Writing this during the period between my first and second dose of the Pfizer-BioNTech mRNA vaccine against COVID-19, hearing from friends and colleagues about their reactions to the second shot, I won’t be at all surprised to be hit with a fever for several hours and/or arm soreness, or headache much worse than after the first dose. I’m not worried. Actually, I will think “Wonderful…phewww….they kept it cold.” Soreness in the shoulder is from a local inflammatory reaction and chills and/or fever, or just elevated body temperature not reaching febrile levels —that’s a sign that the immune is responding to the vaccine, or some aspect of it. It’s something that should not surprise us after either dose, but it can happen more strongly after the second dose, since it is a reaction of an immune system that has already been primed, already had its first round of target practice. But you may be wondering how to place this in context of pregnancy, given that you may be scheduled soon for your first or second dose of COVID-19 vaccine and also may remember from previous posts that fever is not a good thing during pregnancy.
In a few countries, vaccination has really moved quickly, such as in Israel, where more than half of the population has received at least the first dose of either the Pfizer-BioNTech or Moderna vaccine. Elsewhere, much of the population remains to be vaccinated against SARS-CoV2 (the virus that causes COVID-19), including in the United States, but many women of reproductive age work in health care and thus are at the top of the list in terms of risk and priority for vaccination. In many US states, teachers also are being given priority, and vaccination is coming for everybody soon, so, one way or another, it will be available to you. For simplicity in this post though, let’s imagine that you’re approaching your second dose, having received your first dose, with some arm soreness, but otherwise not enough discomfort to lead you to consider taking anti-pain, anti-fever (anti-pyretic) medication, but are worried that you might need it the second time around. There are three factors to discuss. One factor is the guidelines, what health authorities recommend that people do. Another factor, which is related to the first, is whether there is a concern that taking anti-fever medication will blunt the process through which the immune system learns to defend against SARS-CoV2. And finally, there is the pregnancy factor.
As for the health authorities, the US Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) say that it is acceptable for recipients of COVID-19 mRNA vaccines to take analgesic (anti-pain) and antipyretic medication to treat vaccine effects, such as arm soreness, headache, and chills and fever, if and once such effects develop, but the CDC recommends against taking such medications prophylactically, meaning before you get the first or the second shot to prevent such symptoms. Such authorities are talking about two main categories of such medications, one being acetaminophen in the United States (and a similar drug called paracetamol in many other countries). This first category of medications is analgesic and antipyretic, but is not anti-inflammatory, meaning it does not counter inflammation. The other main category is non-steroidal anti-inflammatory drugs (NSAIDs), the most popular of which is ibuprofen, which in addition to treating fever and pain also interfere with inflammation, and there are some other categories of medicines that work similarly, but with slightly different mechanisms.
This brings up the second factor, the concern about interfering with the target practice of the immune system. The rationale for avoiding the medications prior to the shot is that the medication could be blunting immunological processes that lead your immune system to recognize what it would see on the virus, if you are ever exposed. In the case of the vaccines against SARS-CoV2, the thing to be recognized is the spike protein. The recommendation that it’s okay to take anti-fever/anti-pain/anti-inflammatory medications once symptoms develop, but not before getting the shot, is based on experience with various other vaccines, such as vaccines against seasonal flu. This is weighted against concerns about hypothetical scenarios that blunting the fever response, could interfere with the training of the immune system, since the fever response involves chemicals called interleukins that are part of the immune response and also part of the disease process when people develop symptomatic COVID-19. Included among the hypothetical concerns is the idea that drugs like acetaminophen may cause less interference than NSAIDs, since the latter interfere, not only with fever, but also with inflammation, and thus with more pathways connected with generating an immune response.
