Spotting Invasive Pulmonary Aspergillosis In COVID-19 Patients

Professor Arunaloke Chakrabarti
Head, Department of Medical Microbiology
Postgraduate Institute of Medical Education and Research
Chandigarh, India, and
President, International Society for Human and Animal Mycology

One of the complications of coronavirus disease 2019 (COVID-19) is secondary infection, and recent reports from several countries show that patients in the intensive care unit (ICU) with COVID-19 are indeed at risk of developing COVID-19-associated pulmonary aspergillosis (CAPA).^1,2

To address this concern, Verweij et al published Diagnosing COVID-19-associated pulmonary aspergillosis on behalf of the European Confederation of Medical Mycology, the International Society for Human and Animal Mycology, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group, and the ESCMID Study Group for Infections in Critically Ill Patients. The article provides current data on CAPA – its incidence, relevant challenges and some recommendations moving forward. Below are some of the article’s key points.

Recent reports on CAPA in ICU patients

In Europe, CAPA was reported in patients admitted to the ICU: 26% of 19 patients in a center in Germany³; 33% of 27 patients in a center in France⁴; and 19% in 31 patients in a center in The Netherlands.⁵

In China, earlier reports suggested that 7 patients (3%) were diagnosed with fungal infections in a cohort of 221 patients with COVID-19.⁶ However, because galactomannan (GM) testing is not widely available in the country, the causative fungal pathogens were not identified, and the real incidence of CAPA was likely underestimated by the report.¹

A retrospective study reported in a letter to the editor from Lei et al in China reported that patients with severe COVID-19 demonstrated high rates of positive GM, emphasizing that concomitant fungal infection in these patients is very probable, and is likely correlated with age. The rates of positive GM were higher in patients aged ≥50 years old than in those aged 20–49 years.²

 

“Patients with severe COVID-19 demonstrated high rates of positive GM; concomitant fungal infection in these patients is very probable”

Challenges in diagnosing CAPA

Diagnosing CAPA can be challenging for various reasons. For instance, GM sensitivity is lower in patients with COVID-19 than in those with influenza, possibly because of exposure to chloroquine, but the exact causes are unknown.¹

In addition, many patients with CAPA did not have the European Organization for the Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) host factors for invasive aspergillosis, which increases the risk of a missed diagnosis.^1,3

According to recommendations from the American Association for Bronchology and Interventional Pulmonology (AABIP), there is restricted role of bronchoscopy in patients positive for COVID-19 due to aerosol generation. Therefore, collection of upper respiratory samples is the preferred method for collecting respiratory specimens in patients with confirmed or suspected COVID-19 infection; in intubated patients, on the other hand, tracheal aspirates and nonbronchoscopic alveolar lavage are preferred.⁷

Bronchoalveolar lavage GM testing should not be routinely done, as bronchoscopy is an aerosol-generating procedure that puts patients and staff at considerable risk of infection. Bronchoscopy can be justified only when bronchoscopic intervention is deemed necessary and lifesaving, such as when a secondary infection is suspected.¹ Bronchoscopy is indicated in ICU patients suspected of invasive pulmonary aspergillosis (IPA) particularly because radiological and clinical signs of IPA in non-neutropenic patients are nonspecific, and cannot establish a definitive diagnosis.¹

 

“Bronchoscopy can be justified only when bronchoscopic intervention is deemed necessary and lifesaving, such as when a secondary infection is suspected”

 

Recommendations for treatment and future research

It is still uncertain whether the presence of Aspergillus spp in respiratory samples indicates an inevitable progression to invasive disease and immediate antifungal therapy. Undeniably, more insight into the interaction between Aspergillus spp and the SARS-CoV-2-infected lung is needed, as Verweij and colleagues pointed out.¹ Further research on CAPA should be able to explore alternative blood tests for CAPA, differences in radiological signs between CAPA and COVID-19 without IPA, the usefulness of fungal prophylaxis, underlying host factors, optimal treatment, and so on.

To date, only histopathology, direct microscopy by fine needle aspiration, lung biopsy, or autopsy of deceased patients can prove IPA in patients positive for COVID-19. The authors conclude that until histopathological evidence of CAPA is obtained, patients with COVID-19 who are critically ill with evidence for Aspergillus spp in bronchoalveolar lavage or positive serum GM detection should receive antifungal therapy according to national and international guidelines.¹

 

“Until histopathological evidence of CAPA is obtained, patients with COVID-19 who are critically ill with evidence for Aspergillus spp in bronchoalveolar lavage or serum should receive antifungal therapy”

References

1. Verweij PE, et al. Lancet Microbe 2020;1:e53-e55.
2. Lei Y, et al. J Microbiol Immunol Infect 2020 May 25;S1684-1182(20)30124-9. [Online ahead of print].
3. Koehler P, et al. Mycoses 2020;63:528-534.
4. Alanio A, et al. Lancet Respir Med 2020;8:e48-e49.
5. van Arkel ALE, et al. Am J Respir Crit Care Med 2020 May 12.
6. Zhang G, et al. J Clin Virol 2020;127:104364.
7. Wahidi MM, et al. J Bronchology Interv Pulmonol 2020;10.1097/LBR.0000000000000681. [Online ahead of print].