ADE and hyperinflammation in SARS-CoV2 infection- comparison with dengue hemorrhagic fever and feline infectious peritonitis

“Abstract: The COVID-19 pandemic has rapidly spread around the world with significant morbidity and mortality in a subset of patients including the elderly. The poorer outcomes are associated with ‘cytokine storm-like’ immune responses, otherwise referred to as ‘hyperinflammation’. While most of the infected individuals show minimal or no symptoms and recover spontaneously, a small proportion of the patients exhibit severe symptoms characterized by extreme dyspnea and low tissue oxygen levels, with extensive damage to the lungs referred to as acute respiratory distress symptom (ARDS). The consensus is that the hyperinflammatory response of the host is akin to the cytokine storm observed during sepsis and is the major cause of death. Uncertainties remain on the factors that lead to hyperinflammatory response in some but not all individuals. Hyperinflammation is a common feature in different viral infections such as dengue where existing low-titer antibodies to the virus enhances the infection in immune cells through a process called antibody-dependent enhancement or ADE. ADE has been reported following vaccination or secondary infections with other corona, Ebola and dengue virus. Detailed analysis has shown that antibodies to any viral epitope can induce ADE when present in sub-optimal titers or is of low affinity. In this review we will discuss ADE in the context of dengue and coronavirus infections including Covid-19…

2.2. ADE in Coronaviridae: Pathogenic members of the Coronavirus family infect primarily the epithelial cells in the respiratory and gastrointestinal tracts. Among the various members, immune responses have been well characterized in vivo in cats following natural infection with feline corona virus…

Immunization with vaccinia virus expression the Spike protein generated low titer of antibodies in kittens and accelerated the disease following challenge with the virulent virus by ADE. Again, transfer of antibodies from FIP [feline infectious peritonitits virus] or seropositive healthy cats accelerated the disease process following infection of recipients. The role of preexisting antibodies is not clear as vaccination with low virulent with ORF3abc truncated strain of FCoV induced comparable neutralizing antibodies in SPF-reared [specific pathogen free] and conventional cat. However, protection from subsequent lethal challenge was seen only in cats reared in SPF but not in conventional facilities. As the 2 strains of cats were different in this study it is not possible to arrive at conclusions by comparing the 2 groups. Nonetheless, cats that showed high titers following vaccination succumbed at later timepoints to fatal disease supporting a protective role of high titer neutralizing antibodies in keeping viremia under check.”