The effect of COVID-19 on the frequency of Pneumocystis jirovecii pneumonia: a monocentric, retrospective, and observational study (preprint)

Background Pneumocystis jirovecii pneumonia (PCP) and SARS-CoV2 share some similarities in their effects on the respiratory system, clinical presentation, and management. The COVID-19 pandemic required rapid action to curb transmission and mitigate its lethiferous impact. Non-pharmaceutical interventions (NPIs) were globally adopted. We hypothesized that these measures reduced the transmission and acquisition of P. jirovecii in both hospital and community settings.Methods We conducted a retrospective observational study on 2950 respiratory specimens from patients with suspected pulmonary infection, analyzed at the Laboratory of Parasitology Unit of the Policlinico Tor Vergata of Rome, Italy, from January 2014 to December 2022.Results We show a significant reduction in the frequency of PCP in the COVID-19 pandemic era, compared to the previous period. Among the four sequence types of P. jirovecii identified, genotype 1 was the most prevalent (37%). We observed a non-significant trend of decreasing cases with genotype 1 and increasing cases with genotype 3 over the study period.Conclusions The nationwide implementation of NPIs against COVID-19 may have changed the microbiological landscape of exposure, thereby decreasing the exposure to P. jirovecii and consequently reducing the incidence of PCP.

The Association between Burnout, Social Support, and Psychological Capital among Primary Care Providers in Togo: A Cross-Sectional Study.

Background and Objectives: Job burnout is prevalent among primary care providers (PCPs) in different countries, and the factors that can alleviate burnout in these countries have been explored. However, no study has addressed the prevalence and the correlates of job burnout among Togolese PCPs. Therefore, we aimed to examine the prevalence of burnout and its association with social support and psychological capital among PCPs in Togo. Material and Methods: We conducted a cross-sectional study in Togo from 5 to 17 November 2020 among 279 PCPs of 28 peripheral care units (PCUs). Participants completed the Maslach Burnout Inventory, Job Content Questionnaire, and Psychological Capital Questionnaire. Data were analyzed using the Mann-Whitney U test, Kruskal-Wallis H test, Pearson correlation analysis, and multiple linear regression. Results: We received 279 responses, out of which 37.28% experienced a high level of emotional exhaustion (EE), 13.62% had a high level of depersonalization (DP), and 19.71% experienced low levels of personal accomplishment (PA). EE had a significant negative correlation with the supervisor's support. In contrast, self-efficacy, hope, optimism, and resilience had a significant negative correlation with DP and a significant positive correlation with PA. Furthermore, supervisors' support significantly predicted lower levels of EE. Optimism significantly predicted lower levels of DP and higher levels of PA. Conclusions: Burnout is common among Togolese PCPs, and self-efficacy, optimism, and supervisors' support significantly contribute to low levels of job burnout among Togolese PCPs. This study provided insight into intervention programs to prevent burnout among PCPs in Togo.

Rare Case of Persistently Depressed T Lymphocyte Subsets After SARS-CoV-2 Infection.

BACKGROUND On rare occasions, viral infections are known to also depress immune cell lines, further worsening clinical outcomes. We describe a patient who presented 3 weeks after recovery from mild COVID-19 disease with clinical features of an atypical pneumonia and was found to have a low CD4+ T-cell count. CASE REPORT An 82-year-old man with a past medical history of coronary artery disease, rheumatoid arthritis, gout, hypertension, and atrial fibrillation presented with a 1-week history of progressively worsening shortness of breath and cough. He was noted to have recovered from mild SARS-CoV-2 infection 3 weeks prior to his current presentation and had been at his baseline level of health following infection. A T cell subset panel was obtained, which revealed an absolute CD3 count of 92 (reference range 840-3060), absolute CD4 count of 52 (reference range 500-1400), absolute CD8 count of 37 (reference range 180-1170), and a normal CD4: CD8 ratio. He was subsequently started on atovaquone for pneumocystis jiroveci pneumonia prophylaxis. CONCLUSIONS This case highlights the need for a high index of suspicion for lymphocyte depletion in older patients with multiple comorbidities who present during or after SARS-CoV-2 infection with atypical symptoms that are suggestive of immunosuppression. In such instances, there should be a low threshold to start prophylactic therapy for possible opportunistic infections.

