COVID-19 vaccination policy in the U.S. is highly variable, whether in regard to boosters, vaccinations for children, or workplace requirements. While many states require vaccination for state employees and workers at state-funded institutions, other states are banning vaccination requirements. Despite the political nature of vaccination policy, best practices should be based on scientific evidence. So, what does the evidence say regarding people who have previously been infected with SARS-CoV-2?
While COVID-19 vaccination is safe and highly effective, several studies show that people who have recovered from COVID-19 are at least equally protected compared to fully vaccinated COVID-naive people. Therefore, vaccination in those who have recovered may not be medically necessary. Rather than blanket mandates requiring vaccination, it may be more politically tenable and scientifically sound to focus on the documentation of immunity — whether through infection or vaccination — to control the pandemic and stratify persons at risk. Identifying immunity is not challenging, and several other countries already have models on which the U.S. could base its approach.
Immune System Protection From COVID-19
After SARS-CoV-2 infection or vaccination, the body’s immune system reacts to the presence of foreign SARS-CoV-2 molecules by producing antibodies and expanding immune system cells to clear the foreign material. Within a period of weeks to months, the newly produced antibodies decline and the recently created immune system cells go into various tissues, lymph nodes, or bone marrow, waiting for the next exposure to the virus or viral proteins. Observed reinfection in people with healthy immune systems who have recovered from COVID-19 is uncommon, on the order of 0 to 1 per 100 persons per year, showing high levels of protection in this population.
One argument some have put forth in favor of vaccination after recovery from infection is that antibody levels increase with vaccination after recovery. Indeed, recent studies have found that people who had SARS-CoV-2 and later received one dose of the Pfizer mRNA vaccine were more highly protected against reinfection than those who once had the virus and were still unvaccinated. However, the benefit is generally modest. Also, it is well known that repeat exposure to the virus or viral proteins created by vaccination will quickly boost antibodies and at least temporarily further reduce risk for reinfection. What remains unknown is whether that antibody increase truly adds additional long-term protection against getting infection or illness.
Researchers at the Cleveland Clinic Health System conducted a study of 52,238 employees with and without a history of COVID-19, with or without vaccination. They found that those who recovered from COVID-19 and were vaccinated had equally low rates of repeat infection when compared with those who recovered and were unvaccinated. The investigators concluded that those previously infected were unlikely to benefit from COVID-19 vaccination. In another study looking at the duration of immunity among the COVID-19-recovered, researchers found that the immune response against SARS-CoV-2 was persistent and relatively stable for at least a year. While a recent CDC study concluded that mRNA vaccination provides stronger protection against COVID-19 hospitalization than prior infection, there were several study limitations, including that it was not a randomized controlled trial and that the follow-up period was short. The findings also don’t negate the robust protection from prior infection. In fact, in a CDC science report published last week that reviews the totality of evidence, agency staff found that both infection-induced and vaccine-induced immunity are durable for at least 6 months.
However, for select groups of people, such as the immunocompromised or those with a history of low antibody response to vaccination, getting at least one dose of vaccination after recovery from COVID-19 may be beneficial. That brings us to the question of medical necessity.
What Is Medical Necessity?
The definition of medical necessity describes a broad standard for medical insurance coverage. While the term is not formally defined by the federal government and varies by state, medical necessity generally refers to services that improve health or lessen the impact of a condition, prevent a condition, or restore health.
For those who have not been infected with COVID-19, vaccination is an absolute medical necessity. But for those who already have protection against SARS-CoV-2 from prior infection, vaccination or vaccine boosters after initial vaccination may not be medically necessary.
There is currently a lot of tension regarding vaccination requirements for essential workers. One way to reduce that tension, and possibly increase public confidence in government, would be for policymakers to explore alternatives to blanket mandates — they could allow those who can prove prior COVID-19 infection to qualify for a medical exemption or perhaps only be required to get one mRNA dose.
Diagnosis of Previous COVID-19 Infection
To establish a COVID-19 diagnosis, accurate and reproducible tests are needed to detect the causative virus, SARS-CoV-2. Most high-quality COVID-19 testing relies on the polymerase chain reaction (PCR). Other methods use the presence of proteins of SARS-CoV-2 (antigen) in clinical specimens or antibodies that are specific for viral proteins. However, antigen and antibody tests may be less accurate than PCR tests, although when positive, they are highly likely to correctly indicate current or past infection.
Demonstrating prior infection is not medically difficult. Prior infection can be documented with: a previous positive PCR test, clinic or a laboratory-based antigen test, a positive antibody test, or a T-cell test. A physician can easily interpret those test results and confirm that an individual was previously infected. While some have expressed concern that we haven’t yet established a definitive antibody titer that guarantees protection, quantitative testing isn’t necessary. Studies clearly show that those with prior infection are highly protected.
Because many symptoms of COVID-19 are non-specific, an individual’s “word” that they were previously infected would not be sufficient.
Several countries have introduced COVID-19 workplace, travel, or access mandates based on vaccination or infection history or the absence of current infection. In the European Union, Greece requires employees to carry a vaccination certificate to gain access to their place of work. Additionally, Greece allows for documentation by a healthcare professional or authorized laboratory of prior COVID-19 within 30 days after the day of the first positive COVID-19 test as sufficient for travel within 180 days. France requires documentation of vaccination to enter cafes, bars, and restaurants. If one has recovered from infection, only one vaccination dose is required.
Some countries have used history of prior COVID-19 as equivalent to vaccination to obtain COVID-19 certificates/passports. Italy requires all workers to be either vaccinated, recovered from COVID-19, or have a recent negative test result to avoid suspension from employment. Switzerland will grant COVID-19 certificates — needed to enter bars, restaurants, and fitness centers — to people who have been either vaccinated or recovered from COVID-19 within the past 365 days as documented by a prior positive PCR test or current positive antibody test.
We unequivocally support vaccination as a critical individual and public health intervention to control the COVID-19 pandemic. But the case for mandating vaccination in those who have recovered is much less strong. It is likely unethical to mandate a medical intervention in people who may not benefit, and may only be exposed to the risks, however small. Public health policy must be updated to recognize that recovery from prior infection is equivalent to vaccination. Healthcare professionals can play a key role in advocating for equivalence by understanding the evidence, educating the public, and knowing how to confirm prior infection.
Jeffrey D. Klausner, MD, MPH, is a former CDC medical officer and current professor of medicine and population public health science at the University of Southern California Keck School of Medicine. Noah Kojima, MD, is an internal medicine resident at University of California Los Angeles.
Klausner is medical director of Curative, a testing company, and disclosed fees from Danaher, Roche, Cepheid, Abbott, and Phase Scientific. He has previously received funding from the NIH, CDC, and private test manufacturers and pharmaceutical companies to study new ways to detect and treat infectious diseases. Kojima has received payments from Curative for clinical research services.