The Latest Research and Information on COVID-19: Immunity Research

COVID-19 Immunity Research as of May 21, 2020

Summary

Control of SARS-CoV-2 (the virus that causes COVID-19) will largely depend on having the majority of the population immune, either through infection or vaccination. Some early research suggests recovered COVID-19 patients are immune to reinfection, at least in the short term, but a lack of conclusive evidence warrants caution in assuming infection confers immunity and that people who are immune cannot transmit the virus.

  • Recovered individuals appear to produce neutralizing antibodies in response to infection.
  • Experimentally infected monkeys were protected against subsequent SARS-CoV-2 challenge.
  • Early data from vaccine research suggest vaccination produces immune responses similar to convalescent COVID-19 patients, which may provide some level of protection against infection.
  • Serologic testing for antibodies can provide useful information on who has been infected but cannot determine whether antibodies neutralize the virus and protect against reinfection.
  • There is not enough evidence and too many unsolved ethical challenges to support the use of 'Immunity Passports' at this time.

Does infection confer immunity?

  • It is too early to definitively claim that previous COVID-19 infection protects people from reinfection or from infecting others, but emerging evidence offers some hope that this may be the case:
    • Specific antibodies to SARS-CoV-2 have been detected in patients with confirmed COVID-19. Detection of antibodies in serum samples is occurring on average between 7 to 15 days after onset of disease (Zhao et al., 2020; Okba et al., 2020; Wölfel et al, 2020).
      • In a small pre-print study measuring antibodies in 175 recovered patients with mild disease, 10 (5.7%) had no detectable antibodies.
  • What antibody level is needed to protect against the virus and whether individuals without detectable antibodies are susceptible to re-infection is not yet known. Antibodies represent just one element of the immune response. For example, T cells contribute to protective immunity to viruses.
    • Recent research looking at T cell and antibody immune responses in recovered, non-hospitalized COVID-19 patients, found virus-specific helper (CD4+) T cells in all patients, and killer (CD8+) T cells in 70% of patients (Grifoni et al., 2020).
  • Although indicative of past infection, the presence of antibodies does not necessarily mean people are protected against future infection. A few early studies suggest that antibodies produced in response to infection can inactivate or neutralize the virus:
    • An early study found that COVID-19 patient serum samples, positive for viral antibodies, neutralized SARS-CoV-2 (Zhou et al., 2020).
    • A recent pre-print found that the antibodies in serum from convalescent patients were neutralizing and capable of binding to SARS-CoV-2,blocking virus entry into human host cells.
    • A recently published study in rhesus monkeys suggests that initial SARS-CoV-2 infection results in protective immunity against later SARS-CoV-2 infection, at least in the short term (Chandrashekar et al., 2020).

How long does immunity last?

  • There is currently no evidence that points to how long naturally acquired protection will be in people who have had COVID-19. However, researchers have found that antibodies to SARS may persist for up to two years while antibodies to MERS may persist for up to three years.   
    • A recent study involving a small sample of SARS survivors has found neutralizing antibodies 9–17 years after initial infection (Andersen et al., 2020).

Will a vaccine yield immunity to SARS-CoV-2?

  • A number of different types of candidate vaccines are currently in development and in various stages of clinical evaluation. These candidate vaccines include DNA- and RNA-based formulations, adenovirus-based vectors, and purified inactivated virus (WHO).
  • The goal of vaccine development is to identify a candidate vaccine that offers complete protection from infection (sterilizing immunity) that persists over a lifetime (Bouvier, 2018).
  • Three studies involving rhesus monkeys offer encouraging results and cautious optimism in the search for a potential vaccine that confers immunity:
    • Sinovac Biotech in partnership with researchers in China, published early results testing an inactivated virus vaccine candidate in mice, rats, and monkey. The vaccine induced SARS-CoV-2-specific neutralizing antibodies and provided partial or complete protection (at the higher dose) against subsequent infection (Gao et al., 2020).
    • In a study led by researchers at Beth Israel Deaconess Medical Center (BIDMC), monkeys were immunized with one of six variant DNA vaccines, which encode different antigens of the virus. Vaccination induced neutralizing antibodies and cellular responses by specific T cells. Following later exposure to the virus, vaccinated monkeys had significantly lower viral loads than non-vaccinated control animals (Yu et al., 2020).
    • The University of Oxford Vaccine Centre has released a pre-print study investigating the ChAdOx1 vaccine in rhesus monkeys. The vaccine, which uses a modified chimpanzee virus to deliver a genetic copy of the SARS-CoV2 'spike' protein, induced neutralising antibodies and vaccinated animals experienced less severe clinical symptoms compared to unvaccinated animals.
  • Moderna Inc., in partnership with the US National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center, have released early results from Phase 1 of a clinical study evaluating a candidate mRNA vaccine. Patients treated twice with low and medium doses of the vaccine developed neutralizing antibody 15 days after inoculation. Moderna has also suggested that the vaccine has been well tolerated by participants in the study. The findings should be interpreted with caution because the sample size is low (n=8) and critical data have thus far been withheld. 

Are people susceptible to reinfection?

