Resident Eagle: Antibody Response After the COVID-19 Vaccine, Part 2

Resident Eagle 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 other key international cities. The Gathering of Eagles 2022 is scheduled for June 14–17 in Hollywood, Florida. See useagles.org.

As described in last month’s column, a group of EMS physicians used point-of-care (POC) assay testing to determine percentages of neutralizing antibodies produced following receipt of the Pfizer-BioNTech COVID-19 vaccine in residents of a Florida assisted living facility (ALF), as well as how long their neutralizing antibodies  lasted. This column reports the results. (Note: the results of this study were not used for clinical decision-making.) 

Antibodies After Vaccination

Results found antibody production was strong, with rapid response in adults under 60 unless there were existing immunomodulating conditions. 

Antibody (Ab) production was inversely related to age, with the appearance of Ab on the POC test taking longer as persons were progressively older. Nevertheless, those elders, especially those under 80, eventually displayed an improved general IgG antibody response 21 days after their second dose of the Pfizer vaccine. While the investigators  also demonstrated the percent of neutralizing Ab followed the same age-related pattern as basic IgG Ab testing, the POC testing of individuals for antibodies neutralizing to SARS-CoV-2 (nAb) also identified persons at greater risk in real time. For example, while most persons older than 90 were Ab-positive, half had no neutralizing Ab whatsoever detected as late as 21 days after their second doses.

Meanwhile, subsequent longitudinal testing of the percentage of neutralizing antibodies (%nAb) in a community-based comparison cohort of healthy persons showed the same pattern as the ALF group in terms of age-related response, but these subjects also showed progressive deterioration of %nAb over ensuing months, even including a significant decline in %nAb among healthy persons under 50. A summary of the results measured prior to third doses is annotated in Tables 1 and 2.

The data reported by the investigators several months after vaccination indicated post-dose 2 declines in %nAb, and those concerning observations were clinically manifested in subsequent breakthrough infections across the US, particularly among the elderly. However, such breakthrough infections occurred even in young, healthy persons who had been vaccinated, and these POC findings predicted these subsequent epidemiological trends. These findings led the authors to recommend to CDC contacts and others as early as February 2021 that the elderly should perhaps receive more concentrated doses (like those provided with the influenza vaccine) or perhaps booster doses, especially for those who showed exceptionally low levels of nAb. Likewise, they were able to provide early warnings for the evolving decline in %nAb even among the young and healthy. 

A Game-Changer

In other words, by using the POC test for nAb, the authors were not only able to report the worrisome signal for waning immunity as early as spring 2021 but detect the most susceptible individuals as well. The tests provided reproducible results, and cumulative results predicted subsequent global clinical trends.

However, the findings indicated third doses were a potential game-changer (Table 3). Not only were the %nAb levels after dose 3 strikingly more pronounced, even among the older populations, but the levels became quantitatively optimal and were sustained for a longer period.

The final part of this series will further discuss these third-dose results.

The authors wish to include Lauren M. Rosenberg; Maricar Cabral, RN, CCRN; Remle P. Crowe, PhD; Jonathan Jui, MD, MPH; Megan C. Marino, MD, FAAP; and Aileen M. Marty, MD.  

Table 1: Onset of General Humoral (IgG) Antibody Production After Initial Vaccination

• Paralleling the original Pfizer vaccine trial, by day 14 after dose 1, 27 of 39 persons (69%) who were less than 70 years of age had new Ab production.
• At the same time, no Ab were detected in 84% of the 38 persons older than 70. 
• By day 21, even before dose 2 was administered, 100% of those under 60 had become Ab-positive except two individuals with immunomodulating conditions (IMCs). 
• For each successive decade of age, a progressively smaller number of persons were Ab-positive (eg, only 20% of those older than 90). 
• On day 7 after second doses, 100% of those under 80 were Ab-positive (except the 2 with IMCs), as well as 89% in their 80s (n=18) and 78% of those older than 90s (n=10). 
• 2 weeks later only 2 persons remained Ab-negative, 1 with an IMC and 1 who was 93 years old.
• Semiquantitative results (darker band versus a much lighter band on the lateral-flow chromatography cassette) indicated very strong Ab response in 100% of persons under 80 tested by day 42.
• The POC assay used had consistent and reproducible results.

Table 2: Magnitude and Duration of Neutralizing Antibodies After Second Doses

ALF Group

• Paralleling the qualitative (positive or negative) POC test results, at day 7 after dose 2, the average percentages of %nAb levels were 95%–99% in the ALF workers/residents who were in the 23–50 age groups.
• However, the average %nAb remained borderline or inadequate for those older than 70 or with IMCs. 
• By day 21 after dose 2, average %nAb levels had begun to elevate and rose to 91% for those ages 61–70, 75% for 71–80, and 55% for 81–90. 
• While the average percentage reflected relative trends, that data set did not reflect the actual variation among individuals.
• Among the 8 persons older than 90, the average %nAb was 35%, but half still had no detectable nAb. 

Community Group

• The initial findings on days 7 and 21 after dose 2 in the community-based cohort of healthy individuals fully matched the ALF findings, with strong levels of neutralizing Ab found in those under 50 but progressively lower %nAb with increasing age.
• Nevertheless, even among those in the 30–70 age groups, the %nAb assay progressively declined from the 90%–95% range to much lower levels within the ensuing several months. 
• An interesting finding was that tested adolescents sustained relatively high levels of %nAb 6 months after dose 2 while most adults over 20 had borderline/inadequate levels at that same 180-day mark.

Table 3: Striking Neutralizing Ab Responses Following Dose 3 of Vaccine

• In contrast to dose 2, with few exceptions, almost every tested adult had more than 99% nAb by day 21 after a third dose.
• Most important, those same optimal levels of nAb persisted at 100 days and 150 days, respectively. 
• For example, a 71-year-old man who had age-predicted modest levels of 68% nAb at 21 days after dose 2 fell to 55% at day 100, 42% at day 150, and 16% at day 180 post-dose 2.
• However, in contrast to dose 2, that same person had striking and markedly sustained elevations after dose 3.
• Versus the age-predicted 68% nAb found 21 days post dose 2, the %nAb rose from 16% (day 180 after dose 2) to 99.3% at day 21 after dose 3, with sustained levels of 99.2% at day 100 and 99.7% at day 150.
• Of important note are the initial 180-day results. Keeping in mind that the results here are taken from only 2 persons to date (the first 2 reaching the 180-day mark post-dose 3), the previously mentioned 71-year-old and another 49-year-old still retained a robust percent of nAb at 92.7% and 89.6%, respectively. However, those 180-day numbers were lower than the 99%-plus nAb observed for the first 5 months after dose 3.
• This first downward trend is nowhere near the rapid rate of decline seen after dose 2, but it still bears watching and perhaps subsequent considerations for another (4th) dose sometime in the near future. 

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 department’s state EMS medical director and medical director for 7 fire-rescue agencies across Palm Beach and Martin counties.