Two bags of fresh frozen plasma. The bag on the left was obtained from a patient with hypercholesterolaemia. The bag on the right shows typical plasma. Photo: DiverDave, Wikimedia Commons, CC BY-SA 3.0.
The COVID-19 pandemic has been crippling the health systems of even the world’s wealthier of the nations, and all efforts are now being directed towards halting its rapid spread. No definitive treatment is currently available for this disease at present, although researchers are actively considering multiple drugs. Work on developing a preventative vaccine is also on but it’s likely to be at least a year before a commercial one is available.
As a result, the only options available to manage a patient are to manage their symptoms themselves, with oxygen support and ventilators in severe cases.
At this juncture, one option doctors in every nation are considering is the use of convalescent plasma.
Convalescent plasma refers to plasma obtained from an individual who has recuperated from an infection. During the infectious period, the individual’s immune system would have mounted an attack on the foreign virus. By the time the virus is vanquished, the body would have developed ammunition specifically to beat the virus, which will be a type of antibody. These antibodies are suspended in the circulating blood, and can be separated out from one of the components of blood – the plasma.
Convalescent plasma has been shown to be effective against other infections, all the way back to the ‘Spanish flu’, which struck the world as a pandemic in 1918. Then, the US military used convalescent plasma to treat flu patients. More recently, the WHO approved it as empiric treatment against Ebola virus infections in 2015, and it was deployed with success against the SARS and MERS coronaviruses as well (whose outbreaks occurred in 2002-2003 and 2012, respectively).
Early reports from China have already indicated that this therapy has also shown promise in severely ill COVID-19 patients. It has been approved for clinical trials in multiple countries, including in India.
A donor can’t simply donate convalescent plasma. First, the donor must have recovered from a COVID-19 infection and have been free of the disease, or any symptoms, for at least 28 days or should have been free of symptoms and have tested negative for the virus at least 14 days before the plasma can be used. There aren’t likely to be many donors of such plasma if the COVID-19 case load is low to begin with or the transmission rate is approaching its peak.
A donor can donate her plasma up to twice a week with a minimum gap of 48 hours, and a maximum of 24 times in a year in India. A special medical technology called apheresis, using expensive equipment, is used to draw blood from the patient, separate the plasma out, and return the rest of the blood back into the body. The plasma thus obtained can be stored in a blood bank.
Now, the plasma needs to contain a certain level of antibodies for it to be effective in the treatment of a COVID-19 patient. Every individual’s response to the virus is unique: some may have more antibodies in their blood than the other. So not all convalescent plasma from different donors can be considered to be equally effective. Moreover, the fewer antibodies there are in one’s blood the longer it has been since one recovered from the infection. Finally, we still don’t know what ‘dose’ of antibodies is required in order to treat a critically ill COVID19 patient.
The next question that arises is who should receive convalescent plasma. Since we already know that the availability of convalescent plasma is limited, we need to carefully prioritise its use.
Thus far, some small clinical trials performed with severely ill patients have been promising. Researchers found that antibodies in the transfused plasma ‘neutralise’ the virus in the patient, thus improving their symptoms. The antibodies have also been recorded to improve the patient’s own immune response, and fight the virus better.
In theory, convalescent plasma is likely to be more effective in the early stages of an infection, when the viral load is lower, and the patient can be ‘saved’ from more severe stages. This is akin to the protection granted by HBIg – short for Hepatitis B immune globulin – against hepatitis B infections. Similarly, frontline healthcare workers treating coronavirus patients, who are at higher risk than the general population of contracting COVID-19, could be given convalescent plasma to protect them and to keep our healthcare workforce from being depleted at such a crucial time.
Among patients: convalescent plasma should be given right at the time of diagnosis to the most vulnerable patients, like elderly people and those with comorbid medical conditions.
Like all therapeutic techniques, there are also downsides. For one, transfusing plasma that contains antibodies is a form of ‘passive’ immunity, and in doing so we interfere with the patient’s normal immune response. As a result, even if the patient recovers, she could still be at risk of reinfection.
More importantly, plasma transfusion can be associated with severe adverse reactions, especially among patients with respiratory failure. So doctors must consider the risk-benefit ratio before signing off on the procedure. The antibodies can be obtained from the plasma, and then a carefully selected dose could be administered to the patient, but this requires more expertise and time – both of which are bound to be limited as the pandemic rolls on.
Dr Atif Irfan Khan is a junior resident (academic) in the department of transfusion medicine, AIIMS New Delhi.