Pneumocystis jirovecii pneumonia among pediatric inpatients before and after COVID-19 pandemic: molecular diagnosis, predisposing factors, and outcomes in Northeastern Iran (preprint)

Background: Pneumocystis  pneumonia (PCP), caused by P. jirovecii, is one of the opportunistic fungal infections that can cause life-threatening pneumonia in children with underlying diseases. Due to the similarity of the symptoms of PCP with other lung infections, such as tuberculosis, differential and accurate diagnosis is necessary. The current study investigated the molecular diagnosis of P. jirovecii , predisposing factors, and the outcomes, among pediatric inpatients in Northeastern Iran. Method: In this study, 180 bronchoalveolar lavage (BAL) specimens were obtained from hospitalized children with respiratory disorders. The specimens were examined using Giemsa stain, and the genomic DNA was extracted according to the protocol of the AmpliSens® kit. Real-time polymerase chain reaction technique was used to detect P. jirovecii by the AmpliSens Pneumocystis jirovecii ( carinii )-FRT PCR kit. Results: : Among the patients studied, 34 (18.9%) were positive, and 8 (4.4%) were suspicious for the presence of P. jirovecii . Among the 34 positive cases, 12 (35%) were related to before, and 22 (65%) were affected during the COVID-19 pandemic. Only 2 cases (5.88%) of the positive cases detected by Real-time PCR method were observed using Giemsa staining. Also, no correlation was observed between positive cases of infection and the sex, the outcomes, and underlying diseases. Conclusion: The results showed that PCP has a relatively high prevalence among pediatric inpatients with respiratory disorders. Neutropenia is a significant predisposing factor in these patients. However, there is no correlation between PCP cases and the outcomes and underlying diseases. Most of patients with PCP were affected during the COVID-19 pandemic.

[Pneumonia by Pneumocystis jirovecii after COVID-19 in non-HIV patient]. / Neumonía por Pneumocystis jirovecii posterior a COVID-19 en un paciente sin infección por VIH.

Infection by Pneumocystis jirovecii in patients with severe respiratory infection caused by SARS-CoV-2 is a situation that we must take into account today. Corticotherapy along with other risk factors predisposes to it. It is a diagnostic challenge and, after treatment, the prognosis is favorable. We report the case of a male with severe pneumonia due to SARS-CoV-2 who received corticosteroid treatment, later developing pneumonia due to P. jiroveci.

Pneumocystis jirovecii Pneumonia with a Normal Early Chest Radiography and Complicated with Drug-Induced Immune Hemolytic Anemia: A Case Report.

BACKGROUND Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection that commonly occurs in immunocompromised patients, especially those with HIV. Early diagnosis and prompt treatment are important because PJP is a potentially life-threatening infection. However, the diagnosis of PJP in the early stage can be challenging due to various factors. Furthermore, the early presentation of PJP, which includes normal chest radiograph and examination findings along with the subacute presentation of PJP in patients with HIV, makes an early diagnosis of the disease even more challenging for doctors. CASE REPORT In this case report, we present the case of a 39-year-old man who had normal chest X-ray findings during the initial stage of his presentation. Coupled with non-disclosure of HIV status, these led to a delay in PJP diagnosis. The diagnosis of PJP with underlying HIV was later supported by the patient's clinical features, initial blood investigations, and presence of high-risk sexual activity. The diagnosis was confirmed when the PJP polymerase chain reaction test from the respiratory sample was positive. He was successfully treated with oral trimethoprim-sulfamethoxazole. However, he subsequently developed rare adverse effects of drug-induced immune hemolytic anemia, which was diagnosed based on the presence of hemolytic anemia and recent exposure to a new drug. Trimethoprim-sulfamethoxazole was promptly discontinued, which resulted in symptom improvement. CONCLUSIONS This case report aims to create awareness among primary care doctors to be vigilant of the PJP diagnosis and its nonspecific presentations as well as to the rare adverse effects of medications to treat PJP.

Pneumocystis jirovecii Pneumonia Associated with COVID-19 in Patients with Interstitial Pneumonia.

