Convalescent Serum to Treat COVID-19

History

Before the advent of antibiotics, physicians treated infectious diseases with serum from other patients who previous recovered from the same illness.

The basic idea is that when people are infected from a pathogen like bacteria, virus, fungi, or parasites, they develop antibodies against that specific pathogen. These antibodies are contained in the plasma or serum of blood, and can be theoretically transferred to someone else to fight the same pathogen. This is called passive antibody transfer, and had been used in the 1890s-1930s to treat a variety of illnesses including pneumonia, meningitis, diphtheria, measles, poliomyelitis, and mumps. At the time, this treatment option was relatively costly since it took a lot of resources to collect serum and inactivate the pathogen, but also came with side effects of serum sickness, characterized by weeks of rash, body aches, and joint pains. After the first sulfanamide drugs and penicillins were discovered in the 1930s-1940s, serum therapy quickly fell out of favor.

In more recent times, people used convalescent serum to fight against emerging pandemics. For example, convalescent serum was used in the Ebola crisis and decreased the fatality rate from 44% to 27.9% (Sahr et al. Journal of Infection 2017).

In light of our current COVID-19 pandemic, doctors and scientists have speculated about whether convalescent serum could be a viable treatment strategy.

Convalescent Serum to Treat Past Coronaviruses

Mair-Jenkins et al. provided a systematic review to assess the evidence of convalescent serum to treat the 2003 SARS pandemic.

In their analysis, this therapy significantly reduced the viral load of SARS, decreased hospital length of stay, and decreased mortality. They suggested that early initiation of treatment is critically important for effective therapy.

Source: Mair-Jenkins et al. Journal of Infectious Diseases 2015.

In Vitro Virus Neutralization of SARS-CoV-2

Zhou et al. examined whether serum from patients who recovered from COVID-19 can be used to neutralize the coronavirus grown in a petri dish. They showed that IgG antibodies collected from patients who recovered from COVID-19 can neutralize the virus at a dilution of 1:40-1:80.

Source: Zhou et al. Nature 2020

Clinical Studies

China has begun convalescent serum therapy on their patients infected with COVID-19 and even sent some serum to Italy.

A recent pilot study from Duan et al. assessed the clinical response to convalescent serum in 19 patients. Although this was not a clinical trial and had many confounding therapies, they showed that patients who received convalescent serum had decreased C-reactive protein, increasing oxygen saturation levels, decreasing RNA viral loads, and decreasing ground glass opacities on CT imaging, all shown below. Importantly, none of the patients who received this therapy had any significant adverse effects.

Source: Duan et al. 2020
Source: https://www.medrxiv.org/content/10.1101/2020.03.16.20036145v1.full.pdf
Source: Duan et al. 2020
Source: https://www.medrxiv.org/content/10.1101/2020.03.16.20036145v1.full.pdf
Source: Duan et al. 2020
Source: https://www.medrxiv.org/content/10.1101/2020.03.16.20036145v1.full.pdf

Shen et al. published a case series of 5 critically ill patients with COVID-19 and ARDS who received convalescent serum therapy. Following transfusion, the patients had improved oxygen saturation, decreased viral loads, normalized body temperature, and improvement of vital signs. These patients were critically ill, and lots of experimental antiviral therapies and steroids were also coadministered. It is really remarkable to see this level of therapeutic improvement so quickly.

Clinical improvement with convalescent plasma in critically ill patients
Shen et al. JAMA 2020.

Logistics of Convalescent Serum Therapy

Casadevall and Pirofski outlined the logistics, benefits, and risks of convalescent serum to treat COVID-19. Source: https://www.jci.org/articles/view/138003#B3

In brief, they recommend this therapy to patients who are at high risk for decompensation. For this therapy to be effective there needs to be

  • A population of donors who recovered from COVID-19
  • Blood banking facilities to process serum
  • Availability of assays to detect SARS-CoV-2 in serum and measure viral neutralization
  • Randomized clinical trials showing efficacy
  • Regulatory compliance

One pharmaceutical, Takeda, is already gearing up infrastructure for this treatment strategy.

Future of Convalescent Therapy

I am personally intrigued by this treatment option as we have a ton of patients who have the illness but will recover without adverse symptoms. This means we will have a ton of serum in the population that can be redirected to help people who are suffering from COVID-19. I do not know if this will be more effective than standard of care supportive therapy, but I am all in favor of anything that can lighten the load of limited ventilators.

New York will be the first state to try this out in the United States.

Source: https://www.nbcnews.com/health/health-care/new-york-will-be-first-state-test-treatment-coronavirus-blood-n1167136

The FDA just approved convalescent serum on March 24, 2020. This is a major breakthrough.

Source: https://www.npr.org/sections/coronavirus-live-updates/2020/03/24/820939536/fda-expedites-treatment-of-seriously-ill-covid-19-patients-with-experimental-pla

More details from the FDA are here:

https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/investigational-covid-19-convalescent-plasma-emergency-inds

The FDA writes: Therefore, given the public health emergency that the expanding COVID-19 outbreak presents, while clinical trials are being conducted, FDA is facilitating access to COVID-19 convalescent plasma for use in patients with serious or immediately life-threatening COVID-19 infections through the process of single patient emergency Investigational New Drug Applications (eINDs) for Individual patients under 21 CFR 312.310. 

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