Sepsis Opportunities: Lessons from the COVID-19 Pandemic

Sepsis is the body’s extreme response to an infection. It is a life-threatening medical emergency. Sepsis happens when an infection you already have triggers a chain reaction throughout your body. Infections that lead to sepsis most often start in the lung, urinary tract, skin, or gastrointestinal tract. Without timely treatment, sepsis can rapidly lead to tissue damage, organ failure, and death.

The ongoing COVID-19 pandemic has caused hundreds of millions of infections, millions of deaths, and disrupted daily life worldwide¹. Thanks to the combined work of countless scientists, medical professionals, and epidemiologists, we have rapidly learned about the pathogenesis, prevention, and treatment of this disease. Severe COVID-19 is characterized by the body’s extreme reaction to the infection, which means it could be considered as a form of sepsis requiring specific interventions, as well as typical sepsis supportive care². Many hospitalized COVID-19 patients are diagnosed with sepsis. For Sepsis Awareness Month 2021, we can draw several lessons from global efforts to track and mitigate the impact of COVID-19, or SARS-Cov-2 infection.

Preventing Infections

The COVID-19 pandemic has highlighted the valuable role of thoughtful, evidence-based policies and layered intervention strategies for preventing infections and improving safety in communities, places of work, places of worship, schools, and healthcare settings. These include the use of face masks when appropriate, increased attention to hand hygiene, and staying home when sick — all of which are strategies that prevent the transmission of SARS-CoV-2 and other kinds of infections. Implementing these actions in high-risk settings will help prevent infection overall, and therefore sepsis.

In addition, the rapid development of COVID-19 vaccines gives hope that similar technologies will form the basis for devising novel prevention strategies for other infectious diseases that lead to sepsis in both high- and low-resource settings around the world. A renewed emphasis on infection prevention practices in healthcare settings highlights the importance of protecting patients and the healthcare workers responsible for their care.

Classifying Sepsis to Inform Treatment 

Treatment has become increasingly specific and tailored over the course of the COVID-19 pandemic. The treatment of severe COVID-19 is evolving, but may include corticosteroids or other immune modulators, antiviral therapies, and specific approaches to respiratory dysfunction³. These interventions directed specifically at COVID-19 have differences from typical sepsis bundled care.  Seeing the improvements in COVID-19 treatments over time, it stands to reason that a more nuanced understanding of sepsis — with more rapid identification of the bacteria or virus causing the infection, a deeper understanding of how the infection started, and more tailored therapies — may improve the care of sepsis from other infections as well.

A more targeted approach may also reduce unnecessary use of antibiotics. Any antibiotic use contributes to antibiotic resistance, which makes sepsis more difficult to treat. Improving antibiotic use helps preserve the effectiveness of antibiotics when patients, like those who have sepsis, need them most. Unfortunately, for most patients with sepsis, clinicians are often unable to identify the bacteria or virus causing the infection. They are also often unable to identify it for several days after the onset of illness, which reduces the opportunity to quickly tailor treatment to address the specific infection⁴. The specific interventions recommended for COVID-19 treatment remind us that improvements in diagnostic technologies, particularly tests that can rule out bacterial infection, could help clinicians better focus on specific treatments for the causes of sepsis and contribute to improvements in appropriate antibiotic use.

Care for Sepsis Survivors

Many long-term effects of COVID-19 have been described, including fatigue, difficulty thinking or concentrating, shortness of breath, cough, chest pain, and diarrhea. Thus far, clinicians have drawn upon knowledge gained from treating the long-term health conditions seen in sepsis survivors to understand these patients and to develop post-acute care clinics where their symptoms are recognized and treated⁵. As we learn more about identifying and treating post-COVID conditions, some of this knowledge may, in turn, translate to the care of all sepsis survivors.

Health Equity and Vulnerable Populations

The COVID-19 pandemic has brought health disparities to the forefront with many communities of color experiencing higher infection, hospitalization, and death rates⁶. Similar disparities in sepsis identification, treatment, and outcomes have been described in communities of color^{7, 8}. While the causes may be multifactorial and complex, it is important to continue to identify disparities in patients with sepsis to inform targeted efforts and use various approaches to improve health equity.

