Efficacy and Safety of Recovered Covid 19 Plasma Transfusion to Covid 19 Severly Ill Patients

Coronavirus disease 2019 (COVID-19) is a highly contagious pulmonary disease caused by a
newly discovered strains of coronavirus family. The clinical pictures could range from a
symptomatic to severe and can lead to hospitalization, breathing difficulties and death.
Unfortunately, no vaccine or specific treatment is available so far. 1 There have been
encouraging clinical researches using immunotherapy as a recent treatment modality against
Covid 19 viral infections. Of particular interest, is passive immunotherapy which is the
passive transfer of readymade antibodies (humoral immunity) from recovered individuals to
patients in active illness. 2 Plasma of recovered patients, a classic cell transfer therapy,
has been used successfully to prevent and treat many infectious diseases in the past
including: H1N1 pandemic influenza A, avian influenza A (H5N1), SARS-CoV and, Ebola virus
disease, MERS-CoV respiratory syncytial virus, Zika viruses, human cytomegalovirus and
rabies. Unfortunately, recovered plasma did not show successful results in combating Ebola
outbreak3 Neutralizing antibody from recovered SARS patients could interfere with SARS-CoV-2
from penetrating through host cells in vitro. 4 Moreover, neutralizing antibodies (NAbs) from
recovered SARS-CoV patients were highly correlated, peaking at month 4 after the onset of
disease, could be titrated in plasma of 90% of patients for as long as 2 years, decreasing
gradually thereafter.5

SARS-CoV-2 is a member of β-coronavirus family. It is a single-stranded RNA genome consists
of 30 kb nucleotides, which transcript 4 main structural proteins: spike (S), membrane (M),
envelope (E), and nucleocapsid (N) proteins. The virus characteristic appearance stems from,
the S protein which is club shape glycoprotein radiating in a crown like configuration. 6
Genome researches have shown that interlocking between the receptor-binding domain of S
protein and the angiotensin-converting enzyme 2 (ACE2) facilitates SARS-CoV-2 entry into the
host cells. 7 The similarity of the receptor-binding sites between SARS-CoV-2 and SARS-CoV
explains their shared pathogenicity and biological traits. Moreover, both covid-19 and SARS
share common clinical (fever, cough, body aches, and dyspnea) and typical radiological
manifestations (multifocal ground-glass opacities (GGOs) and subsegmental areas of
consolidation). 8 Nevertheless, both viruses are highly contagious with incubation period
range from several days to two weeks.

Patients with SARS-CoV-2 infection produce different antibodies against different viral
antigenic proteins (epitomes), and some of these antibodies mediate their action by virus
neutralization or by phagocytosis and antibody gated cell toxicity.9 There have been
published studies claiming successful patient outcome after transfusion of recovered plasma.
One study showed improved clinical pictures, higher discharge rate. 10 Another study
demonstrated that viral RNA disappeared in patient serums a week post transfusion. 11 Another
study compared the clinical improvement of recovered plasma transfusion with steroids in SARS
patients with critical condition. They observed that recovered plasma patients had a high
hospital discharge rate, better clinical outcome than the steroid group, with no transfusion
related unwanted effects.12 A large meta-analysis of 1703 influenza pneumonia patients who
had been transfused recovered plasma, showed a marked decrease of viral load and 21% decrease
in mortality. 13 There are fast growing numbers of new COVID-19 cases every day, and
disease-related morbidity and mortality is increasing. The purpose of our study was to test
the efficacy and safety of transfusing plasma from patients who have recovered from COVID-19,
to patients with COVID-19 in severe condition.