Prevention and treatment of COVID-19 disease by controlled modulation of innate immunity

Abstract

The recent outbreak of coronavirus disease 2019 (COVID-19), triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an enormous threat to global public health and economies. Human coronaviruses normally cause no or mild respiratory disease but in the past two decades, potentially fatal coronavirus infections have emerged, causing respiratory tract illnesses such as pneumonia and bronchitis. These include severe acute respiratory syndrome coronavirus (SARS-CoV), followed by the Middle East respiratory syndrome coronavirus (MERS-CoV), and recently the SARS-CoV-2 coronavirus outbreak that emerged in Wuhan, China, in December 2019. Currently, most COVID-19 patients receive traditional supportive care including breathing assistance. To halt the ongoing spread of the pandemic SARS-CoV-2 coronavirus and rescue individual patients, established drugs and new therapies are under evaluation. Since it will be some time until a safe and effective vaccine will be available, the immediate priority is to harness innate immunity to accelerate early antiviral immune responses. Second, since excessive inflammation is a major cause of pathology, targeted anti-inflammatory responses are being evaluated to reduce inflammation-induced damage to the respiratory tract and cytokine storms. Here, we highlight prominent immunotherapies at various stages of development that aim for augmented anti-coronavirus immunity and reduction of pathological inflammation.

Keywords: COVID-19; SARS-CoV-2; cytokine; innate immunity; lung.

Figure 1

Immunological interventions to enhance responses to Covid‐19 disease. On the left panel are interventions that can be used prior to infection including specific vaccines, IFNs, agents to train or boost innate immunity or agents to address dysbiosis. On the right are interventions following infection that include passive transfer of convalescent antiviral sera or virus‐specific monoclonal antibodies, immunomodulatory antiviral drugs, and anti‐inflammatory treatments, particularly inhibitors of deleterious cytokines.