COVID Free Corner: Vaccine primer from an open-minded infectious disease specialist
Dr. Ng is a full-time provider at the Chung Institute. He practices part time as an infectious disease specialist at Cooper University Hospital and researcher with the Won Sook Chung Foundation. His wife, Anna, is also a health care provider and they have been quarantining with her parents through the pandemic and thankfully all vaccinated. Their five-year-old son, Christian, has been attending school in person full time through the pandemic.
What makes SARS-CoV2 different and so infectious?
It is a novel virus with a naïve immune response. Pre-symptomatic spread may lead to a lack of protective measures.1 It appears to be more contagious – potentially intrinsic to the virus related to viral load, site of infection, affinity to bind to host receptors etc.
How is it spread?
Respiratory droplets>aerosol>fomites (contaminated surfaces)
What leads to severe disease and poor outcomes?
Host factors, viral inoculum, different or delayed treatment measures, viral strain/mutations?
What is my opinion for preventing severe COVID?
The measures above may be good advice as public health measures, but need to be tailored for each individual’s physical and social situation. That is why information you can obtain over the internet is not intended as medical advice and may not be applicable to your situation.
I hope to discuss each topic more in depth starting with the hot topic of vaccines. As an integrative health specialist, I often find that my patients are the most educated and frequently the most vulnerable to vaccine side effects. On the flip these patients may also be the most vulnerable to developing severe COVID after contracting the virus. I’ll explain first why I think vaccines are beneficial followed by reasons why individuals may want to delay or avoid getting vaccinated.
Benefits of the vaccines:
Above I touched on the rationale behind what leads to severe COVID. The reason to consider vaccination is if you are at risk for developing moderate to severe COVID or at risk of spreading it to others who may be. The efficacy of the vaccines to prevent severe COVID despite the variant mutations appear to be very promising as well as the developing information on its ability to curb transmission2,6. My years of experience as an infectious disease specialist tells me that the understated aspect of this disease can be explained by our ability to lower the initial viral inoculum, in other words the total amount of virus that we are exposed to3.
We know across the board that disease burden of bacteria and virus correlate to severity of illness as well as likelihood of transmission. We have actually studied and defined the percent risk of transmitting diseases such as HIV based the amount of body fluid one is exposed to4. That is the reason why specific masks and the 6 feet distancing rule have been implemented. If this implies that COVID prevention is a numbers game then how does this apply to the vaccines?
The vaccines lower the rate of mortality and rate of hospitalizations5,6. The vaccines lower the number of asymptomatic cases and some experts have reasonably deducted that this would likely reduce asymptomatic infection. For those who did develop COVID symptoms the measurable virus was significantly reduced which again I would reason reduces symptoms and infectivity.
As a physician providing informed consent for an intervention involves weighing the potential benefits against the risks to help our patients make an informed decision. The difficult aspect of providing this information is the lack of long-term data. In theory, the idea of the two mRNA vaccines being currently administered is a short window of stability of the mRNA that rapidly degrades in our bodies without ever needing to enter the nucleus or control center of our cells. We know that these vaccines are highly immunogenic eliciting significant symptoms that are an expected response from our immune systems7. These symptoms are clearly to a greater degree than other vaccines we have experienced, commonly causing individuals to miss time from work. The most worrisome symptom to date is the concern of anaphylaxis with low rates of 11.1 cases per million doses for the Pfizer- BioNTech vaccine8 and 2.5 cases per million doses administered of the Moderna vaccine9. A prior history of significant allergies was noted in these subjects. Another concern not addressed in the clinical trials is how these vaccines might affect those with family or personal history of severe autoimmune diseases in terms of triggering a new condition or flaring an existing condition10. Unfortunately, there is no data to guide us, with only expert opinions and should be discussed with your physician. The other population excluded from clinical trials were pregnant women which deserves its own section to discuss the data we know so far.
Pregnancy, fertility, and lactation concerns
The issue of possible fertility issues related to the vaccine had become a hot topic of debate. Early in the vaccine development process a former Pfizer employee raised concerns about the similarities of a placenta protein(syncytin-1) with the vaccines target spike protein which should be further investigated11. The information we know at this point is that in animal models of lab rats, there were no observed effects on fertility, pregnancy or fetal development12,13. Subsequently, laboratory studies have not demonstrated binding of SARS-CoV2 antibodies to the syncytin-1 protein11. In the clinical trials accidental pregnancies was equally distributed between those who were vaccinated and those who were not. To date we have not observed any issues with natural COVID infection and fertility or miscarriages.
