4.3 Convalescent Plasma
Convalescent plasma refers to the plasma collected from patients
recovered from an infection and the development of the corresponding
antibodies. The plasma is infused into patients with the disease. This
passive antibody administration may provide immediate immunity to
susceptible individuals (Bloch et al., 2020). The unique characteristic
of convalescent plasma is that it does not only contain antibodies but
instead has all the ”molecular tools” extracted from the COVID-19
healer. The repertoire of plasma-based factors that are infused with
neutralizing antibodies include anti-inflammatory cytokines,
anti-clotting factors, natural antibodies, specialized pro-resolving
mediators (e.g., resolvins, protectins, maresins), defensins, pentaxins,
collectins, plus an undefined number of unknown mediators (Rojas et al.,
2020). This molecular arsenal can play a role in improving virus
clearance, participating in B and T lymphocytes, limiting the cascade of
inflammation, preventing microembolism and promoting tissue repair
(Rojas et al., 2020). Anti-SARS-CoV-2 non-neutralizing antibodies that
bind to the virus without hindering virus replication can still promote
recovery by recruiting innate immune cells (Rojas et al., 2020).
Convalescent plasma has aroused great interest for prophylaxis in health
care workers and other caregivers while no other treatment for virus
infections is available or in an emergency (Jahrling, Frame, Rhoderick,
& Monson, 1985; Jahrling & Peters, 1984). Historical data have
reported the safety and effectiveness of convalescent plasma in other
infectious diseases. Spanish flu was the first viral infection that is
effectively responded to convalescent plasma in clinical studies. A
meta-analysis of 8 studies on Spanish influenza (1703 patients) showed
that treatment with convalescent plasma can reduce mortality (Luke,
Kilbane, Jackson, & Hoffman, 2006). There are studies on the treatment
of SARS-CoV (Cheng et al., 2005), MERS-CoV (Ko et al., 2018), and H1N1
(Hung et al., 2011) with convalescent plasma. Prior studies reveal that
three infected healthcare workers recovered from SARS-CoV infection
after administration of convalescent plasma from three recovered
SARS-CoV patients, and there was no residual virus from the convalescent
plasma as determined using RT-PCR. The ultimate results of no viral load
and increased anti-SARS-CoV IgM and IgG indicated that efficacy of
convalescent plasma and it can be a potential treatment for virus
infections. One of the healthcare workers got pregnant later and
positive anti-SARS-CoV IgG was detected in the newborn, which indicated
a possibility that anti-SARS-CoV antibody can transfer from mother to
newborn passively (Yeh et al., 2005).
There is new data on convalescent plasma used to treat COVID-19 in the
current pandemic. Mechanical ventilation was given to five crucially ill
COVID-19 patients (age range, 36-65 years; 2 women); all had received
antiviral agents and methylprednisolone concurrently. The patients
recovered from SARS-CoV-2 infection after plasma transfusion from donors
(age range, 18-60 years) and continuously improved as follows; 4 of 5
patients got their body temperatures normalized within 3 days. The viral
loads declined and became negative within 12 days after the transfusion,
while SARS-CoV-2–specific ELISA and neutralizing antibody titers
increased after the transfusion. 3 patients was released from the
hospital (hospitalization time : 53, 51, and 55 days), and 2 were in
stable condition 37 days after transfusion (Shen et al., 2020). The
administration of convalescent plasma was monitored in this preliminary
uncontrolled case series, and improved the patient’s clinical status.
However, the limited sample size cannot effectively demonstrate the
efficacy and safety of convalescent plasma. Therefore, clinical trials
of COVID-19 patients treated with convalescent plasma are needed. A
pilot study on 10 patients with severe COVID-19 showed that the
tolerance is good and clinical symptoms improved with the increase of
oxyhemoglobin saturation after a single dose of 200 mL convalescent
plasma transfusion (K. Duan et al., 2020). The advantages of
convalescent plasma include potencial clinical efficacy, easier
accessibility from a large donor pool, prophylactic benefits for
healthcare workers, short-time (Casadevall & Pirofski, 2020), and
low-cost over some experimental antivirals (Leider, Brunker, & Ness,
2010). However, there are risks of passive administration of
convalescent plasma, including identification of ideal donors due to the
lack of widely available and validated SARS-CoV-2 antibody assays,
finding donors with a robust humoral response, consenting, collecting,
and testing donors (Arabi et al., 2016; Park et al., 2015; Sullivan &
Roback, 2020). There are known risks concerning blood substances
transferation. One among the risks is that convalescent sera
administration could imbue individuals with pulmonary disease, which
would cause plasma infusion and pose certain risks for
transfusion-related acute lung injury (TRALI) (Gajic et al., 2007). The
phenomenon of antibody-dependent enhancement of infection (ADE) is
another theoretical risk. Evidence from 245 COVID-19 patients who take
the treatment of convalescent plasma suggests that it is safe
(Viswanathan et al., 2020). Therefore, the advantages and disadvantages
of convalescent plasma therapy must be weighed through the data in the
literature review and specific patient situation.