What happened to natural immunity?


On September 9th, President Joe Biden ordered the Occupational Safety and Health Administration (OSHA), a federal agency tasked with regulating workplace safety, to promulgate an emergency rule mandating all employees in workplaces with at least 100 people be “fully vaccinated” for COVID-19, or require weekly testing of those who remain unvaccinated. The order also extended the mandate to all federal employees and contractors, but without a testing alternative. Interestingly, the mandate does not apply to members of Congress or legislative staff.

Violations of the rule, which are yet to be defined by OSHA, are reportedly punishable by a fine of up to $13,600 per violation. It remains to be seen whether this new mandate will withstand legal scrutiny and make it to full enforcement. In the meantime, large companies across the country are reacting, notifying their employees of the change in policy or declaring they will not comply with the rule.

Legal precedent allows businesses to require vaccinations for their employees with reasonable exceptions. The more pertinent question is, can the federal government, acting through private industry, compel the same activity? That will be one sorted out by the courts.

While narrow medical exemptions are available, the US CDC does not recognize immunity from previous infection as one, yet health authorities in Europe, the United Kingdom (UK), and Israel do. On Tuesday, Prime Minister of the UK, Boris Johnson, in his briefing to the press, announced that 90% of the British population currently has antibodies for SARS-CoV-2, the virus that causes COVID-19 illness. While the CDC has updated its estimate of the total number of Americans infected to be more than 120 million between February 2020 and May 2021, it is merely a broad estimate. There have been no similar US government efforts to actually measure COVID antibody levels within the American population.

In addition, new mandates requiring Maine’s health care workforce to be inoculated against COVID-19 do not recognize natural immunity as an exemption to vaccination. Why has acquired immunity via infection, a concept widely understood within the medical community and among the general public (until last year, apparently) been diminished by state scientists? Worse yet, why are tech companies trying to stop the general public from talking about the concept of natural immunity on social media platforms?

On Monday morning, Dr. Nirav Shah, director of Maine CDC, was asked about his current understanding of natural immunity on the WGAN Morning News. Shah prefaced his answer with the statement that “natural immunity is a thing,” but he maintains that vaccination provides “stronger, quicker, and longer lasting” protection than previous infection based on “the weight of scientific opinion.”

Shah notes that we have a more solid understanding of vaccine effectiveness because “that is a controlled group” and because the “vaccine path is a lot easier to follow than the natural immunity path.” He argues that there is not yet enough information out there to be sure about immunity from natural infection. Referencing a paper published in the New England Journal of Medicine (NEJM), Shah notes the path to natural immunity carries greater risk than that of vaccination.

Another study in NEJM studied patients with a previous infection combined with a single dose of either Pfizer or Moderna mRNA vaccine, sometimes referred to as “hybrid immunity.” According to Shah, this is “thought to be the strongest level of immunity” against COVID-19 illness. Though it only studied 110 people after vaccination—67 of whom were never infected (seronegative) and 43 with previous infection (seropositive)—the NEJM paper concluded that antibody levels of the seropositives “were 10 to 45 times as high as those without preexisting immunity at the same time points after the first vaccine dose.” Seropositive patients’ antibody levels exceeded those of seronegative participants after the second vaccine dose by more than a factor of six. The previously infected also experienced greater prevalence of side effects from vaccination than seronegative individuals.

Interestingly, the researchers found that although vaccinated-but-never-infected participants had increased antibody levels after the second vaccine dose, no increase was observed in the Covid-19 survivors after their second vaccine dose. The benefits of vaccination for the previously infected, if significant, seem to end after the first dose. Is it right to mandate people take on the risk of a second dose if they won’t get much benefit from it?

This raises an important question for Dr. Shah: If not for immunity from infection, what about a single mRNA vaccine dose would produce a sufficiently protective antibody response? One is not considered “fully vaccinated” with only one mRNA dose; state and federal COVID-vaccine mandates require two doses of mRNA to be fulfilled. Is it possible that someone with a previous infection would only see the immunity benefits of that before receiving a dose of mRNA vaccine? Unlikely, given evidence that the infected-but-never-vaccinated produce strong immune responses as well.

Dr. Anthony Fauci, a leading voice on the federal pandemic response, recently admitted that he could not provide an adequate answer to why Biden’s new mandate does not allow a natural immunity exemption. Like Shah, Fauci questioned the availability of evidence on how long immunity from previous infection lasts, also referred to as durability.

