The document summarizes convalescent plasma therapy for COVID-19. It discusses the workflow and mechanism of plasma collection and transfusion. It notes some positive aspects like a decrease in viral loads and improvement in clinical status seen in studies. However, it also outlines several risks and limitations, such as potential for transmission of infections, immunosuppression of the recipient, and a lack of standardized dosing. The document lists hospitals in India that are approved to conduct clinical trials of the therapy. It discusses some combination therapies being studied, as well as the costs associated with plasma therapy in India.

1. Presented by :
Manali R. Chavan
M. Pharm. 1ST Year
(Pharmaceutics Dept.)
Guided by :
Prof. R.J. Jarag
Head, Dept. of Pharmacology
Bharati Vidyapeeth College of Pharmacy, Kolhapur

2.  Introduction
 Workflow of plasma collection and transfusion
 Positive aspects of Plasma Therapy
 Negatives aspects of Plasma Therapy
 Effects of other drugs along with Plasma Therapy
 Cost of therapy and Hospitals involved in Plasma
Therapy
 Failure of Plasma Therapy in India.
 Conclusion
 References

3.  Plasma Therapy :
• Plasma therapy involves transfusion of antibodies from
someone who has recovered from COVID-19 (convalescent
coronavirus patient) into a critical patient. The therapy is
based on the principle that the blood of a recovered patient is
rich in antibodies needed to combat COVID-19. Antibodies
are Y shaped proteins produced by human body and used by
the immune system to identify and neutralize the foreign
objects such as bacteria and viruses. These antibodies are
expected to help critical patients recover.

4.  Mechanism of Plasma Therapy :
• Blood plasma, a yellowish liquid is a component of blood and
consists of protein, minerals and antibodies. If someone has
recovered from COVID-19 there are chances that the person's
body has developed antibodies that helped him/her to fight the
virus. The same antibodies, if infused into a critical patient
may provide passive immunity and help in the recovery
process.
• The SARs-CoV-2 virus’s spike glycoprotein, which sits on its
surface, functions to facilitate the virus entry into body’s cells.
These antibodies binds to spike protein and prevent the virus
from entering the cells.

5.  Procedure of Convalescent Plasma Therapy :
• It is also called Plasmapheresis procedure.
• First blood is drawn from the potential donor to check for the
presence of antibodies. Once it is clear that an individual can
donate plasma, the blood is extracted and plasma is separated
from the blood. Any automated cell separator (Apheresis
machine) is used and maximum CP volume collection allowed
is 500ml.
 Who can donate Plasma?
• Patients who have gone through the cycle of Coronavirus and
have recovered from COVID-19 can donate plasma. 500 ml of
plasma can be donated after 14 days of recovering from the
disease. Most importantly, they need to have high antibody
level in their plasma, Donor and the recipient must have
compatible blood type.

6. • Donating plasma should not weaken the donor’s immune
system nor make more susceptible to getting reinfected with
the virus.
• According to the information available on Delhi's plasma bank
website, there are seven categories of people who cannot
donate plasma. This includes diabetics on insulin, pregnant
women, people having body weight less than 50 kg, cancer
survivor, among others.
 At what stage of COVID-19 is Plasma Therapy
recommended?
• According to Dr. Sandeep Budhiraja, Group Medical Director,
Max Healthcare who did the first plasma therapy in India for a
COVID patient back in April, the best stage to give plasma is?
moderate severity' - when the patient's requirement of oxygen
increases.

7. He says, 'The convalescent plasma therapy is not much effective
when a patient is on a ventilator.'
• Dr. Suresh Kumar, Medical Director at LNJP (Lok Nayak) Hospital
in Delhi says that plasma therapy benefits people more who:
 are under 65 years of age
 have only SARI (severe acute respiratory infections)
 have acute respiratory failure because of COVID-19
 have oxygen saturation less than 90
 Risks :
• Blood transfusion related infections can be transmitted, therefore,
before plasma transfusion, test for HIV and other diseases, which
are usually done for all transfusions are conducted.

