T Helper 17 Response to Severe Acute Respiratory Syndrome Coronavirus 2: A Type of Immune Response with Possible Therapeutic Implications.

The initial immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) includes an interferon-dependent antiviral response. A late and uncontrolled inflammatory response characterized by high activity of proinflammatory cytokines and the recruitment of neutrophils and macrophages develops in predisposed individuals and is potentially harmful in some cases. Interleukin (IL)-17 is one of the many cytokines released during coronavirus disease 2019 (COVID-19). IL-17 is crucial in recruiting and activating neutrophils, cells that can migrate to the lung, and are heavily involved in the pathogenesis of COVID-19. During the infection T helper 17 (Th17) cells and IL-17-related pathways are associated with a worse outcome of the disease. All these have practical consequences considering that some drugs with therapeutic targets related to the Th17 response may have a beneficial effect on patients with SARS-CoV-2 infection. Herein, we present the arguments underlying our assumption that blocking the IL-23/IL-17 axis using targeted biological therapies as well as drugs that act indirectly on this pathway such as convalescent plasma therapy and colchicine may be good therapeutic options.

Considerations for safety in the use of systemic medications for psoriasis and atopic dermatitis during the COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) is responsible for at least 2 546 527 cases and 175 812 deaths as of April 21, 2020. Psoriasis and atopic dermatitis (AD) are common, chronic, inflammatory skin conditions, with immune dysregulation as a shared mechanism; therefore, mainstays of treatment include systemic immunomodulating therapies. It is unknown whether these therapies are associated with increased COVID-19 susceptibility or worse outcomes in infected patients. In this review, we discuss overall infection risks of nonbiologic and biologic systemic medications for psoriasis and AD and provide therapeutic recommendations. In summary, in patients with active infection, systemic conventional medications, the Janus kinase inhibitor tofacitinib, and biologics for psoriasis should be temporarily held until there is more data; in uninfected patients switching to safer alternatives should be considered. Interleukin (IL)-17, IL-12/23, and IL-23 inhibitors are associated with low infection risk, with IL-17 and IL-23 favored over IL-12/23 inhibitors. Pivotal trials and postmarketing data also suggest that IL-17 and IL-23 blockers are safer than tumor necrosis factor alpha blockers. Apremilast, acitretin, and dupilumab have favorable safety data and may be safely initiated and continued in uninfected patients. Without definitive COVID-19 data, these recommendations may be useful in guiding treatment of psoriasis and AD patients during the COVID-19 pandemic.

The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response.

The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as 'cytokine storm'. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes for critically ill patients with COVID-19 with the administration of cytokine-modulatory therapies, especially anti-IL-6 agents. Although ongoing trials are investigating anti-IL-6 therapies, access to these therapies is a concern, especially as the numbers of cases worldwide continue to climb. An immunology-informed approach may help identify alternative agents to modulate the pathological inflammation seen in patients with COVID-19. Drawing on extensive experience administering these and other immune-modulating therapies, the Society for Immunotherapy of Cancer offers this perspective on potential alternatives to anti-IL-6 that may also warrant consideration for management of the systemic inflammatory response and pulmonary compromise that can be seen in patients with severe COVID-19.