Resident Eagle: How Long Will the COVID-19 Vaccine Protect You? Part 1

Resident Eagle is an intermittent column that profiles the work of top EMS physicians and medical directors from the Metropolitan EMS Medical Directors Global Alliance (the "Eagles"), who represent America’s largest and key international cities. For information on the Gathering of Eagles 2022 conference, see useagles.org.

Early in the COVID-19 pandemic, long before vaccines were available, some top emergency medicine investigators conducted studies of antibody (Ab) production following COVID-19 infection. At that time controversies existed about the various point-of-care (POC) Ab tests being sold, especially around their apparent lack of sensitivity in identifying persons previously infected with COVID-19. Accordingly, for our investigations addressing those concerns, we employed POC assays of blood samples taken from persons shown to be positive on PCR (polymerase chain reaction) tests for SARS-CoV-2 genetic material a month or two earlier. For this we used either the Assure Ecotest (from Able Diagnostics) or the Cellex qSARS-COV-2 (Cellex) products, depending on the site of study. 

What we found and later reported was that these POC “lateral-flow chromatographic immunoassays” for humoral antibodies (IgG, IgM) may have been more accurate than previously suggested. We indeed found, consistently, that 30% of persons who had tested positive on their COVID-19 PCR (ie, previously infected persons) were testing negative for Ab, regardless of the study locale or product manufacturer. 

However, our studies also revealed that those who were testing PCR-positive but Ab-negative consisted entirely of younger adults (less than 50 years of age) who had had milder symptoms, with a trend for more men than women. 

These findings were wholly reproducible in individuals. For example, for purposes of this study, we compared both fingerstick and venous blood sampling in the same individuals and found identical results on different test cassettes. Furthermore, these tests were consistent and reproducible across the whole spectrum of PCR-positive and PCR-negative persons, even when examining a broader reference group of persons representing all ages from the community at large who had never had COVID-19 symptoms or tested PCR-positive.

To better validate our work, we used different manufacturers’ POC lateral-flow testing products in different venues (cities) that were geographically and sociologically varied. Despite those “ecological” and product differences, we found the same consistent, reproducible results in all settings. 

In retrospect, these early prevaccine results were similar to the findings of previous studies of coronavirus epidemics such as SARS and Middle East Respiratory Syndrome (MERS). The presumption, based on other studies and the broader knowledge of immunological response, was that those younger persons had other types of robust immune response, such as good T-cell response for coronaviruses (eg, the common cold), and did not need the “backup” immune response from classic (more measurable) humoral antibodies. 

In essence these early findings, from the spring of 2020, helped resolve some of the early controversies about POC tests for Ab and prompted us to better trust their findings. In turn, these findings led us to conduct additional studies across all age groups once vaccinations became available. Because vaccinations were intended (primarily) to induce humoral Ab, we specifically planned to study the IgG Ab response to COVID-19 vaccinations and use these tests as soon as vaccinations became available.

Postvaccination Antibody Response

COVID-19 vaccines first became available to healthcare workers in December 2020. Based on the vaccine formulations and results of clinical trials, it was presumed most adults receiving SARS-CoV-2 mRNA vaccines would indeed produce protective IgG antibodies to the S1 spike proteins following their second doses. However, the relative onset of Ab production and correlates of protection were not yet fully understood, particularly in terms of individual recipients. In addition, the duration of that protection was not yet appreciated back in January 2021 when this study began.

One potential basic indicator of protection might be the new appearance of Ab production and the relative onset (timing) of testing Ab-positive. A more indicative metric may be the magnitude of so-called neutralizing antibodies (nAb). The percentage of nAb (%nAb) detected is a relative measure of how many of those COVID-19 antibodies produced by an individual would be capable of specifically targeting the SARS-CoV-2 receptor binding domain, the original purpose of the mRNA vaccine’s design. For various reasons some persons—the elderly, for example—may not always construct the produced antibodies properly even when generating an apparently strong Ab response to the vaccine based on the more generic POC lateral-flow test for Ab presence alone.

Our purpose, therefore, was to use two types of point-of-care assays—the basic test for Ab presence and the other measuring the %nAb—in individual adults of all age groups to: 

• Better define the onset of general COVID-19 IgG Ab positivity and also assess any key factors that would affect the rate onset among all individuals tested;
• Attempt to better quantify the percent of Ab that were neutralizing following second doses while again identifying any key variables; and
• Report evolving data regarding the magnitude and duration of nAb presence prior to and after third doses.

While many of our early findings were later found consistent with what is now public knowledge, the POC data we were developing were rapidly shared in real time with our liaisons at the Centers for Disease Control and Prevention beginning in February 2021. In addition, the early “signals” from our ongoing assays in spring 2021 regarding the duration of neutralizing Ab studies (more on that to come) were routinely being reported to our CDC contacts thanks to the influence and networking abilities of the Metropolitan EMS Medical Directors Global Alliance (aka Eagles). 

This multipart discussion describes how these early important public health signals were identified and how they predicted, early on, what would become clinically manifest worldwide many months later.

How the Antibody Observations Were Made

Soon after vaccines became available in December 2020, persons residing and working in assisted living facilities (ALFs) were prioritized for COVID-19 vaccination using the Pfizer-BioNTech mRNA vaccine. On January 17, 2021 all 77 persons living or working in one ALF in South Florida, whose ages ranged from 23–100 years, were tested for IgG and IgM using a POC test (Assure Ecotest) just prior to receiving their first dose. Tests were repeated 2 weeks later (day 14) and on day 21 just prior to receiving the second dose. More follow-up testing was conducted on days 28 and 42 (3 weeks after second doses).

For this follow-up study on vaccinations, we used the same point-of-care lateral-flow chromatography assay (Assure Ecotest) we had previously studied when evaluating why some PCR-positive persons were testing IgG-negative. This assay was designed to simply test for any Ab targeting the recombinant nucleocapsid and spike (S1) proteins conjugated with colloid gold. Individual results of the assay were observed and recorded at the 15-minute mark after fingerstick blood sampling. 

In addition another POC assay (DrAccu from Assure Tech) was used to detect the percent of neutralizing Ab by quantifying the percent of antibodies produced that specifically targeted the SARS-CoV-2 receptor binding domains. In Part 1 of this nAb substudy, the same ALF residents/staff had blood sampled for nAb on days 7 and 21 after their second doses. In Part 2 a complementary small cohort of healthy individuals from the local community were also studied for %nAb and followed longitudinally to determine the duration of nAb response. Based on existing studies, %nAb measurements under 30% were deemed inadequate for protection. 

The next installment of this column will describe the results.  

The authors wish to acknowledge Lauren Rosenberg, Remle Crowe, Jonathan Jui, Megan Marino, and Aileen Marty for their assistance with this article. 

Paul E. Pepe, MD, MPH, is coordinator of the Metropolitan EMS Medical Directors (aka “Eagles”) Global Alliance, Dallas, Texas.

Peter M. Antevy, MD, is EMS medical director for the Coral Springs-Parkland Fire Department and Davie Fire Rescue, Broward County, Florida.

Kenneth A. Scheppke, MD, is deputy secretary for health for the state of Florida. Prior to his appointment, Scheppke served as the state EMS medical director and medical director for seven fire-rescue agencies across Palm Beach and Martin counties. 

Maricar Cabral, RN, CCRN, is a critical care nurse at Joe DiMaggio Children’s Hospital in Hollywood, Florida and director of nursing for Pediatric Emergency Standards, Inc. in Davie, Florida.