Alleviating the Health, Economic, and Human Burden of Sepsis and the COVID Pandemic 

We know that every three seconds, one person shockingly dies of sepsis worldwide. Seventy-five percent of the survivors suffer long-term effects. People experiencing poverty were affected more than anybody else. However, amid the global health emergency of COVID-19, there is now an opportunity to create a platform that strengthens the entire health system to address the burden of infectious and non-communicable diseases. 

Understanding Sepsis Will Alleviate This Hidden Public Disaster

Sepsis is a leading cause of morbidity and mortality worldwide. In hospitals, it is one of the primary reasons for admission to intensive care units (ICUs) and is associated with a higher risk of death compared to other conditions. 

Sepsis rates are especially higher in low- and middle-income countries (LMIC), where limited resources, inadequate infection control practices, and challenges in accessing healthcare contribute to a higher burden of infectious diseases. 

Moreover, the COVID-19 pandemic only exacerbated the burden of sepsis on healthcare systems around the world. The SARS-CoV-2 infection was a significant cause of sepsis. 

As Dr. Carolin Fleischmann-Struzek, a physician-scientist from Jenny University Hospital, Germany pointed out, “Approximately one out of three hospitalized COVID-19 patients is affected by sepsis. The burden is very high, but we still lack knowledge of the population incidence of sepsis in most countries, particularly LMIC. Therefore, sepsis was called a hidden public health disaster, and the World Health Organization (WHO) had urged all member states to improve the knowledge on the epidemiology in the database for that area of research.” 

To illustrate the burden of sepsis, Dr. Fleischmann-Struzek said that the global burden of sepsis study estimated that every year, 49 million patients are affected by sepsis worldwide, more than four times that of stroke cases annually. 

“That is equivalent to 677 cases per 100 000 population, and half of these cases occur in children, mostly under five years. So, sepsis is really a huge public health burden,” she added. 

A better understanding of sepsis will alleviate the health, economic, and human burden of sepsis. At the recent 4th World Sepsis Congress, Keith Martin, Consortium of Universities for Global Health, United States of America led a panel discussion featuring:

• Carolin Fleischmann-Struzek, Jena University Hospital, Germany
• Syed Masud Ahmed, BRAC University, Bangladesh.
• Tim Buchman, Emory University School of Medicine, United States of America.
• Roy Small, United Nations Development Programme, United States of America.
• Rob Yates, Chatham House, United Kingdom. 

To listen to and receive continuing medical credits for this World Sepsis Congress session on the health, economic, and human burden of sepsis and the COVID Pandemic, please click here.

The Global Burden of Sepsis

Another recent global burden of disease study estimated that in 2019, the number of sepsis-related death was around 13.7 million deaths, and more than 50 percent of sepsis-related death are caused by just five pathogens, namely Staphylococcus aureus, Escherichia coli, Streptococcus pneumonia, Klebsiella pneumonia, and Pseudomonas aeruginosa. 

About six million deaths are estimated to be caused by three bacterial infectious syndromes: lower respiratory tract infections, bloodstream infections, and peritoneal and intra-abdominal infections. 

These episodes have important implications for sepsis prevention, such as improving hygiene standards, vaccination, and providing acute care services. According to Dr. Fleischmann-Struzek, the successes of these preventive methods have helped reduce sepsis mortality in the last 30 years by 30 percent in LMIC countries.

However, the number of sepsis admission continues to rise. 

For instance, in the case of the US, Dr. Timothy George Buchman, Director of Emory Healthcare Critical Care Center, explained the increase (see the figure below).  

“The sepsis at-risk population that we are going to be speaking of are those adults 65 or older and those with chronic conditions. Let us look at the Medicare sepsis rates just prior to the pandemic. We can see that the number of sepsis emissions was steadily increasing from the bottom of the slide up as the Medicare Advantage (MA), then the fee for service (FFS), and then the solid line is total. The solid total line shows the system was admitting close to hundred and fifty thousand patients each month diagnosed with sepsis.”

The burden of true sepsis epidemiology assessment

Despite the high occurrences, understanding the true burden of sepsis is complicated by the lack of detailed and evidence-based estimates of the cause and burden of sepsis. The sepsis incidence and mortality varied substantially across regions, with the highest burden in the sub-Saharan region, further limiting the monitoring of sepsis epidemiology in these countries. 

“When we talk about the global burden of sepsis, it is also important to keep in mind that most sepsis cases and the majority of sepsis-related mortality occur in LMIC with sepsis mortality rates up to 10 times higher than in high-income countries,” said Dr. Fleischmann-Struzek. “A recent systematic review and meta-analysis found that sepsis patients in these countries are younger and predominantly HIV infected compared to cohorts from high-income countries and that sepsis mortality is higher in cohorts with a higher proportion of HIV infected patients.” 

Dr. Fleischmann-Struzek therefore advised, “The most common pathogen related in blood cultures was mycobacterium tuberculosis. It means treating sepsis in LMIC may need other strategies for antibiotic treatment, for example. Therefore, it is important to better understand the underlying pathogens’ risk groups and long-term outcomes in these regions.”. 

