August 20, 2020 (updated Sept. 11, 2020) — New research compares April’s federal guidance for recording the cause of deaths possibly due to the COVID-19 virus to assessments of the cause of death of patients infected with other pathogens, namely life-threatening “superbugs.” The research’s findings presented below are incomplete. The entire article will be posted soon. (Article by: Lawrence F Muscarella PhD, President LFM Healthcare Solutions, LLC)
In April the Centers for Disease Control and Prevention (CDC) published guidance for recording the deaths of confirmed or suspected cases of the COVID-19 disease. This document — which is displayed to the right — includes an appendix featuring three practical examples of death certifications, or cause-of-death statements.
One of these examples presents the death of an 86-year-old woman with an unconfirmed case of the disease. Testing to verify infection was not performed, but according to this case’s description, the coroner determined that “given the patient’s symptoms and exposure to an infected individual,” the likely underlying cause of death was COVID–19.
While this federal guidance advises that “testing for COVID–19 should be conducted whenever possible,” the CDC’s document does not require, as a prerequisite, such testing to confirm viral positivity. It states instead that “it is acceptable to report COVID-19 on a death certificate” without confirmatory testing “if the circumstances are compelling within a reasonable degree of certainty.”
Lacking confirmatory testing, it therefore becomes plausible that, in some cases, adherence to the CDC’s guidance could result in recording COVID-19 on the death certificate of a decedent not infected with the virus. The SARS-CoV-2 virus, also known as the severe acute respiratory syndrome coronavirus 2 virus, causes COVID-19 disease.
“Probable” or “presumed” infection
The CDC’s April guidance further advises that if a case cannot be definitely diagnosed but the disease is “suspected or likely (e.g., the circumstances are compelling within a reasonable degree of certainty),” like the third example described in this federal document’s appendix, COVID–19 may be reported on the death certificate as “probable” or “presumed.” The guidance includes the caveat that, in these instances, “certifiers should use their best clinical judgement in determining if a COVID–19 infection was likely.”
During an April webinar discussing this federal guidance, the CDC stated that it encourages use of the words “probable” and “likely” when testing is not available. The CDC noted during this on-line presentation that the agency is not concerned that writing “probable” or “presumed” on a death certificate could result in the “overcounting the number of deaths.” (Other CDC guidance too permits listing a condition as “probable” even if it has not been definitively diagnosed.)
Clarifying whether the CDC would “count” a probable (or unconfirmed) case as a true definitive COVID-19 infection, a CDC representative stated during this April webinar that, “If you’re pretty sure that it was a COVID-19 infection and you’ve written probable COVID-19, I don’t think that there’s necessarily a need to amend the death certificate. And, of course, you may do that if you like, but in a case of probable COVID-19 we will count it as COVID-19.”
The potential for misreporting cases notwithstanding, a death certificate’s accurate recording of the cause of a death related to an infection — whether COVID-19, a multidrug-resistant organism, or another infectious agent — or alternatively to a preexisting condition is integral to sound assessments of the pathogen’s mortality rate and public health threat. An increase or spike in a pathogen’s mortality rate could compel public health officials to adopt more robust measures to improve safety, while a decline in this rate might cause easing or removal of imposed precautions.
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Case Reviews, Expert “On-Call” Consulting Services: LFM-Healthcare Solutions, LLC provides medical expertise and guidance for healthcare facilities (hospitals), device manufacturers and legal representatives of the public, specializing in medical device designs and both the causes and prevention of healthcare-associated infections linked to medical equipment.
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Superbug-associated deaths: Multidrug-resistant organisms — or “superbugs” — are another public health scourge. For perspective, while the COVID-19 death rate has been estimated to be less than 1%, the U.S. mortality rate for some superbug infections, such as “CRE” and Candida auris, is significantly higher, and can be as high as 50%.
A peer-reviewed report in 2018 re-estimated the number of deaths in the U.S. in 2010 due to a superbug infection to be as high as 162,000, which is not starkly different from the number of deaths in the U.S. attributed to the COVID-19 disease reported to date. For reference, CRE are members of the Enterobacteriaceae family of bacteria that are resistant to “last resort” carbapenem antibiotics. Examples of CRE include NDM-1-producing E. coli and carbapenemase-producing Klebsiella pneumonia.
In today’s clinical settings, COVID-19 and bacterial infections can become intertwined. A study published in Lancet reporting on the deaths of 54 hospitalized patients with laboratory-confirmed COVID-19 found that half (27) experienced a secondary infection, such as ventilator-associated pneumonia. Fifty three of these patients (98%) received antibiotics and 12 (22%) received antivirals. Superbugs are microorganisms that have developed resistance to several types of antibiotics.
