COVID 19 Missed Opportunities
Updated: Dec 3, 2022
I'm often asked what motivated my company. A large part was the firsthand tragedy we on the front line witnessed in COVID 19. My experience is that most of those we lost in 2021 to COVID 19 could have been saved if they had received the appropriate early treatment. If this sounds surprising, then let's talk about some realities of COVID 19 that are not generally known to the public at large but should be. Hold on tight... this one may be lengthy!
Most laypersons are unaware of how early in the pandemic effective treatment was developed and recognized. Highly effective therapy for COVID 19 emerged fall of 2020 and showed approximately 80% effectiveness at preventing severe illness. Most of the early 2021 efforts were geared at making these treatments accessible to the public. However, despite these efforts, we continued to see surges of severely ill and deaths that did not capitalize on these treatments.
To best appreciate how things developed, we'll take a look back on the timelines of COVID 19 as viewed from the front lines. We'll talk about the establishment of national treatment guidelines, the timelines in which highly effective treatment emerged, the continued surge of mortalities despite effective treatments, and the implications of such widespread failure to adhere to standards.
2020 In review: Spring, the establishment of COVID 19 authoritative resources.
The Infectious Disease Society of America (IDSA) and The National Institutes of Health (NIH) emerged early as the necessary centers of expertise in COVID 19 treatment. These bodies are well recognized and serve to establish guidelines for COVID 19. The IDSA has been a premier body since 1963 and sets treatment standards for pneumonia, viral infections, septic shock, fungal infections, and others. In response to the pandemic, the IDSA established a COVID 19 care panel in April 2020 to advise practitioners nationwide.
Similarly, the NIH is well recognized and established its COVID-19 treatment panel April of 2020. It is an impressive panel and combines numerous federal, academic, and professional bodies shown below:
NIH's Impressive Roster of Contributors
Food and Drug Administration Infectious Diseases Society of America Centers for Disease Control and Prevention Department of Defense Society of Critical Care Medicine American College of Chest Physicians American College of Emergency Physicians American Thoracic Society Biomedical Advanced Research and Development Authority Department of Veterans Affairs National Institutes of Health Pediatric Infectious Diseases Society Society of Infectious Diseases Pharmacists.
The recommendations of these two bodies are made publicly available and it is the expectation of physicians who treat COVID 19 patients to be aware of these standards.
2020 in Review: Fall, A New Breakthrough in Treatment
In the pandemic’s initial months, only the sickest patients received investigative treatments due to scarcity. However, most of these therapies proved either ineffective or only marginally effective. For example, steroids became a mainstay of treatment for hospitalized patients, but studies showed only a 12.1% improvement in mortality when applied to intensive care patients and only a 2.8% improvement in mortality when applied to all hospitalized patients at large(1). These were helpful treatments but would not sufficiently blunt the surge of patients and deaths that communities were experiencing. Better treatments were needed.
Breakthrough
A breakthrough in COVID 19 treatment occurred October 2020. Researchers developing monoclonal antibody (MOAB) therapies showed that early treatment in the initial days of infection using monoclonal antibodies reduced the chance of severe illness by 75%. These patients were treated early in their infection rather than later in a hospitalized phase of disease. Similar studies confirmed 80% reductions in severe disease by early treatment with MOAB.(2) Importantly, when MOAB therapies were applied to patients who had already developed severe illness requiring hospitalization, the therapy was not effective and had no impact on the patient’s illness.(3) Early treatment was the key.
Importantly, when MOAB therapies were applied to patients who had already developed severe illness requiring hospitalization, the therapy was not effective and had no impact on the patient’s illness. Early treatment was the key.
The positive impact such a breakthrough in COVID 19 treatment were clear. Early recognition and early treatment with monoclonal antibody would halt the progression of illness in a large percentage of patients and could curtail the pandemic’s surge substantially. The FDA granted emergency use authorization for MOAB therapy November of 2020 and federal, state and hospital networks began programs to distribute MOAB as a new care option for those with early symptoms at risk for severe disease. (4) Federal distribution of monoclonal antibody ramped up to close to 1 million initial doses and healthcare networks throughout the state developed infusion centers for practitioners to refer patients for treatment. The initial scarcity of these treatments restricted the infusions to those with high risk for severe disease such as older age, diabetes, hypertension, obesity, or other medical conditions.
Industry Response
By March of 2021 both the IDSA and the NIH recognized early treatment by monoclonal antibody as the recommended care standard.(5,6) Later, the Texas Department of State Health Services, working with regional councils, continued to increase access to the therapy by establishing publicly accessible infusion centers. Many hospital networks also began offering the infusions on-site in emergency rooms at the time of COVID 19 diagnosis to those with initial symptoms at risk for severe illness. As COVID 19 variants and resistances developed, new formulations of MOAB were adapted and continue to be developed.