Here, we report two cases of patients with interstitial pneumonia (IP) on steroids who developed Pneumocystis jirovecii pneumonia (PJP) following coronavirus disease 2019 (COVID-19) infection. Case 1: A 69-year-old man on 10 mg of prednisolone (PSL) daily for IP developed new pneumonia shortly after his COVID-19 infection improved and was diagnosed with PJP based on chest computed tomography (CT) findings and elevated serum ß-D-glucan levels. Trimethoprim-sulfamethoxazole (TMP-SMZ) was administered, and the pneumonia resolved. Case 2: A 70-year-old woman taking 4 mg/day of PSL for IP and rheumatoid arthritis developed COVID-19 pneumonia, which resolved mildly, but her pneumonia flared up and was diagnosed as PJP based on CT findings, elevated ß-D-glucan levels, and positive polymerase chain reaction for P. jirovecii DNA in the sputum. The autopsy revealed diffuse alveolar damage, increased collagen fiver and fibrotic foci, mucinous component accumulation, and the presence of a P. jirovecii cyst. In conclusion, steroids and immunosuppressive medications are well-known risk factors for PJP. Patients with IP who have been taking these drugs for a long time are frequently treated with additional steroids for COVID-19; thus, PJP complications should be avoided in such cases.

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.

Pneumocystis pneumonia with respiratory failure in a HIV-negative patient following short course of low-dose to moderate-dose prednisolone for a dermatological condition.

A woman in her 80s was admitted with 5 days of progressive dyspnoea and hypoxic respiratory failure, in the setting of receiving a 3-week course of low-dose to moderate-dose prednisolone for a pruritic skin rash. Her medical history was not significant for major medical comorbidities or any other clear risk factors for secondary immunosuppression apart from advanced age. CT revealed widespread small-airway and parenchymal disease with ground-glass opacities consistent with atypical respiratory infection. Sputum PCR confirmed Pneumocystis jirovecii She was diagnosed with Pneumocystis jirovecii pneumonia (PJP) in the context of her clinical presentation, radiological features and PCR result. Her HIV status was negative. The patient was treated with 4 weeks of trimethoprim-sulfamethoxazole and 3 weeks of adjunctive prednisolone. She initially required high-dependency unit support with non-invasive ventilation. In this case report, we review the literature regarding PJP in the dermatology setting.

The first detection of Pneumocystis jirovecii in asthmatic patients post-COVID-19 in Jordan.

Pneumocystis jirovecii pneumonia (PCP), caused by fungal species named Pneumocystis jirovecii, is a frequent opportunistic infection in those with human immunodeficiency virus (HIV) infection. However, PCP has been documented in immunocompetent patients. This study aims to determine if P. jirovecii detection occurs in asthma patients following coronavirus disease 2019 (COVID-19) in a Jordanian cohort. Also, to evaluate a method of TaqMan quantitative polymerase chain reaction (qPCR) assay to detect P. jirovecii, from sputum samples. The nasopharyngeal swabs were used to detect SARS-CoV-2 and sputum samples were tested for P. jirovecii using real time qPCR assay. Beta-tubulin (BT) and Dihydrofolate reductase (DHFR) genes were the directed targets of P. jirovecii. The results showed that the mean qPCR efficiencies of BT and DHFR were 96.37% and 100.13%, respectively. Three out of 31 included patients (9.7%) had a positive P. jirovecii. All of the three patients had used oral corticosteroids (OCS) in the last two months due asthma exacerbation and were treated with OCS for COVID-19. This is the first study based in Jordan to demonstrate that P. jirovecii and COVID-19 can co-exist and that it is important to maintain a broad differential diagnosis, especially in immunocompromised patients. Chronic lung disease can be a risk factor for the P. jirovecii colonization possibly due to corticosteroid's immunosuppression.

Acute respiratory distress syndrome precipitated by granulocyte colony-stimulating factor in undiagnosed Pneumocystis jirovecii pneumonia.

We present the case of a 62-year-old man with rheumatoid arthritis who developed a leukaemoid reaction and acute respiratory distress syndrome (ARDS) following granulocyte colony-stimulating factor (G-CSF) administration that had been given to treat neutropenia secondary to methotrexate and leflunomide toxicity. Later it was established that he had Pneumocystis jirovecii pneumonia, which was treated to complete resolution with a course of corticosteroids and antibiotics. This case highlights the potential risk of G-CSF administration in an immune compromised individual in the midst of bone marrow recovery in the context of active infection. Recognition of immune escape syndromes is vital and requires an understanding of potential triggers and risk factors.

