after dose 1, and fatigue, headache, and sleep disturbances, after dose 2. The same increasing trend between the two doses, and a declining or plateauing trend after the second, were seen, though the study was underpowered to confirm these trends as significant.

Thus, long COVID increased between the first and second doses if the first dose was received 24 weeks from infection and the second 12 weeks from this point. Factors related to overall health, the type of vaccine used, or the time interval that elapsed between infection and vaccination were not significant in this association. No obvious effect of sociodemographic characteristics was found, either.

What are the implications?

The results of this study suggest that people who already had long COVID symptoms seemed to be less likely to have continuing symptoms following vaccination, with the change being observable over the follow-up period after the second dose of the vaccine was taken. The odds of such symptoms fell by 13% and 9% after the first and second dose, with the latter persisting over the study follow-up period of 67 days.

The underlying mechanism may be diverting the immune response from autoimmune responses and clearing any residual virus by the immune boost delivered by the vaccine. The persistence of the decline after the second dose could be due to the need for two doses to elicit an adequate immune response. Longer monitoring is required to identify the actual period of protection, however.

These findings suggest that COVID-19 vaccination may reduce the population prevalence of Long Covid by reducing the risk of continuing to experience persistent symptoms in those who already have them when vaccinated; developing persistent symptoms following breakthrough infections; being infected in the first place; and transmitting the virus following infection.”

Being an observational study, it cannot be inferred that vaccination reduces pre-existing long COVID symptoms. Still, this association deserves to be further explored to understand its underlying biological mechanisms.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.


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