8. • Sometimes, the therapy might fail for some patients and can
result in an enhanced form of the infection.
• In some cases, a recipient's immunity does not accept
transfusion. The antibody administration may end up
suppressing the body’s natural immune response, leading a
patient vulnerable to subsequent reinfection.

9. 
Confirmed and recovered case of COVID-19
• Confirmation of SARS-CoV-2 infection by RT-PCR
• Confirmation of recovery by negative RT-PCR test for SARS-Cov-2
Planning for plasma collection ≥14 days following
resolution of symptoms
Pre-donation assessment
• Clinical assessment for absence of symptoms of COVID-19
• Negative nasopharyngeal swab result for SARS-Cov-2 by RT-PCR
• Serum collection and screening of serum for presence of anti-SARS-CoV-2
neutralizing antibodies in optimal titre
Plan for collection of plasma at designated collection
centre
Antibody testing: ideally, CLEA certified lab testing
using a validated test (eg. ELISA for anti-SARs-CoV-2)

10. Before and during collection
• Assess for all eligibility criteria for donation as per standard protocol
• Collect 400-800ml (if aphaeresis-collected ) plasma
• Testing of plasma for Transfusion- associated infections and HLA antibodies if
donor is female
• Store at – 400 C for one year or at – 800 C for more than one year
For Transfusion
• Confirmed positive case of COVID-19
•Consent for transfusion
•Transfusion of one dose of 200ml or 400ml in two divided doses : 7 to 14 days of
infection
Post Transfusion Monitoring
• Monitoring of adverse effects
• Monitoring of clinical outcome
• Monitoring of laboratory parameters

11. Author count
ry
Study
design
No. of
cases
Dose of CP Outcomes Mort
ality
Shen et al. China Case
series
5 Two
consecutive
doses of
200-250ml
(Total
400ml)
Decrease in viral
loads, increase in
SARS-CoV-2-
specific antibody
titres, improvement
of clinical status.
Nill
Duan et al. China Clinical
trial
10 One dose of
200ml
Improvement in
clinical symptoms &
radiological findings,
decrease in viral
loads, increase in Ab
titre.
Nill

12. Zhang et
al.
China Case
series
4 200ml –
2400ml
Clinical recovery of all
the patients
Nill
Ye et al. China Case
series
6 Two
consecutive
doses of 200-
250ml
Decrease in viral load,
increase in Ab titre,
improvement in clinical
symptoms &
radiological
abnormalities
Nill
Ahn et al. South
korea
Case
report
2 Two
consecutive
doses of
250ml (Total
500 ml)
Decease in viral loads,
increase in Ab titre,
improvement in clinical
symptoms
Nill

13.  Reduction in mortality rate :
• Although, the mortality rates of 6.3% in patients receiving
plasma therapy before 14 days and 21.9% in patients receiving
plasma therapy after 14 days have been reported in patients
suffering from SARS-CoV-1 infection, no mortality has been
reported in the patients receiving CP therapy for SARS-CoV-2
infection in all five studies.
 Beneficial effects of other plasma components :
• Plasma is a mixture of organic compounds, inorganic salts and
water. It has been shown to contain more than 1000 proteins
including albumin, immunoglobulin, coagulation and
antithrombotic factors, complement components, etc. These
plasma components may exert beneficial effects, e.g.
replenishing coagulation factors are useful in patients with
hemorrhagic fevers as in Ebola virus infection.

14. • Plasma proteins, especially albumins contribute to maintain
colloidal osmotic pressure of body fluid compartments. It has
been also shown that plasma from healthy donors has
immunomodulatory effects through antiinflammatory
cytokines and antibodies by blocking complement activation,
inflammatory cytokines and autoantibodies.
 Tolerance to CP therapy :
• As far as tolerance to CP therapy is concerned, the CP
transfusion is well tolerated by all patients and could
potentially improve the clinical outcomes in severe COVID-19
cases although associated with some adverse effects.

