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Is One Vaccine Dose Enough After COVID-19 Infection?

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COVID-19 vaccination record card
Credit: iStock/Bill Oxford

For the millions of Americans now eligible to receive the Pfizer or Moderna COVID-19 vaccines, it’s recommended that everyone get two shots. The first dose of these mRNA vaccines trains the immune system to recognize and attack the spike protein on the surface of SARS-CoV-2, the virus that causes COVID-19. The second dose, administered a few weeks later, boosts antibody levels to afford even better protection. People who’ve recovered from COVID-19 also should definitely get vaccinated to maximize protection against possible re-infection. But, because they already have some natural immunity, would just one shot do the trick? Or do they still need two?

A small, NIH-supported study, published as a pre-print on medRxiv, offers some early data on this important question [1]. The findings show that immune response to the first vaccine dose in a person who’s already had COVID-19 is equal to, or in some cases better, than the response to the second dose in a person who hasn’t had COVID-19. While much more research is needed—and I am definitely not suggesting a change in the current recommendations right now—the results raise the possibility that one dose might be enough for someone who’s been infected with SARS-CoV-2 and already generated antibodies against the virus.

These findings come from a research team led by Florian Krammer and Viviana Simon, Icahn School of Medicine at Mount Sinai, New York. The researchers reasoned that for folks whose bodies have already produced antibodies following a COVID-19 infection, the first shot might act similarly to the second one in someone who hadn’t had the virus before. In fact, there was some anecdotal evidence suggesting that previously infected people were experiencing stronger evidence of an active immune response (sore arm, fever, chills, fatigue) than never-infected individuals after getting their first shots.

What did the antibodies show? To find out, the researchers enlisted the help of 109 people who’d received their first dose of mRNA vaccines made by either Pfizer or Moderna. They found that those who’d never been infected by SARS-CoV-2 developed antibodies at low levels within 9 to 12 days of receiving their first dose of vaccine.

But in 41 people who tested positive for SARS-CoV-2 antibodies prior to getting the first shot, the immune response looked strikingly different. They generated high levels of antibodies within just a few days of getting the vaccine. Compared across different time intervals, previously infected people had immune responses 10 to 20 times that observed in uninfected people. Following their second vaccine dose, it was roughly the same story. Antibody levels in those with a prior infection were about 10 times greater than the others.

Both vaccines were generally well tolerated. But, because their immune systems were already in high gear, people who were previously infected tended to have more symptoms following their first shot, such as pain and swelling at the injection site. They also were more likely to report other less common symptoms, including fatigue, fever, chills, headache, muscle aches, and joint pain.

Though sometimes it may not seem like it, COVID-19 and the mRNA vaccines are still relatively new. Researchers haven’t yet been able to study how long these vaccines confer immunity to the disease, which has now claimed the lives of more than 500,000 Americans. But these findings do suggest that a single dose of the Pfizer or Moderna vaccines can produce a rapid and strong immune response in people who’ve already recovered from COVID-19.

If other studies support these results, the U.S. Food and Drug Administration (FDA) might decide to consider whether one dose is enough for people who’ve had a prior COVID-19 infection. Such a policy is already under consideration in France and, if implemented, would help to extend vaccine supply and get more people vaccinated sooner. But any serious consideration of this option will require more data. It will also be up to the expert advisors at FDA and Centers for Disease Control and Prevention (CDC) to decide.

For now, the most important thing all of us can all do to get this terrible pandemic under control is to follow the 3 W’s—wear our masks, wash our hands, watch our distance from others—and roll up our sleeves for the vaccine as soon as it’s available to us.

Reference:

[1] Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine. Krammer F et al. medRxiv. 2021 Feb 1.

Links:

COVID-19 Research (NIH)

Krammer Lab (Icahn School of Medicine at Mount Sinai, New York, NY)

Simon Lab (Icahn School of Medicine at Mount Sinai)

NIH Support: National Institute of Allergy and Infectious Diseases

221 Comments

  • Nancy Rene says:

    Please continue to study the Covid survivors. If their response is already much stronger than those without Covid, it seems like their immunity could last much longer. Very important news, thank you.

