The SARS coronavirus-2 (SARS-CoV-2) that emerged as an outbreak in China’s Hubei province has now spread rapidly to many parts of the world causing a pandemic. Infection with SARS-CoV-2 results in a lung disease called Covid-19, which is proving to be a major global health burden.
A substantial proportion of cases progress to severe disease, with approximately 5% of patients requiring intensive care and more than 20% of critical cases succumbing to disease. While the overall death rate is likely to be lower than current estimates, given that the prevalence of mildly symptomatic cases has yet to be clearly defined, Covid-19 nonetheless represents a global health emergency. There are no licensed vaccines or antiviral therapies proven to protect or treat against Covid-19.
Therefore, once infected, case management is entirely supportive care []. Antiviral therapy that effectively stops the progression of the disease and effective vaccines that protect against severe Covid-19 are urgently required to meet medical and public health needs.
To meet these needs, several groups have made remarkable strides in bringing new therapies and vaccines into clinical development in a very short period of time. A convergence between therapeutics and vaccines for Covid-19 is the harnessing of the immune response to SARS CoV-2.
A rapidly implementable approach to antiviral development is the use of plasma-derived polyclonal hyper immunoglobulin. 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 in acutely ill Covid-19 patients. Alternatively, fresh frozen plasma could also be administered without further fractionation.
These approaches have been explored for patients with viral pneumonia, including SARS and severe influenza [3,4,5]. Results have been mostly positive, although many of these therapies have not been formally evaluated in a randomized, double-blind, placebo-controlled clinical trial. Theoretically, high titers of neutralizing antibodies could reduce viral shedding from infected to uninfected cells in the respiratory tract.
When given shortly after disease onset, this therapy could not only prevent disease progression but could also lead to faster viral shedding and thus removal of isolation from the patient. The latter would allow limited isolation rooms to be available to new Covid-19 patients sooner, allowing for the management of a larger number of Covid-19 patients despite finite containment capacity.
Under normal circumstances, vaccine development would take years to move from concept to clinical trials. However, the lessons of research on SARS-CoV and related MERS-CoV have enabled the rapid design of SARS-CoV-2 candidate vaccines for clinical development. These vaccines have a common goal, namely to elicit polyclonal antibody responses against the SARS-CoV-2 spike protein to neutralize the viral infection.
Vaccine candidates span a wide variety of vaccine platforms including mRNA, DNA, nanoparticles, subunits, and viral vectors. Some of the new technology platforms, such as DNA and mRNA vaccines, can theoretically allow millions of doses of vaccines to be rapidly manufactured in months and implemented in regions of need. In fact, unprecedented in the modern history of infectious diseases and vaccines, a vaccine candidate entered Phase I clinical trials within three months of the discovery of SARS-CoV-2.
The World Health Organization (WHO) has announced that a licensed vaccine should be available for widespread use by mid-2021.
While the development of hyperimmune globulin therapy and the SARS-CoV-2 vaccine are promising, they both pose a common theoretical safety concern. Experimental studies have suggested the possibility of immune-enhanced disease from SARS-CoV and MERS-CoV infections, which therefore may occur similarly with SARS-CoV-2 infection (as discussed below). continuation). Therefore, the aim of this mini-review is to examine the evidence for such concerns.