Pneumocystis jirovecii pneumonia complicated a case of SARS-CoV-2 infection and multiple sclerosis after treatment with rituximab.

Although immunodeficient patients are less prone to develop Coronavirus disease 2019 (COVID-19)-mediated cytokine storm, secondary infections can cause serious complications in this vulnerable population. They are more likely to develop opportunistic infections that can mimic the symptoms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Herein, we presented a 27-year-old male patient of SARS-CoV-2 infection, who was complicated with Pneumocystis jirovecii pneumonia (PJP), following treatment with rituximab. First, he was hospitalized for 5 days with fever, cough, and dyspnea due to COVID-19 infection, and treated with remdesivir and glucocorticoid. Then, he has been referred to our center with cough, dyspnea, body pain, and fever. Due to persistent fever, the progression of pulmonary lesions, and reduced oxygen saturation, we began treatment with piperacillin + tazobactam, vancomycin, and levofloxacin. Nevertheless, the patient's fever did not stop after the aforementioned empiric treatment and his condition got worse and he was admitted to the intensive care unit. The result of BAL fluid, tested for P. jirovecii by RT-PCR, turned out to be positive. Therefore, we started trimethoprim-sulfamethoxazole and dexamethasone, which improved his condition. We hope this article helps clinicians consider causes other than COVID-19, especially opportunistic infections such as PJP, in patients with respiratory symptoms and fever.

Pneumocystis jirovecii and methicillin-resistant Staphylococcus aureus superinfection, a challenge in a post-COVID-19 scenario

We present a case of an 87-year-old nonsmoker female who recovered after infection by SARS-CoV-2 and was readmitted two weeks later due to respiratory sepsis. Radiological imaging showed a significant radiological worsening with extensive areas of bronchopneumonia and ground-glass opacities suggestive of organizing pneumonia. Empirical treatment with meropenem 1g/8h was started;however, clinical worsening persisted with tachypnea and desaturation requiring heated high-flow nasal cannula oxygen therapy, with poor response. Methicillin-resistant Staphylococcus aureus was isolated both in nasal screening swab and sputum, and RNA polymerase chain reaction in induced sputum was positive for P. jirovecii. Serum (1-3)-beta-D-glucan was normal, and blood cultures were sterile. Antibiotic therapy was adjusted with intravenous linezolid 600mg/12h and trimethoprim-sulfamethoxazole 320/1600mg/6h, plus methylprednisolone 40mg/day. Unfortunately, the patient had no response to optimized treatment and finally died. Clinicians should be aware of opportunistic and resistant microorganisms superinfections in relation to SARS-CoV-2 infection, even more, when corticosteroids are widely used.

Molecular and microscopy detection of Pneumocystis jirovecii in hospitalized patients during the COVID-19 pandemic.

Introduction: Early detection of Pneumocystis jirovecii as an opportunistic pathogen that may endanger predisposed persons, including COVID-19 patients, may help to choose the optimal management. Methods: In this study, 585, including 530 COVID-19 patients, with clinical and radiological evidence of respiratory diseases, were investigated for P. jirovecii screening. Clinical specimens were examined by direct microscopy and PCR, and randomly selected positive PCR products were confirmed through DNA sequence analysis. Results: Thirty-one (5.3%) samples were positive in P. jirovecii-specific nested-PCR, while by direct microscopic tests, Pneumocystis was observed in 22 (3.76%) samples. Males (61.7%) and patients over 50 years old (75.6%) were more commonly affected than others, and malaise and fatigue (84%), and wheezing (75%) were the most common symptoms, followed by fever (40.48%) and dyspnea (39.51%). Among the Pneumocystis-positive patients, three cases had coinfection with Aspergillus fumigatus, A. flavus, and A. niger (each n = 1), as documented by direct microscopy, culture, and species identification by PCR-sequencing. Conclusion: Pneumocystis pneumonia is still a diagnostic challenge; therefore, additional large-scale studies are needed to clarify the epidemiology of the disease in immunocompromised or COVID-19 patients.

Pneumocystis jirovecii Infections Among COVID-19 Patients: A Case Series and Literature Review.

Background: Pneumocystis jirovecii pneumonia (PCP) is a serious, emerging complication of coronavirus disease 2019 (COVID-19). Methods: We performed a systematic review of published cases. We describe 6 new cases of PCP/COVID-19 coinfection. Among our cases (n = 6) and those in the literature (n = 69) with available data, the median age (interquartile range [IQR]) was 59 (44-77) years (n = 38), 72% (47/65) were male, and the mortality rate was 30.9% (21/68). Results: Long-term corticosteroid use was noted in 45.1% (23/51), advanced HIV infection (defined as a CD4 count <200 cells/µL) in 17.6% (9/51), and antineoplastic chemotherapy in 13.7% (7/51), consistent with known PCP risk factors. Notably, 56.7% (38/47) had verifiable risk factors for PCP (high-dose corticosteroids, immunosuppressive therapy, and HIV infection) before COVID-19 infection. A median absolute lymphocyte count (IQR) of 0.61 (0.28-0.92) ×103 cells/mm3 (n = 23) and CD4 count (IQR) of 66 (33-291.5) cells/mm3 (n = 20) were also discovered among the study population. Conclusions: These findings suggest a need for greater attention to PCP risk factors among COVID-19 patients and consideration of PCP prophylaxis in these high-risk populations.

