Plasma therapy in COVID-19 patients, a review

Since the starting of the COVID-19 pandemic, neither specific therapy is discovered, which can cure the patient nor any vaccine which can prevent the disease. So only one therapy, convalescent plasma from a recently recovered virus-negative patient, may be useful in treating the critically ill patient, which can recover the patient if it can be administered within 10 – 15 days of onset of disease. 

In the last part of December 2019, there was COVID-19 outbreak started in Wuhan, China, which ultimately spread in more or less all the countries worldwide within three months and declared as “Pandemic” by WHO on March 11th, 2020. On March 12th, 80980, and 44377 confirmed cases were reported in China and other 108 countries, respectively, with the reported death of 3173 in China and 1446 in other countries. So it needs urgent intervention in the form of a particular drug or administration of passive immunization. 

Concept

The concept of convalescent plasma therapy started nearly one century back when in 1890, German Physiologist Emil Von Behring demonstrated that sera obtained from a rabbit infected with diphtheria effectively prevented diphtheria infection. For that, he received Nobel prize in the subject of Medicine in the year 1901. After that, in the 1918 diphtheria outbreak, in the 1930 flesh-0eatting bacteria epidemic, it failed to demonstrate its affectivity; on the other hand, a large number of side-effects. After several years, the antibody fraction was separated, but unintended antibodies present in the convalescent plasma produces side-effects still now.

Different reviews

Till date after the outbreak of COVID-19 from Wuhan in China to become pandemic no specific therapy is proven effective worldwide in this disease other than supportive therapy, like oxygen therapy, fluid balance in mildly symptomatic therapy or invasive ventilation or extracorporeal membrane oxygenation in case critically ill patients, only lots of researches are going on throughout the World to get any specific drug against this virus. In the United States of America first affected patients were treated with intravenous Remdesivir along with intravenous hydration, the patient recovered and discharged enhancing the researcher to do further research on the efficacy and any adverse effect in the body. 

So randomized controlled trial is very urgent on this drug. Those patients who deteriorate despite giving providing all the supportive therapies, and intravenous pulse methylprednisolone, convalescent plasma containing immunoglobulin were given as a last resort to save their life. Later on, several studies demonstrated the usefulness of giving plasma therapy as it reduces the hospital stay; it increases the immunity and lowers mortality of the affected patients. 

In the 2014 Ebola outbreak, the plasma was collected from the patients recovered from the Ebola virus and was recommended by the World Health Organization (WHO) to give it to all empirically in outbreak. A prospective cohort study of Chinese researchers in 2009 demonstrated the reduction of mortality in the pandemic of H1NI (H1N1pdn09) by the administration of convalescent plasma. It reduced the viral load within seven days of plasma administration without any complication or adverse effects, similarly, in 2015 convalescent plasma against Middle East respiratory syndrome coronavirus. 

Later on, a meta-analysis was also done, and it was shown that the administration of convalescent plasma reduced viral load without any adverse effect of its administration. Again, another meta-analysis based on eight studies demonstrated that on the administration of human convalescent plasma of patients recovered from influenza in various dosages to 1703 patients suffering from influenza-pneumonia from 1918 to 1923 reduced the crude overall case fatality rate by 21% (p<0.0001) in those patients. A possible explanation for this effective therapy was based upon the fact that antibodies present in that plasma reduced the viremia that has been recommended to by WHO in any coronavirus infection. In Wuhan, China, in the COVID-19 pandemic, plasma therapy was tried in 10 severely ill COVID-19 patients with a median age of 53.4 years receiving many antiviral therapies, 4 with chronic morbid illness and 3 in mechanical ventilators. Most of the patients, within three days of administration of convalescent plasma, demonstrated the following features:

  • Improvement of clinical symptoms.
  • Increased lymphocyte counts
  • Oxygen level in the blood improved
  • C-reactive protein lowered. 
  • Undetected viral load
  • Computerized tomographic features in the chest were improved. 
  • Rapid wean from ventilators in two patients.

Amongst the three patients were discharged, and the rest seven patients were much improved. This treatment was successful in those patients who received treatment within 14 days of onset of symptoms. Whereas in case the same number control group of patients not receiving this convalescent plasma therapy, three patients died, six were stable, and one was a bit improved. 

In another study in Shenzhen Third People’s Hospital, China, five critically ill COVID-19 patients with acute respiratory syndrome from January to March 2020 were treated with convalescent sera between 10 to 22 days of admission and clinical of those patients prior and post-administration of sera were measured. Their blood demonstrated COVID-19 specific IgG antibodies titer of more than 1 in 1000 by ELISA test and neutralization titer of greater than 1 in 40 and recovered from this disease. Measures of clinical outcomes were the following:

  • Temperature level
  • Sequential organ measurement score
  • PaO2/FiO2
  • Serum antibody titer
  • Viral load in the body
  • Routine blood biochemistry
  • Acute respiratory distress syndrome prior and post-administration
  • Ventilatory support prior and post-administration
  • Extracorporeal membrane oxygenation prior and post-administration. 
 

The process of donating plasma is the same as that of blood; it takes one hour to transfuse. Houston Methodist, the first Academic medical Centre, transfuses the plasma from COVID-19 patient to a critically ill COVID patient. Later on, three Indian-American critically ill patients were transfused with convalescent plasma; all of them were recovered. 

In the process of donation, the donor is hooked up to a small device, which only removes plasma returning the red blood cells into the donor body. So, there is no loss of plasma, and the donor can donate plasma twice a week. Nevertheless, most of the sufferers are mainly aged and with a large number of co-morbidities, so the effectiveness of convalescent plasma is questionable. The critically ill patient receives passive immunization, but it will be present in the patient’s bloodstream for less than a week. So, it is opposite to the vaccine in terms of days of immunity as active vaccine immunity persists for life long. 

Plasma therapy is the infusion of convalescent patient’s plasma containing IgG antibody against coronavirus antigenic protein, mainly spike protein and nucleocapsid protein. But prior to administration, plasma should be checked for neutralizing antibodies. A person can be accepted as donor 14 days after hie or her reported full recovery. According to different researchers, these antibodies develop immunity in sick patients. Immunity develops much early in asymptomatic patients or mildly symptomatic patients. However, in the case of severely ill or critically ill COVID-19 patients, it will develop later. In the case of HIV patients, a school demonstrated that 3BNC117 based immunotherapy containing neutralizing antibody to HIV virus reduced viral load, accelerated clearance of virus, and blocked new viral infection. Since in the first 14 days, there is primary immune response followed by viral clearance, hence convalescent plasma should be competent in the early stage of therapy. To date, which is not able to declare any definitive therapy of COVI-19 other than emphasizing the case detection, monitoring, and prevention of it, so healing plasma-based therapy should be the choice in the early phase of the disease. 

Conclusion

Since millions and millions of peoples are affected by COVID-19, so, obviously a large pool of plasma should be in the fridge to save the life of critically ill patients worldwide.

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