    • Dan C says:

      I am wondering if the vaccine is really necessary if a single dose expressing so only one protein of the virus could activate strongly the antibody production against this particular protein, why not wait more time to see whether already infected people keep memory T cell against a large number of viral protein that could easily be activated by a second infection and not the vaccination. I say this because there is a serious lack of vaccine for many people who have not already been infected. Waiting before vaccinating people who have resolved COVID-19 would give them access more quickly and therefore more quickly we will get rid of this virus. And then when more than 70% of people are seropositive for this virus, start injecting everyone in a single dose.

      • María B says:

        Hi Dan. I can agree with what you are saying, but I know several persons that have died after the second infection.

        • Mike N says:

          Seriously? How many? If that is the case then they need to stop allowing people that have had Covid to get the Vaccine.

    • Brooke G says:

      I was infected with COVID in September 2020, had a negative test before returning to work, then received the 1st Moderna vaccine on 1/7/21. I then tested positive the end of January and was told by my Public Health Department to NOT get the 2nd vaccine.
      My problem is that my employer announced that they will be making full vaccination mandatory, and I would have to restart the whole process because it has been well past the 42 day grace period. That being said, I’m not sure if I should revaccinate, and if I so, should I get the Moderna again, or can I get the Pfizer?

  • Patricia R says:

    As for the above article on those who have had Covid and getting the first vax and more antibodies than those who have not had Covid… for instance, I had 3 blood draws after Covid to check for antibodies as I wanted to give plasma.. Non of the 3 showed any Igg antibodies.. So for me, and who knows how many others, for some reason my body didn’t produce the antibodies.. or the lab made a mistake in testing the draw… the last of the 3 blood draws was done 2 months after I got the diagnosis of having Covid.. with the other 2 draws between the diagnosis and the 3rd… So they were definitely spaced out.. My family doc suggested that I should have had the draws done and tested by another lab … My point in leaving this comment.. that in my case.. I think I most definitely need 2 doses.. > I have always wondered if my body even produces antibodies from the Vax.. wish I could get tested again after my vax.

    • Dan C says:

      Dear Patricia, I think you do not have to worry about your body producing correctly antibodies, because if you got Covid and could cure yourself from it, the unique responsible for this is your immune system, that is then working as expected properly with production of antibodies or other molecules from virus-activated immune cells. I am agree with your family doc, you should be at least and right now tested again by another lab. Moreover, you said you were diagnosed as having Covid-19: did they test you for IgM or IgG at this time or by PCR?

  • Angela says:

    I have just recovered from Covid. I am 65 years old. How long before I should receive the vaccine?

    • Moderator says:

      Thanks for your comment, Angela. On its website that answers Frequently Asked Questions about COVID-19 vaccines, https://www.cdc.gov/coronavirus/2019-ncov/vaccines/faq.html, the U.S. Centers for Disease Control and Prevention says:

      “You should be vaccinated regardless of whether you already had COVID-19. That’s because experts do not yet know how long you are protected from getting sick again after recovering from COVID-19. Even if you have already recovered from COVID-19, it is possible—although rare—that you could be infected with the virus that causes COVID-19 again. Learn more about why getting vaccinated is a safer way to build protection than getting infected.

      If you were treated for COVID-19 with monoclonal antibodies or convalescent plasma, you should wait 90 days before getting a COVID-19 vaccine. Talk to your doctor if you are unsure what treatments you received or if you have more questions about getting a COVID-19 vaccine.

      Experts are still learning more about how long vaccines protect against COVID-19 in real-world conditions. CDC will keep the public informed as new evidence becomes available.”

  • Calvin S Lau says:

    Detailed update and perspective of where the science is now and how it might move forward

  • Patricia Chieffo says:

    So grateful to finally receive my 1st vaccination. The 2nd is scheduled!
    However, very distressed that my neighbors, half of them, all seniors,
    refuse to get theirs!

  • Paul says:

    I had the first vaccine shot (Moderna) on January 21. I tested positive for Covid-19 on February 13, I missed my second vaccine dose because of quarantine. Should I get the second vaccine after quarantine?

