“Thank you for that question, Senator Rosen; it’s an excellent one. In all of the therapeutic interventions that the scientific and medical world are developing, and you mentioned several of them, they could be direct antivirals along the line of Remdesivir, but that’s just one potential therapy since there are several viral targets in the replication cycle of this virus. Using convalescent plasma, as well as monoclonal antibodies as preventive modalities are in fact all feasible and will be pursued in parallel with the development of a vaccine.” – excerpted from Dr. Anthony Fauci, U.S. Senate Committee on Health, Education, Labor & Pensions Hearing, May 12, 2020.
We are very pleased that Dr. Fauci gave a national spotlight to convalescent plasma therapy (CPT) as a possible treatment option against the coronavirus SARS-CoV-2 that causes COVID-19 disease.
What is CPT?
The beauty of CPT against SARS-CoV-2 is in its simplicity. Once a person recovers from a viral infection, the blood contains antibodies that usually can neutralize the virus if re-infection happens. Basically, these antibodies now recognize the virus and can fight against it, if re-exposure occurs.
I heard reinfection can occur.
Most experts agree that reinfection of SARS-CoV-2 cannot occur at least for a certain period of time. The duration of protective immunity against SARS-CoV-2 is what we don’t know. We do know that people who have recovered from SARS-CoV-2 have varying levels of antibodies to the virus.
Plus, a study infected rhesus monkeys with SARS-CoV-2. Once they recovered, attempts at reinfection were unsuccessful. So, we know that we do have some duration of immunity.
Have any human studies been completed?
Two limited pilot studies – conducted in China – showed promising results after the administration of CPT in fifteen severely or critically ill patients. None of the patients died. Bear in mind, the CP therapy was given in combination with other treatment methods such as the use of ventilators and antiviral medications.
But, Dr. Fauci mentioned “preventive”.
Yes; preventive is definitely earlier in the onset of progression to disease than severely or critically ill patients.
Many pathologists, hematologists and immunologists were imploring physicians to use CPT earlier as a prophylaxis (preventive) or right after the onset of symptoms. They pointed to numerous examples of successful CPT throughout history including against other coronaviruses such as Severe Acute Respiratory Syndrome-1 (SARS-CoV-1) and Middle East Respiratory Syndrome (MERS).
Now, several U.S. Food and Drug Administration approved clinical trials are exploring the use of CPT as a preventive or right after the onset of symptoms to lessen the severity of the disease. It gives the body a chance to produce its own antibodies against a virus.
Currently, members of households or health care workers who were exposed to SARS-CoV-2 may be considered as possible candidates as a preventative measure.
However, caution is necessary here because patients that have recovered from COVID-19 could still have virus present in their bodies and blood, just not in amounts that allow detection by the currently available tests. In fact, the predicted “second wave of infection” with Sars-CoV-2 could be a resurgence of residual virus from recovered patients that return too early to their former lifestyle.
How is this different from a vaccine?
A vaccine or actual infection with a virus induces active adaptive immunity, and typically produces long-lasting or lifetime immunity.
CPT is passive immunity. While beneficial results are immediate, they wane over time.
What about the HIV crisis and blood donations?
Yes; human immunodeficiency virus (HIV) can be passed through plasma donations. However, HIV is a retrovirus, which is completely different than the betacoronavirus SARS-CoV-2. SARS-CoV-2 is not considered to be a relevant transfusion-transmitted infection, although as stated above, some recovered patients could still harbor the virus.
Why is a vet writing about CPT?
W. Jean Dodds accepted a position in 1965 with the New York State Health Department in Albany and began comparative studies of animals with inherited and acquired bleeding and immunological diseases, as models for their human counterparts. Her position there began as a Research Scientist and culminated as Chief, Laboratory of Hematology, Wadsworth Center. In 1980, she also became Executive Director, New York State Council on Human Blood and Transfusion Services during the AIDS crisis. This work continued full-time until 1986 when she moved to Southern California to establish Hemopet, the first nonprofit national blood bank program for animals. Thus, she has had a career devoted to studying and implementing the comparative aspects of the hematology and immunology fields.
Are there examples of CPT use in companion dogs and cats?
A small clinical study was conducted with fourteen dogs that had naturally occurring canine parvovirus (CPV) infection. Seven dogs were given a saline solution as a placebo while the other seven received a single 12-mL intravenous dose of immune plasma soon after the onset of CPV enteritis regardless of their size and weight. They concluded (erroneously) that CPT was not effective against CPV.
While this study was fraught with methodological issues, the most glaring error was failing to take the size and weight of the dogs into account. The CPT-group ranged from 1.9 to 57.2 pounds, whereas the placebo-treated group’s weight ranged from 2.6 to 37.4 lbs. Why would you give a Chihuahua the same amount of CPT as a Labrador retriever?
The protocol Hemopet routinely recommends is three doses of plasma from immunized dogs at 3 to 5 mL/lb either intravenously or intraperitoneally with the first two doses given 12 hours apart on the first day and the third dose given the following morning. Additional doses of plasma are given as needed. In instances when apparently healthy puppies have been exposed to affected puppies, we recommend that one or two doses (3 to 5 mL/lb) of plasma be given prophylactically.
Another use of CPT in dogs is to help prevent loss of 3-10 day old neonates born to pregnant females infected with canine herpes virus. Harvesting the plasma from these females and using it on their newborns of subsequent litters can be successful.
For cats, CPT from recovered cases has been successful in treating kittens or older cats at risk for or exposed to feline panleukopenia virus (a parvovirus of cats).
In order to have a maximal beneficial effect, immune plasma (serum is not preferred as it contains the bioactive breakdown products released from blood cells during clotting) should be given at the time of proven or suspected infection, but prior to the onset of clinical signs. In this case, CPT is best provided within 24–48 hours of infection and a large amount of high titered plasma with high antibody titer is required. The plasma needs to be given intravenously, subcutaneously or intraperitoneally but not orally, as it cannot be absorbed through the bowel lining beyond the first 24-36 hours of life.
Please visit Hemopet’s webpage for indications and use of canine universal blood products.
Dodds, W Jean. Known medical indications for using fresh-frozen plasma. DVM Magazine 1993; 24(4):42–43.