2021 The Surge Continues and Opportunities Lost
Unfortunately, the 2021 tidal wave of COVID 19 hospitalization and mortalities continued. The chart below shows the continued surges of mortalities despite care guidelines, infusion centers and MOAB referral programs. Patients who had severe life-threaten stages of COVID 19 continued to present to the hospital emergency rooms. Those of us on the front line had the opportunity to interview these individuals and many of them had sought their initial diagnosis and care at outpatient care facilities. Despite having risk factors for severe illness and qualification for early MOAB therapy, they had not been advised of therapeutic options, nor offered early referral. These patients had continued to progress to severe sickness, presented later in their illness to the hospital, and had missed the opportunity for early effective care. Many would progress to respiratory failure, intensive care, mechanical ventilation, and a significant number would not survive. The avalanche of severe disease and mortality continued
Serious Implications
The implications of such commonly encountered scenarios are worrisome. Massive numbers of patients did not know of the treatment's existence. Even more disturbing was the implication that a significant subset of healthcare clinics and practitioners were not staying abreast of COVID 19’s effective treatments. They were not staying abreast of care standards, were not referring to effective therapy, and were not informing their patients of the therapy’s existence. Consequently, many these patients continued to worsen, the opportunity to curtail their illnesses was lost, and many would become mortalities. A compounding ‘epidemic of poor information and substandard care’ had emerged in the pandemic and the onslaught of severe illness and mortality continued throughout the Summer of 2021.(7)
Current State
In its current state, COVID 19 treatment has developed even more options. Other researchers saw MOABs success and mimicked the approach to early therapy, creating treatments aimed at early disease. Nirmatrelvir-ritonavir (Paxlovid) is an oral treatment for COVID which demonstrates 89% effectiveness at preventing severe disease and emerged December 2021. The antiviral Remdesivir when applied to late disease was only marginally beneficial (3.8%), but when applied to early phases of infection produced an 87% reduction in severe illness. The current options to practitioners treating COVID 19 are numerous. Paxlovid, monoclonal antibody, remdesivir, and molnupiravir (another oral antiviral) all emerged winter of 2021 as treatment options for those infected and at risk for progression to severe disease, if applied to early diagnosis and treatment. Today, there are even treatment options before symptoms manifest to those at risk for critical illness.
Hard Numbers
Is it possible to estimate the magnitude of lives lost due to missed opportunity? Not easily. One study published out of Harvard’s Beth Israel Deaconess Medical Center gives partial insight. These researchers studied MOAB use in the initial four months of availability from November 2020 to April 2021. They found the rates of use less than doses available.(8) It must be noted however, that this time-period was largely before the IDSA and NIH had recognized MOAB therapy as a care standard which limits its interpretation. However, their data suggests deficits in information distribution in practitioners at large.
A look at Texas’ 2021 numbers is helpful, but more data collection is needed. Texas COVID 19 data shows approximately 86,000 COVID19 deaths since the start of the pandemic. 28,000 of those deaths occurred between March 2021 and December 2021.(9) This time represents the period when MOAB became standard of care, but before oral treatments were discovered during Omicron’s predominance. Additional those 70 years old and above represent the highest rates of mortality, an age group that would have qualified for early treatment. What is lacking for a more complete analysis are the number of patients in those mortalities that would have qualified for early therapy and how many were initially evaluated by outpatient care services that did not refer. Our front-line experience suggest that a significant portion of those deaths would have qualified for, and saved by, early effective treatment. Quantification is needed.
Roadmaps Ahead
It appears we are well passed the worst of COVID 19, but attention to these issues will have future ramifications. Historically, public health threats emerge every 3-6 years. SARS 1 (2003), Swine Flu (2009), Middle Eastern Respiratory Syndrome (2012), Ebola (2015), and COVID 19 (2019) are all examples. In future threats of epidemic or contagion, we must have an informed citizenry and informed healthcare providers to prevent unnecessary loss of life.
In future threats of epidemic or contagion, we must have an informed citizenry and informed healthcare providers to prevent unnecessary loss of life.
Health care authorities and physician organizations will need start robust discourse and establish root cause analysis to look at the public health deficiencies revealed by COVID 19.
Efforts to improve our future response require more reliable flows of information. Information bottlenecks and single point failures will need to be removed. Efforts to establish reliable information distribution to physicians to ensure updated knowledge will be necessary. For those that have already suffered severe illness, irreversible lung damage, or lost loved ones from the 2021 COVID 19, no future strategy can reconcile their loss. However, it is our obligation to learn from our experiences and work to ensure no future opportunities to save lives are missed. We as a healthcare industry cannot bring back those that could have been saved, but we can at least learn from our mistakes and do better in the future.
Benjamin J. Blow, M.D.
Physician Legal Consulting of Dallas
Selected References
1. Peter Horby, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med 2021. Feb 25;384(8):693-704.
2. Peter Chen, et al. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N Engl J Med 2021; 384:229-37.
3. ACTIV-3/TICO LY-CoV555 Study Group. A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19. N Engl J Med 2021; 384:905-914
4. Emergency Use Authorization (EUA) for casirivimab and imdevimab. FDA. https://www.fda.gov/media/144468/download. Taken from the web 6/2022.
5. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. March 5, 2021. https://www.idsociety.org/globalassets/idsa/practice-guidelines/covid-19/treatment/idsa-covid-19-gl-tx-and-mgmt-v4.1.0.pdf. Taken from the web 6/2022
6. The COVID-19 Treatment Guidelines Panel’s Statement on the Emergency Use Authorization of the Bamlanivimab Plus Etesevimab Combination for the Treatment of COVID-1. March 2, 2021. https://files.covid19treatmentguidelines.nih.gov/guidelines/archive/statement-on-bamlanivimab-plu-03-02-2021.pdf. Taken from the web 6/2022
7. Texas COVID 19 Dashboard. https://www.arcgis.com/apps/dashboards/45e18cba105c478697c76acbbf86a6bc. Taken from the web 6/2022
8. Timothy S. Anderson, et al. Uptake of Outpatient Monoclonal Antibody Treatments for COVID-19 in the United States: a Cross-Sectional Analysis . J Gen InternMed 2021; 36(12):3922–4
9. Texas COVID-19 Data. https://dshs.texas.gov/coronavirus/AdditionalData.aspx. Taken from the web 6/2022