15.  Adverse effects :
• Adverse reactions ranging from mild fever to allergic reactions
to life–threatening broncho-spasm, and circulatory overload in
patients with cardio-respiratory disorders, renal impairment
have been reported. Other adverse reactions like chills, lung
injury and metabolic complications are valid clinical concerns
that should not be overlooked.
 Immunological reactions :
• Administration of plasma may cause severe allergic reactions.
Response to donor plasma/serum ingredients may lead to
serum sickness and anaphylaxis. Transfusion of plasma leads
to immune mediated reactions which include anaphylactic

16. reactions, hemolytic reactions, febrile nonhemolytic reaction.
 Risk of transfusion associated infections :
• Although very rare, administration of CP carry the risk of
transmission of potential pathogen, i.e. another infectious
agents such as hepatitis B virus (HBV), hepatitis C virus
(HCV), Human Immunodeficiency virus (HIV), Treponema
pallidum as well as SARS-CoV-2 itself. Hence, screening for
presence of these pathogens is obligatory to avoid the risk of
transfusion associated infections.
• It includes transfusion related acute lung injury, haemolysis,
post transfusion purpura, transfusion associated circulatory
overload.

17.  Risk of reinfection :
• Administration of CP, i.e. passive Abs may suppress/attenuate
the humoral immune response of recipient thereby inhibiting
the synthesis of specific Abs against SARS-CoV-2 (pathogen
specific Abs). This may make an individual susceptible to
reinfection by SARS-CoV-2.
 Other adverse reactions :
• CP therapy has been reported to cause an evanescent facial red
spot in one patient under study. Phlebitis and generalized
jaundice have also been reported to occur in some patients.
 Antibody dependent enhancement (ADE) :
• There is a remote possibility of antibody dependent
enhancement of disease process. ADE is a process in which
antibodies present in donor’s plasma may exacerbate disease
by enhancing entry of virus into host cell and multiplication of
virus.

18.  Lack of neutralizing antibodies in patient plasma :
• The patients recently recovered from the SARS-CoV-2
infection can be effective donors for preparation of plasma for
treating COVID-19 cases. The most important requirement for
this is that donor must have a high titre of neutralizing
antibodies in their plasma. The studies show that not all
patients recovered fromSARSCoV-2 infection have desired
levels of antibodies in a convalescent stage.
• Around 30% of patients recovered from SARS-CoV-2
produced very low titre of antibodies. Another problem is that
these antibodies last only for a short duration which is to be
measured in weeks or months.

19.  Large infusion volumes :
• Another important limitation of CP therapy is the requirement
of large infusion volumes. Different studies show that
transfusion of 200 ml–2400 ml CP is required for treatment
purpose. There is no standardization of transfusion dose of CP
and different doses have been used in different studies.
Depending on the patient, a dose of 200 ml–2400 ml was used
by Zhang et al. However, Duan et al. infused one unit of 200
ml of CP.
 Time of administration :
• Another important limitation is time of administrations of CP
to infected patients. It is expected to be more effective, if
administrated before the development of humoral immune
response to SARS-CoV-2.Hence,testing recipient(patient)for
neutralizing antibodies would be beneficial in identifying the
best recipient for treatment purpose.

20.  Waning of plasma Abs :
• As mutations are common in SARS-CoV-2 there is a
possibility of waning of plasma Abs.
 Bridging the gap between COVID 19 positive and
recovered cases :
• There is an addition of a large number of COVID 19 positive
cases every day in almost all countries; however, the number
of cases being recovered from SARS-CoV-2 infection is
comparatively very less. Hence, it is very difficult to meet the
requirement of large quantity of plasma needed to treat large
number of cases being added every day. The bridging of this
gap between recovered cases and new cases appears to be very
difficult, because of which this treatment option may not be
feasible in terms of availability of large quantity of
convalescent plasma.

21.  Basic administrative and logistical barrier :
• The important barriers include identifying, consenting,
collecting and testing donors. Identifying/finding donors with
robust humoral response (donors of high level of desired
antibodies) is an important hurdle. Lack of suitable assay
method for detection of neutralizing antibodies may hamper
the identification of suitable/ideal donors. Written informed
consent for donations of plasma by patients recently recovered
from COVID-19 disease may be an another important hurdle.
Use of CP as a treatment for COVID-19 has received
authorization for off-label use in India. This authorization
paralleled by questionable practices such as calls for donors on
social media and the sale of CP on the black market with
exorbitant price tags in India is major hurdle.