  • G. Dianne Wilkes says:

    Thanks for this information. I have a good friend on the West Coast who tested positive, but did not have to be hospitalized – before she received her first immunization. She now has received the 2nd injection also. It was frightening to hear she had tested positive – especially as she also has mild C.P. and related issues. Thank you for all you have done at NIH to attempt to keep the public informed – as well as CDC, FDA, et al – and for all you continue to do as the virus mutates.

  • Julie Beal says:

    I had Covid in late October and tested positive for antibodies in early November. I had a 101 plus fever for 5-6 days but was not hospitalized. Labored breath and cough lasted for a month or so.
    After my first Moderna vaccine shot, I had a bad reaction (chills, fever, nausea and headache) that lasted about 24 hours. I plan to get the second shot in two weeks but am asking if I should expect to have a similar reaction to the second shot. Please let me know if there is any information to guide me.

  • Henry says:

    If you had COVID but did not receive antibody treatment, how long should you wait before getting vaccinated?

  • Julie B says:

    My uncle just got his first Moderna shot and he tested positive for covid in January he had fever and chills for about 24 hours after the shot and a very sore arm as well …. interesting article and comments thank you

  • George Oviatt says:

    We had a positive covid and recovered. Three weeks later took our first vaccination. Wow, long term sore arm, chills, malaise, stomach discomfort. So the question. Should we have the second shot, knowing from public response, that the effects may even be worse?

  • ceyloncocopeat says:

    Is this vaccine active for other Covid viruses as well? Is there any possibility to test positive for Covid after getting vaccinated?

  • Linda L. says:

    I had Covid in March 2020. I was positive for over two months. The end of August I tested negative for IGG antibodies. I received the first Pfizer vaccine dose a week ago. I was ill for four days with fever, chills, headache, joint and muscle pain. The sore arm was the least of the issues. Now I am very concerned about what to do about getting the second. The advice is always to contact your physician. Problem is they are as clueless about this as they were about the virus at the time I had it.

    • Elaine says:

      Hi Linda, I was in a similar position to you, I had moderate symptoms with COVID-19 in March 2020. After recovering I enrolled in a research study of long-term immunity. In October 2020, I had very low levels of neutralizing antibodies but found to have good T-cell immunity (this was measured in a university research lab – not a commercial lab like Quest). In January, my study bloodwork revealed no detectable neutralizing antibodies but very good B & T cell immunity. I work in healthcare and had the first Pfizer vaccine at the beginning of Feb. I experienced severe arm pain, low grade fever, body aches, headache, diarrhea, and fatigue, it took 3-days to recover. I was uncertain about the second dose, however did go ahead and had the second shot. I had the arm pain again but much less so, I again had the generalized symptoms and they were slightly more intense, but I recovered in one day. I hope that helps.

  • jan says:

    It would seem to make eminent sense to start screening for antibodies prior to vaccination and if the single dose for antibody-positive people is confirmed to be sufficient this would then allow for the vaccines to be distributed more widely. It would also have the benefit of collecting clinically important real world data on the interaction of the primary dose with pre-existing immunity and the spectrum of post-infectious outcomes.
    It could also reduce the chance of “over-egging” the cake via a hyper-stimulated immune response leading to unpleasant and possibly dangerous pathology for those with antigen persistence (testing positive over a long period, or recurring symptoms as seen wth “Long Covid”).
    This virus is quite cryptic due to the range of presentations- not everybody who has had it, knows that they have- and obviously won’t have acquired evidence of infection and its sometimes silent effects on organ systems. To some degree there is a growing iceberg of data that will only become apparent after the acute stage of the pandemic is over.
    Until then the confidence to use a common sense approach and take into account that as far as immunity is concerned, the least you can say is that previously infected are a different population to the naive and are likely to need different protocols.

  • Gail P. says:

    I had my first dose of Pfizer vaccine but 5 days later was exposed to a positive case & contracted the virus. I ended up having a monoclonal antibody infusion & am aware therefore that I have to wait 90 days thereafter to have my 2nd dose vaccine. My question is do I need the 2nd dose vaccine if I’ve already had 1 dose + contracting covid + monoclonal antibodies? …& if the answer to that is yes then do I need to start over after 90 days & thereby that would then be my new dose 1?

