Fungal Infections Plague Intensive COVID-19 Units

In global crises like the COVID-19 pandemic, responses naturally focus on minimizing the impact of the primary pathogen at hand. As a result, it’s easy to overlook some of the secondary consequences of the pandemic. 

"C. auris survives and transmits particularly well in crowded hospital settings with long-term patients undergoing multiple procedures for concurrent health conditions."

The Centers for Disease Control and Prevention (CDC) recently alerted health care providers of emerging infectious outbreaks of the fungal opportunist Candida auris. An alarming number of outbreaks were reported in COVID-19 units both in the United States and internationally, serving as a stark reminder that a pandemic’s challenges are not limited to the primary pathogen at hand. 

We must also account for changes in health care settings that enable opportunistic pathogens to wreak havoc on susceptible populations. The severe nature of these outbreaks demands a concerted effort by health care providers to enhance preventative measures, enact efficient surveillance and identification protocols, and facilitate swift responses to reduce patient morbidity and mortality in the face of an outbreak.

 A problematic environment: What is Candida auris?

C. auris outbreaks have steadily increased since the pathogen was first identified in 2009. The organism is characteristically described as an opportunistic fungal pathogen that can cause invasive infections of the bloodstream in susceptible individuals. Though C. auris preceded the COVID-19 pandemic, it is almost always associated with nosocomial transmission, i.e., infections acquired while receiving care in a health care setting. 

C. auris survives and transmits particularly well in crowded hospital settings with long-term patients undergoing multiple procedures for concurrent health conditions, often including invasive medical devices such as central venous catheters that readily provide a route of infection.

The COVID-19 pandemic has, by necessity, brought rapid and often dramatic changes to hospital settings during surges of viral transmission. Intensive care units (ICUs) in hard-hit areas were filled to capacity with the sudden influx of severely infected patients, demanding the conversion of some ICUs into specialized COVID-19 units. Patients with severe symptoms often require extended stays, immune-inhibiting corticosteroids, and a myriad of invasive procedures while providers grapple with shortages in medical supplies and PPE. 

"Of the patients with candidaemia (fungal infection of the bloodstream), there was an 83.3 percent mortality rate." 

As evidenced by numerous reported outbreaks in COVID-19 units, these sudden changes in health care settings create an ideal environment for the rapid spread of C. auris, often with devastating consequences in affected patients.

In May 2020, a patient in an ICU in Mexico tested positive for C. auris during the hospital’s transition to an exclusive COVID-19 facility. Over several months, an outbreak was confirmed in 12 COVID-19 patients in the same facility. Notably, all patients were using ventilation devices and had central lines for COVID-19 treatment. Of the patients with candidaemia (fungal infection of the bloodstream), there was an 83.3 percent mortality rate. 

In the US, 52 percent of patients admitted to the COVID-19 unit of an acute care hospital in Florida in August 2020 tested positive for C. auris. Of those who had available medical records, eight patients (40 percent) died within a month of screening, though it is unclear whether fungal infection was directly responsible in these cases. The CDC similarly reports a high mortality rate of 30–60 percent, but it is difficult to discern the role of patient comorbidities as contributing factors.

These outbreaks are just a few examples of many outbreaks in COVID-19 units around the world, demonstrating the dangers of long-term hospitalization for the most vulnerable patients. Similar reports of C. auris infections have appeared from units in South America, the Middle East, and long-term care facilities in the US. The alarming scale of these outbreaks has prompted widespread investigations into the genetic origins of isolated strains and the efficacy of commonly used antifungals for treatment.

A resistance problem: How do you kill Candida auris?

Just as antibiotic resistant bacterial infections plague the health care system, emerging fungal pathogens such as C. auris exhibit concerning resistance to antifungals. 

Three major classes of antifungals are commonly used to treat invasive infections: azoles, polyenes, and echinocandins. A large proportion of C. auris isolates in the US are resistant to azoles and polyenes, while only approximately 1 percent are resistant to echinocandins, making echinocandins critical for treatment of these infections. 

"Pan-resistant strains have already been isolated from ICUs in New York, Texas, and Washington, DC."

Thus, the appearance of echinocandin-resistant C. auris strains, especially in combination with azole and polyene resistance (pan-resistance) is of significant concern. Pan-resistant strains have already been isolated from ICUs in New York, Texas, and Washington DC.

Among 101 screened cases of C. auris in a long-term care unit in Washington DC, three patients had an isolate that was pan-resistant. Another long-term facility in Texas screened 22 cases of C. auris, and found that two patients were colonized with pan-resistant strains, and an additional five patients had strains with multidrug resistance. 

In the aforementioned COVID unit outbreak in Mexico, approximately half of the screened isolates were multidrug resistant. These findings indicate that our current antifungals will often fail to control outbreaks, and novel therapeutics will be necessary to treat infections with pan-resistant strains.

Meeting the challenge of Candida auris outbreaks

The emergence of C. auris infections in susceptible COVID-19 patients demands that health care providers enact preventative measures to protect vulnerable patients. 

"Current PPE and sanitation strategies provided ample opportunity for contamination, indicating a need for additional training and improved adherence to standardized practices to improve prevention."

After Florida’s first case of C. auris was identified in 2017, the state implemented screening and contact tracing in an effort to prevent its spread. Incoming intensive care patients were screened, and those that were colonized were isolated in a separate ward to prevent nosocomial transmission to susceptible patients. Nonetheless, crowded hospital conditions during the pandemic allowed an outbreak to occur, highlighting the challenges facing health care providers. A CDC investigation of the outbreak found that current PPE and sanitation strategies provided ample opportunity for contamination, indicating a need for additional training and improved adherence to standardized practices to improve prevention.

It is also critical that effective therapeutic options are available, particularly for patients infected with multidrug- or pan-resistant C. auris. Recent studies have shown that some pan-resistant isolates are susceptible to combination antifungal therapy, but it’s likely that the emergence of newly resistant strains will demand the innovation of new antifungals.

 The COVID-19 pandemic has changed ICUs around the world, forcing them to accommodate high patient volumes under the strain of severe resource shortages. In doing so, opportunistic and often drug-resistant C. auris outbreaks have run rampant in susceptible patients. This threat demands careful attention to surveillance and prevention strategies, as well as new treatment approaches to minimize morbidity and mortality of vulnerable populations.