22.  Combination therapy of Convalescent plasma,
Remdesivir and Decadron :
• In a small study done in California, patients with severe
COVID-19 and were hospitalized showed a reduction in
intubation and mortality rates when they were given a
combination therapy of remdesivir, Decadron, and
convalescent plasma (CP).
 Combination therapy of convalescent plasma with
antiviral drugs :
• The study was carried out in 10 severe COVID-19 patients,
where Convalescent plasma combined with antiviral drugs and
supportive care. There is improved clinical outcome in covid-
19 patients, increased lymphocytes count and decreased CRP
level.

23.  Combination of Convalescent plasma therapy with
Tocilizumab :
• A retrospective cohort study was conducted on 110 patients
from Tertiary care hospital in Oman. It is associated with
improvement in inflammatory and ventilatory parameters but
no effect on mortality.
• A total 110 patients were enrolled with an overall mean age of
50±16 years. Patients on this treatment were more likely to
have had acute respiratory distress syndrome, chest X-ray
abnormalities. After treatment, all measured inflammatory
marker showed an overall steady decline overtime.

24.  Combination of Convalescent plasma, remdesivir and
corticosteroid in periviable pregnancy :
• Infection with novel SARs-CoV-2 may leads to puemonia
characterized by an intense inflammatory response similar to
acute respiratory distress syndrome. Current management
guideline in pregnancy are limited.
• In the setting of severe COVID-19 in pregnancy, including in
periviability period, combination of multitargeted therapy
should be strongly considered. Study case of severe COVID-
19 pneumonia in periviable pregnancy treated with
concurrent combination of convalescent plasma, remdesivir
and corticosteroid leading to rapid maternal pulmonary
improvement.

25. • Sept 24,2020, Maharashtra state's Minister of Public Health
and Family Welfare Rajesh Tope announced,” For COVID-19
patients, the fixed rate of plasma therapy for all hospitals will
be Rs.5,500.”
• On May 2020, ICMR has began clinical trials of convalescent
plasma treatment. The biomedical research body has
shortlisted 21 hospitals across the country to initiates trials on
critically ill-Covid-19 patients.

26. States Medical Institutes
Gujarat Smt. NHL Municipal Medical College, Ahmedabad
Gujarat B.J. Medical College and Civil hospital, Ahmedabad
Gujarat Government Medical College, Bhavnagar
Gujarat Government Medical College, Surat
Rajasthan Sawai Man Singh Medical College, Jaipur
Rajasthan Mahatma Gandhi Medical College and Hospital,
Jaipur
Punjab Satguru Pratap Singh Hospital, Ludhiana

27. Maharashtra B.J. Government Medical College, Pune
Maharashtra Poona Hospital and research centre, Pune
Maharashtra Sir H. N. Reliance Foundation Hospital and Research
Centre, Mumbai
Maharashtra Rajarshee Chhatrapati Shahu Maharaj Government
Medical College and CPR Hospital Kolhapur
Maharashtra Government Medical college, Nagpur
Tamil Nadu Madurai Medical college, Madurai
Tamil Nadu Madras Medical College, Chennai
Madhya Pradesh Gandhi Medical College, Bhopal
Madhya Pradesh Mahatma Gandhi Memorial Medical College, Indore

28. Uttar Pradesh Government Institute of Medical
Sciences, Noida
Uttar Pradesh Sanjay Gandhi Postgraduate
Institute of Medical Sciences,
Lucknow
Karnataka Karnataka Institute of Medical
Sciences, Hubli
Telangana Gandhi Medical College, Telangana
Chandigarh Postgraduate Institute of Medical
Education and Research

29.  Study Case 1
• Convalescent plasma therapy failed to benefits covid-19
patients, the largest trial conducted across 39 hospitals in India
and spearheaded by the Indian Council of Medical Research
(ICMR) found.
• The trial spanning April-July enrolled 464 hospitalized
patients with “moderate” COVID-19 and administered
convalescent plasma – antibodies derived from plasma filtered
from blood of those who have recovered from COVID-19.
• The idea was that such antibodies would neutralize replicating
viruses and check the growth of the infection.

