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An unexpectedly high proportion of Pneumocystis jirovecii-positive pulmonary samples was observed in critically ill coronavirus disease 2019 (COVID-19) patients, according to a study published in Journal of Infection.
“Based on our findings, we advocate systematically searching for P. jirovecii in deep respiratory specimens in these patients. We believe that this strategy may be useful in limiting enhanced inflammation due to the presence of P. jirovecii in the lung and avoiding inter-patient P. jirovecii transmission,” wrote Alexandre Alanio, Saint-Louis Hospital, Paris, France.
A total of 108 HIV-negative COVID-19 patients with a median age of 62 years and mostly (81.5%) males admitted to the intensive care unit (ICU) between March 15 and May 1, 2020 were included in the study. All except three patients were intubated on admission. Respiratory samples including 80 bronchoalveolar lavage (BAL) samples, 22 tracheal aspirates, 4 sputa and two bronchial aspiration fluids were obtained. Meanwhile, 34 (31.4%) patients who developed acute respiratory distress syndrome (ARDS) received at least one day of corticosteroids before BAL sampling.
Of the patients, 10 (9.3%) had a positive RT qPCR result for P. jirovecii. Median delay between sampling and ICU admission was 2 days. The median quantitative cycle value was 32.6. Study data showed that clinical characteristics of the patients carrying P. jirovecii did not significantly differ from the other patients except for lower plasma D-dimer (median, 1,270ng/mL vs 2,610ng/mL; P = 0.03), more prevalent lopinavir/ritonavir administration (40.0% vs 12.2%; P = 0.04) and more prevalent long-term corticosteroid prescription (30.0% vs 8.2%; P = 0.06).
Among the 10 P. jirovecii carriers, five concomitantly met the criteria for COVID-19-associated pulmonary aspergillosis. Meanwhile, four (40%) patients received co-trimoxazole as prophylaxis (80/400mg once daily). One co-trimoxazole-treated and two non-treated patients died while the seven remaining patients were discharged.
“We found an unexpectedly high proportion of critically ill COVID-19 patients detected with P. jirovecii (10/108 patients; 9.3%), [similar] to previous findings in influenza patients (3/45; ~7%),” the author wrote. “COVID-19 patients mostly exhibited marked lymphopenia and alterations in lymphocyte functions, likely explaining the high-rate of P. jirovecii detection.”
Further, serum β-D-glucan concentrations were measured in four of those five P. jirovecii RT qPCR-positive patients and low values (<120pg/mL) were obtained which the author said was in accordance with the low nucleic acids fungal loads in the lung alveoli. Meanwhile in two out of nine tested P. jirovecii RT qPCR-negative patients, higher β-D-glucan concentrations (450 and 500pg/ml) led to the diagnosis of pulmonary aspergillosis. “Although a recent meta-analysis questioned its sensitivity in non-HIV patients, β-D-glucan has been widely used to rule out pneumocystosis because of its high negative predictive value,” the author wrote. “This finding may support the hypothesis that our patients were carrying P. jirovecii, yet not being infected per se. Thus, although interesting in the context of invasive fungal infections diagnosis, serum β-D-glucan should be interpreted with caution when excluding the diagnosis of pneumocystosis.”
“Our study limitations include the relatively small number of patients, the bi-center setting, and the short study period,” the author acknowledged. “However, to the best of our knowledge, this is the first study evaluating the prevalence of P. jirovecii in COVID-19 patients.” Nonetheless, the author said P. jirovecii prevalence in less severe patients remains to be determined since the study focused on critically ill COVID-19 patients.