The primary reason so many people have died from COVID-19

When one looks back over the past 10 months of the pandemic, several things are apparent. The overall response to the pandemic had fits and starts, and there were many missteps in recommendations about wearing masks, disease testing, and contact tracing.  However, while these measures impacted the number of people who became infected, none of these was the primary reason patients with COVID-19 are dying. 

COVID-19 clearly is a binary disease: either you have asymptomatic or mild disease, or you become deathly ill. Unfortunately, most of the people that became severely ill did not survive. While we still don’t know why this subset of individuals became so ill, often very quickly, one thing is clear –, we still have no drug that can effectively treat severe COVID-19.

Drug therapy was supposed to be the easy part of the medical approach to this viral infection. Vaccines were expected to take years to develop and then be of marginal protection, but it was thought that drug therapies, especially drugs repurposed from other diseases, would be available in the near term to treat patients and reduce mortality from COVID-19. Remarkably, this has not happened.

While mortality from COVID-19 has fallen, this reduction appears related to medical management changes. Earlier diagnosis, improved handling of people with respiratory distress, and more conservative use of ventilators all seem to have made improvements in patients with early disease. However, once patients developed inflammatory syndromes or severe pneumonia, there is little that appears to be beneficial. Young, otherwise healthy people either died or languished for months in hospital or on lung bypass machines (ECMO).

Drug therapies that have been applied to or developed for COVID-19 have had some marginal benefit, but mainly when used early in the treatment of the disease. Both Remdesivir and steroids have been beneficial early on in COVID-19, but do not reverse severe pneumonia. None of the anti-inflammatory drugs tested to treat cytokine storm has shown efficacy. While monoclonal antibodies to the virus do seem to have benefit, again it is early in disease. None of these interventions appears to be able to reverse disease in severely ill patients. 

This may not be surprising given the difficulty in treating other viral respiratory infections. We still don’t have an effective drug for influenza pneumonia. Respiratory Syncytial virus (RSV) kills millions of children around the world, and there is no effective antiviral therapy for that disease either. It might have been too much to expect to find a drug that would be useful for treating severe COVID-19. 

In conclusion, while there have been many failures in the pandemic response, the inability to find an effective drug to treat COVID-19 pneumonia may be the most important one.