In March while testifying before Congress, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said that COVID-19 is 10 times more lethal than the flu. As the pandemic unfolded, we began to better understand the disease transmission and risk factors that lead to poor outcomes, however there is considerably more to learn about this pathogen and the mitigation of the disease severity in susceptible subpopulations.
COVID-19 is caused by a novel, possibly modified, virus with infection spectrum ranging from an asymptomatic contagious state to a severe cytokine cascade, and storm, and hampered microcirculation resulting in a high mortality in patients often with underlying comorbid conditions. Although several therapeutics are under development and clinical evaluation, there remains to be identified clearly efficacious clinical algorithms to mitigate severe, late-stage disease. Even eight months after the first recognition of this pandemic, a COVID-19 diagnosis leads to a lot of uncertainty for not only patients but for the healthcare providers. The vast majority (>99%) of those infected are either asymptomatic or suffer mild symptoms with many describing their experiences as being similar to the flu. However, what about those that become critically ill?
Why Are Viruses Hard to Combat
Viruses are often difficult to treat due to 1) the limited number of antiviral medications available that target specific viral replication or adherence properties and 2) the potential side-effects of these medications. Unlike many other microorganisms, a virus relies upon a host cell to replicate and this dependency complicates treatment modalities by requiring specific targeting of viral infection, replication and/or transmission. These drugs must prevent infection or halt viral replication/propagation without causing damage to the host cells or end organs.
Once viruses adhere to the host cell, they often replicate rapidly before a host’s immune system is able to develop an immune response. The goal of antiviral drug treatment is to limit or halt the viral replication process without harming or killing the host cell. Because of these challenges, there are a limited number of potential antiviral treatments available, and consequently it has been exceptionally difficult to find one that specifically targets the SARS-CoV-2 virus.
Unfortunately we have been forced to discover countermeasures to the COVID-19 infection in the midst of a global pandemic and, what now appears to be, an unwarranted population lockdown, making it difficult to respond quickly and decisively with limited and often contradictory information.
What has become clearer is that this disease is highly contagious, spreads relatively easily, and has a limitation of mortality to subsets of the global population. Earlier this year Dr. Fauci has also noted that he has “never seen a single virus—that is, one pathogen—have a range where 20% to 40% of the people have no symptoms” making this even more difficult to mitigate its spread.
Access to Treatments for COVID-19 Is Improving
Treatments with benefits that outweigh their side effect risk for patients are key, and we are finding as the weeks go by that more options are being discovered and becoming available. There are more than 1,500 ongoing or completed clinical trials being conducted around the world. Not all have been or will be a success, but the discoveries made from each will help to inform doctors and the medical community on how to properly manage this pandemic.
The FDA has granted Emergency Use Authorization (EUA) to a number of treatments and therapies since the onset of the pandemic and these treatments have given hospitals a number of response options. Doctors and nurses are desperately trying to determine the optimal treatments regimens for each stage of the disease, however, there has not been a unified guidance or response by the medical community, often varying from hospital to hospital and physician to physician.
Promising Options Are Available
Some infectious disease specialists initially thought only a drug could be effective. In the early days of the pandemic, there was significant attention given to a variety of potential therapies however, the studies were often poorly designed, or lacked sufficient numbers to achieve statistical significance in the prevention and treatment of COVID-19. A variety of clinical trials are now underway to evaluate a wide array of potential therapeutics, some of which include Arbidol, Tocilizumab, Chloroquine/Hydroxychloroquine plus Zinc, Lopinavir, Favipiravir, Ivermectin, as well as many others.1 The antiviral drug Remdesivir, administered via IV by medical professionals, is currently undergoing clinical trials however it is not yet proven to increase survival rates in late stage disease. This lack of efficacy could be attributable to the fact that the host’s immunologic overresponse to the existing viral antigen load and cellular damage is actually the driving force toward poor clinical outcome and not continued viral replication. In addition, COVID-19 disease is leading to acute renal injury in some patients, which prevents many from receiving Remdesivir. Remdesivir was approved by the FDA on October 22, 2020, but the efficacy of the drug is still highly debated by the international medical community.
In addition to antiviral drugs, a medical device—a blood filter—is proving to be a reliable treatment for critically ill COVID-19 patients (i.e., patients with respiratory failure or those in the early stages of respiratory failure). The blood filter is designed to rapidly extract viruses, RNA, viral proteins, bacteria and other pathogens from the blood, thereby limiting the antigenic load placed upon the immune system and its overresponse to the infection. Interestingly, within a few hours of the treatment, the clinical status of a COVID-19 patient has been shown to improve significantly: Their blood pressure often stabilizes, body temperature and breathing rates normalize and oxygen saturation improves.2 Because the virus negatively affects the microcirculation of blood in the lungs, the importance of stabilizing pulmonary function and oxygen saturation is critical to reversing clinical outcomes. In a study, nearly three-quarters of the ‘Seraph 100 Blood Filter’ patients who had been on ventilators in the EU survived. A randomized clinical trial of treatment for COVID-19 is scheduled to start soon, funded by the Department of Defense (PURIFY OBS is an observational study specific to COVID19 patients. It will collect data to characterize clinical outcome/data on patients treated with Seraph Filter versus control for COVID19 patients.).
With all of these options available, and others in the pipeline, we can be optimistic about the coming months as we continue to fight the pandemic using new drugs in combination with augmentation therapies, to include blood filtration.
- Nittari, G., et al. (September 5, 2020). “Current pharmacological treatments for SARS-COV-2: A narrative review”. European Journal of Pharmacology. Vol. 882, No. 5. doi: 10.1016/j.ejphar.2020.173328
- Olson, Stephen W., et al. “Treatment for Severe Coronavirus Disease 2019 With the Seraph-100 Microbind Affinity Blood Filter.” Critical Care Explorations 2.8 (2020).