Antimicrobial resistance: Underscoring the dangers of superbugs, U.S. federal health officials reported earlier this year that “antibiotic resistance is one of the biggest public health challenges of our time.” Last year a United Kingdom public health representative warned about “a danger to humanity” that is “as big a danger as climate change or warfare,” referring to antimicrobial resistance. Also last year, the CDC stated in a report discussing certain superbugs as “urgent threats” that the agency “has taken aggressive action,” in coordination with other stakeholders including state and local health departments, “to rapidly detect, prevent spread, and innovate against antibiotic resistance.”
In May a former director of a CDC division warned that superbugs could be another “hinder danger” of COVID-19. A September news report quoted the biosecurity research director at Australia’s national science agency to say “Covid is not anywhere near the potential impact” of antimicrobial resistance. Last year the World Health Organization concluded that if no action is taken, “drug-resistant diseases could cause 10 million deaths each year by 2050.”
OBJECTIVES, METHODS: This article reviews the CDC’s April guidance for recording the cause of deaths related to the COVID-19, and compares its policies and criteria to the standards and practices state and health health officials in the U.S. have used to assess the cause of death of patients infected with a superbug.
Several publications were reviewed in addition to the CDC’s COVID-19 guidance, including superbug outbreak investigations, other federal guidelines, state guidance documents, news reports, and other relevant sources. Federal and state guidance for reporting cases and deaths that could be due to the influenza virus, which causes the flu in humans, was also reviewed for some perspective.
FINDINGS, DISCUSSION: This review’s findings suggest that the standards and measures the CDC’s guidance uses for the certification of deaths that could be due to COVID-19 appear to differ in some respects from the practices and paradigms that health officials in the U.S. have used at times to assess the potential contribution of a superbug infection to patient death.
For instance, the CDC advises that COVID-19 be specified on the death certificate if it “played a role in the death.” However, health officials in Illinois investigating the cause of a superbug outbreak in 2013 linked to reusable medical equipment appear to have applied a different standard, reporting that the associated deaths “did not appear” to be related to the infection, that officials “could not say whether the bacteria had contributed to any deaths,” or that “no one had died as a direct result of infection or exposure” — despite the high in-hospital mortality rate associated with this outbreak’s superbug.
In a reviewed case involving four deaths linked to the C. auris superbug, a news source similarly reported that “health officials said it’s not clear if the deaths were due to the (fungal) infection or the patients’ underlying health conditions.” In another reviewed case linking superbug infections in Washington, in 2012 and 2013, also to reusable medical equipment, the investigators observed that “[b]ecause affected patients all had severe underlying disease, the role of the outbreak strain in patient deaths cannot be determined.”
That a comorbidity could potentially hinder or interfere with clinical assessments of the role played by a pathogen, at least apparently a superbug, in an infected patient’s death is salient, particularly in today’s context of certifying and recording COVID-19 as a cause of death in patients with comorbidities.
The aforementioned March Lancet study reported that two thirds of the COVID-19 patients who died were diagnosed with a comorbidity, 26 of them (48%) with hypertension. Also in March, the CDC reported that approximately 90% of hospitalized patients identified through a COVID-19 surveillance network “had one or more underlying conditions.” And in updated August findings, the CDC similarly reported that 94% of the individuals in the U.S. who died of COVID-19 had at least one pre-existing condition, such as obesity or heart disease.
In a second reviewed fungal case, three chronically ill patients in New York who died were identified with pan-resistant C. auris infection. Appearing again to have applied a different standard (if more wary approach) regarding the cause of death, the CDC reported that for two of the patients “the role of C. auris in their deaths is unclear,” and that the third infected patient “died from underlying medical conditions.” These assessments that the C. auris infection did not cause any of these three deaths notwithstanding, the CDC reports that 30-60% of individuals infected with C. auris die.
None of this article’s reviewed superbug cases (which are discussed in more detail in the full article) concluded that the superbug infection caused or directly contributed to patient death. (It is understood that the circumstances surrounding these three superbug cases may be significantly different that the discussed COVID-19 cases. Bacteria and viruses are dissimilar in many regards.)
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The following set of three peer-reviewed articles by Dr. Muscarella (and in one case, a co-author) may be the most comprehensive and historical collection published to date discussing associations between deadly superbugs and reusable medical equipment:
(1) Muscarella LF. Use of ethylene-oxide gas sterilisation to terminate multidrug-resistant bacterial outbreaks linked to duodenoscopes. BMJ Open Gastroenterol 2019 Aug 5;6(1):e000282. || (2) Mehta AC, Muscarella LF. Related “Superbug” Infections. Chest 2019 Aug 14;pii:S0012-3692(19)31457-6. || (3) Muscarella LF. Risk of transmission of carbapenem-resistant Enterobacteriaceae and related “superbugs” during gastrointestinal endoscopy. World J Gastrointest Endosc 2014 Oct 16;6(10):457-74.
