CHEARS

ALL YOU NEED TO KNOW ABOUT CONVALESCENT PLASMA THERAPY

Convalescent plasma (CP) is a mode of passive immunization wherein preformed antibodies against an infectious agent are infused into a susceptible host with the aim of either preventing or treating the infection. It is a classic adaptive immunotherapy that has been applied to the prevention and treatment of many infectious diseases for more than one century. Over the past two decades, CP therapy was successfully used in the treatment of SARS, MERS, and 2009 H1N1 pandemic with satisfactory efficacy and safety. Since the virological and clinical characteristics share similarity among SARS, Middle East Respiratory Syndrome (MERS), and COVID-19, CP therapy might be a promising treatment option for COVID-19 rescue.

Patients who have recovered from COVID-19 with a high neutralizing antibody titer may be a valuable donor source of CP. CP, obtained from recovered COVID-19 patients who had established humoral immunity against the virus, contains a large quantity of neutralizing antibodies capable of neutralizing SARS-CoV-2 and eradicating the pathogen from blood circulation and pulmonary tissues. After CP transfusion, patients were found to have an increase of oxygen saturation and lymphocyte counts, and the improvement of liver function and CRP. Studies suggest that the inflammation and overreaction of the immune system were alleviated by antibodies contained in CP.

GENERAL INFORMATION REGARDING CP THERAPY:

1. Eligibility of convalescent COVID‐19 patients to donate whole blood or plasma should be based on:

2. Confirmation of previous infection with SARS‐CoV‐2 by a record of a validated diagnostic test at the time of illness.

3. An interval of at least 14 days after full recovery.

4. Standard selection criteria for whole blood or plasma donation according to local requirements and standards (age, weight, collection frequency, vital signs, freedom from deferral criteria) in line with ‘WHO Blood Regulators Network (BRN): Donor selection in case of pandemic situations.

5. Non‐reactivity of blood samples for transfusion‐transmitted infections including HIV, HBV, HCV, syphilis (for whole blood) and locally transmitted infections using approved serological and/or nucleic acid tests, consistent with local requirements for collection of blood components for transfusion.

6. To avoid the risk of transfusion‐related acute lung injury (TRALI), preference should be given to use of plasma from male donors or from female donors who have never been pregnant including abortions. This measure lowers the possibility of presence in the plasma of the antibodies to HLA or granulocyte antigens that cause TRALI. Testing for these antibodies in female donors who have been pregnant is desirable as an added precaution where feasible. TRALI occurs within 6 h after transfusion of implicated plasma and can be severe [3].

7. Pre‐screening and pre‐donation testing of convalescent COVID‐19 donors

8. Recovery from COVID‐19 infection should be confirmed through:

9. Physical examination of the donor to establish good health including absence of fever and respiratory symptoms.

10. If plasma is collected prior to 28 days after full recovery from illness, then confirmation of the resolution of the infection should be obtained through demonstration of two non‐reactive nucleic acid tests (NAT) for SARS‐CoV‐2 performed at an interval of at least 24 h on nasopharyngeal swabs.

11. Viral inactivation of convalescent plasma is encouraged to address residual risks of known transfusion‐transmissible viruses in an experimental product.

12. The approximate date of COVID‐19 infection, history of symptoms, treatments received and date of resolution of all symptoms documented and traceable.

13. When feasible, the total and neutralizing titres of anti‐SARS‐CoV‐2 antibodies should be determined as part of product characterization before use. Furthermore, donor blood/serum/plasma samples should be saved frozen at −80°C for retrospective testing and further scientific investigations.

14. Criteria for collection of COVID‐19 plasma.

15. Performed in certified blood establishments (or under exceptional circumstances hospitals and other healthcare facilities routinely engaged in performing whole blood collection with plasma separation and/or apheresis procedures) by appropriately trained staff.

16. Use only of legally authorized blood collection or plasmapheresis equipment under standard operating procedures.

17. Supervision of the collection process by trained staff.

18. Volume of plasma to be collected: at least 200–600 ml (without anticoagulant) based on the procedure and regulatory limits.

19. Plasma units intended for use as convalescent plasma should be clearly labelled (ISBT128 product description codes for convalescent plasma are available for establishments using the ISBT128 information standard).

20. The first plasma donation can be followed by further donations at a frequency compliant with local regulations and taking into full account the health status of the donor including monitoring of serum protein levels. In many jurisdictions, the interval between apheresis plasma donations of 600 ml or more should not be less than 7 days and that between whole blood donations should be at least 8 weeks.

21. Post‐donation treatment of plasma:

22. Where feasible, pathogen inactivation of plasma using a licensed technology is highly desirable to control residual risks of transfusion‐transmitted infectious diseases and to allay concern about possible superinfections with SARS‐CoV‐2.

23. Freezing as soon as possible at −20°C or preferably colder and stored frozen until administration.

24. Convalescent plasma collected from donors who do not fulfil post‐COVID‐19 suitability criteria for blood donation should be stored separately from other blood products in inventory.

