Can convalescent plasma therapy help treat coronavirus disease? – analysis
The coronavirus pandemic (Covid-19) has spread worldwide with no immediate solution in sight. The first case was reported on December 30, 2019 in China, but so far, no country in the world has been able to develop any vaccine that prevents the disease or an antiviral drug that cures it. However, there is one inexpensive and readily available antiviral agent that has received little attention: the virus neutralizing antibody found in people who have fully recovered from SARS-CoV2 infection.
To give a bit of background, human blood contains a yellow liquid known as plasma in which red and white blood cells are suspended. Plasma contains albumin, globulins, and hundreds of other proteins that are essential for the body’s physiological functions. Those deficient in these proteins undergo plasma replacement, which is no longer rare. The process requires a plasmapheresis machine, which takes blood from the donor (healthy and free of HIV and hepatitis B and C viruses) and, after removing the plasma, returns the rest of the blood cells to your body. The extracted plasma is frozen in the blood bank for later use, as in the case of hemophilia, a well-known bleeding disorder with a deficient protein, Factor VIII. The disorder requires infusion of plasma into the body, a standard treatment for hemophilia until purified Factor VIII is commercially available. In addition, there are many “autoimmune” disorders affecting multiple organs that require plasma-derived “immunoglobulins”.
Blood also contains red blood cells, which have different antigens in different people and act as a marker for blood groups. For transfusion, blood is compatible with compatibility, which, in case of mismatch, can cause a fatal transfusion reaction. But without cells, plasma is safe from the transfusion reaction.
Plasma-derived immunoglobulins are commonly used to prevent serious viral infections. To treat a dog bite, for example, rabies immunoglobulin is the first medical treatment given after first aid. Or needle stick injury in hospitals that carries the risk of infection with the hepatitis B virus, hepatitis B immunoglobulin from positive antibody donors is the first treatment. In both cases, the antibodies neutralize the virus that has just entered the body through a dog bite or needle stick injury. When exposed to measles or chickenpox, immunoglobulins derived from people with antibodies are the standard treatment to protect children receiving chemotherapy against cancer.
Covid-19 is particularly dangerous for older people, as they have a relatively weak immune system and younger people with chronic lung disease, a heart condition, hypertension, diabetes, and those receiving therapies that affect the immune system. Critical Covid-19 pneumonia affects both lungs simultaneously, leading to severe oxygen deficiency (hypoxemia), which affects the body’s organs and tissues. If not corrected immediately, this can lead to death. Treatment of hypoxemia requires placing the patient on a mechanical ventilator below the intensive care unit. But despite aggressive oxygen therapy, many patients die.
So, to get to the original question, why aren’t doctors using or recommending life-saving therapy that uses antibody-containing plasma to treat Covid-19 pneumonia? Because all over the world, doctors are taught to practice “evidence-based medicine.” This treatment has little evidence, but it’s not because the plasma method has been tried and failed, but because doctors are waiting for concrete evidence to emerge.
However, the evidence may come from the accumulated experience of plasma therapy or simply from research studies. In an emergency situation, the most prudent approach is to use the empirical application on several seriously ill patients who do not recover with aggressive oxygen therapy. The accumulated data will give statisticians the opportunity to obtain evidence of efficacy, if that is really the case.
The research, on the other hand, will involve a pharmacological trial with one treatment arm and one control arm, both with standard ventilator treatment. Cases have to be randomized into two groups, one with plasma therapy and the other with placebo. After the trial is complete, the efficacy of the treatment can be quantified by a statistical comparison of the results in both arms.
One wonders if the research approach is a wise idea in the current context, as convalescent plasma is known to contain antiviral immunoglobulins and is reasonably safe. We have no reason to justify their denial to a control group just because the randomization dice fell against them while others were offered the plasma.
Chinese doctors have published two reports of convalescent plasma therapy in very severe cases of Covid-19 pneumonia in ventilators: five patients in one report and 10 in the other. All 15 showed rapid improvement. The fever dropped and the viral loads decreased.
We urge physicians working at Covid-19 hospitals to gain experience in plasma therapy, with careful observation and documentation of all details. Adverse reactions have rarely been reported for plasma therapy for other conditions, but for very sick Covid-19 patients who do not recover despite aggressive standard therapy, the benefit far outweighs the risk. .
This approach requires testing for immunoglobulin G or IgG antibodies to SARS-CoV2 in recovered convalescent people and healthy people in the community with previous Covid-19 infections. For each positive case, four or five people would become infected silently. Health authorities should design antibody surveys with the dual purpose of identifying individuals with positive antibodies: one, this will allow them to return to work safely; and two, if they were healthy and willing, they could donate plasma.
Dr. T Jacob John is a retired professor and chair, department of clinical virology, and Dr. MS Seshadri is a retired professor and head, department of endocrinology at Christian Medical College, Vellore.
The opinions expressed are personal.