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The “flu”: Some of the criteria the CDC use for reporting influenza-associated deaths also apparently differ in certain respects from the agency’s April guidance for recording deaths that could be due to COVID-19.
In the context of pediatric mortality, the CDC has defined an influenza-associated death for surveillance purposes as “a death resulting from a clinically compatible illness that was confirmed to be influenza by an appropriate laboratory or rapid diagnostic test.” The CDC adds that there “should be no period of complete recovery between the illness and death,” and that influenza-associated deaths in individuals less than 18 years of age “should be reported.” (While flu-associated deaths in children are nationally notifiable, states are not required to report to the CDC adult deaths related to influenza infection.)
Influenza infection can range from asymptomatic illness to viral pneumonia and death. The seasonal “flu” is caused by influenza A and B viruses, and like COVID-19, it is a contagious respiratory illness. While there are important differences between these viruses, influenza and SARS-CoV-2 may be transmitted by contact, droplets and fomites.
In an on-line document discussing influenza and confirmatory testing, the CDC advises that infection “cannot be diagnosed accurately based on signs and symptoms alone. Laboratory testing is necessary to confirm the diagnosis.” Adding additional detail, the CDC maintains that “individual cases of influenza cannot be distinguished from other respiratory virus infections based on clinical information alone.”
Regarding deaths possibly due to influenza, states in the U.S., similar to the CDC’s pediatric mortality guidance, may require laboratory testing to confirm infection. For instance, the Washington State Department of Health advises that “[o]nly lab-confirmed fatal cases are reportable.” According to this state’s reporting policies, which do not appear to distinguish between pediatric and adult cases, the purpose of reporting and surveillance of (laboratory confirmed) influenza-associated deaths is, in part, to determine mortality rates and to “detect emerging threats such as avian and other novel influenza strains.”
Similarly, the North Carolina Department of Health and Human Services advises that, for both adult and pediatric cases, all influenza-associated deaths “are reportable to the Local Health Department. An influenza-associated death is defined for surveillance purposes as a death resulting from a clinically compatible illness that was confirmed to be influenza (any strain) by an appropriate laboratory or rapid diagnostic test.”
This state health department emphasizes that a “death should not be reported” if there is “no laboratory or rapid test confirmation of influenza virus infection” (or if the “influenza illness is followed by full recovery to baseline health status prior to death,” or after review and consultation, “there is an alternative agreed upon cause of death”).
Restating the distinction, whereas the CDC and these state policies’ definition of an influenza-associated death (for surveillance purposes) requires testing to confirm influenza, the CDC’s April guidance and definition of a “COVID-19 case” both permit recording COVID-19 as a cause of death without requiring testing to confirm infection (provided “the circumstances are compelling within a reasonable degree of certainty”).
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Scientific Advisor: LFM-Healthcare Solutions, LLC provides medical expertise and guidance for healthcare facilities (hospitals), device manufacturers and legal representatives of the public, specializing in medical device designs and both the causes and prevention of healthcare-associated infections linked to medical equipment.
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Data validation: In health care, validation can be a critical tool for confirming the quality of safety data. According to the CDC, validation is “double-checking, or confirming” the accuracy and completeness of reportable infection data. Central line-associated bloodstream infections are reportable data that have been validated for years to assess accuracy and the potential for inadvertent reporting bias.
A 2017 inspector general report states that “accurate data are fundamental to the integrity of the (Centers for Medicare and Medicaid Services’) quality-based payment programs,” adding that the reporting of imprecise data could affect payment accuracy. Infection data can be validated using different methodologies (e.g., “external validation”). In 2012 the CDC published guidance for the validation of central line-associated bloodstream infections in intensive care units.
Validation of death certificate data associated with the COVID-19 disease, for instance, might involve reviewing a statistically reliable and randomly selected sample of patient medical records (or autopsy findings) to evaluate their consistency with the associated death certificate documentation and data, or another model type might be used instead. Death certificates state a certifier’s medical opinion and therefore can have mistakes, especially if a pathogen (like COVID-19) was listed as the cause of death of a decedent who was not tested to confirm infection.
