Monday, March 30, 2020

COVID-19: Convalescent plasma as a treatment option

As the pandemic of COVID-19 continues, researchers have been looking at treatment options, most recently the use of convalescent plasma has generated a great deal of interest.

So let's dive in and understand convalescent plasma therapy and its scope:

Convalescent plasma therapy is based on the theory that a patient in the convalescence phase develops antibodies for that disease in their serum, which can be used to treat other patients, after ensuring that safe blood banking practices are being followed.

Historically, convalescent plasma was used as a prophylactic agent against measles. [1] But with the advent of vaccine development and monoclonal antibodies, the use of convalescent plasma went out of practice. It has also been used for scarlet fever [2] and poliomyelitis [3]. The use of convalescent plasma was recommended as an empirical treatment during outbreaks of the Ebola virus in 2014 [4], and a protocol for the treatment of Middle East respiratory syndrome coronavirus with convalescent plasma was established in 2015 [5].

A case series of 5 critically ill patients with laboratory-confirmed COVID-19 and ARDS was done in Shenzhen, China from January 20, 2020, to March 25, 2020. [6] In this study, 5 patients with severe pneumonia (rapid progression and high viral load requiring mechanical ventilation) received SARS-CoV-2 specific antibody (via convalescent plasma), with a binding titer>1:1000 and neutralization titer>40 along with interferon, lopinavir/ritonavir, and methylprednisolone. On 28th March 2020, the FDA gave approval of IND, i.e. Investigatory new drug application to use of convalescent plasma (after approval) to treat critically ill patients. [7]


Criteria for a critically ill patient include:

  • dyspnea,
  • respiratory rate >30/min,
  • SpO2 93% or less,
  • PAO2/FIO2 < 300
  • lung infiltrates of >50% within 24-48 hrs.
While it's life-threatening, if:

  • respiratory failure,
  • septic shock,
  • multiple organ failure set in.
So why did the FDA approve it as an IND?

The case series showed that the clinical conditions of patients treated with convalescent plasma improved. [6] This was indicated by body temperature reduction, improved Pao2/Fio2, and chest imaging. Four patients who had been receiving mechanical ventilation and ECMO no longer required respiratory support by 9 days after plasma transfusion.

In this study, it was noted that the body temperature normalized within 3 days in 4 out of 5 patients, the SOFA score decreased, and Pao2/Fio2 increased within 12 days. Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2–specific ELISA and neutralizing antibody titers increased following the transfusion. ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation.

Each patient received 2 consecutive transfusions of 200 to 250 mL of ABO-compatible convalescent plasma.

For the IND, to be a donor the following criteria should be fulfilled:

  • Prior lab-confirmed diagnosis
  • Complete resolution (at least 14 days, with the max titer at day 28)
  • If testing can be done for SARS COV-2, then with neutralizing antibody titers (>1:320).

As the cases continue to rise this is a promising option to act as a stopgap, with further evaluation by RCTs and can help the healthcare community until monoclonal antibodies or a vaccine can be developed.

Written by Shriniwas Mathur

References:
[1] ZINGHER A. CONVALESCENT WHOLE BLOOD, PLASMA AND SERUM IN PROPHYLAXIS OF MEASLES. JAMA. 1924;82(15):1180–1187. doi:10.1001/jama.1924.02650410022011
[2] Casadevall A, Scharff D. Return to the past: The case for antibody-based therapies in infectious diseases. Clin Infect Dis 1995; 21: 150–161.
[3] Kuttner A, Ratner B. The importance of colostrum to the new-born infant. Am J Dis Child 1923; 25: 413.
[4] Winkler AM, Koepsell SA. The use of convalescent plasma to treat emerging infectious diseases: focus on Ebola virus disease.mCurr Opin Hematol. 2015 Nov;22(6):521-6. doi:10.1097/MOH.0000000000000191.
[5] Ko JH, Seok H, et al. Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience. Antivir Ther. 2018;23(7):617-622. doi:
10.3851/IMP3243.
[6] Shen C, Wang Z, Zhao F, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. Published online March 27, 2020. doi:10.1001/jama.2020.4783
[7] Investigational COVID-19 Convalescent Plasma - Emergency INDs. (2020). Retrieved 30 March 2020, from https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/investigational-covid-19-convalescent-plasma-emergency-inds

2 comments:

  1. Excellent paper.... Waiting for a cure in the near future

    ReplyDelete
  2. We all hope for a breakthrough soon.... great work

    ReplyDelete

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