25. Plasma sample aliquots should be taken for archiving at −80°C and future potential scientific investigations.

26. Recommendations for plasma transfusion:

27. Follow standard hospital procedures and recommendations for thawing and transfusion of plasma.

28. It is crucial to ensure ABO compatibility between the donor and the recipient.

29. Transfusion of plasma from at least two donors may be therapeutically beneficial to achieve more effective immune protection from delivery of diverse antibodies.

30. In the absence of published peer‐reviewed reports of transfusion of convalescent COVID‐19 plasma, patients could receive an initial dose of 200 ml, followed by one or two additional doses of 200 ml according to disease severity and tolerance of the infusions.

31. Blood/serum/plasma samples of the recipient prior to and after transfusion should be taken for future potential scientific investigations.

MECHANISM OF ACTION OF PLASMA THERAPY: (Figure 1)

GENERAL DOSING:

• SETTINGPost-exposure prophylaxis

• DESCRIPTION High risk contacts such as healthcare workers or contacts of COVID-19 patients who have high risk comorbidities

• SUGGESTED DOSING One unit of 50-100ml plasma

• SETTING: Asymptomatic to mild illness

• DESCRIPTION These patients are asymptomatic or mildly symptomatic with no organ dysfunction. This category also includes patients with high risk comorbidities such as T2DM, obesity, hypertension, age

• SUGGESTED DOSING 1-2 units of standard volume (200-250ml) plasma

• SETTING: Moderate to severe illness

• DESCRIPTIONPatients with organ dysfunction, hypoxia, requiring oxygen supplementation

• SUGGESTED DOSING 2-4 units of standard volume(200-250ml) plasma

• SETTING: Critically ill

• DESCRIPTIONPatients on life support such as mechanical ventilator and ECMO

• SUGGESTED DOSING Higher doses upto 7 units of standard volume plasma, administered once daily

ADVERSE EFFECTS OF PLASMA THERAPY:

The most common adverse reaction of CP therapy are transfusion-related events, involving chills, fever, anaphylactic reactions, transfusion-related acute lung injury, circulatory overload and hemolysis, etc. Meanwhile, the risk of transfusion-transmitted infections, such as human immunodeficiency virus, hepatitis B virus, hepatitis C virus and syphilis, is limited but should not be neglected

DO’S AND DON’T’S FOR PLASMA THERAPY DONATION:

First of all, donors need to have tested negative for COVID-19 and recovered from the illness. They should also not have any symptoms for the last 14 days. Most importantly, they need to have high antibody levels in their plasma. Moreover, a donor and the patient must also have compatible blood types. Once the plasma is donated, it is screened for other infectious diseases, such as HIV. One recovered, each donor produces enough plasma to treat one to three patients.

1. Always carry a hard copy of the COVID-19 negative report (RT-PCR or rapid antigen test) within 4 months of the day of donation and your Aadhar Card (front and back).

2. Donate only after 14 days of a COVID-19 positive report if the person is asymptomatic or after 14 days of symptoms if the person is symptomatic.

3. Women who have ever been pregnant cannot donate COVID-19 convalescent plasma.

4. A person who has received COVID-19 vaccination will not be able to donate plasma for 28 days from the date of vaccination.

5. A person cannot donate if he/she gets rejected for the lack of adequate antibodies in the blood.

6. Please contact hospital authorities for any other information in advance, on phone.

List of websites for information on plasma donation in India:

• covidplasma.online/

• https://dhoondh.com

• http://needplasma.in/

ADVANTAGES AND CHALLENGES OF PLASMA THERAPY IN INDIA:

CP therapy is an easily accessible, promising, and safe rescue option for severe COVID-19 patients.

Multiple barriers for CP donation exist among donors.

1. Voluntary blood donation has always been a challenge in India, and these problems are compounded further for CP.

2. The most common reasons for reluctance to donate include fear of visiting a healthcare facility during an epidemic,

3. Fear of waning of immunity and risk of reinfection due to CP donation.

4. The imposition of lockdowns and curfews also leads to restricted mobility of donors to visit CP donation sites

Setting up a centralized antibody titre determination system under the aegis of a competent authority may help overcome such problems. Another operational requirement would be to ensure that patients receive CP units as soon as possible, ideally targeting infusions within three days of diagnosis.

The scarcity of donors is another major problem. Creating a CP stockpile large enough to treat patients, provide prophylaxis for healthcare workers and provide enough raw materials for producing purified products in the future requires a major public health initiative. Motivating eligible donors for multiple sessions of plasmapheresis is necessary to overcome these shortages.

REFERENCES

1. Zhao Q, He Y. Challenges of Convalescent Plasma Therapy on COVID-19. J Clin Virol. 2020; 127:104358.

2. Khaire NS et al., Use of convalescent plasma for COVID-19 in India: A review & practical guidelines. Indian J Med Res 2021; 153:64-85.