CONCLUSIONS, SUMMARY: This review’s findings suggest that the standards and measures the CDC’s guidance uses for recording deaths that could be due to COVID-19 may not be consistent in some respects with the practices and paradigms that health officials in the U.S. have used at times to assess the potential contribution of a superbug infection to patient death.
Whereas the CDC’s April guidance permits specifying COVID-19 on the death certificate if it “played a role in the death” or is “assumed to have caused or contributed to death” (as well as, of course, if the disease “caused” death), several reviewed superbug cases suggest adoption of an apparently different paradigm for causal plausibility, with health officials reporting that mortality “was not necessarily attributable” to the superbug infection, that the role of the superbug infection in death “is unclear,” or that the infected patient’s death was due to underlying medical conditions.
That a comorbidity could potentially hinder or interfere with clinical assessments of the role played by a pathogen, at least apparently a superbug, in an infected patient’s death is salient, particularly in today’s context of certifying and recording COVID-19 as a cause of death in patients with comorbidities. None of the reviewed superbug cases (which are discussed in more detail in the full article) concluded that the superbug infection caused or directly contributed to patient death.
Moreover, lacking confirmatory testing, it therefore becomes plausible that, in some cases, adherence to the CDC’s guidance could result in recording COVID-19 on the death certificate of a decedent not infected with the virus (since this guidance does not, under all circumstances and as a prerequisite, require testing to confirm infection).
Also suggesting the application of differing rules, public health definitions and requirements in the U.S. for reporting an influenza-associated death require confirmation of influenza virus infection using an appropriate laboratory or rapid diagnostic test. As discussed in this article, however, the CDC’s April guidance, like the case definition for COVID-19, does not require confirmatory testing to record COVID-19 as a cause of death.
If in the future the criteria and policies for reporting and recording the cause of death of an infected patient became more standardized — for example, requiring confirmatory testing to ensure infection, or specifying the infection on the death certificate as long as it either contributed to or likely played a role in death — could have potentially significant impact on public health and infection prevention. (In 2016, a California state senator introduced a bill that would require clinicians to record antibiotic-resistant infections on death certificates if the superbug “played a role in the death,” the Los Angeles Times reported at that time.)
In closing, this article focuses on assessments of the cause of death associated with superbugs and COVID-19, understanding there are important differences between bacteria and viruses. Enhanced efforts to improve surveillance for antibiotic resistance and advance public awareness about superbug infections, particularly during today’s COVID-19 pandemic, are recommended to understand with greater accuracy the impact, mortality and costs of primary and secondary superbug-related infections in patients with and without underlying medical conditions.
LIMITATIONS, COMMENTS: This article has several limitations. First, it is a shortened version of the complete article, which will be published soon. Second, the several superbug outbreak investigations that this article identified for reviewed could have conceivably introduced inadvertent publication bias and error into its methodology and findings due to the lack of randomization, although this is unlikely and efforts were taken to avoid such bias.
Third, it is recognized that: (a) assessments of the cause of death of a patient infected with a superbug, the COVID-19 virus, or another pathogen can be complicated and more challenging in the presence of pre-existing underlying health conditions; and (b) the circumstances surrounding this discussed superbug cases may be significantly different in important respects than the discussed cases discussing COVID-19 and influenza, which might, possibly, justify the application of different standards. The characteristics of bacteria and viruses can be markedly different.
Fourth, an association between an infection and the use of medical equipment does not indicate the equipment caused the infection. Fifth, the rationale for the CDC’s April guidance not mandating, as a prerequisite, confirmatory testing to record COVID-19 infection as the cause of death was not investigated. Fifth, the percentage of recorded deaths attributed to COVID-19 that may have been due instead to a comorbidity (and/or were associated with someone not infected with the virus) could not be evaluated.
Sixth, the justification for this federal COVID-19 guidance to appear to differ in certain respects from the practices and standards health officials have used in the past to assess the role that a superbug infection may have played in patient death also was not investigated.
Last, also not studied were the clinical and diagnostic similarities and differences between COVID-19 and the influenza viruses (which are not coronaviruses), or the impact that data validation might have on published mortality rates of either COVID-19 or superbug-related infections.
Article by: Lawrence F Muscarella, PhD. Posted August 2020. Copyright (2020). LFM Healthcare Solutions, LLC. All rights reserved. Dr. Muscarella is the president of LFM Healthcare Solutions, LLC, an independent quality improvement company. Click here for more details about his quality improvement healthcare services.
Case Reviews, Expert “On-Call” Consulting Services: LFM-Healthcare Solutions, LLC provides medical expertise and guidance for healthcare facilities (hospitals), device manufacturers and legal representatives of the public, specializing in the causes and prevention of healthcare-associated infections linked to medical equipment.