30. • However, in 235 patients that received the plasma along with
the “best standard of care”(called the control arm), there was
not a significant difference in the proportion of those who did
not progress to severe illness over 28 days, nor did the trial
save a significant fraction of patients from death.
• “Thirty-four patients (13.6%) died in intervention arm and
Thirty-one (14.6%) in the control arm.
• No reduction in deaths – CP was not associated with reduction
in mortality or progression to severe COVID-19.

31.  Study Case 2
• A team of doctors at AIIMS conducted a study to assess the
efficacy of this mode of treatment. The sample size was 30.
The group was divided into two, 15 were given standard
treatment protocol and rest were administered plasma therapy.
• An interim analysis of the randomized controlled trial revealed
that mortality is similar in both groups with not many clinical
benefits for either of the groups.
• The plasma therapy still remain part of the investigational
treatments for COVID-19 as per ICMR guidelines. Another
study on plasma therapy that is being done by the ICMR is yet
to be published.

32. • “The synthesis of global evidence is not supporting the usage
of plasma therapy,” said Samiran Panda, head, epidemiology
and infectious disease, ICMR.
• Experts at the ICMR have been reviewing the available data
and have not found any benefits.
• So, the Convalescent Plasma Therapy, widely used in India to
treat COVID-19 patients, is likely to be dropped.

33.  Study Case 3
• Simonovich et al. published the results of a randomized
controlled trial in hospitalized patients with severe COVID-19
pneumonia that questions this treatment.
• In the study, patients with severe COVD-19 pneumonia were
randomized to receive convalescent plasma or placebo in
addition to standard care to assess impact on a six-point
ordinal status scale ranging from total recovery to death, 30
days after the intervention.
• Overall, 228 patients were randomized to receive convalescent
plasma and 105 to receive placebo in a ratio 2;1.
• At 30 days, no significant difference was found between
convalescent plasma and placebo for any clinical outcome,
including mortality.

34. • Plasma Therapy has previously shown to be effective in severe
pandemics of Ebola, SARS-CoV-1, MERS and even swine flu
with an acceptable level of safety and efficacy.
• Blood plasma is readily available from survivors and boosts
fight against the virus as it transfer immunity or antibodies
from one body to another.
• Convalescent plasma was not associated with a reduction in
progression to severe covid-19 or all cause mortality.
• The current research evidence unanimously indicates that
there is no benefits offered by convalescent plasma for
treatment of COVID-19. However, it continues to be
prescribed rampantly in hospitals across India. And rampant
use of plasma therapy without prior testing for neutralizing
antibodies will do more harm than good.

35. • The government however, had not dropped this investigational
therapy from the COVID-19 treatment protocol; despite
suggestions by researcher and scientists that its rampant use
may be leading to unwanted mutation in SARs-CoV-2 virus.
• We have to maintain judicious use of therapies which are
going to benefit, if their benefit is not established, we should
not use those therapies otherwise they would put tremendous
immune pressure on virus, and virus will tend to mutate more.

36.  https://www.journals.elsevier.com/journal-of-infection-and-
public-health
 https://www.dovepress.com/convalescent-plasma-therapy-for-
management-of-covid-19-perspectives-an-peer-reviewed-
fulltext-article-RMHP
 https://www.thehindu.com/sci-tech/health/plasma-therapy-
didnt-help-covid-19-patients-icmr/article32564888.ece
 https://economictimes.indiatimes.com/news/india/plasma-
therapy-may-be-dropped-from-covid-care-
protocol/articleshow/82690633.cms?from=mdr
 https://www.the-scientist.com/news-opinion/indian-study-
shows-no-survival-benefit-of-plasma-in-covid-19-67931