5/20/2020 COVID ANTIBODY TESTING UPDATE

Since March, I have been very interested in any data from SARS-CoV-2 antibody testing.  We were hopeful that this information would provide some COVID prevalence information for Douglas County.  In Oregon, the PCR assays became available relatively late in the course of this pandemic and were initially limited for use in those that met CDC testing criteria (COVID-like symptoms, foreign travel and hospitalized patients). I have impatiently waited for COVID antibody testing to become available in Douglas County to better understand our urgent care experience treating thousands of patients since January.

I was interested in using an antibody assay that had some reasonable validity data to avoid too many false positive and negative results.  To date, LabCorp seemed to have the most complete validity testing available.  From May 11th to May 15th, we tested the COVID-19 antibody status of 46 urgent care staff and found that no one tested positive for COVID antibodies.  This observational study is posted below.

Some people may think that this is additional evidence that COVID-19 prevalence is very low in Douglas County and non-existent in our Urgent Care staff.  Although possible, I think that this is unlikely to be the case.  First, the urgent care had direct contact with 7 out of the 25 confirmed COVID positive patients and likely saw thousands of patients with COVID- like symptoms from January to the present.  Second, there is evidence that antibodies may become undetectable rapidly during the recovery phase in other coronavirus strains. This may explain the unexpected negative antibody results among Evergreen Urgent Care staff since they were exposed months before the testing was performed. Third, there is a local example of one who tested positive by PCR testing but approximately one month later tested negative using the Quest IgG antibody assay.

Even if antibodies do become undetectable soon after recovery, there may be some protection by T-cell or cell-mediated immunity.  Unfortunately, if antibodies do not last very long, a vaccine that makes a meaningful long-term impact may be even more difficult to develop.  Recently, Moderna announced evidence of positive results for their novel messenger RNA (mRNA) vaccine in a phase one trial.  They tested 45 people between the ages of 18 and 55 and saw an antibody response similar to those who were infected with COVID.  They intend to test another 600 volunteers in the next phase using this vaccine.   Will the antibodies remain effective for very long and if not, does the vaccine stimulate other aspects of the immune response to provide some level of protection? This will take time to determine and will require extensive testing for safety before it will be ready for mass inoculation.  Vaccine safety will be particularly important since we understand that the infection lethality rate of COVID-19 is much lower than initially feared.  Also, a novel method of producing a vaccine would usually require additional scrutiny by the FDA.

With these developments, I have the following thoughts:

  1. Unfortunately, I think that using current serology testing to determine community prevalence of our immunity to COVID is of little value at this time.

  2. It is important to understand that there has never been a successful vaccine for coronaviruses to date – including SARS and MERS. 

  3. The novel Moderna mRNA vaccine method or any vaccine for that matter, will need to show meaningful protection to those most at risk (the elderly and those with multiple comorbid conditions). Demonstrating efficacy and safety for any COVID-19 vaccine will likely be measured in years, not months. The fastest that we ever produced a vaccine for a novel virus was for the Mumps.  It took approximately 4 years and it was done using a standard, well-understood method.

  4. It is unlikely that we will eradicate COVID-19 from the planet any time soon.  More likely, it will become endemic in our population like the other strains of coronavirus that we deal with every year. Fortunately, as exposures increase and reoccur, the severity of the illness will likely lessen.  Fortunately, COVID-19 is not smallpox with a 30% mortality rate.

  5. At this time, it is unlikely that any metric other than regional emergency department, intensive care, and other hospital capacity measures will be helpful in determining who gets to “open up”.  Community support will be important as it relates to the discharge of hospitalized elderly and chronically ill people who had COVID and are unable to immediately return to a skilled nursing or assisted living facility.  I see very little value in strict contact tracing at this point other than estimating an “R0” or the reproduction number to describe the intensity of the outbreak. These numbers do not reflect a community’s capability to manage a surge of COVID cases. Douglas County is ready to open up in my opinion.

  6. In the U.S., we are approaching 40 million newly unemployed citizens in the last 2 months.  The adverse impacts of this economic disaster on physical health, mental health, and other social determinants of health are real and attributable to the current pandemic restrictions.  The effects are tearing through the social fabric of our community. I understand that there are no risk-free paths forward but I do not accept that a life adversely impacted by the current policy is worth less than a life impacted by COVID-19. Deaths will continue to occur in both circumstances.  We need a balanced approach to minimize the total harm.

  7. I would recommend that the elderly and especially those with comorbid conditions to avoid crowds and to use reasonable social distancing.  There is no convincing data for the use of face masks on asymptomatic individuals in my opinion.  If one is ill, they should not depend on a mask to prevent the spread of COVID-19 and if a person is fragile from advanced age and/or chronic illness, they should not depend upon masks worn by themselves or others to protect them.  Ultimately, everyone will need to come to terms with their own risk tolerance.  For all Douglas County citizens, I recommend that we wash our hands often and for those who can, let’s get back to working, recreating and stimulating the economy - lives depend on it.

John Powell M.D.

P.S. I have attached a link of an interview from 5/5/20 with Professor Hendrik Streeck, a virologist from the University of Bonn in Germany.   He authored an antibody study in Germany. His research and insight about vaccines and other coronaviruses were helpful.



An Urgent Care Experience with COVID-19 IgG Antibody testing of Staff in Roseburg, Oregon

Purpose:

To understand the prevalence of COVID-19 antibodies among Evergreen Urgent Care staff members in order to estimate a high exposure cohort prevalence rate for a population in Douglas County, Oregon.

Background:

Evergreen Urgent Care is a high volume semi-rural clinic that had 40,518 patient visits in 2019 and 10,918 patient encounters from 1/1/20 through 3/31/20. The clinic has served as an access point for Douglas County residents with COVID-like symptoms during the pandemic.