Recognition early in the pandemic of the tremendous challenges faced by long-term care facility (LTCF) residents and staff led to increased focus on early identification of COVID-19 infection, health education, and infection prevention and control efforts in those settings. Similarly, better sepsis care and prevention can be achieved by including LTCF personnel in broader sepsis efforts.

Health Informatics and Collaborative Research

Before the pandemic, a growing number of hospitals were incorporating technologic advancements and machine learning approaches to aid in the prediction of sepsis onset and outcomes⁹. These approaches hold tremendous promise for reducing sepsis deaths and severe illnesses. Advances in data system interoperability, accelerated by the urgent need to track COVID-19 cases and outcomes, could help to move these efforts forward and improve the retrospective tracking of sepsis incidence and outcomes. Healthcare settings could leverage improved accuracy in sepsis screening and surveillance to improve the quality of sepsis care provided to patients.

In addition to highlighting areas for improvement in data collection and utilization, the pandemic has spurred large multinational collaborative research networks that have rapidly tested COVID-19 therapeutics^{10, 11}. Such networks, if continued, could be very useful for advancing new strategies to treat and manage sepsis.

Conclusion

The ongoing COVID-19 pandemic has brought immense suffering and disruption around the world. It also presents a unique challenge and opportunity for deepening our knowledge of how an infection originates, how to care for sepsis patients, and how to structure healthcare systems that can lead to improved infection prevention, reduced deaths and severe illness caused by sepsis, and better care of sepsis patients and survivors.

1. World Health Organization. Coronavirus Disease (COVID-19) Pandemic. Accessed August 20, 2021. https://www.who.int/emergencies/diseases/novel-coronavirus-2019
2. Shappell CN, Klompas M, Rhee C. Does Severe Acute Respiratory Syndrome Coronavirus 2 Cause Sepsis? Critical Care Medicine. Dec 2020;48(12):1707-1709. doi:10.1097/ccm.0000000000004601
3. National Institutes of Health. What’s New in the Guidelines. Accessed August 20, 2021. https://www.covid19treatmentguidelines.nih.gov/about-the-guidelines/whats-new/
4. Fay K, Sapiano MRP, Gokhale R, et al. Assessment of Health Care Exposures and Outcomes in Adult Patients With Sepsis and Septic Shock. JAMA Network Open. 2020;3(7):e206004-e206004. doi:10.1001/jamanetworkopen.2020.6004
5. Prescott HC, Girard TD. Recovery From Severe COVID-19: Leveraging the Lessons of Survival From Sepsis. JAMA. 2020;324(8):739-740. doi:10.1001/jama.2020.14103
6. Centers for Disease Control and Prevention. Risk for COVID-19 Infection, Hospitalization, and Death By Race/Ethnicity. Accessed August 20, 2021. https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-death-by-race-ethnicity.html
7. Raman J, Johnson TJ, Hayes K, Balamuth F. Racial Differences in Sepsis Recognition in the Emergency Department. Pediatrics. 2019;144(4):e20190348. doi:10.1542/peds.2019-0348
8. Jones JM, Fingar KR, Miller MA, et al. Racial Disparities in Sepsis-Related In-Hospital Mortality: Using a Broad Case Capture Method and Multivariate Controls for Clinical and Hospital Variables, 2004-2013. Critical Care Medicine. Dec 2017;45(12):e1209-e1217. doi:10.1097/ccm.0000000000002699
9. Goh KH, Wang L, Yeow AYK, et al. Artificial intelligence in sepsis early prediction and diagnosis using unstructured data in healthcare. Nature Communications. 2021/01/29 2021;12(1):711. doi:10.1038/s41467-021-20910-4
10. World Health Organization. WHO COVID-19 Solidarity Therapeutics Trial. Accessed August 20, 2021.https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments
11. REMAP-CAP Investigators. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.New England Journal of Medicine.2021;384(16):1491-1502.doi:10.1056/NEJMoa2100433.