Hope from Blood Plasma


The super-virus that causes COVID-19 in Indonesia is taking more and more victims and is estimated to have not yet reached its peak. In the midst of this difficulty is some good news, like a light at the end of the tunnel. The Eijkman Institute of Molecular Biology immediately started the treatment of COVID-19 patients using blood plasma from patients who have been declared healthy.

This method can be called plasma recovery. On Monday (20/4/2020), head of the Eijkman Institute of Molecular Biology Amin Subandrio said his agency, with the support of the Food and Drug Agency (Badan POM) and the Health Ministry, was ready to implement the plasma recovery method treatment in the coming weeks. On Tuesday (28/4), Kompas reported, state-owned pharmaceutical company PT Biopharma and Gatot Soebroto Army Hospital joined in this fast-moving innovation.

The plasma recovery method is not a new method. It has been applied for a century. However, in the context of facing the COVID-19 pandemic, this method has just been applied. The Eijkman Institute of Molecular Biology’s plan also follows those of several countries. Iran is the first country outside of China to use this method and announce its success. The Iran website’s front page on 11 April 2020 wrote an article explaining that the plasma recovery protocol in Iran was completed on 24 February. The Ethics Committee of the Ministry of Health and Medical Education of Iran gave permission for this method to be used and took in 200 patients with COVID-19. At least 500-600 cc blood plasma from a number of patients who had been declared healthy were taken to be transfused to patients who had not yet recovered. The results were positive, the condition of many patients improved and even healed. The Iranian government considers the method of plasma recovery effective with side effects at a tolerable level.

After this success, Iran immediately shared its experiences with several friendly countries, such as Germany, Italy and France. If Iran approved the plasma recovery protocol method on 22 February 22, the US through the Food and Drug Agency (FDA), such as business as usual, only ratified a similar protocol by the end of March. In fact, the addition of new cases and deaths substantially jumped in this country. This protocol will be applied to 600 patients in severe condition and is still in the context of research. When the US was about to start taking blood plasma from patients who had recovered, Iran had passed the transfusion process to 200 patients.

Before Iran, it was only China that had tried this method, but it had not applied it in a research format consistently and no reports on it were available. In other words, it was Iran that was the first to use the blood plasma method for the recovery of COVID-19 patients with a complete research format. Iran itself, with various methods of healing, recorded a high rate of total recovery. According to the 28 April edition of Worldometers, in Iran there were 91,472 people with COVID-19 and 70,933 recovered (77.5 percent). Good records also exist in China; out of 82,836 positive cases, 77,556 recovered (93.6 percent). European countries with a high recovery were Austria where out of 15,274 positive cases, 12,362 healed (80.9 percent). In Switzerland, 29,164 tested positive and 22,200 were treated (76 percent).

Compare that with Indonesia, where out of 9,096 positive cases, 1,151 recovered (12.7 percent). In the US, 1,010,356 cases were recorded and 138,900 recovered (13.9 percent). The world average is 30 percent, with 3,064,161 positive cases and 922,369 recoveries.

 

Similar to a tight transfusion

Plasma is part of the blood, in addition to red blood cells (erythrocytes), white blood cells (leukocytes), and tiny blood cells (platelets). The process of blood plasma therapy is actually the same as the blood transfusion process that is performed every day by doctors to patients, namely with blood from the donor’s own family or collected by the Indonesian Red Cross (PMI).

If there is a patient with an acute hemoglobin (Hb) drop due to bleeding, what will the doctor do? Yes, there could be transfusion with red blood cells. If the patient experiences long bleeding due to impaired function of the blood clotting (coagulation), what will the doctor do? The patient will be transfused with fresh plasma from a donor. If lymphocytes (a group of white blood cells that play a role in building immunity/immune cells with immunoglobulins as its product) of the patient drops because it is destroyed by COVID-19, what would doctors do? They would use transfusion with blood plasma (which contains immunoglobulin) from donors, namely patients who have been treated for COVID-19.

