Convalescent Plasma : A bridge to Life?

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Corona Virus Disease-2019 is a big threat to entire global health and has gripped almost the entire world today. More than 200 countries are infected.    

However, the intensity differs in different countries.V

When it all started with China, it was believed that the countries having the best standard of medical facilities, need not worry about it much. But the fact was that the pandemic is so contagious spreading from man to man, not just by hand-to-hand touch but even by maintaining social distance or wearing protecting kit or personal protecting equipment (PPE) for frontline workers. V

There is still confusion going on about the minimum distance, one should adhere to.

Let us look at the details of the kit, the doctor and staff, nursing a Covid-19 patient has to wear.

1. Surgical gown;
2. Hand glove;
3. Respiratory protection;
4. Eye protection;
5. Face shield;
6. Lace-up shoes;
7. N-95 respirator mask, which filters 95% of airborne particles.

VThe above kit is not only used by Doctors but the nurses too.

These are minimum PPE kits, used during treatment to be given by medical staff, in case a patient is found positive of such pandemics.

This is very much similar to what virologists wear in labs.

But the concerning part is, these PPEs are limited in stock, a regular scene, in such worldwide spread pandemics.

The alarming part is, despite these PPE, doctors, nurses are infected and some death is also recorded.

As we know that this virus is new to us, hence there is no antivirus available for it. Since it's unique in its nature, where our RNA is attacked, the respiratory system is damaged in its advanced stage, making  chances fatal to the highest degree.
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Scientists are working round the clock on a vaccine for Covid-19, as it is gripping the whole world, gradually and day-by-day.

This pandemic is highly contagious as mentioned above. Looking at how deeply this pandemic has spread, caution not thought of or ignored by so many European countries and even the USA, the panic button is pressed in almost all countries in the world.
Hence scientists are working on a war-footage basis to counter this pandemic. In several countries, 55+ senior citizens are vulnerable to this pandemic.

USA has urged India to re-start the production and export the stock of banned medicine Hydroxychloroquine (HCQ) tablets at the earliest. Following supply to the US, Brazil and other countries too have asked for the export.

But since HCQ medicine is for controlling malaria, its ability to control Corona at the initial stage and its believed side-effects to occur as well, the importance of early vaccine to eliminate Corona is increasing.

As this will take a very very long time, its uncertain to declare the date, another way of treatment is looked upon.

One of them is plasma treatment. Lets us know about it:

In this process, plasma is abstracted from a  Convalescent Plasma i.e. CP transfusion to treat coronavirus patients in the advanced stages. 

People with AB type blood I (positive or negative) are universal plasma donors. Only 4% of the population has type AB blood. Plasma from AB donors can be given to patients with any blood type, making it extremely important for those in need. AB donors are encouraged to donate Plasma or Platelets.

The experiment showed that one dose of 200ml CP donated by the recently recovered patients, which has neutralizing antibody titers above 1:640 was transfused to Covid patient and have seen effective in 10 severe cases, neutralizing antibodies at a high level, within 7 days. The clinical symptoms and paraclinical criteria also improved quickly within 3 days.
The health of the transfused patient was primary. 

Next, it is required to see that there is an improvement in clinical symptoms in the patients and also in laboratory parameters. 
Several medical parameters showed improved status, as compared to the status before the CP.V

Examining through radiology showed several parts of the lungs, which were affected, showed varying degrees of absorption within 7 days. The viral symptoms were not detected after the CP, among 7 patients out of 10 patients. There was also no severe adverse effect noticed.  

This CP therapy was well accepted by the bodies of the patients. It also increased immunity power to improve clinical outcomes, as the virus in the blood was neutralized in severely infected Covid-19 patients.V

The pandemic is pneumonia associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was named as Corona Virus Disease 2019 or COVID-19, which outbreak from Wuhan, China. 
The epidemic was declared a pandemic by WHO, on 11th March 2020, three months after it leaked in Wuhan. 

As of today, i.e. 14th April 2020, the pandemic has spread in 212 countries, with total cases of 1.9 million with 123000+ deaths. Although 463594 have recovered from the sickness, yet more than 1.38 million are active cases. This shows the magnitude of the seriousness of the pandemic. 

This magnitude is only possible because we have yet not developed a perfect vaccine on Covid 19.

There are other possibilities tried and tested, like remdesivir and lopinavir /ritonavir : V

https://www.pnas.org/content/early/2020/04/02/2004168117#ref-5

but they have certain limitations and doubtful of their results. 

Convalescent Plasma therapy is century old. Its classic adoptive immunotherapy, being successfully tested during SARC, MERS & 2009 H1N1. It's not only regarded as satisfactory but also safe. 
The CP therapy had reduced the mortality in the above-cited epidemics. 