Another major challenge in assessing sepsis epidemiology is the lack of studies in community-based designs or among long-term survivors to assess long-term outcomes. 

“Existing studies on sepsis epidemiology are limited in their comparability and validity, given that study designs differ vastly among the studies. Data sources are barely comparable. Furthermore, we lack standardized sepsis definitions and definitions that can be applied in all settings, including resource-restricted settings,” she said. 

Compounding the challenge further is the need for standardized and complete recording and reporting of outcomes in such studies. 

Dr. Fleischmann-Struzek cautioned, “Many studies in high-income countries rely on administrative data with inherent limitations as these data are collected for reimbursement rather than research purposes. They only mirror the proportion of sepsis cases with diagnosed and coded sepsis, which can lead to underestimating sepsis cases.”.

Extended health consequences

Sepsis is not only burdensome in terms of acute mortality, but survivors often suffer from significant long-term impairments in the physical, cognitive, and psychological domains. 

Common new impairments were neuromuscular, musculoskeletal, and cardiovascular diseases, cognitive impairments, and fatigue. Depression anxieties were also common. These are like Long COVID” or “Post-COVID Conditions (PCC).” 

The 12th-month mortality was also high. “More than 30 percent of patients died within the 12th month after sepsis,” she added. 

Increased dependency on nursing care 

“Using health claims data of around 23 million insurance holders from a large health insurance in Germany, we found that three out of four survivors suffer from new impairments in the 12th month after sepsis. These impairments are often overlapping and commonly lead to new nursing care dependency. One-third of survivors without pre-existing nursing care dependency required such care at the 12-month of sepsis and 25 percent of survivors who previously worked were not able to resume work in the first year after that disease,”explained Dr. Fleischmann-Struzek. 

The extended health consequences implied that the number of sepsis survivors that need structured aftercare or rehabilitation would be high, and there is an urgent need to develop strategies to care for these patients and set structures in the healthcare system for their demands.

The economic burden on the individual and public health

Sepsis patients are generally treated in intensive care units (ICUs) for close supervision and intensive care treatment by a competent team. with adequate equipment can be provided. Besides staffing costs representing 40% to >60% of the total ICU budget, there is also a high proportion of fixed costs in ICU treatment. The total cost of ICU care mainly depends on the ICU length-of-stay (ICU-LOS). 

“The monthly cost of sepsis during inpatient admissions and as you can see in the United States for Medicare has reached as high as two billion dollars during the winter of 2017-18. We had hoped that these costs were coming down, which you can refer to in the lower panel, the cost per admission. Unfortunately, by the time we got to 2016, those costs were on the rise.” Dr. Buchman said, using the U.S. Medicare system to explain the cost burden.

In 2013, Torio and Moore calculated that the national cost, which includes Medicare and all the other payers, was about 23.7 billion, with Medicare accounting for 14.6 billion.   

“We continued to study this, and we found that even though those present on admission is plateauing around 2015, the cost per case continued to rise,” Dr. Buchman said. See Figure 6 below.

Projecting this forward using a conservative number to include the aging of the United States population in the 2018 paper, Dr. Buchman said the total inpatient cost for the United States is not 4 billion but, in fact, 53 billion dollars. 

Using the additional Medicare data leading into the pandemic, Dr. Buchman and his team refined their projection into the actual cost instead of 16.5 billion (see Figure 6 above). It brings the actual costs and the projections aligned at about 22.9 billion in 2019 (see below).

“When we move those numbers out to the entire U.S. population, we estimate that the 2019 cost of sepsis was not 24 billion but in fact 57.5 billion dollars in the United States for sepsis for 2019,” he explained (see Table 2 below).

A decreased number of non-sepsis admission over the years also drives the high-cost sepsis cost projections. (see the figure below).

“It turns out that the population that we’re seeing in hospitals is changing. I’ve plotted here on two axes on the left in brown which are the total number of admissions per month per million enrolled beneficiaries. Those are the non-sepsis submissions in brown down up to 25 000 per million enrolled beneficiaries over time, declining over the seven or eight years shown here. In Black, the count of the sepsis admissions shown on the right Axis is rising and what it shows is that we are losing significant numbers of non-sepsis patients. Those elective patients are going elsewhere outside the hospital,” he explained.

“The sepsis inpatient admissions are rising almost doubling the rate of Medicare beneficiary population growth. Though the cost per admission was declining, then started to rise again prior to COVID. The total cost burdens of society remain unknown, but we continue to underestimate those costs,” he cautioned.

Lessons from COVID-19

COVID-19 tested the global health systems and emergency preparedness.

“COVID-19 laid bare the weaknesses of the health systems of South Asia from poor infrastructure and poor investments in terms of service where the non-COVID-19 services suffered greatly,” Professor Syed Masud Ahmed cited the case for South Asian countries. He is the Director of the Centre of Excellence for Health Systems and Universal Health Coverage (UHC) at BRAC University, Bangladesh. 

