Clinician holding syringe and vaccine vial in both hands

COVID-19 and Long Covid:

COVID Vaccine: Side Effects in Women & the Purpose of Two Doses

April 1, 2021

Retrospective hospital analyses and cohort studies have shown that people with autoimmune disease are not more susceptible to severe COVID-19 symptoms. Moreover, health experts now offer concrete recommendations for autoimmune disease patients about the COVID-19 vaccine. What do we understand about vaccine side effects in the general population, and how does it parallel outcomes for autoimmune disease (AD)? Moreover, how do the two doses of both the Moderna and Pfizer vaccine fully protect people against severe COVID-19 infection while also mitigating the spread of variants? 

According to news reports and clinical observations, women may be more susceptible to experiencing side effects from the new COVID-19 vaccines than men. Last month, the Centers for Disease Control and Prevention (CDC) published a report monitoring the 13.7 million doses of the Pfizer-BioNTech and Moderna vaccines distributed between December 14, 2020 and January 13, 2021. Around 60% of people who received the vaccine were women, and 79% of side effects were reported by women. Headaches, dizziness, and fatigue were the most common side effects experienced.

Women experience COVID-19 side effects more often than men

Health experts are unable to discern precisely why women account for the majority of those experiencing side effects. While social factors may be at play—e.g. a greater willingness to get vaccinated, as well as an increased likelihood of reporting side effects – there are also biological reasons that can substantiate this occurrence.

Myriad factors underscore the prevalence of women experiencing vaccine side effects in general. This prevalence parallels the rate of autoimmune disease in women. While the overall prevalence of autoimmune disease is far from being known, it has been consistently established in the scientific literature that around 78% of people experiencing autoimmune disease are women (1). Autoimmune diseases are characterized by the activation of T cells or the presence of B cells (autoantibodies), often in response to a viral infection (2). In response to the vaccine and autoimmune diseases, the immune system creates a robust response.

When someone receives the vaccine, the immune system produces antibodies, and a noticeable physiological reaction indicates an appropriate and healthy immune response. According to the CDC, “side effects are normal signs that your body is building protection” (3). That being said, almost 50% of patients don’t experience side effects. Experts are unsure as to why some people experience side effects, and others don’t. As far as we know, the severity of side effects (or lack thereof) does not impact the vaccine’s efficacy.

The production of estrogen—a hormone involved in regulating the immune system—is one determining factor responsible for higher rates of side effects and encouraging the production of T-cells. T-cells play a role in both innate and adaptive immunity, and studies have shown that a higher number of T-cells are activated during the adaptive immune response in women versus men (4). These T-cells increase the immune response, which can also lead to increased efficacy of the vaccine. The heightened immune activation dampens the virus’ severity; in fact, women typically have a lower viral load (number of viral particles in the body) than men because their bodies can generate a more robust immune response. This same biological response plays a role in the predisposition women have towards developing diseases from an overactive immune system, a.k.a. autoimmune disease (5).

Additionally, research has shown that women generally need a lower vaccine dose to elicit an immune response (6). This may be partially due to the fact that immune-related genes are found within the X chromosome (of which women have two copies, whereas men have one). X chromosomes hold more genetic information and create more genetic mutations than Y chromosomes, leading to the potential development of autoimmune diseases.

Because vaccine doses are the same across the board, women may be receiving a higher amount than necessary to elicit an immune response and gain protection against COVID-19. 

Women, in general, have more immunity than men—whether towards a virus, a vaccine, or their own body. Regardless, the CDC encourages women to receive the COVID-19 vaccine amidst concerns of possible side effects, as the majority are short-lived and mild in nature. 

The CDC recommends that patients stay away from ibuprofen, aspirin, or acetaminophen directly before their vaccination appointment, as it may damper the body’s immune response, thereby impacting the vaccine’s efficacy (7). It is possible to have an allergic reaction within 4 hours of getting vaccinated. This can include hives, swelling, and wheezing. Even though these reactions may not require emergency care, the CDC recommends that you do not get a second shot of that mRNA vaccine (8). The Johnson & Johnson vaccine only requires one dose. General fatigue, pain, redness and swelling around the injection site, headache, chills, low-grade fever, and nausea are some of the common side effects. For updates on possible side effects to the COVID-19 vaccine, check out this page by the CDC. 

The purpose behind two doses 

It has been noted that patients more commonly experience side effects after receiving their second dose of the COVID-19 vaccine. This may be due to the fact that the body creates two separate immune responses after each dose. After being inoculated with the COVID-19 vaccine for the first time, the body recognizes the outside invaders and is prompted to create a first-line response. Instead of fighting to kill the invader, it slows down the rate of infection. This is innate immunity. While your body isn’t actually being infected with COVID but rather, an incomplete copy of its genetic material, the body still fights as if it’s in contact with a live virus. 

After the body’s innate response, it begins the production of T cells and B cells to fight against infection. The production of antibodies spurs the body to react at the tissue level, offering more protection against the virus. While the body is creating antibodies from the first COVID-19 vaccine dose, the second dose “supercharges” the antibody response since the body has actively been building immunity (9). 

