When the body detects a viral infection, the immune system responds by attacking the infected cells. Sometimes, the immune system can overreact to an infection, leading to inflammation, tissue damage, organ failure, and even death. This reaction by the immune system to an infection is referred to as sepsis. Each year, sepsis impacts an estimated 47-50 million people and is responsible for at least 11 million deaths. Most sepsis cases are caused by bacterial infections, but any viral, fungal, or parasitic infection can also cause sepsis.

A study published in the European Journal of Clinical Microbiology & Infectious Diseases concluded that viral infections are under-diagnosed in patients with sepsis or septic shock. In a paper for Frontiers in Immunology, the authors write that, “Up to 42% of sepsis presentations are culture negative, suggesting a non-bacterial cause. Despite this, diagnosis of viral sepsis remains very rare.” However, the initial standard of care for all cases of sepsis, even those that are subsequently proven to be culture negative, is the immediate use of broad-spectrum antibiotics. They go on to state, “[T]his inevitably leads to unnecessary antimicrobial use, with associated consequences for antimicrobial resistance, effects on the host microbiome and excess healthcare costs.” Because bacterial and viral infections can cause similar symptoms such as weakness, fever, and muscle pain, diagnostic tests in this setting can be critical for distinguishing between infections. Diagnostic tests also support the judicious use of antimicrobials in cases of sepsis by providing the information needed for clinicians to determine which type of antibiotic is right for the patient. 

The COVID-19 pandemic has led scientists to further explore viral sepsis due to a a high number of patients with severe COVID-19 having sepsis symptoms. The most common site of infection among patients with sepsis is the respiratory tract (64–68%). In critical cases of COVID-19, patients suffer from respiratory failure or other organ dysfunction. Two major complications of COVID-19 are immunosuppression and hyperinflammatory response. 

A pre-print meta-analysis found, “a considerable proportion of patients with COVID-19 present viral sepsis.” The authors also noted that some complications from severe COVID-19 may be unique to the disease, while others are common features of both viral and bacterial sepsis.

Although the current understanding of the pathophysiology of sepsis has improved, viruses as pathogens of sepsis have not received attention in proportion to their healthcare burden. The pandemic highlights why it is important to consider viral causes in septic patients when lacking evidence of bacterial, parasitic, or fungal infection.

To better diagnose and treat viral sepsis, additional research will be necessary. “Future studies should not only focus on understanding the host immune response in the development of sepsis, especially viral sepsis, but also explore how to stratify patients into more homogeneous subgroups on the basis of their pathophysiology,” say the authors of an article in European Respiratory Review. “The identification of biomarkers that can differentiate who might benefit from a specific intervention can help the application of new treatments into clinics with monitoring the effects of future therapies.”

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