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Side effects of COVID-19 vaccination: Do not treat too early

Paracetamol and other antipyretic pain relievers are used regularly to treat vaccine side effects. However, what this means for effectiveness is being discussed.

In its information sheet on vaccination against COVID-19 dated January 21, 2021, the Robert Koch Institute (RKI) recommends under the subheading "How do I behave before and after the vaccination?", In the event of pain and fever after the vaccination pain reliever and antipyretic drugs are taken. Paracetamol is mentioned as an example (1).

Antipyretic pain relievers such as paracetamol are indicated to treat flu-like vaccination side effects such as fever, headache, fatigue and myalgia. However, given the extensive reports on the side effects of the COVID-19 vaccination, some patients may be taking it in anticipatory panic.

The working group around Dr. Mahyar Etminan, a pharmacologist at the University of British Columbia in Vancouver, Canada, said in a recent publication that it was not known whether this could affect the effectiveness of the COVID-19 vaccinations (2). He points to a much discussed randomized study in the Lancet, according to which the simultaneous intake of paracetamol to prevent side effects when vaccinating a cohort of children had significantly reduced the antibody titers compared to controls (3).

He also quotes the US Centers for Disease Control and Prevention (CDC), which, in line with the WHO, do not recommend the use of antipyretic drugs before or immediately after vaccination, but which do not suggest anything against it in the days after (4).

Prof. Dr. med. Thomas Herdegen, Deputy Director of the Institute for Experimental and Clinical Pharmacology at the University of Kiel, explains that the question of whether non-steroidal anti-inflammatory drugs (NSAIDs) can suppress the vaccination response is not specific to COVID-19, but applies to many vaccinations. It is known that inhibitors of cyclooxygenase-2 (COX inhibitors or NSAIDs) - including paracetamol - effectively weakened the accompanying pseudo-flu reactions as side effects of vaccination by suppressing prostaglandin synthesis. They also reduced the vaccination titer by inhibiting prostaglandin synthesis. "However, it is unclear whether and how much such a reduction weakens the immune response in a clinically relevant manner," Herdegen told Deutsches Ärzteblatt.

Nevertheless, a clinically relevant weakening of the immune response must be expected - at least for patients with a restricted immune response or immunization - in terms of pharmacovigilance in general and also with COVID-19 vaccinations. A study from 2014 shows for adults that paracetamol had no influence on the immune response after 6 hours, while administration immediately after the vaccination weakened it (5).

Rather treat later

"From this one could derive the recommendation to give COX inhibitors after 6 hours at the earliest, when the primary immunization processes have expired," says the Kiel pharmacologist. Like the group from Vancouver, he emphasizes that so far there have been no scientific studies that specifically examine the effects of antipyretic pain killers - whenever taken - on COVID-19
Vaccination checked.

Nothing was published about this in the context of the Moderna study. The Pfizer vaccine study mentioned that the higher the vaccine dose, more antipyretic drugs were used, but no data on the resulting immunogenicity were made available. The AstraZeneca vaccine was even treated prophylactically with paracetamol. This was reported to have no effect on immunogenicity, but no data were provided for verification. Therefore, many ambiguities still need to be scrutinized, demand the Canadian scientists.

Rather not a preventive gift

"For example, it remains to be seen whether there will be a certain latency period after which COX inhibitors will no longer reduce the titer or the immune response," explains Herdegen. In addition, it is important to clarify which of the various anti-inflammatory drugs have what effect on antibody titers and immogeneity.

From the facts known so far, one could at most infer that prophylactic administration should generally be avoided if this is not absolutely necessary in order to avoid a vaccination reaction. Otherwise, therapy should only be given when the first vaccination reactions occur, but (if possible) not earlier than 6 hours after administration of the vaccine. And you should know that fast-acting COX inhibitors like ibuprofen lysinate actually work within 30 minutes, but only if they are taken on an empty stomach. Dr. med. Martina Lenzen-Schulte

Literature on the Internet:
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Information sheet from the Robert Koch Institute (RKI): https://www.rki.de/DE/Content/Infekt/Impfen/Materialien/Downloads-COVID-19/Aufklaerungsbogen-de.pdf?__blob=publicationFile (last accessed on 16 March 2021).
Etminan M, Sodhi M, Ganjizadeh-Zavareh S: Should Antipyretics be used to Relieve Acute Adverse Events Related to COVID-19 Vaccines? Chest 4 Feb 2021 (preproof online) doi: 10.1016 / j.chest.2021.01.080 (last accessed on 16 March 2021) CrossRefMEDLINEPubMed Central
Prymula R, Siegrist CA, Chlibek R, et al .: Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomized controlled trials. Lancet 2009; 374 (9698): 1339-50 Cross Ref
Centers for Disease Control and Prevention (CDC): Vaccine Administration - General Best Practice Guidelines for Immunization: Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP), https://www.cdc.gov/vaccines/hcp/acip- recs / general-recs / administration.html (last accessed on 16 March 2021).
Doedée AM, Boland GJ, Pennings JL, et al .: Effects of prophylactic and therapeutic paracetamol treatment during vaccination on hepatitis B antibody levels in adults: two open-label, randomized controlled trials. PLoS One 2014; 9 (6): e98175 CrossRefMEDLINEPubMed Central