The next question is how does pregnancy affect the natural progression of COVID? A concern some individuals have is that pregnancy is a form of immunocompromised state that down regulates the immune response to the fetus from rejecting it like a transplant recipient. What immunologists have observed is a down regulation of the T cell response, but an upregulation of certain Antibodies. In a retrospective study published in JAMA 95% of infected pregnant patients were asymptomatic to mild with similar hospitalization rates14. A systematic review and meta-analysis did find an increase in ICU admission with an odds ratio (OR) 1.6 and invasive ventilation OR 1.88 without change in mortality15.
In terms of fetal and neonatal health there is no evidence of intrauterine infection. The systematic review mention above observed an increase in neonatal unit admission and increase in pre-term birth with odds ratio ~3.0. There was no change to apgar scores, fetal distress or mortality. In general, COVID does not seem to effect children severely, but does lead to increased risk of hospitalization at less than 1 year of age16.
What do we know about the vaccines effect on pregnancy? Based on data from the FDA and the vaccine adverse events reporting system as of 2/26/21 (which is 74 days from the date of the first vaccine given on 12/14/20) there were 30,494 pregnancies reported17. The V-Safe program has been following 1815 participants. The number of spontaneous abortions noted was 29 which is ~1.5% a low number considering baseline rates for age less than thirty-five is 9-20%. In the coming month there is expected to be further clinical trial data. There does not seem to be significant concern for lactation at this time as negligible excretion in breast milk.
Indications: Who should get the vaccine first?
Those with high risk of being exposed and/or infecting others such as healthcare workers caring for COVID patients without health or moral/religious exemptions. The next group are those with substantially elevated to severe risk for severe COVID or mortality. See table 2 or you can use an online screening tool such as covid19risktools.com to estimate your risk and risk of mortality20. The next group of individuals should be those with moderate risk of severe disease or at increased risk of spreading it to vulnerable individuals.
Reservations: Who should consider waiting?
Those who have history of anaphylaxis, severe allergy/reactions to prior vaccinations, or other contraindications should be the last to get vaccinated if considering it at all. Those with religious or moral exemptions. The moral dilemma that some have raised for vaccines in the past is the use cells lines from an aborted fetus in the development of the vaccines. The Oxford-AstraZeneca vaccine uses HEK-293, which is a fetal cell line from a fetus aborted in 197218,19 Those with recent (3-6 months) symptomatic COVID infection and natural immunity. Others reasons for considering delaying until more safety data could include those with severe autoimmune or neurologic issues particularly if they are not frequently exposed to unvaccinated individuals. Those at low risk for disease and spread such as the young and healthy. Healthy pregnant women can discuss further with their physicians if concerned about immunogenicity reactions or fetal health concerns. There is data that the vaccine effects the fetus with measurable antibodies in laboratory rat’s offspring as well as case reports in humans of detectable antibodies in cord blood and the fetus. This is a data free zone where the real vs theoretical risks need to be weighed in terms of possibility of contracting COVID, developing severe disease, spreading it to the vulnerable can be weighed against the known and unknown effects of the vaccines. One reason to consider getting one of the current vaccines sooner is if you have concerns about later DNA vaccines as they do enter the control centers of the cells(nucleus) as well as shorter history of safety data. You can review the University of Massachusetts pregnancy decision making guide here for more information: Here22. See the decision making algorithm to help you make your decision.
- If you are low to lowest risk group you should probably wait and allow those who need the vaccine to get it first.
- If you are in the medium necessity group and have significant concerns about the vaccine safety, I would consider waiting.
- If you are in the medium to highest risk group without significant vaccine safety concerns you should get the vaccine.
Please see our vaccine decision algorithm to help you make an informed decision.
- Gandhi, M., Yokoe, D.S. and Havlir, D.V., 2020. Asymptomatic transmission, the Achilles’ heel of current strategies to control Covid-19.Xie, X., Liu, Y., Liu, J., Zhang, X., Zou, J., Fontes-Garfias, C.R., Xia, H., Swanson, K.A., Cutler, M., Cooper, D. and Menachery, V.D., 2021. Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nature Medicine, pp.1-2.
