In a recent article posted to the medRxiv* preprint server, investigators in Norway and Sweden compared medical complaints after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection following second and third dose SARS-CoV-2 vaccinations.

Study: Medical complaints after 3 vs 2 doses SARS-CoV-2 mRNA vaccination. Image Credit: MattLphotography / ShutterstockStudy: Medical complaints after 3 vs 2 doses SARS-CoV-2 mRNA vaccination. Image Credit: MattLphotography / Shutterstock


Following mild coronavirus disease 2019 (COVID-19), the most prevalent persistent complaints are fatigue and respiratory issues like shortness of breath and cough, commonly referred to as the post-COVID condition. 

The present study’s authors recently reported that these complaints are similarly prevalent following the SARS-CoV-2 Omicron and Delta infections. However, uncertainty exists regarding the impact of COVID-19 messenger ribonucleic acid (mRNA) vaccination on these post-COVID complaints. Furthermore, it is unknown whether vaccine reactogenicity might result in such complaints long and short term.

According to a recent rapid review, people who received one or two doses of the SARS-CoV-2 vaccine were less likely to get long-COVID symptoms. A better understanding of the overall effects of the third dose COVID-19 vaccine on medical complaints are required to comprehend its implications for health services. Any apparent health service effects could be considered when deciding whether to administer the fourth dose of the SARS-CoV-2 vaccination.

About the study

In the current work, the researchers at the Norwegian Institute of Public Health, University of Oslo, Oslo University Hospital, Oslo and Lund University analyzed whether those who received three SARS-CoV-2 vaccine doses within 20 and 30 weeks following receiving the second dose had a different risk of experiencing medical complaints after COVID-19 about 90 days later than those who did not receive the third shot. They also evaluated whether any varied incidence was most likely associated with distinct COVID-19 occurrences between groups.

In the prospective cohort investigation, the team used information from the Norwegian Emergency Preparedness Register to assess people who were 18 to 70 years old and residing in Norway on January 1, 2021. The research covered working-age males and females in two cohorts: 18-44 and 45-70 years. 

The scientists acquired a matched sample of 138,581 participants aged 18 to 70 who received the third dose of the vaccine 20 to 30 weeks after receiving the second dose and an equally sizable control cohort who did not. For this, they utilized longitudinal exact 1:1 matching on days following the two-dose vaccination, calendar month, and a set of covariates. The study’s key outcomes were medical records showing frequent post-COVID complaints encountered in primary care for about 90 days following vaccination.


The study results indicated that following the third dose of the COVID-19 vaccination, the projected 90-day cumulative incidence of medical complaints following SARS-CoV-2 infection ranged between 70 and 5,000 per 100,000 people, depending on the complaint type.

Three vaccination doses resulted in fewer medical complaints among people aged 18 to 44; i.e., 662 respondents (662 per 100,000 immunized) reported fatigue, 160 reported shortness of breath, and 65 reported brain fog. The team noted that compared to those who were not vaccinated, individuals who had three doses of the vaccine at intervals of 20 to 30 weeks after the second dose had a 20% to 40% decreased risk of experiencing post-COVID medical complaints up to 90 days later. No decline in occurrence was seen for cough, musculoskeletal pain, or heart palpitations.

Following the exclusion of subjects aged 18 to 44 according to the date of the COVID-19-positive test, these absolute differences were less pronounced. This inference suggested that variations in COVID-19 incidence may have contributed to the variations in complaints. 

Similar studies censoring positive tests produced more unclear results. Yet, higher estimates for people between the ages of 45 and 70. This observation was because of skewing linked with healthy vaccinees.

Importantly, none of the present analyses revealed any immediate hike in medical complaint incident outcomes following the third shot of the mRNA vaccine, demonstrating that possible side effects might not put a strain on primary care facilities.


The authors claimed that the present study was the first to assess how the third SARS-CoV-2 mRNA vaccine dose may affect complaints linked with vaccination seen in primary care.

The study findings suggested that three-dose COVID-19 vaccinated subjects experienced a lower rate of complaints versus matched controls with two-dose vaccination. Studies comparing analyses with and without filtering positive SARS-CoV-2 tests indicated that a lower incidence of COVID-19 among those who had three doses of vaccination could account for this decrease.

On the whole, the present study showed that COVID-19 and post-COVID complaints were less common in those who received a third dose of the SARS-CoV-2 mRNA vaccine at 20 to 30 weeks after their second dose than in their matched controls. This may be at least partially explained by variations in SARS-CoV-2 incidences. These results may be relevant for deciding when and if a fourth shot of the mRNA vaccine should be given in public health scenarios.

*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.


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