Related to the above, we should note something about the timing of the immune response with respect to getting each shot. Recall from some of my previous posts the way that the Pfizer-BioNTech and Moderna vaccines work. The business end of the vaccine is a strip of mRNA, which is contained within a lipid nanoparticle. The nanoparticles merge with the cell membranes that surround cells. This process delivers numerous, identical strands of vaccine mRNA into numerous body cells of different kinds. The mRNA is translated, meaning that its sequence is read to make spike protein, which then is processed —the translation of each strand of mRNA produces a subunit of spike protein and three subunits must be combine into a full molecule of spike protein. Ultimately, the process results in the assembled spike protein being transported to the surface of the cell, where —depending on whether it is attached to a more generic kind of other protein called MHC-1, or to a more specialized protein called MHC 2, present only on certain cells— stimulates different aspects of the immune response. Relevant to our discussion today, one thing that scientists have learned from recent research is that most of the mRNA that is delivered into cells is destroyed within 24 hours, whereas it takes about 48 hours from the time of injection for the amount of spike protein on affected body cells to reach its peak amount. Presumably, what’s happening between the time when the mRNA gets in and starts being translated, going through several rounds of translation, and then being destroyed within 24 hours, and the time at 48 hours after the shot when the amount of spike protein peaks, is processing of the spike protein. What I mean by processing is that the three subunits are being combined and other things are happening to the initial protein product before it is a ready-to-use spike protein that gets to the surface of the cell and is attached either to MHC-1, or MHC-2.
But the arm soreness and fevers after the first, and especially the second, shots are peaking somewhere in the range of 6 to 18 hours after the shots, not 48 hours plus, so what’s really happening? The answer is not yet clear. Maybe it’s a response to some spike protein getting to the surface of cells and starting the immune system’s target practice long before the peak at 48 hours, or maybe it’s the immune system, reacting to the nanoparticles on their way to deliver the spike protein. If it’s the latter, then taking anti-fever medication after, or even before, symptoms start is not going to blunt the immune response to the spike protein, which is the immune response that interests us the most, since that’s the response that will lead to protection against the virus. If it’s the former, well then we’d want to take the medications only if needed, which is a good approach anyway when it comes to medications.
This brings us to the pregnancy factor, where, in addition to the goal of keeping the vaccine effective, we need to consider effects of the drugs, and effects of elevated body temperature. When it comes to the drugs, acetaminophen and paracetamol are not bad during pregnancy, or for that matter during lactation. As for NSAIDs, like ibuprofen, these drugs should be avoided in late pregnancy —onward from gestational week 28 or week 30, depending on which research study you read— because they can cause what’s called premature closure of the ductus arteriosus —a blood vessel that connects the aorta (the big artery carrying blood from the heart’s left ventricle) and the pulmonary artery (the big artery carrying blood from the right ventricle) in the fetus and normally closes up after birth, when we don’t want the aorta and pulmonary artery to be connected. There is also some concern that NSAIDs may pose risk if used earlier in pregnancy, such as the risk of spontaneous abortion (miscarriage) if used in the first trimester, but the evidence for early pregnancy risk is not as strong as the evidence involving the late pregnancy use and patent ductus arteriosus.
But when you are pregnant, all of this must be weighted against the dangers of maternal fever, which has been associated with a range of bad outcomes for the fetus/embryo, such as spontaneous abortion, preterm birth, growth restriction, stillbirth, and neural tube defects (the spine or skull does not completely close around the spinal cord or brain, respectively). Such dangers are very much related to the duration and magnitude of temperature increase in the mother. The way that it all works out is that health authorities issuing guidelines, such as the American College of Obstetricians and Gynecologists (OCOG) recommend that a pregnant woman not let her body temperature rise above 39° C (102.2° F). The chances are that your temperature is not going to get this high in response, either to your first or second shot of one of the COVID-19 mRNA vaccines, nor would you likely spike —excuse the pun— a high temperature for very long. But you should take your temperature after you get home from getting your shot and keep doing that every couple of hours or so, as you feel the effects of the vaccine. Based on the recommendations of the health authorities, the very hypothetical nature of the concerns about blunting the immune response, and experience with other vaccines, it’s fine to hold out for as long as you are comfortable after your shot, but then to take acetaminophen or paracetamol when you feel that you need it, such as for chills or headache. And, if your temperature is approaching 39° C, then by all means, treat the fever, as keeping your body temperature down becomes the priority at that point.