UC Davis Health System

10/15/2021 | News release | Distributed by Public on 10/15/2021 11:33

Debunking Common Misconceptions of COVID-19 Related Testing and Transfusion Practices

Nam K. Tran, PhD; Sarah Barnhard, MD

INTRODUCTION

The 2019 novel coronavirus infectious disease (COVID-19) pandemic resulted in a constant and massive surge of information. Over 100,000 scientific articles related to COVID-19 were published in 2020 alone.1 Some 30,000 papers were also released as "pre-prints" - providing readers with timely, but not peer-reviewed data. Unfortunately, the rapidly evolving nature of COVID-19 science (peer-reviewed or not) combined with varying degrees of scientific understanding by the lay public has created misconceptions which could impact public health safety. In particular, the underlying science behind clinical testing and transfusion practices has been fraught with varying degrees of understanding by both scientifically oriented individuals and the public. To this end, the goal of this blog article is to debunk common misconceptions related to COVID-19 testing and transfusion practices:

PCR is the best method for COVID-19 testing.
Polymerase chain reaction, or PCR is one of many molecular methods used to detect the severe acute respiratory syndrome - coronavirus - 2 (SARS-CoV-2). Although PCR is often considered the "gold standard" for the detection of respiratory viruses, there are many other molecular approaches that produce comparable results. Examples include transcription mediated amplification (TMA), isothermal amplification, next generation sequencing, among others.2

COVID-19 PCR tests have been recalled by the FDA
Recent social media posts have misinterpreted an FDA recall of a single SARS-CoV-2 test from the market.3 Tests (COVID-19 related or not) may be recalled for many reasons including performance issues or due to manufacturing problems. Clinical laboratories and diagnostic test manufacturers are required to stop testing of any tests recalled by the FDA. As of August 23, 2021, there are 255 COVID-19 PCR tests that have FDA EUA2 and all tests at UC Davis Health are considered class-leading commercially available platforms as proven in scientific literature.4 In fact, new tests in development are often compared to our platforms since they serve as reference methods.

Antigen performs poorly and should not be used for COVID-19 screening
SARS-CoV-2 antigen tests detect the protein structure of the virus.5 In contrast, molecular methods, like PCR, detect the virus' genetic make-up. Antigen tests carry three benefits over molecular approaches: (a) low-cost, (b) speed, and (c) availability/accessibility. It is true that the relative sensitivity of antigen tests may be lower, however, these tests can be conveniently deployed for frequent testing and providing results in minutes. It is believed that frequent testing (e.g., every 36 hours) in at risk individuals enables detection as the virus replicates in the body. To test frequently by PCR may not always be cost-effective, rapid (<1 hour), and often not feasible at the point of care. To this end, antigen testing is ideal for workplace, school, and travel screening.

Serology results determine if someone is (or not) immune
Serology testing allows detection of antibodies we produce against pathogens, such as SARS-CoV-2.6 However, there are many elements to immunity which prevents or limits infection. This includes the type (e.g., IgA vs. IgM vs. IgG) and titer of antibodies, and the activity of other immune cells such as T-cells. Although there is increasing evidence on the amount of anti-SARS-CoV-2 antibodies does contribute to infection susceptibility, it is uncertain what exact titer and immune cell activity predicts immunity. Therefore, at present, serology testing is best used by healthcare professionals to determine prior exposure to SARS-CoV-2. It must be noted that T-cell activity tests have recently been emergency use authorized by the Food and Drug Administration7, however, there is very little data, presently, that would promote use of these tests for assessing COVID-19 immunity.

Being PCR or antigen negative means you are not infected by SARS-CoV-2.
Unfortunately, molecular and antigen techniques only provide a "snapshot" of your COVID-19 status.8 Being SARS-CoV-2 negative at the time of testing will miss early infection (not enough virus replicating for detection) and of course not pick up any subsequent infection after testing.

COVID-19 is just a severe cold
As highlighted in the introduction, COVID-19 science has evolved greatly.9 Although SARS-CoV-2 is a member of the coronavirus family which includes viruses that cause the common cold, this novel virus carries several attributes that has caused significant global mortality and morbidity. It is now appreciated that the SARS-CoV-2 can cause severe illness in certain individuals. Laboratory testing in many symptomatic and asymptomatic individuals have identified the presence of inappropriate clotting, respiratory issues, heart injury.10 It is also unknown what long-term complications may arise after being exposed to SARS-CoV-2, regardless of symptom status and lack of "long-COVID" presentation.

After being fully vaccinated for COVID-19, donating whole blood diminishes the vaccine's effect.
You have approximately 5 liters of blood in your body. Donating blood takes out only a small amount (approximately 500 milliliters). Your body's ability to make antibodies against SARS-CoV-2 (the virus that causes COVID-19) relies on your plasma cells. The plasma cells are in your bone marrow and pump out antibodies after vaccination continuously. You may lose a small number of antibodies from blood donation, but these are made up by continuous production. It is safe to donate blood after vaccination and you are encouraged to do so if you are an eligible donor. Most blood donors are eligible to donate every 2 months.11 We need your consistent help as a blood donor because patients need ongoing blood transfusions, and every donation has a fixed shelf life.

Transfusions transmit COVID-19.
There have been no reported cases of transfusion-transmitted coronavirus, including SARS-CoV-2, worldwide.12 Interestingly, case reports have emerged of viral RNA detectable in the blood donor population however there have been no reports of the virus spreading through transfusions and causing the clinical disease COVID-19 in transfusion recipients. The corresponding plasma of these donors has also been shown non-infectious in cell culture. Presumably, this is due to the route of transmission. In order to cause the disease COVID-19 and severe respiratory manifestations, the SARS-CoV-2 virus must be transmitted through respiratory droplets. Blood donors and transfusion recipients should remain masked or follow other public health guidelines as instructed due to the risk of exposure to others around them at the blood drive or in healthcare settings.

