Antibodies, Immunity, and COVID-19 | Coronavirus (COVID-19) | JAMA Internal Medicine | JAMA Network
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Invited Commentary
November 24, 2020

Antibodies, Immunity, and COVID-19

Author Affiliations
  • 1Los Angeles County + University of Southern California Medical Center, Los Angeles
  • 2Department of Public Health Sciences, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, Illinois
  • 3Department of Microbiology and Immunology, Johns Hopkins School of Medicine, Baltimore, Maryland
JAMA Intern Med. 2021;181(4):460-462. doi:10.1001/jamainternmed.2020.7986
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    4 Comments for this article
    COVID-19: Immunity and Vaccination
    Gary Ordog, MD, DABMT, DABEM. | County of Los Angeles, Department of Health Services, Physician Specialist (Ret.)
    Thank you for the  very insightful commentary. From your discussion and others, it appears that herd immunity may neither completely control nor eradicate this virus. It may be possible, with a tremendous vaccine initiative, to actually consider eradication at the point, not just control. Unlike H1N1 in 1918, which is still prevalent, a massive small pox like vaccine initiative could lead to eradication. 
    Herd Immunity and COVID-19
    Michael McAleer, PhD(Econometrics),Queen's | Asia University, Taiwan
    The detailed commentary by experts on antibodies and naturally acquired immunity for populations in the COVID-19 era begs the question as to whether herd immunity to control the spread of the virus and disease is possible.

    The research study examines updated information on SARS-CoV-2 seroprevalence in the USA, with recognition of serum containing antibodies that recognize the virus at below 20% in Spain and Italy.

    The latest information as of 28 November 2020 ranks India, Brazil, Russia and France ahead of Spain, with the UK between Spain and Italy (

    A striking finding is that there
    is little evidence in the USA of prior COVID-19 infection by antibodies to SARS-CoV-2, with the seroprevalence of antibodies declining over time.

    The primary goal of herd immunity involves inducing long-term protective natural immunity against reinfection following natural infection, although eradication of a disease requires a safe, effective, and durable vaccine that induces protective immunity.

    Modelling and extrapolated empirical analysis from related diseases, as distinct from laboratory clinical trials, would seem to suggest that a threshold of 60% - 80% is required to develop adequate herd immunity at the population level to halt the continuing cycles of infection and disease, as distinct from eliminating the disease.

    Although Sweden is not mentioned, the attempted herd immunity in the country has sadly been a failed experiment, with an estimated threshold of less than 20% in Stockholm, the largest city with around 22% of the population.

    A vaccine may mitigate the spread of the virus and disease through protective immunity, but herd immunity is a Plan B that will likely lead to disastrous outcomes.
    COVID 19: the role of natural immunity
    Fabrizio Presicce, MD, PhD | Department of Urology - San Filippo Neri Hospital Roma
    As well reported by the authors, little is known about the natural immunity induced by the infection.1 We still do not know its duration, its mechanisms of action, in particular the respective contribution of neutralizing antibodies and the cell-mediated immune response.1 However, some empirical data appear encouraging. More than 60 million people in the world have yet contracted the infection and official reinfection cases are so rare and anecdotal that they always make the front page in newspapers and scientific articles.2 Furthermore Bergamo and Brescia – the Italian provinces most affected during the first wave3 - are those with one of the lowest incidences during the second wave in Italy.4
    Having made these necessary premises, the questions I would like to ask are the following:

    • Why if we trust so much in the immunity conferred by a vaccine, we don't do the same with an immunity induced by previous exposure to the virus and subsequent recovery?

    • The serological tests over the months have gained reliability and now with greater accuracy to ascertain who has developed neutralizing antibodies.5 From studies on vaccines it would appear that after vaccination there is a high correlation between the presence of neutralizing antibodies against the spike protein and the ability of the vaccinated serum to neutralize the virus.5

    Why not subject those recovered from the infection to periodic serological monitoring and allow someone with neutralizing antibodies to return to a "normal" life, without any restrictive measures? How much would this measure allow for savings in terms of PPE and productivity? And if it is not considered prudent to adopt this measure on a large scale, why not start with a group of volunteers - previously infected and recovered from the infection - to monitor periodically to learn more information about the susceptibility of a previously infected subject?

    In conclusion, it seems to me an immunological short-circuit to trust in the efficacy of a vaccine for a given infection without believing equally vehemently in immunity for an infected and cured subject, equipped with neutralizing antibodies.

    1. Spellberg B, Nielsen TB, Casadevall A. Antibodies, Immunity, and COVID-19. JAMA Intern Med. 2020 Nov 24. doi: 10.1001/jamainternmed.2020.7986. Online ahead of print.
    2. Tillett RL, Sevinsky JR, Hartley PD, et al. Genomic evidence for reinfection with SARS-CoV-2: a case study. Lancet Infect Dis. 2020 Oct 12:S1473-3099(20)30764-7.
    3. Perico L, Tomasoni S, Peracchi T, et al. COVID-19 and lombardy: TESTing the impact of the first wave of the pandemic. EBioMedicine. 2020 Nov;61:103069.
    5. Ramasamy MN, Minassian AM, Ewer KJ, et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Lancet. 2020 Nov 18:S0140-6736(20)32466-1.
    Convalesent Plasma Donation
    Ernest Ciambarella, MD | Retired
    In Reply to Dr. Presicce. I was infected with Covid-19 in March and since then I have enrolled in a study looking at the effectiveness of convalescent plasma. I donate monthly and one of the main reasons why I do this is that my neutralizing antibodies are checked each time. I still take all the precautions but I consider myself immune. I presume that this type of data will be collected and reported on.