“There was a huge shortage of human resources for health who are trained, motivated, and well-resourced. The MIS fails to provide the right information at the right time for action, poor risk communication. There’s also a shortage of medical products and stuff, hence the failure to provide common supplies like masks and gloves, not to mention PPE and ventilators. There’s a lack of lab resources to measure properly the exact tool of this Covid-19 in terms of morbidity and mortality Financing allocation was not aligned to meet most needs, and there were problems in leadership and governance,” he added. 

Although WHO declared an end to COVID-19 global health emergency on May 5, 2023, Roy Small, Consultant with United Nations Development Program (UNDP), advised the global health system to remain sustainable and better prepared for another pandemic that may come sooner than we would like to think. 

“Half the world lacked access to essential health services before COVID and still lacks it now. We know that the pandemic halted or reversed UHC virtually everywhere and vaccine inequity shined a spotlight on our failures in universalism and solidarity.” 

“The Sustainable Development Goals (SDGs) were not on track, and six of seven people worldwide felt insecure, and the rich in poor countries alike. This means that we need to dig deeper for our explanations and revisit our prevailing development models and approaches. UHC can help us achieve goals within and beyond health,” he added.

Mitigate by advancing UHC for the SDGs

With sepsis prevalence in the LMIC regions and the longstanding health effects, it can exacerbate healthcare costs, plus potential loss of income because of poor health in the case of severe sepsis. As part of SDG Target 3.8, UHC laid out a pathway to financing the needed cost of care and health services. More importantly, the prospect of establishing public health systems from health promotion to ensuring equitable acute and chronic disease management for all is in view. Besides protecting financial risk for the individual, UHC provides the same for public healthcare costs.

“To understand the importance of UHC to our economics, I would also say look at the COVID-19 pattern. The IMF forecasts that the pandemic will cost the global economy 12 and a half trillion dollars through 2024. Now that is more than the estimated annual cost to finance the SDG agenda in full. The numbers that were put out earlier around 2015 were around five to seven trillion dollars and it is now 500 times as much as some have estimated pandemic prevention measures would have cost us. UHC together with pandemic preparedness I hope can help us to once and for all reframe health as an investment and not a cost,” Roy explained. 

Expounding further that there is now an opportunity to pair urgent action for UHC with similarly urgent action to achieve the Paris Agreement, Rob added that UHC would also help reorient development approaches around healthy societies and planetary health, preserving the environment we live in and depend on.

In addition, many are seeing UHC as one of the best drivers to improve health security, according to Robert Yates.

Director, Global Health Program and Executive Director, Centre for Universal Health at Chatham House, U.K. While the motivations are clear, the transition to UHC is a colossal effort.

“If we think about transitions to UHC, you need to reform all your health systems, the access to medicines, human resources and infrastructure, governance, I.T. systems but the one you absolutely must get right is your health financing system. Particularly if you’re going to have this universal access to services and universal financial protection,” Rob said. 

“Logically the only way that you can do that is through a predominantly publicly financed health system,” he added. 

“What’s also interesting about these transitions to UHC is that they don’t tend to be very smooth, the replacement of private financing by public financing. You get countries making big sort of jumps when they suddenly put a lot of money into their health system to try and improve access and reduce impoverishment. These big jumps are very much associated with interventions that are made at the head of the state level.”

Taking it forward

“First there’s a need for better or more advocacy and funding for generating evidence in sepsis epidemiology. We need to achieve consensus on a sepsis case definition for sepsis surveillance and epidemiological research that can be applied globally,” Dr. Fleischmann-Struzek. 

“We need new or Advanced databases for sepsis epidemiology research and the better and more accurate ICD-coding and standards for sepsis epidemiology studies and core outcomes to make their outcomes comparable,” she added. 

“We saw those pneumococci, for example, caused so many sepsis deaths and can be prevented by vaccines. So that’s a potential we should use in the future.”  

Dr. Fleischmann-Struzek’s emphasis on fostering prevention, primarily through vaccination and hygiene, is backed by Dr. Buchman. 

“We cannot fix sepsis once it’s established. It’s very hard to mitigate. Prevention is our best and I would argue our most important pathway is involving this public awareness campaigns, vaccination, and early mitigation strategies as soon as the host responds to infection and appears to be losing control. Awareness and prevention are key,” he added. 

Dr. Buchman agreed with Rob and Roy that UHC should be set high on the health policy agenda, but it is imperative to make sepsis prevention a social norm for the populace. “We often overlook the fact that politicians can create policy and provide funding but unless the populace is fully engaged, those expenditures will not be as effective as they might be. So, it really must be partially grassroots, but we have to find a way of joining our leaders and our followers in this common cause.” 

To listen to and receive continuing medical credits for this World Sepsis Congress session on the health, economic, and human burden of sepsis and the COVID Pandemic, please click here. 

Authors: Joyce See (Healthcare Writer, Physician-Patient Alliance for Health & Safety) and Michael Wong, JD (Executive Director, Physician-Patient Alliance for Health & Safety)