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.

Successful treatment of a kidney transplant patient with COVID-19 and late-onset Pneumocystis jirovecii pneumonia.

BACKGROUND: Solid transplant patients are susceptible to Pneumocystis jirovecii pneumonia (PJP). While the vast majority of PJP cases occur within the first 6 months after transplantation, very few PJP cases are seen beyond 1 year post-transplantation (late-onset PJP). PJP and coronavirus disease 2019 (COVID-19, caused by infection with SARS-CoV-2) share quite a few common clinical manifestations and imaging findings, making the diagnosis of PJP often underappreciated during the current COVID-19 pandemic. To date, only 1 case of kidney transplantation who developed COVID-19 and late-onset PJP has been reported, but this patient also suffered from many other infections and died from respiratory failure and multiple organ dysfunction syndrome. A successful treatment of kidney patients with COVID-19 and late-onset PJP has not been reported. CASE PRESENTATION: We present a case of a 55-year-old male kidney transplant patient with COVID-19 who also developed late-onset PJP. He received a combined treatment strategy, including specific anti-pneumocystis therapy, symptomatic supportive therapy, adjusted immunosuppressive therapy, and use of antiviral drugs/antibiotics, ending with a favorable outcome. CONCLUSIONS: This case highlights the importance of prompt and differential diagnosis of PJP in kidney transplant patients with SARS-CoV-2 infection. Further studies are required to clarify if kidney transplant patients with COVID-19 could be prone to develop late-onset PJP and how these patients should be treated.

Pneumocystis jirovecii Pneumonia in Non-HIV Patients Recovering from COVID-19: A Single-Center Experience.

OBJECTIVE: to describe a single-center experience of Pneumocystis jirovecii pneumonia (PJP) in non-HIV patients recovering from COVID-19. METHODS: We report the cases of five non-HIV patients with COVID-19 who also developed PJP at a University Hospital. RESULTS: With the exception of one subject, who experienced an atypical and prolonged course of COVID-19, all the patients developed PJP after the clinical resolution of COVID-19 pneumonia. All but one patient had no pre-existing immunosuppressive conditions or other risk factors for PJP development at COVID-19 diagnosis. Nonetheless, following the course of COVID-19 infection, all the patients fulfilled at least one host factor for PJP; indeed, all the patients had received at least 2 weeks of high-dose steroids and three out of five had a CD4+ cell count <200/mm3. CONCLUSIONS: The use of corticosteroids for COVID-19 respiratory impairment seems to be the most common risk factor for PJP, together with viral-induced and iatrogenic lymphopenia. The worsening in respiratory function and the characteristic radiological picture during or after COVID-19 pneumonia should raise the suspicion of PJP, even in immunocompetent patients. PJP primary chemoprophylaxis can be considered in selected high-risk COVID-19 patients, but further studies are needed.

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.

First case of low-dose umbilical cord blood therapy for pediatric acute respiratory distress syndrome induced by Pneumocystis carinii pneumonia.

OBJECTIVE: This study aimed to present the case of a boy with acute distress syndrome (ARDS) treated with low-dose umbilical cord blood (UCB) therapy and explore the underlying possible mechanism. METHODS: A 7-year-old boy with severe Pneumocystis carinii pneumonia and severe ARDS was treated with allogeneic UCB as salvage therapy. RESULTS: The patient did not improve after being treated with lung protective ventilation, pulmonary surfactant replacement, and extracorporeal membrane oxygenation (ECMO) for 30 days. However, his disease reversed 5 days after allogeneic UCB infusion, and he weaned from ECMO after 7 days of infusion. Bioinformatics confirmed that his Toll-like receptor (TLR) was abnormal before UCB infusion. However, after the infusion, his immune system was activated and repaired, and the TLR4/MyD88/NF-κB signaling pathway was recovered. CONCLUSION: Allogenic UCB could treat ARDS by repairing the TLR4/MyD88/NF-κB signaling pathway, thereby achieving stability of the immune system.