SUMMARY: See this health alert for
- Health District After-Hours Calls
- How to Sign Up for Health Advisories
- Serologic Testing
Health District After-Hours Calls
Our after-hours communicable disease (CD) reporting line (425-339-5278) prompts clinicians to select “1.” This then will ring through to the Washington Poison Control Center, which serves as our after-hours call service. You will again be instructed to select “1.” Wait for the operator to answer and tell them you are trying to reach the Snohomish Health District communicable disease response on-call staff. After-hours calls should be reserved for immediately notifiable conditions (e.g., suspected botulism, shellfish poisoning, measles, meningococcal disease, rabies immunoprophylaxis). Visit https://www.doh.wa.gov/Portals/1/Documents/5100/210-001-Poster-HCP.pdf for the full list of notifiable conditions sorted by reporting timeframes.
After hours call for non-communicable disease public health emergencies should be directed to 425-339-5295. The process is much the same as set forth above and also arrives to the Washington Poison Control Center for notifying our on-call duty officer.
How to Sign Up for Health Advisories
Please share this document with your workplace and other health care colleagues, especially those who are not signed up to receive our health advisories through our alert system. To sign up for health advisories for clinicians, please email SHDInfo@snohd.org with the following information:
- Subject: “Request to be added to Health Advisories”
- Your name
- The practice, clinic, hospital, or healthcare organization you are affiliated with
- Best email to receive alerts
- If you would also like to receive a text when there is a new alert, include a phone number with text capability
Serologic Testing for SARS-CoV2
Requested actions:
- Be aware of and educate patients about both the promises and the limitations of serologic testing for SARS-CoV2.
- When serologic testing is pursued, exercise caution in selection of the testing platform and interpretation of results.
- Stay tuned for forthcoming updated guidance on respiratory PCR testing.
Background
The recent emergence of assays for detection of antibodies to SARS-CoV2 (the virus that causes COVID-19) has been met with high hopes among health care providers, patients, and the media. Testing platforms being offered include laboratory-based ELISA or chemiluminescent immunoassays as well as point-of-care lateral flow assays similar to pregnancy tests in concept. IgM antibodies typically appear within about seven days of onset of COVID-19 and IgG antibodies within four weeks. Aspirations for this technology hinge upon the supposition that recovery from COVID-19 affords at least short-term immunity and protection against re-infection. Potential applications include:
- increasing the sensitivity of the diagnostic evaluation by detection of IgM antibodies in acutely ill patients with falsely negative respiratory tract PCR results;
- identification of potential convalescent plasma donors for use in therapeutic clinical trials;
- detection of prior resolved infection and presumed immunity for clinical, infection control, and occupational purposes;
- monitoring of population prevalence of prior infection to inform implementation or modification of social distancing and other mitigation measures;
- identification of antibody correlates of protection for vaccine research; and
- confirmation of vaccine response when an effective vaccine is developed.
While these are some of the benefits we seek from serologic testing, they may not have arrived yet. Key concerns about widespread implementation or over-interpretation of results include:
- It remains to be determined which viral epitopes elicit protective antibodies and the quantitative level of those antibodies necessary for protection.
- Qualitatively positive results without quantitation may be of uncertain meaning.
- Duration of immunity afforded by prior infection remains to be determined.
- False-negative results may be obtained early in the disease course.
- False-positive results may occur in due to technical difficulties inherent in IgM detection.
- False-positive results may occur due to cross reaction with circulating human coronaviruses that can account for up to 10-20% of viral respiratory infections (e.g., HKU1, NL63, OC43, 229E).
Furthermore, this is a relatively unregulated and un-validated market of products—albeit due to the nature of the emergency we are in. Like the multitude of PCR diagnostics for SARS-CoV2, four serology market entrants have received limited Food and Drug Administration (FDA) review and emergency use authorization for clinical use (Cellex, Vitro [Ortho Diagnostics], Mount Sinai Laboratory, and ChemBio). Six others have received emergency use authorization for research purposes only. The rest of the products on the market have utilized an additional pathway afforded by FDA policy that permits marketing and use of tests without prior FDA review, albeit with some provisions for internal manufacturer validation, notification, and labeling (including that the tests are not to be used as a sole basis for diagnosis). Consequently, sensitivity and specificity of these tests remain largely un-vetted, we are left to rely on manufacturer and vendor reports. In some cases, no information is available at all on a test’s performance.
Locally, the University of Washington Department of Virology’s validation of the Abbott Laboratories’ IgG assay showed that it offers about 50% sensitivity at two weeks after onset and “almost 100%” at 25 days. Specificity is reported at 99.67%. LabCorp is also bringing IgM, IgG, and IgA assays online, but test performance has not yet been reported in its marketing literature.
To demonstrate the impact of even small declines in specificity upon the predictive value of a positive test result when population prevalence is low, see the following table.
With nearly 2,500 COVID-19 cases reported to-date in Snohomish County and assuming that only 1-in-10 total cases are actually diagnosed and reported, then a rough estimate of prevalence of antibodies to SARS-CoV2 is 25,000 (~3%) county-wide. If population prevalence of COVID-19 antibodies is in the 2-5% range, even small decrements in specificity can result in the majority of positive results being falsely so. Not only should this prompt cautious use and interpretation of SARS-CoV2 serology, but it also explains why we also discourage respiratory PCR testing of patients who are asymptomatic—especially among those who have not had an exposure: false positive results may equal or exceed true positive results.
FDA is working with the National Institutes of Health and the Centers for Disease Control and Prevention to develop a system for validation of these serologic tests. Meanwhile, the Foundation for Innovative New Diagnostics is conducting independent evaluations of both molecular tests and immunoassays, in collaboration with the World Health Organization, the University Hospitals of Geneva and others. Data from these evaluations are made publicly available as they emerge. A current plot of its findings in SARS-CoV2 serologic test sensitivity and specificity are as follows:
Source: FIND https://finddx.shinyapps.io/COVID19DxData/
In summary, regarding serologic testing for SARS-CoV2:
- SHD makes no systematic recommendation for serologic testing at this time and urges cautious and judicious use of these new products.
- Although some products have had limited review for emergency use authorization from FDA, most have had no review whatsoever, and few of these assays have been independently assessed for accuracy.
- For some assays, cross reactions with antibodies to circulating seasonal coronaviruses may cause a false positive result.
- Relevance of SARS-CoV2 antibody detection to diagnosis of COVID-19 illness and to individual patient management is not clear at this time and, in general, serology does not have a role in the diagnosis of COVID-19 illness.
- Correlation of antibody detection with durable immunity remains to be demonstrated and at the current time great caution should be exercised with respect to making any infection control or occupational placement decisions based on serologic results alone. However, this remains a valuable potential use of serology going forward if evidence emerges to support that application.
- The chief benefits of an accurate test in the present moment are for the monitoring of population prevalence of prior infection, not for the evaluation and management of individuals. The value and precision of that information, and by extension its relevance to individual patient care, will increase with rising prevalence and with independent validation of tests’ performance.
Additional Resources
Chris Spitters, MD
Health Officer
Snohomish Health District