Weekly Update: November 3rd - November 11th
Welcome to the McGraw-Hill COVID-19 channel. This week we have an update on COVID-19 related autoantibodies, information about the culling of mink in Denmark secondary to COVID-19, the announcement of the first test specific for neutralizing antibodies, an emergency use authorization for the first monoclonal antibody in outpatients and an FDA announcement about false positive tests when using rapid detection.
COVID-19 related autoantibodies include prothrombotic antiphospholipid antibodies, anticardiolipin antibodies (aPL), and other prothrombotic antibodies. COVID-19 is associated with the presence of autoantibodies (e.g. a positive ANA1) as well as with prothrombotic events. This study answers the question of whether these two findings are related. This study2 measured levels of eight antiphospholipid antibodies in 172 patients hospitalized with COVID-19. Antiphospholipid antibodies were found in 52% of samples. These were more common in patients with severe lung and renal disease.
In the second part of the study they injected purified IgG antiphospholipid antibodies from patients into mice and noted accelerated venous thrombosis. This suggests that aPL antibodies play a role in the prothrombotic state of many patients with COVID-19.
It is hard to know how to apply this data to our patients, but it is does clarify the nature of at least some of the autoantibodies found in COVID-19 patients. The full study can be found here.
1) Matthew C, Woodruff RP, Ramonsell F. et al. Clinically identifiable autoreactivity is common in severe SARS-CoV-2 Infection medRxiv 2020.10.21.20216192; doi: https://doi.org/10.1101/2020.10.21.20216192 (Prepublication)
2) Zuo Y, Estes SK, Ramadan AA, et al. Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19. Science Translational Medicine 02 Nov 2020: eabd3876 DOI: 10.1126/scitranslmed.abd3876
The FDA is warning about false positive tests for SARS-CoV-2 when using rapid antigen detection. The key points are:
- False positives are expected, especially when testing populations with a low pre-test probability." Consider positive results in combination with clinical observations, patient history, and epidemiological information.”
- In nursing homes and other high-risk situations, consider RT-PCR if the patient is found to be negative. These recommendations can be found here.
- Make sure to follow manufacturer’s instructions as each has slightly different specimen handling requirements, etc.
This is worthwhile reading for those using the rapid antigen tests. One may also consider RT-PCR testing to confirm positive tests, especially if in a low prevalence area. This has implications for quarantine, isolation and contact tracing. This will help alleviate chasing false positives.
The first test for neutralizing antibodies has been approved by the FDA. This has implications for the use of convalescent plasma, which can now be tested for viral suppressing antibodies. It also has implications for post-infectious testing to test the duration of an effective immune response.
The FDA points out that this does not suggest that patients use the test results to “stop taking steps to protect themselves and others, such as stopping social distancing, discontinuing wearing masks or returning to work. Remember that antibody tests are not to be used to rule in or rule out active infection. RT-PCR is still the standard. The full statement can be found here.
The first monoclonal antibody has gotten emergency use authorization (EUA) for treating mild to moderate COVID-19 patients but is not indicated in hospitalized patients. Bamlanivimab is approved in COVID-19 test positive patients over age 12, over 40kg and who are high risk of worsening disease. These include patients over 65 years old, obesity, diabetes, COPD and other conditions that predispose to worse outcomes. It is for outpatient use only and is not approved for patients who require oxygen. These sicker patients seem to have worse outcomes when treated with Bamlanivimab.
The full FDA announcement can be found here. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibody-treatment-covid-19
Briefly, minks are being culled in Denmark because of unique spike proteins associated with transmission from mink to humans (214 cases of transmission total, 12 with unique spike proteins). The WHO notes that many of the vaccines are dependent on a stable spike protein as a target, thus preventing mutations from developing, such as occurs with mink-to-human transmission. So far as we know, this type of transmission/mutation does not occur in dogs or cats. The WHO statement can be found here.