In the case of Ebola, the CP therapy did not give satisfactory results as there was no data on neutralizing antibody titration.

But SARS, MERS & Covid-19 share similar virological and clinical characteristics, CP therapy is looked at as hope in this pandemic. 
The results in the SARC Cov-2 was inspiring.

It is assumed that the patients who have recovered from Covid-19, may have high neutralizing antibody titer, which can be a valuable source in CP. Nevertheless, the potential clinical benefits and risk of convalescent blood products in this pandemic is yet not sure.V

Therefore, experiments are on 10 Covid-19 patients, 6 males and 4 females involving 3 hospitals, to ascertain the feasibility of CP treatment.

THE RESULT:                                      

It was a pleasant surprise to note the missing symptoms of fever, cough, breathing difficulty, and chest pain was largely improved within 1 to 3 days of CP transfusion. They all were treated differently, before CP transfusion. 

Three on mechanical ventilation, three received high-flow nasal cannula oxygenation, two had conventional low-flow cannula oxygenation, and one out of these two was later shifted to intermittent oxygenation. 
The remaining patient with discontinued high flow cannula.  

Later the CT examination showed all ten patients. All patients had varied in reports but none reported any side effects.

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Chest CT of 2 patients:
Patient 9, a 49-year-old female, admitted 1 day after noticing symptom which is called 1 dpoi i.e. Day Postonset Of Illness (dpoi).

A-The CT chest obtained on February 9th (7dpoi), before CP transfusion. B-The CT image on 13dpoi post-CP transfusion. 
The SARS-CoV-2 RNA became negative at 12 dpoi.

Patient 10, a 50-year-old male, admitted at 3 dpoi.
A-The CT chest obtained 20dpoi, before CP transfusion.

B- CT image 5 days after CP transfusion. The SARS-CoV-2 RNA became negative at 25 dpoi. V

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Dynamic changes in laboratory parameters in all patients. The dotted horizontal line represents the reference value range. CRP- C-Reactive Protein; Lym Lymphocytes-the white blood cell; SaO2, oxyhemoglobin saturation; TBIL, total bilirubin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Lym, lymphocyte.

This is laboratory parameters in patient 1:

Remarkably, patient 1, a 46-y-old male admitted 8 dpoi, had a very quick recovery, with the much-improved result of laboratory tests. 

He received antiviral drugs (arbidol and ribavirin) treatment and high-flow nasal cannula on admission. Mechanical ventilation was given at 10 dpoi for critical care support. CP transfusion was performed at 11 dpoi. V
At 12 dpoi, the SARS-CoV-2 test turned to negative, with a sharp decrease of CRP from 65.04 mg/L to 23.57 mg/L and increment of SaO2 from 86% to 90%. The mechanical ventilation was successfully removed 2 days after CP transfusion. At 15 dpoi, there was a steady increase in lymphocyte count, and the aminopherase level was decreased, indicating improvement of the immunity system and hepatic i.e. lever function.V

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The overall study showed positive results, giving a hint that CP transfusion can be applied.  The neutralization of Viremia i.e. presence of a virus in blood was rapid.

Comparison of serum neutralizing antibody titers and parameters of SARS-CoV-2 RNA load before and after CP therapy.
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Patient no.	CP      transfusion date	Before CP transfusion			After CP transfusion
		Date	Serum neutralizing antibody titers	Serum SARS-CoV-2 RNA load (Ct value)	Date	Serum    neutralizing antibody titers	Serum   SARS-   CoV-2   RNA   load        (Ct   value)
1	Feb-09	Feb-08	0.152777778	37.25	Feb-10	0.486111111	Negative
2	Feb-09	Feb-08	Unavailable	35.08	Feb-11	Unavailable	Negative
3	Feb-13	Feb-12	0.263888889	38.07	Feb-14	0.486111111	Negative
4	Feb-13	Feb-12	0.152777778	37.68	Feb-14	0.486111111	Negative
5	Feb-12	Feb-11	0.486111111	Negative	Feb-14	0.486111111	Negative
6	Feb-12	Feb-11	0.486111111	Negative	Feb-14	0.486111111	Negative
7	Feb-12	Feb-11	0.263888889	34.64	Feb-14	0.486111111	Negative
8	Feb-12	Feb-11	0.486111111	35.45	Feb-14	0.486111111	Negative
9	Feb-12	Feb-11	0.152777778	Negative	Feb-14	0.486111111	Negative
10	Feb-09	Feb-08	0.486111111	38.19	Feb-14	0.486111111	Negative

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Going by the above parameters, for the time being, it is assumed, merely on a trial basis, that Convalescent Plasma treatment is a bridge between Covid-19 patient and LIFE.

VILAS EKBOTE
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