Immune status could determine efficacy of COVID-19 therapies

Nearly as soon as the SARS-CoV-2 virus was identified, clinicians started working with repurposed antivirals such as Gilead's remdesivir and the HIV drug combo lopinavir-ritonavir to establish whether these agents had activity against the coronavirus.As ICUs filled up with infected patients who had acute respiratory distress syndrome (ARDS), seemingly caused by runaway immune responses and the resulting cytokine storms, clinicians set about assessing whether approved anti-inflammatory agents could be used to keep immune responses in check and avoid collateral damage.Several months on, the COVID-19 pipeline -spanning more than 1,100 interventional trials on ClinicalTrials.gov,as of mid-June -remains dominated by these two strategies.But a growing number of front-line intensivists are advocating a more nuanced approach to immune modulation in COVID-19.Dampening the immune system when patients are fighting off infections can be a dangerous approach, says Richard Hotchkiss, an intensivist at Washington University in St Louis.Instead, patients might need immune-boosting agents to help fend off infection."I'm personally tired of reading about the cytokine storm, " says Hotchkiss."That's the predominant theory, but I believe that's not correct."Oncologists Santosh Vardhana and Jedd Wolchok, both at the Memorial Sloan Kettering Cancer Center, recently outlined their case for immunotherapies for the treatment of COVID-19 in the Journal of Experimental Medicine, based on their experience with cancer patients who became infected with SARS-CoV-2.The immune system takes on different forms with COVID-19, they wrote.While many patients have hallmarks of inflammation early on in the infection, the virus can outlive the initial burst of immune activity.