Treating COVID-19: are we missing out the window of opportunity?

Abstract

Severe COVID-19 is a biphasic illness, with an initial viral replication phase, followed by a cascade of inflammatory events. Progression to severe disease is predominantly a function of the inflammatory cascade, rather than viral replication per se. This understanding can be effectively translated to changing our approach in managing the disease. The natural course of disease offers us separate windows of specific time intervals to administer either antiviral or immunomodulatory therapy. Instituting the right attack at the right time would maximize the benefit of treatment. This concept must also be factored into studies that assess the efficacy of antivirals and immunomodulatory agents against COVID-19.

Efficacy of tocilizumab in patients with severe COVID-19: Survival and clinical outcomes

“…The best evidence available was recently published in four RCTs, which suggested no mortality benefit when TCZ is used in the treatment of COVID-19 [ 29 ]. However, the results of these studies may be affected by the timing of randomization in the course of the disease [ 30 ]. It is worth noting that these trials were small with a total number of 771 patients.…”

Mounting evidence of impaired viral control in severe COVID-19

“…This model divided the disease course into an initial viral response phase, followed by the inflammatory response phase. 1 , 2 In the inflammatory response phase, the virus is thought to have a minor role, and host inflammatory responses are the predominant mediators of pathophysiology, by triggering tissue damage leading to acute respiratory distress syndrome. 1 , 2 Growing evidence from our group and others suggest that this model might need revising.…”

“… 1 , 2 In the inflammatory response phase, the virus is thought to have a minor role, and host inflammatory responses are the predominant mediators of pathophysiology, by triggering tissue damage leading to acute respiratory distress syndrome. 1 , 2 Growing evidence from our group and others suggest that this model might need revising. Patients with the most severe forms of the disease show the highest viral RNA loads in respiratory samples 3 and prolonged viral shedding.…”

Progress and pitfalls of a year of drug repurposing screens against COVID-19

“…Unlike antiviral therapeutics that are most effective when treatment is initiated at the earliest stage of infection, the highly dynamic nature of acute viral disease mandates careful timing of immune-modulating treatment to limit risks of a compromised initial host antiviral response and secondary nosocomial infections as a result of impaired immune function. Early characterization of COVID-19 in hospitalized patients revealed a biphasic pattern of disease progression, starting with a period of relatively moderate clinical signs that could advance at a second stage to acute respiratory distress syndrome (ARDS), systemic inflammatory responses, and a “cytokine storm” [ 72 , 73 ]. These hallmarks of severe COVID-19 triggered repurposing attempts of different classes of immunoactive drugs.…”