The pandemic spread of a novel coronavirus – SARS coronavirus-2 (SARS-CoV-2) as a cause of acute respiratory illness, named Covid-19, is placing the healthcare systems of many countries under unprecedented stress. Global economies are also spiraling towards a recession in fear of this new life-threatening disease.

Vaccines that prevent SARS-CoV-2 infection and therapeutics that reduces the risk of severe Covid-19 are thus urgently needed. A rapid method to derive antiviral treatment for Covid-19 is the use of convalescent plasma derived hyperimmune globulin. However, both hyperimmune globulin and vaccine development face a common hurdle – the risk of antibody-mediated disease enhancement.

The goal of this review is to examine the body of evidence supporting the hypothesis of immune enhancement that could be pertinent to Covid-19. Are also discussed how this risk could be mitigated so that both hyperimmune globulin and vaccines could be rapidly translated to overcome the current global health crisis.

A rapidly implementable approach to the development of antivirals is the use of plasma-derived polyclonal hyperimmune globulin. Convalescent Covid-19 patients can be expected to have reasonably high titers of neutralizing antibodies against SARS-CoV-2.

Plasmapheresis could be used to collect sufficient volumes of plasma from
individuals who have recovered from SARS-CoV-2 infection, pooled
and fractionated to produce hyperimmune globulin for infusion into
acutely ill Covid-19 patients. Alternatively, fresh frozen plasma could
also be delivered without additional fractionation.

Such approaches have been explored for patients with viral pneumonia, including SARS and severe influenza. Results have been mostly positive
although many of such therapies have not been formally evaluated
through a randomized, double-blind, placebo-controlled clinical trial.

Theoretically, high titers of neutralizing antibody could reduce viral
dissemination from infected to uninfected cells in the respiratory
tract. When given soon after illness onset, this therapy could thus not
only prevent disease progression, it could also lead to more rapid
viral clearance and hence patient de-isolation. The latter would
enable limited isolation wards to be made available to new Covid-19
patients sooner, enabling management of a larger number of Covid19 patients despite finite containment capacity.

Early anecdotal reports that infusion of convalescent plasma to acutely ill Covid-19 patients suggest the potential of hyperimmune globulin as a treatment to halt the progression of infection to severe pulmonary disease.

Hyperimmune globulin treatment, besides inhibiting viral infection, could also downregulate pro-inflammatory responses and reduce disease severity in Covid-19 patients, as Intravenous immunoglobulin infusion is associated with anti-inflammatory responses.

Mechanistically, how this anti-inflammatory effect is mediated remains to be fully defined. High dose antibodies could bind a number of different inhibitory receptors or other receptors to induce the anti-inflammatory response.

Regardless of the mechanism, the presence of neutralizing SARS-CoV-2
antibodies as well as high concentration of total antibodies could produce anti-inflammatory rather than the postulated immunopathology enhancement effects in Covid-19 patients to improve prognosis.

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