US FDA specifies high antibody titre for convalescent plasma and to only use in early COVID-19

Simon Collins, HIV i-Base

On 4 February 2021, the US FDA updated guidelines for using convalescent plasma (CP) as an investigational treatment for COVID-19. [1, 2]

These are important for now specifying that donor plasma needs to have high levels of neutralising antibodies and that the potential treatment should only be used in early infection.

CP was one of the first proposed treatments for COVID-19, supported by the FDA in March 2020 and by expanded donor programmes in both the US and UK. [3]

However, even when US access was further supported by an Emergency Use Authorisation in August 2020, there were no criteria linked to the donated plasma. By this time, more than 70,000 people had received CP treatment. [4]

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There has always been good plausibility for benefit from CP based on use to treat respiratory and other infections. However, the early studies in COVID-19 reported mixed results, often with no evaluation of the donated plasma. [7]

This led to an i-Base review in October 2020 to include the comment that “this suggests that any benefit will need both early use and high antibody titres in the donated plasma, and that ongoing studies should review their design to improve the likelihood of more positive outcomes”. [8]

A very useful editorial review supported continued research, with a likely benefit. [9]

Finally, an Argentinian RCT from Libster et al published in the NEJM using early high-titre plasma reported significantly fewer severe respiratory complications (relative risk, 0.52; 95% CI: 0.29 to 0.94; p=0.03). [10]

References

1. FDA. Investigational covid-19 convalescent plasma—emergency INDs. (4 February 2021).
   https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/investigational-covid-19-convalescent-plasma-emergency-inds (html)
   https://www.fda.gov/media/141477/download (PDF letter)
2. FDA fact sheet for health care providers. Emergency Use Authorisation (EUA) of COVID-19 convalescent plasma for treatment of hospitalized patients with COVID-19. (4 February 2021).
   https://www.fda.gov/media/141478/download
3. FDA News release. Coronavirus (COVID-19) update: daily roundup, March 24, 2020. (24 March 2020).
   https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-daily-roundup-march-24-2020
4. FDA Issues Emergency Use Authorization for convalescent plasma as potential promising COVID–19 treatment, another achievement in administration’s fight against pandemic. (23 August 2020).
   https://www.fda.gov/news-events/press-announcements/fda-issues-emergency-use-authorization-convalescent-plasma-potential-promising-covid-19-treatment
5. Statement from the RECOVERY trial chief investigators. RECOVERY trial closes recruitment to convalescent plasma treatment for patients hospitalised with COVID-19. (15 January 2021).
   https://www.recoverytrial.net/news/statement-from-the-recovery-trial-chief-investigators-15-january-2021-recovery-trial-closes-recruitment-to-convalescent-plasma-treatment-for-patients-hospitalised-with-covid-19
6. No benefit from convalescent plasma in UK RECOVERY study: limited results restrict implications for COVID-19. (13 February 2021).
   https://i-base.info/htb/39928
7. Convalescent plasma therapy for COVID-19. HTB (1 June 2020).
   https://i-base.info/htb/38022
8. Convalescent plasma: randomised controlled study finds no benefit in moderate stage COVID-19. HTB (11 November 2020).
   https://i-base.info/htb/39247
9. Garraud O et al. A look-back at convalescent plasma to treat COVID-19. Transfusion and Apheresis Science. DOI:10.1016/j.transci.2021.103063. (11 January 2021).
   https://www.trasci.com/article/S1473-0502(21)00013-6/fulltext
10. Libster R et al. Early high-titer plasma therapy to prevent severe Covid-19 in older adults. N Engl J Med (2021); 384:610-618. DOI: 10.1056/NEJMoa2033700. (18 February 2021).
    https://www.nejm.org/doi/full/10.1056/NEJMoa2033700

This report was first posted on 6 February 2021.