- Van Damme, W., Dahake, R., van de Pas, R., Vanham, G. and Assefa, Y., 2021. COVID-19: Does the infectious inoculum dose-response relationship contribute to understanding heterogeneity in disease severity and transmission dynamics?. Medical hypotheses, 146, p.110431.
- Cardo, D.M., Culver, D.H., Ciesielski, C.A., Srivastava, P.U., Marcus, R., Abiteboul, D., Heptonstall, J., Ippolito, G., Lot, F., McKibben, P.S. and Bell, D.M., 1997. A case–control study of HIV seroconversion in health care workers after percutaneous exposure. New England Journal of Medicine, 337(21), pp.1485-1490.
- Chagla, Z., 2021. The BNT162b2 (BioNTech/Pfizer) vaccine had 95% efficacy against COVID-19≥ 7 days after the 2nd dose. Annals of Internal Medicine, 174(2), p.JC15.
- Livingston, E.H., 2021. Necessity of 2 doses of the Pfizer and Moderna COVID-19 vaccines. JAMA, 325(9), pp.898-898.
- Walsh, E.E., Frenck Jr, R.W., Falsey, A.R., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Neuzil, K., Mulligan, M.J., Bailey, R. and Swanson, K.A., 2020. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. New England Journal of Medicine, 383(25), pp.2439-2450.
- COVID, C. and Team, R., 2021. Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer-BioNTech COVID-19 vaccine—United States, December 14–23, 2020. Morbidity and Mortality Weekly Report, 70(2), p.46.
- COVID, C. and Team, R., 2021. Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 Vaccine—United States, December 21, 2020–January 10, 2021. Morbidity and Mortality Weekly Report, 70(4), p.125.
- https://www.forbes.com/sites/judystone/2021/02/17/covid-19-vaccines-and-autoimmune-disease/. Visited 3/9/21
- Male, V., 2021. Are COVID-19 vaccines safe in pregnancy?. Nature Reviews Immunology, pp.1-2.
- US Food and Drug Administration, Vaccines and Related Biological Products Advisory Committee meeting—December 17, 2020—FDA briefing document—Moderna COVID-19 vaccine.
- Food and Drug Administration, Vaccines and Related Biological Products Advisory Committee Meefing December 10, 2020. FDA Briefing Document. Pfizer-BioNTech COVID-19 Vaccine.; 2020: 53.
- Adhikari, E.H., Moreno, W., Zofkie, A.C., MacDonald, L., McIntire, D.D., Collins, R.R. and Spong, C.Y., 2020. Pregnancy outcomes among women with and without severe acute respiratory syndrome coronavirus 2 infection. JAMA network open, 3(11), pp.e2029256-e2029256.
- Allotey, J., Stallings, E., Bonet, M., Yap, M., Chatterjee, S., Kew, T., Debenham, L., Llavall, A.C., Dixit, A., Zhou, D. and Balaji, R., 2020. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. bmj, 370.
- Kim, L., Whitaker, M., O’Halloran, A., Kambhampati, A., Chai, S.J., Reingold, A., Armistead, I., Kawasaki, B., Meek, J., Yousey-Hindes, K. and Anderson, E.J., 2020. Hospitalization rates and characteristics of children aged< 18 years hospitalized with laboratory-confirmed COVID-19—COVID-NET, 14 States, March 1–July 25, 2020. Morbidity and Mortality Weekly Report, 69(32), p.1081.
- https://www.fda.gov/media/146269/download. Visited 3/9/21
- Bukhari, M.H., Medical and ethical issues related to COVID-19 vaccine.
- https://www.gps-can.com.au/covid19-blog/covid-vaccine-fetal-cells. Visited 3/17/21
- https://covid19risktools.com:8443. Visited 3/17/21
- Hassan-Smith, Z., Hanif, W. and Khunti, K., 2020. Who should be prioritised for COVID-19 vaccines?. Lancet (London, England), 396(10264), pp.1732-1733.
- https://www.baystatehealth.org/-/media/files/covid19/vaccine-info-for-pregnant-people-updated-12-28.pdf?la=en. Visited 3/17/21
- https://www.uptodate.com/contents/image?search=covid&source=covid19_landing&usage_type=main_graphics&imageKey=PWYS%2F127891. Visited 3/17/21