Pneumocystis jirovecii pneumonia in HIV-negative patients, a frequently overlooked problem. A case series from a large Italian center.

BACKGROUND AND OBJECTIVES: Pneumocystis jirovecii pneumonia (PCP) still has substantial morbidity and mortality. For non-HIV patients, the course of infection is severe, and management guidelines are relatively recent. We collected all PCP cases (European Organization for Research and Treatment of Cancer criteria) diagnosed in HIV-negative adult inpatients in 2019-2020 at our center in northern Italy. RESULTS: Of 20 cases, nine had microbiologic evidence of probable (real-time polymerase chain reaction, RT-PCR) and 11 proven (immunofluorescence) PCP on respiratory specimens. Half were female; the median age was 71.5 years; 14 of 20 patients had hematologic malignancies, five had autoimmune/hyperinflammatory disorders, and one had a solid tumor. RT-PCR cycle threshold (Ct) was 24-37 for bronchoalveolar lavage (BAL) and 32-39 for sputum; Ct was 24-33 on BAL proven cases. Of 20 cases, four received additional diagnoses on BAL. At PCP diagnosis, all patients were not on anti-pneumocystis prophylaxis. We retrospectively assessed prophylaxis indications: 9/20 patients had a main indication, 5/9 because of prednisone treatment ≥ 20 mg (or equivalents) for ≥4 weeks. All patients underwent antimicrobial treatment according to guidelines; 18/20 with concomitant corticosteroids. A total of 4/20 patients died within 28 days from diagnosis. CONCLUSION: Despite appropriate treatment, PCP is still associated to high mortality (20%) among non-HIV patients. Strict adherence to prophylaxis guidelines, awareness of gray areas, and prompt diagnosis can help manage this frequently overlooked infection.

Comparative study of the serum hepcidin level of patients with pneumonia in COVID-19 and Pneumocystis pneumonia.

In the context of a pandemic caused by the SARS-CoV-2 virus, for a patient with respiratory symptoms and bilateral lung damage, COVID-19 becomes the first disease in the differential diagnostic search. Pneumonia in COVID-19 shares many characteristics with Pneumocystis pneumonia. One of the possible markers of the severe course of COVID-19 is hepcidin, a peptide hormone that negatively regulates iron metabolism. There are no data on the value of hepcidin in Pneumocystis pneumonia in the published scientific literature. The purpose of this study is to conduct a comparative analysis of hepcidin in the blood serum of patients with pneumonia in COVID-19 and Pneumocystis pneumonia to clarify their pathogenetic features. A case-control observational study was conducted, including 68 patients with pneumonia in COVID-19 and 44 patients with HIV infection and Pneumocystis pneumonia (PCP/HIV). Determination of hepcidin was carried out by ELISA using the ELISA Kit for Hepcidin. Statistical data processing was carried out using the MedCalc 19.2.6 software. Results. Comparative analysis of serum hepcidin levels in the study groups showed that hepcidin is statistically significantly higher in PCP/HIV than in COVID-19 - the median value is 22 times higher (p <0.0001). When examining the ROC curve for hepcidin, it was found that this biomarker has a high diagnostic potential and indicates a higher probability of COVID-19 than PCP/HIV at values ≤768.044 pg / ml. In the context of the COVID-19 pandemic, it is necessary to remember about other diseases that manifest themselves with a similar clinical and radiological picture. COVID-19 and PCP/HIV share many similarities; the peptide hormone hepcidin has shown itself as a potential differential diagnostic marker between them, and therefore the need for further studies of hepcidin is justified, taking into account the severity of the course of COVID-19, the presence of comorbidities and in a comparative aspect with pathologies that «mimic¼ under COVID-19.

COVID-19-Associated Pulmonary Aspergillosis, Fungemia, and Pneumocystosis in the Intensive Care Unit: a Retrospective Multicenter Observational Cohort during the First French Pandemic Wave.