Despite cagey answers from government health officials, there has been extensive scientific research into this question over the last 12 to 18 months. Many studies have found strong, broad, and durable antibody responses for up to one year, even against variants, with indications that immune memory from white blood cells known as B and T lymphocytes could last for many years.

In May, the journal Nature published a study showing that “data provide strong evidence that SARS-CoV-2 infection in humans robustly establishes the two arms of humoral immune memory: long-lived BMPCs [bone marrow plasma cells] and memory B cells,” even from a mild infection. These findings led the journal to note that natural immunity could last a lifetime.

A peer-reviewed study in the Journal of Clinical Investigation Insight even found that a majority of uninfected adults carry some level of pre-existing antibody reactivity against SARS-CoV-2. Immune response to the virus “occurs in absence of prior viral exposure.” This is an incredible finding which supports another study in NEJM that some people were already prepared to encounter this “novel” coronavirus through exposure to other coronaviruses like those that cause the common cold and the SARS epidemic more than 15 years ago.

In early 2021, the government of Israel made a deal with Pfizer to provide the company’s vaccine exclusively to the Israeli people. This led Pfizer CEO Albert Bourlas in February to dub the small middle-eastern nation “the world’s lab,” which has allowed the world to observe in-depth, real-time data on the protection afforded by the Pfizer vaccine versus infection.

Data collected in Israel between May and July showed that those with a previous infection had greater-than-six-times better protection from COVID-19 than the vaccinated. Of the more than 7,700 new cases detected in that time period, corresponding to “the most recent wave” of coronavirus in that country, only 72 of the new cases were in people with known previous infection: less than 1% of the new cases and 0.0086% of all known recoveries. By comparison, more than 3,000 of the new cases—about 40%—were vaccinated patients who contracted breakthrough infections, or 0.0578% of all vaccinated Israelis. 

Another study out of Israel compared various COVID-19-related outcomes among three groups: those who had no history of previous infection with SARS-CoV-2 (also known as “SARS-CoV-2 naïve”) but were “fully vaccinated” with the Pfizer product, those unvaccinated but previously infected, and those who had a previous infection and took one dose, a cohort referenced on Monday by Dr. Shah. This study is still in pre-print, meaning that it has not yet undergone the process of peer-review, but it carries a compelling data set backed by a strong methodology and large sample sizes: more than 46,000 individuals across the three groups.

In that study, researchers found a 13.06-fold increased risk for vaccine breakthrough infection as opposed to reinfection in the COVID-recovered. They also noted that SARS-CoV-2 naïve vaccine recipients had a 5.96-fold increased risk for breakthrough infection and a 7.13-fold increased risk for symptomatic disease compared to reinfection. For participants with natural infection and one dose of vaccine, the study found those patients saw a statistically significant benefit of 0.53-fold over those with natural infection alone.

While the concept of “hybrid immunity” looks promising, the evidence is truly overwhelming in favor of recognizing natural infection at least as a contributor to overall protective immunity to severe COVID-19. Current vaccines available in the US specifically target the spike protein of SARS-CoV-2, a protein on its surface which facilitates entry into cells. While the spike protein is an important part of the equation, it is less than 5% of the total viral genome (~1,300 out of ~30,000 amino acid sequences). In this vein, most studies measuring vaccine-induced immune response specifically look at neutralizing antibodies to the Receptor Binding Domain (RBD), a subset of the spike which makes initial contact in the first step of viral entry

Top medical organizations understand that natural infection can help the body generate immune memory to other parts of the virus as well as the spike, especially as the virus rapidly evolves. The original strain of SARS-CoV-2 which originated in Wuhan, China, and on which the current vaccines are modeled, has long been extinct. This is not to say that the current vaccines are ineffective, as they have been shown to dramatically decrease risk of severe outcomes for those most at risk, but this is why it makes sense that immunity in the COVID-recovered would be more protective than vaccination alone.

Without breaking down data by age, health status, and other factors influencing risks of each path, risks for contracting the virus and thus obtaining natural immunity are almost certainly greater than that of vaccination. Dr. Shah is right on that point. 

Yet, prevailing data show that acquired immunity is as good or better than protection conferred by COVID-19 vaccination. This is why it must be up to each individual to weigh those risks with their doctor based on their risk and health profiles to choose their path. But, since those who have not been infected but have been vaccinated are still at a higher risk of infection than those with a previous infection, one might be better off assuming that they will encounter the virus at some point, if they have not yet. 

Perhaps the more pertinent question to entertain is how prepared one will be for that encounter when it inevitably arrives.