Receiving plasma from someone who has antibodies against SARS-CoV-2 (i.e. COVID-19 convalescent plasma; CCP) provides protection or aids in recovery from COVID-19.
Near the beginning of the global pandemic, COVID-19 convalescent plasma (CCP) emerged as a possible therapeutic option for those who are hospitalized as well as a possible preventative therapy to reduce the risk of hospitalization and severe disease outcomes. In April 2020, the US FDA sponsored the Expanded Access Program (EAP) coordinated by the Mayo Clinic. This treatment protocol broadened access for hospitalized adults to convalescent plasma under an investigational new drug protocol to any institution that enrolled. A total of 94,287 transfusions were given. In August 2020, the EAP closed and CCP was authorized under an emergency use authorization. The EUA was based on the EAP finding that the relative risk of mortality was lower in hospitalized but non-ventilated patients receiving high titer vs low titer CCP. Over 250,000 total units of convalescent plasma were administered as part of the EAP, the EUA, or clinical trials. Some subsequent studies have shown possible benefit reducing the risk of progressing to severe disease if high titer plasma is administered within 3 days of symptom onset. However, some randomized controlled trials have failed to show benefit. Recently, the NIH halted accrual to the C3PO trial due to futility after 511 out of 900 participants were enrolled.13 This trial administered CCP or placebo to patients presenting to the ED with mild to moderate symptoms within one week of onset. The current NIH treatment guidelines do not recommend the use of CCP in hospitalized patients and state there is insufficient evidence for or against the use of CCP in non-hospitalized or immunocompromised patients. The guidelines instead focus on the use of monoclonal antibody therapy in the appropriate clinical population. Monoclonal antibody therapy has a much safer risk profile than plasma transfusion. Convalescent plasma has now fallen out of favor as a treatment option and the American Red Cross (the nation's largest blood supplier) stopped collecting it in June 2021 and will stop distributing it in September 2021.

Receiving convalescent plasma from a donor who is vaccinated confers immunity to the recipient.
This is unknown at this time.12 Vaccination against SARS-CoV-2 was not a contraindication to convalescent plasma donation, but vaccination in the absence of a prior SARS-CoV-2 infection did not qualify an individual to donate CCP. Passive immunity from a donor with the antibody profile resulting from only vaccination has not been well studied. Individuals who have been vaccinated are still eligible to be regular donors of plasma, red blood cells, and platelets.

Receiving a transfusion from a donor who is vaccinated harms the recipient.
The coronavirus vaccine is administered into the muscle of the arm.14 Cells of the immune system then recognize the inoculum as foreign and mount an immune response to it. The immune response protects the host from the disease. Components of the vaccine do not circulate in the bloodstream. Only the antibodies from the immune response are present in the bloodstream. Most of our blood supply has been impacted by COVID-19. It is estimated that as many as 60 to 70% of blood donors have been vaccinated and over 90% of blood donors have been infected or been vaccinated. Any blood transfusion confers risk to the recipient due to other relevant transfusion transmitted diseases and known risk of transfusion reactions. However, nearly 21 million blood components are transfused each year in the United States and there is no scientific indication that receiving a blood transfusion from a blood donor who has been vaccinated may harm the recipient due to a specific risk of the donor's SARS-CoV-2 vaccination.11,15

REFERENCES

  1. Else H. COVID in papers: A torrent of science. Nature 2020;588:553.
  2. FDA IVD EUA website, Accessed on August 23, 2021.
  3. Reuters Article, Accessed on August 23, 2021.
  4. Hanson G, Marino J, Wang ZX, et al. Clinical performance of the point-of-care cobas Liat for detection of SASR-CoV-2 in 20 minutes: A multicenter study. J Clin Microbiol 2021;59:e02811-20.
  5. Centers for Disease Control and Prevention Interim Guidance on SARS-CoV-2 Antigen Testing, Accessed on August 23, 2021.
  6. Centers for Disease Control and Prevention Interim Guidance on SARS-CoV-2 Antibody Testing, Accessed on August 23, 2021.
  7. Sheridan C. COVID-19 testing turns to T-cells. Nature Biotech 2021;39:533-534.
  8. He X, Lau EH, Wu P, et al. Temporal dynamics of viral shedding and transmissibility of COVID-19. Nature Med 2020;26:762-675.
  9. Paules CI, Marston HD, Fauci AS. Coronavirus infections - more than just the common cold. JAMA 2020;323:707-708.
  10. Lopez-Leon S, Wegman-Ostrosky T, Perelman C, et al. More than 50 long-term effects of COVID-19: A systematic review and meta-analysis. Sci Rep 2021;11:16144.
  11. US FDA Updated Information for Blood Establishments Regarding the COVID-19 Pandemic and Blood Donation. Updated January 29 2021, Accessed on August 23, 2021.
  12. Cappy P et al. No evidence of SARS-CoV-2 transfusion transmission despite RNA detection in blood donors showing symptoms after donation. Blood (2020) 156(16):1888-1891.
  13. Korley FK et al for the SIREN-C3PO investigators. Early Convalescent Plasma for High-Risk Outpatients with COVID-19. N Engl J Med 2021 [Early Access].
  14. Meo SA, Bukhari IA, Akram J, et al. COVID-19 vaccines: comparison of biological, pharmacological characteristics and adverse effects of Pfizer/BioNTech and Moderna vaccines. Eur Rev Med Pharmacol Sci 2021;25:1663-1669.
  15. Jabal KA et al. Convalescent plasma from people vaccinated after COVID-19 infection. Lancet Microbe 2021;2:e171-172.