The aim of this study was to evaluate diagnostic means, host factors, delay of occurrence, and outcome of patients with COVID-19 pneumonia and fungal coinfections in the intensive care unit (ICU). From 1 February to 31 May 2020, we anonymously recorded COVID-19-associated pulmonary aspergillosis (CAPA), fungemia (CA-fungemia), and pneumocystosis (CA-PCP) from 36 centers, including results on fungal biomarkers in respiratory specimens and serum. We collected data from 154 episodes of CAPA, 81 of CA-fungemia, 17 of CA-PCP, and 5 of other mold infections from 244 patients (male/female [M/F] ratio = 3.5; mean age, 64.7 ± 10.8 years). CA-PCP occurred first after ICU admission (median, 1 day; interquartile range [IQR], 0 to 3 days), followed by CAPA (9 days; IQR, 5 to 13 days), and then CA-fungemia (16 days; IQR, 12 to 23 days) (P < 10-4). For CAPA, the presence of several mycological criteria was associated with death (P < 10-4). Serum galactomannan was rarely positive (<20%). The mortality rates were 76.7% (23/30) in patients with host factors for invasive fungal disease, 45.2% (14/31) in those with a preexisting pulmonary condition, and 36.6% (34/93) in the remaining patients (P = 0.001). Antimold treatment did not alter prognosis (P = 0.370). Candida albicans was responsible for 59.3% of CA-fungemias, with a global mortality of 45.7%. For CA-PCP, 58.8% of the episodes occurred in patients with known host factors of PCP, and the mortality rate was 29.5%. CAPA may be in part hospital acquired and could benefit from antifungal prescription at the first positive biomarker result. CA-fungemia appeared linked to ICU stay without COVID-19 specificity, while CA-PCP may not really be a concern in the ICU. Improved diagnostic strategy for fungal markers in ICU patients with COVID-19 should support these hypotheses. IMPORTANCE To diagnose fungal coinfections in patients with COVID-19 in the intensive care unit, it is necessary to implement the correct treatment and to prevent them if possible. For COVID-19-associated pulmonary aspergillosis (CAPA), respiratory specimens remain the best approach since serum biomarkers are rarely positive. Timing of occurrence suggests that CAPA could be hospital acquired. The associated mortality varies from 36.6% to 76.7% when no host factors or host factors of invasive fungal diseases are present, respectively. Fungemias occurred after 2 weeks in ICUs and are associated with a mortality rate of 45.7%. Candida albicans is the first yeast species recovered, with no specificity linked to COVID-19. Pneumocystosis was mainly found in patients with known immunodepression. The diagnosis occurred at the entry in ICUs and not afterwards, suggesting that if Pneumocystis jirovecii plays a role, it is upstream of the hospitalization in the ICU.

Narrative review of the relationship between COVID-19 and PJP: does it represent coinfection or colonization?

BACKGROUND: Pneumocystis jirovecii (P. jirovecii) is increasingly identified on lower respiratory tract specimens of COVID-19 patients. Our narrative review aims to determine whether the diagnosis of pneumocystis jirovecii pneumonia (PJP) in COVID-19 patients represents coinfection or colonization based on the evidence available in the literature. We also discuss the decision to treat COVID-19 patients with coinfection by PJP. METHODS: A literature search was performed through the Pubmed and Web of Science databases from inception to March 10, 2021. RESULTS: We identified 12 COVID-19 patients suspected to have PJP coinfection. All patients were critically ill and required mechanical ventilation. Many were immunosuppressed from HIV or long-term corticosteroids and other immunosuppressive agents. In both the HIV and non-HIV groups, severe lymphocytopenia was encountered with absolute lymphocyte and CD4+T cell count less than 900 and 200 cells/mm, respectively. The time to PJP diagnosis from the initial presentation was 7.8 (range 2-21) days. Serum lactate dehydrogenase and beta-D-glucan were elevated in those coinfected with PJP. All patients were treated with anti-PJP therapy, predominantly sulfamethoxazole-trimethoprim with corticosteroids. The overall mortality rate was 41.6%, and comparable for both HIV and non-HIV groups. CONCLUSION: As the current evidence is restricted to case reports, the true incidence, risk factors, and prognosis of COVID-19 patients with PJP coinfections cannot be accurately determined. Comorbidities of poorly controlled HIV with lymphocytopenia and multiple immunosuppressive therapies are likely predisposing factors for PJP coinfection.

Fungal co-infection in COVID-19 patients: Should we be concerned?

Critically ill COVID-19 patients have higher pro-inflammatory (IL-1, IL-2, IL-6, tumor necrosis alpha) and anti-inflammatory (IL-4, IL-10) cytokine levels, less CD4 interferon-gamma expression, and fewer CD4 and CD8 cells. This severe clinical situation increases the risk of serious fungal infections, such as invasive pulmonary aspergillosis, invasive candidiasis or Pneumocystis jirovecii pneumonia. However, few studies have investigated fungal coinfections in this population. We describe an update on published reports on fungal coinfections and our personal experience in three Spanish hospitals. We can conclude that despite the serious disease caused by SARS-CoV-2 in many patients, the scarcity of invasive mycoses is probably due to the few bronchoscopies and necropsies performed in these patients because of the high risk in aerosol generation. However, the presence of fungal markers in clinically relevant specimens, with the exception of bronchopulmonary colonization by Candida, should make it advisable to early implement antifungal therapy.

Opportunistic Fungal Infections in the Epidemic Area of COVID-19: A Clinical and Diagnostic Perspective from Iran.

The coronavirus disease 2019 (COVID-19) pandemic emerged in Wuhan, China, in late 2109, and has rapidly spread around the world. Until May 25, 2020, there were 133,521 confirmed COVID-19 cases and 7359 deaths in Iran. The role of opportunistic fungal infections in the morbidity and mortality of COVID-19 patients remains less defined. Based on our multicenter experiences, we categorized the risks of opportunistic fungal infections in COVID-19 patients in Iran. The COVID-19 patients at high risk included those with acute respiratory distress syndrome, in intensive care units, receiving broad-spectrum antibiotics, immunosuppressants or corticosteroid, and supported by invasive or noninvasive ventilation. The patients were most likely to develop pulmonary aspergillosis, oral candidiasis, or pneumocystis pneumonia. Most diagnoses were probable as the accurate diagnosis of opportunistic fungal infections remains challenging in resource-poor settings. We summarize the clinical signs and laboratory tests needed to confirm candidiasis, aspergillosis, or pneumocystosis in our COVID-19 patients.