  • The Korea Centers for Disease Control and Prevention (KCDC) reported that a growing number of COVID-19 patients were testing positive again for COVID-19, possibly from reinfection. This has raised concerns about future immunity and sustained infectivity.
    • Two alternative explanations have been proposed: 1) the virus was never cleared and patients experienced a flare-up of symptoms; or 2) the virus was never cleared and patients had false-negative RT-PCR tests, as has previously been reported.
    • Subsequent research undertaken by the KCDC, has demonstrated that patients with prolonged positive PCR results have neutralizing antibodies and are no longer infectious.
  • Viruses that frequently mutate can cause re-infection if they are sufficiently different to evade the activity of neutralizing antibodies. More research will be needed to understand whether SARS-CoV-2 behaves in this way.

Can serological tests tell us if someone is immune?

  • Serological tests, including rapid serology antibody tests (immunochromatographic technology, point-of-care lateral flow assay) and enzyme-linked immunosorbent assays (ELISA), detect the presence of virus-specific IgM and IgG antibodies in blood, plasma, or serum. An ELISA can also provide information on how much antibody is circulating in the sample (antibody titres).
    • The extent to which these serological tests reflect protective immunity can only be confirmed using a serum virus neutralization assay, which discriminates between neutralizing (usually IgG) and non-neutralizing antibodies (Truelove, et al. 2016). 
  • The accuracy of antibody tests is dependent on how sensitive the test is at detecting antibodies in people who have been infected and how specific that detection is to antibodies for the virus in question and not related viruses (cross-reactivity). 
    • An important metric to consider in using these tests to determine who has been infected, is the rate at which a test returns a false positive result.
    • False positive test results are observed when nonspecific reactions occur among people who have never been infected. False positive tests are also more likely to occur when disease prevalence is low. Positive predictive value, the probability that a person has a disease, is influenced by the sensitivity and specificity of the test as well as the prevalence of the disease in the population being tested (Trevethan, 2017).
  • A group of physicians and researchers in the US have established the COVID-19 Testing Project to evaluate and compare 12 commercially available antibody tests. Their pre-print findings highlight large variation in the specificity of tests, with only three demonstrating fewer than 1% false positives.
  • As of April 27, the US Food and Drug Administration has cleared six commercial antibody tests through Emergency Use Authorizations.
  • On May 12, Health Canada authorized the first serological test for use in Canada. The test is manufactured by DiaSorin LIAISON® and claims to have a specificity of 98.5%.

Why are serological studies and seroprevalence surveys important?

  • Serological testing employed on a large scale can be useful to determine:
    • How widespread exposure to SARS-CoV-2 has been in communities and populations (seroprevalence);
    • What proportion of the population has been infected but were asymptomatic or had subclinical disease;
    • What proportion of infected people have died (infection fatality rate).
  • Determining the proportion of the population that has been infected has implications for easing restrictive measures and return-to-work policies (Abbasi, 2020).
    • Serological studies have been proposed as a way allow for health care workers and other essential workers with potential protective immunity to return to work and daily life more safely and quickly (Weitz, Beckett et al. 2020).
  • A number of serological studies are currently underway at the population level and in specific groups:
    • The US National Institute of Allergy and Infectious Diseases (NIAID) has launched a serological study to determine what proportion of the population, who were not confirmed COVID-19 cases, have the virus antibodies.
    • The Robert Koch Institute in Germany is leading national large scale random testing of households.
    • The Canadian government recently announced the launch of the COVID-19 Immunity Task Force to survey representative samples of the population for the presence of antibodies to the virus.
    • The largest Michigan hospital system will test 38,000 employees for SARS-CoV-2 antibodies.
  • Early seroprevalence survey results from California, Germany, Spain, and the Netherlands have found anywhere from 2 to 15% of these populations have been infected, numbers much greater than confirmed cases. Estimated prevalence from serological testing is significantly higher in outbreak epicentres such as New York City (21%) and Chelsea, Massachusetts (30%).
    • While some people have argued that these studies indicate COVID-19 is more common and not as deadly as initially assumed, others point out that these prevalence rates are still far from what is necessary for herd immunity.  
    • Few studies have yet been peer reviewed and critics have noted sampling and recruitment bias as well as test inaccuracies among the problems in some of these studies.

  • A number of serological studies are currently underway at the population level and in specific groups:
    • The US National Institute of Allergy and Infectious Diseases (NIAID) has launched a serological study to determine what proportion of the population, who were not confirmed COVID-19 cases, have the virus antibodies.
    • The Robert Koch Institute in Germany is leading national large scale random testing of households.
    • The Canadian government recently announced the launch of the COVID-19 Immunity Task Force to survey representative samples of the population for the presence of antibodies to the virus.
    • The largest Michigan hospital system will test 38,000 employees for SARS-CoV-2 antibodies.
  • Early seroprevalence survey results from California, Germany and the Netherlands have found anywhere from 2 to 15% of these populations have been infected, numbers much greater than confirmed cases. Estimated prevalence from serological testing is significantly higher in outbreak epicentres such as New York City (21%) and Chelsea, Massachusetts (30%).
    • While some people have argued that these studies indicate COVID-19 is more common and not as deadly as initially assumed, others point that these prevalence rates are still far from what is necessary for herd immunity.  
    • None of the studies have been peer reviewed and critics have noted sampling and recruitment bias and test inaccuracies among issues with these studies.