This protocol of action must be strict to prevent various risks, such as the risk of acute pulmonary injury related to transfusion, fluid overload, allergic/anaphylactic reaction (rejection reaction), or risk of transmission of infection. Therefore, it must be prepared as well as possible in order to minimize this risk. After being declared healed through two polymerase chain reaction (PCR) tests, prospective donors have to go through a waiting period of 14-21 days, which goes past the virus incubation period. During this time, the immunoglobulin content is still large because it has won the battle against the attack of millions of coronaviruses.

If the donor waits too long after being declared healthy, the immunoglobulin content will decrease naturally because it is no longer needed to fight against the virus. This is the basic simple method of therapy using blood plasma. Of course, once again, with strict protocol, it should be more stringent than the protocol used in the normal blood transfusion process. In blood plasma, there are proteins, antibodies, saline solutions, enzymes, and coagulants (blood clots). When someone is sick (for example due to the virus), their blood plasma contains a lot of antibodies (produced by lymphocyte cells) that are used as defense forces to deal with the virus. If these antibody forces lose against the virus, the patient can be fatal, or even die. However, if these antibody forces win against the virus, the patient is cured.

Well, in patients who have just recovered, the antibody forces are still very much in the blood plasma. While the blood plasma still contains many antibody forces, just donate it to other patients whose antibody forces have already been destroyed by the virus. It is like sending troops to the battalion of friends who perish due attack by this super-virus enemy. The antibody protein that is donated to sick patients will work against the coronavirus, reduce inflammation, and boost the immune system so that the recipients are expected to start producing their own antibodies.

Patients who have been declared healthy from COVID-19 can donate 200-400 ml of blood plasma to patients (recipients) who are still struggling with this malignant virus. With this method, a former COVID-19 patient who has recovered can save one to two other patients, without causing significant side effects. This donor method can be repeated the following week, depending on the donor’s condition. Thus, a recovering former patient can contribute as much as needed by referring to the strength of his body as a donor.

 

It has been tested for a century

Plasma therapy, known as convalescent plasma (recovery plasma), was in facing the Spanish flu epidemic in 1918 which killed millions of people worldwide and the measles outbreaks in Pennsylvania, USA, in 1934. In the last two decades, this method has also been used for the treatment of acute respiratory syndrome pandemic SARS (Coronavirus, 2002-2003), H1N1 (influenza A, 2009), and acute Middle Eastern respiratory syndrome (MERS Coronavirus, 2012) with satisfying efficacy and safety results. In the case of the Spanish flu, the administration of blood plasma suppressed about 50 percent of the mortality rate. Now it is being tested on COVID-19, aka SARS-CoV-2. According to the latest news, Japanese pharmaceutical manufacturer Takeda Pharmaceutical Co. is developing a new coronavirus drug derived from the blood plasma of people who have recovered from COVID-19.

Ideally, research needs to be carried out on a large scale and over a long time to test the reliability of this method of blood plasma therapy, especially to deal with SARS-CoV-2 as a new virus that is very virulent. However, it must be realized, now the situation is in high emergency. We are very short of all kinds of “ammunition”. Rapid tests, PCR tests, reagents, ventilators, hazmat, and masks are all in shortages. Room facilities, doctors and medical personnel are also very limited. Many doctors and medical personnel have died while on duty. The total number of positive patients, people being monitored (ODP) and people suspected of being tested positive with the virus under supervision (PDP) and deaths being reported has not yet reflected the actual incidence because the government has not been able to conduct rapid tests and mass PCRs due to limitations over facilities. The financial and managerial capacity of the government is very limited when it comes to dealing with the soaring transmission of this outbreak.

The method of blood plasma therapy is feasible as a temporary solution given the potential risks mentioned while waiting for the discovery of vaccines and drugs for COVID-19. The initiative of Eijkman Institute of Molecular Biology and PMI to immediately implement this method should be supported. Bureaucratic obstacles must be removed.

 

Djoko Santoso, Professor at the School of Medicine, the University of Airlangga