  • Bob R says:

    tested positive in late January 2021. Now have tested negative. Received first vaccination 2 weeks ago and had bad covid symptoms for 2 days. Fever, aches, general malaise. Don’t really want to have to get the second vaccination on March 3rd unless I’m certain it help benefit me and others. Sure wish somebody would give me a straight answer. It’s all well we think maybe, or yeah you might not need it, or yeah you should follow guidelines etc.

  • Linda D says:

    I was among the first in my state to get Covid (March 1, 2020) and had my first vaccine on Feb. 3, 2021 with my second one scheduled for next week. In light of recent studies and the question of whether the Moderna vaccine is effective against the African variant, should I still get the second vaccine? (I had intense reactions to the first one.) Hard finding an authoritative answer to this question. Is there a vaccine more effective against the variants on the short horizon and will I be eligible for that if I cancel this appointment? How protected am I from the variants with the current Moderna vaccine being offered?

  • KS says:

    I am researching this because my husband and I both got the first dose of the Moderna vaccine 2 days ago. The first few hours afterwards were fine, nothing major, but the night was awful!! Body aches so bad I took a hot bath at mid-night to try and stop the pain. The second day we couldn’t even go to work we felt so bad. We both had fevers, chills, and extreme body aches. 3 months ago we had an outbreak of the virus in my family. My husband actually tested positive, so we know 100% he had it. I am pretty sure I also had a mild case of the corona virus. My point is, older people with less aggressive immune systems seem to have minimal side affects from the first or second doses of the vaccines. Younger to middle age people that HAVE NOT had the virus seem to have minimal side affects from the first dose, and mild side affects from the second dose. We are middle aged, healthy individuals, who have had the virus, and wanted to share our experience so that others might be prepared!! Day 3 is today, and I am not 100%, but I am back at work and I am trying to move around as much as possible to help with the aches. Basically, the first 24 hours were hell after the shot, but after personally experiencing it, and knowing it will get better by the third day, I would say 24 hours of hell is better than weeks of the severe corona virus. This article seems to prove what we experienced, our bodies reacted fast and hard to the FIRST dose of the vaccine because our bodies recognized it!

  • geraldine k. says:

    I’m a 68 year healthy woman. I don’t take medication for anything as I have no sicknesses that require medication. The only tablets I take daily is Vitamin D3 since 2010, and Vitamin B12, Vitamin C, and Zinc.. I had Covid 19 Dec 09 2020, no fever, very congested, wet cough, very bad cough, sore hips, headache, very very tired, lethargic tested positive Dec 15th. I honestly thought I had the flu. I received the Moderna Vaccine on Monday Feb 22, at 2PM they held me 30 minutes after the vaccine to see of allergic reaction. That night about 3am I got extremely nauseous, shivering and extreme headache. I was so sick I could hardly get my muscles to move me out of the bed and get down the stairs in my house to let my dogs outside. I had a fever of 101.3, chills, brain fog, pressure on the sides of my head, headache, and tired and my muscles hurt so bad it was so hard to walk. Fever broke on Tuesday at about 4PM and started to feel slightly better. Finally Tuesday night I was say I was on the road to recovery. It is now Thur. Morning still woke up with headache, and still have brain fog. The sickness I had on Tuesday was definitely worse than the Covid i was diagnosed with. This was the worst sickness I have felt in years can’t ever remember feeling this sick. I called Kaiser my primary care Dr. and got the script read to me, “Nobody can guarantee nothing is standard, and nobody can assure you of anything on the second vaccine.” Well exactly what I thought I would hear. Yes, I was angry. I know the second shot is recommended, but at the same time if I got that sick after first shot, how sick will I get after the second 2? This was not a mild case after my 1st shot. I’m scared to go for the second shot. The reaction to the shot proves that I have antibodies? Does more antibodies hurt you?

  • v says:

    medical experts have yet again stressed upon the need to maintain Covid-19 appropriate behavior even after one has received the first shot of vaccine. This for the simple reason that one is not immune against the virus till both the doses have been taken.

    • simone a. says:

      I think it is not only the fear of pain that might stop me from getting the second vaccine (my experience was almost the same as Geraldine K, and I am 75 y old,), what scares me is the reaction of our immune system. Could the immune system overreact and turn against itself?

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