It takes around two weeks after the second shot of Moderna or Pfizer’s vaccine for a complete immune response that provides protection against COVID-19. This is the five to six week mark after the first dose. While one dose of the Pfizer vaccine reduces a person’s risk of getting COVID-19 by around 50%—and 80% for Moderna’s—this increases to around 95% after the second dose. The CDC recommends that the Pfizer vaccines be spread 21 days apart, whereas for the Moderna vaccine, 28 days. That being said, there is some wiggle room (10). 

It takes around four weeks for full immunity against COVID-19 after getting Johnson & Johnson’s vaccine (11). Johnson and Johnson reported that T-cell response was detected in clinical trial participants 15 days post-inoculation. By day 29, 90% of participants had coronavirus-neutralizing antibodies in their blood, regardless of age (11). 

Mitigating the spread of variants

While questions have surfaced regarding the need for two doses, experts continue to agree that a second dose of the Pfizer or Moderna vaccine is necessary to suppress the emergence of COVID-19 variants (12). As more people become vaccinated and create antibodies to ward off the novel coronavirus, the virus will mutate to evade those defenses. By only getting partially vaccinated (receiving one dose), the body is left with holes in its defenses to fully protect itself from COVID variants (12). Variants tend to spread faster and are more transmissible as people have lower immunity to fight against them. This is one reason why experts have shown mounting concerns around mutations such as the B.1.1.7 variant. The CDC updates their website regularly with real-time numbers on COVID-19 cases caused by variants across the US

If one dose of the vaccine creates partial immunity, the body could become defenseless against antibody-resistant variants of the virus. Providing the body with full protection will limit the number of variants to grow and spread. 

Read more about recent developments on COVID-19 and vaccine recommendations in the context of autoimmune disease by reading our latest featured article. You can also check out our timeline for up-to date information regarding COVID-19.

If you’ve received the COVID-19 vaccine and have experienced an allergic reaction(s) or side effects, report them to the CDC using their V-Safe After Vaccination Health-Checker app
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To the best of our knowledge, this article is accurate as of the date specified. Because the COVID-19 pandemic is rapidly evolving, as is the scientific community’s understanding of this virus, information and insights are constantly updating. Please read resources provided by the CDC, WHO, and public health authorities to stay informed, and seek professional medical advice for best practice pertaining to your medical plan.


  1. Article Sources and Footnotes
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    2. Rodriguez, Y., Novelli, L., Rojas, M., De Santis, M., Acosta-Ampudia, Y., Monsalve, D.M., Ramirez-Santana, C., Costanzo, A., Ridgway, W.M., Aftab, A.A., Gershwin, M.E., Selmi, C., & Anaya, Juan-Manuel. (2020). Autoinflammatory and autoimmune conditions at the crossroad of COVID-19. Journal of autoimmunity, 114 (102506).

    3. Center for Disease Control and Prevention. (2021). Possible side effects after getting a COVID-19 vaccine. National Center for immunization and respiratory disease.

    4. Klein, S., & Flanagan, K. (2016). Sex differences in immune responses. Nat Rev Immunol 16, 626–638.

    5. Takahashi, T., Ellingson, M.K., Wong, P., Israelow, B., Lucas, C., Klein, J., Silva, J., Mao, T., Eun Oh, J., Tokuyama, M., Lu, P., Venkataraman, A., Park, A., Liu, F., Meir, A., Sun, J., Wang., E.Y., Casanovas-Massana, Wyllie, A.L., Vogels, C.B.F., Earnest, R., Lapidus, S., Ott, I.M., Moore, A.I., Yale IMPACT research team, Sahw, A., Fournier, J.B., Odio, C.D., Farhadian, S., Dela Cruz, C., Grubaugh, N.D., Schulz, W.L., Ring, A.M., Ko, A.I., Omer, A.B., & Iwasak, A. (2020). Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature 588, 315–320.

    6. Klein S. L. (2012). Sex influences immune responses to viruses, and efficacy of prophylaxis and treatments for viral diseases. BioEssays: news and reviews in molecular, cellular and developmental biology, 34(12), 1050–1059.

    7. Center for Disease Control and Prevention. (2021). Getting your COVID-19 vaccine. National Center for immunization and respiratory disease.

    8. Center for Disease Control and Prevention. (2021). What to do if you have an allergic reaction after getting a COVID-19 vaccine. National Center for immunization and respiratory disease.

    9. Stappenback, T. (2021). If you don’t get sick after your COVID-19 vaccination, does it mean your immune system isn’t working? Health essentials.

    10. Kelen, G.D., Maragakis, L.L. (2021). Getting the COVID-19 vaccine: what to expect. Johns Hopkins Medicine.

    11. Sadoff, J., Le Gars, M., Shukarev, G., Heerwegh, D., Truyers, C.,de Groot, A.M., Stoop, J., Sarah Tete, S., Van Damme, W., Leroux-Roels, I., Berghmans, P.J., Kimmel, M., Van Damme, P., De Hoon, J., Smith, W., Stephenson, K.E., De Rosa, S.C., Cohen, K.W., McElrath, J.M., Cormier, E., Scheper, G., Barouch, D.H., Hendriks, J., Struyf, F., Douoguih, M., Van Hoof, J., & Schuitemaker, H. (2021). Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine. New England journal of medicine.

    12. Broadfood, M. (2021). Is It Safe to Delay a Second COVID Vaccine Dose? Scientific American.