As of 5/17/20, there have been 25 PCR confirmed cases and zero deaths from COVID-19 in Douglas County, Oregon. The urgent care staff had direct contact with 7 of those confirmed positive SARS-CoV-2 cases.

Forty-six Evergreen Urgent Care staff participated in this antibody assay. They included receptionists, managers, physicians, advanced level providers, lab personnel and clinical staff.

Methods:

Evergreen Urgent Care front office and back office clinical staff were offered LabCorp IgG antibody (serological) testing.  They must have been symptom free for at least 14 days to ensure improved sensitivity of the test.  Potential participants were informed that PCR testing would be more appropriate if they were symptomatic or were within 14 days of onset of their illness.

Forty-six Evergreen staff volunteered to participate in a LabCorp COVID-19 IgG antibody test offered by our clinic free of charge. Six of the staff had been previously tested using COVID-19 PCR testing in the previous months. Of the 6 PCR assays, 4 staff members were negative and 2 individuals had inconclusive PCR results (QNS). Forty-two reported either a prior known COVID-19 exposure or COVID- like symptoms between January and March 2020.  Four individuals reported no known exposure to the virus or symptoms consistent with the disease. Twenty-six individuals reported a known COVID-19 exposure. Thirty participants were physicians, advanced level practitioners or clinical support staff with direct patient care duties. Six were laboratory staff or phlebotomists.  Six were urgent care receptionists and 4 were managers.

We used a LabCorp IgG serologic test approved for diagnostic use under an FDA Emergency Use Authorization. The testing was performed between May 11 – 15, 2020. The LabCorp validation testing showed a sensitivity of 100% for 88 PCR confirmed COVID-19 positive patients 14 days or longer after their symptoms began. There were 4 “false positive” tests in 997 patients’ blood samples that were drawn in September 2019- before the outbreak of the COVID-19 pandemic.  This data was the basis for selecting this particular serologic test for our Evergreen employees. Unfortunately, IgG detection rates were not reported for patients beyond 14 days after they became symptomatic in LabCorp’s validity testing. 

LabCorp provided the following validation data in their clinical performance statement.

Results:

There were no positive COVID-19 IgG antibodies identified in any of the 46 tested staff members.

Discussion:

This COVID-19 antibody screen of Evergreen Family Medicine Urgent Care staff was performed to understand the prevalence of SARS-CoV-2 virus in a high exposure setting in our semi-rural community.    There were no members of our staff who tested positive for COVID IgG antibodies. These findings were unexpected since our staff members participated in the care of 7 known positive COVID positive cases and likely thousands of patients with COVID-like symptoms since January 2020.  Many patients who had a febrile respiratory illness tested negative for influenza but were evaluated before COVID PCR testing was available or limited by CDC testing criteria. Staff use of PPE to care for patients with respiratory illness did not begin until COVID-19 was declared a pandemic in March of 2020 and guidance on appropriate use of PPE was provided by the Oregon Health Authority.

There are many possibilities to consider in this observational study.  First, the prevalence of COVID-19 may actually be zero in the Evergreen urgent care staff.  Second, Douglas County and urgent care staff are extremely effective at preventing the spread of COVID-19.  Third, the overall prevalence of COVID-19 in Douglas County is very low and the 25 confirmed PCR cases per approximately 100,000 residents represents the prevalence of the disease in our county.  It is understood that the majority of the 25 positive cases in Douglas County were without a travel or a known exposure history.  Public health authorities have been unable to explain how these sporadic cases occurred. Therefore, it seems unlikely that the number of confirmed COVID-19 cases represent an accurate assessment of the prevalence of the disease in our community. Fourth, our findings may suggest that individuals infected with this virus were very effective in preventing the spread of the disease before and after their positive status was known and it may also reflect Douglas County’s low population density.

Finally, the validation process for this serology test may be flawed or more likely, the assay may not detect COVID IgG antibodies for more remote infections because antibodies rapidly become undetectable in the recovery period.   There is a possibility that serologic testing is unable to detect IgG antibodies months after exposure to SARS-CoV-2.  Our staff experienced exposures or illness months prior to the antibody testing.

 A rapid decline in IgG antibody levels would be consistent with other “common cold viruses” including other strains of coronavirus and rhinoviruses.  Unfortunately, this might also suggest that humoral immunity does not last long and securing a meaningful vaccine may be more challenging. Perhaps, other cell-mediated immunity mechanisms provide some level of protection to reduce the severity of reinfection.

After considering the possibilities above, the presently understood transmissibility of COVID-19 and our urgent care clinical experience, it seems more likely that serology testing is not currently useful in determining the prevalence of COVID-19 among our staff and by extension, our community.   These findings may suggest that this assay may not be effective in determining seropositivity in persons with more remote infections to COVID-19.

Conclusion:

The seroprevalence of COVID-19 remains unknown at the Evergreen Family Medicine Urgent Care. It remains unclear how effective the current serology testing is to detect IgG antibodies for those who may have been exposed to or infected by SARS-CoV-2 over a month prior to this method of testing. We recommend continued study of the current commercial serologic assays regarding the length of time that IgG antibodies remain detectable in individuals with confirmed positive COVID-19 infections.  At this time, we do not recommend the current serology assays to diagnose previous infections or to determine immunity to SARS-CoV-2.  We are not confident that the currently available commercial serologic assays accurately measure seroprevalence of this virus in a population.  Our experience supports the hypothesis that COVID-19 IgG may become undetectable soon after recovery from an infection.  This would be consistent with other coronavirus strains.

John Powell M.D.

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