Value of CT examination in the differential diagnosis of Corona Virus Disease 2019 and pneumocystis jirovecii pneumonia during normal prevention and control period

Objective To compare the computed tomography (CT) signs of Corona Virus Disease 2019 (COVID-19) and pneumocystis jirovecii pneumonia (PJP),and improve the level of differential diagnosis.Methods The first CT data of 32 COVID-19 patients admitted to Bao Ding No.1 Central Hospital and Bao Ding infectious Diseases Hospital of Hebei Province and 10 PJP patients admitted to Bao Ding No.1 Central Hospital of Hebei Province from December 2019 to March 2020 were collected, and their CT signs were compared.Results The COVID-19 patients were mainly characterized by multiple lung lesions in subpleural area, and their probability of pleural parallel sign and vascular thickening sign were significantly higher than those of the PJP patients, while the probability of pulmonary balloon sign, lunar arch sign and map sign were significantly lower than those of the PJP patients, with statistical significance (P<0.05) .Conclusion COVID-19 and PJP not only share common CT features but also have typical imaging features and chest CT plays an important role in the differential diagnosis of COVID-19 and PJP. (English) [ FROM AUTHOR]

A comprehensive clinical guide for Pneumocystis jirovecii pneumonia: a missing therapeutic target in HIV-uninfected patients.

INTRODUCTION: Pneumocystis jirovecii is an opportunistic, human-specific fungus that causes Pneumocystis pneumonia (PCP). PCP symptoms are non-specific. A patient with P. jirovecii and another lung infection faces a diagnostic challenge. It may be difficult to determine which of these agents is responsible for the clinical symptoms, preventing effective treatment. Diagnostic and treatment efforts have been made more difficult by the rising frequency with which coronavirus 2019 (COVID-19) and PCP co-occur. AREAS COVERED: Herein, we provide a comprehensive review of clinical and pharmacological recommendations along with a literature review of PCP in immunocompromised patients focusing on HIV-uninfected patients. EXPERT OPINION: PCP may be masked by identifying co-existing pathogens that are not necessarily responsible for the observed infection. Patients with severe form COVID-19 should be examined for underlying immunodeficiency, and co-infections must be considered as co-infection with P. jirovecii may worsen COVID-19's severity and fatality. PCP should be investigated in patients with PCP risk factors who come with pneumonia and suggestive radiographic symptoms but have not previously received PCP prophylaxis. PCP prophylaxis should be explored in individuals with various conditions that impair the immune system, depending on their PCP risk.

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.

Pneumonia Caused by Coinfection with Cytomegalovirus and Pneumocystis jirovecii in an HIV-Negative Infant Diagnosed by Metagenomic Next-Generation Sequencing.

Background: Pneumonia produced by coinfection with Pneumocystis jirovecii (PJ) and cytomegalovirus (CMV) in infants and young children without timely diagnosis and treatment is often fatal due to the limitations of traditional tests. More accurate and rapid diagnostic methods for multiple infections are urgently needed. Case Presentation: Here, we report a case of a 2-month-old boy with pneumonia caused by Pneumocystis jirovecii (PJ) and cytomegalovirus (CMV) without HIV infection. Chest computed tomography (CT) showed massive exudative consolidation in both lungs. Microscopic examination of stained sputum and smear specimens and bacterial and fungal culture tests were all negative, and CMV nucleic acid and antibody tests were positive. After a period of antiviral and anti-infective therapy, pulmonary inflammation was not relieved. Subsequently, sputum and venous blood samples were analysed by metagenomic next-generation sequencing (mNGS), and the sequences of PJ and CMV were acquired. The patient was finally diagnosed with pneumonia caused by PJ and CMV coinfection. Anti-fungal combined with anti-viral therapy was given immediately. mNGS re-examination of bronchoalveolar lavage fluid (BALF) also revealed the same primary pathogen. Therapy was stopped due to the request of the patient's guardian. Hence, the child was discharged from the hospital and eventually died. Conclusion: This case emphasizes the combined use of mNGS and traditional tests in the clinical diagnosis of mixed lung infections in infants without HIV infection. mNGS is a new adjunctive diagnostic method that can rapidly discriminate multiple causes of pneumonia.

Concurrent COVID-19 and pneumocystis carinii pneumonia in a patient subsequently found to have underlying hairy cell leukemia.

SARS-CoV-2 infection manifestation has great diversity and it becomes even greater while co-infection occurs or there is a serious underlying disease in an affected patient. In this case report, we present a case of a 71-year-old man who underwent a chest CT scan following the development of fever, weakness, and pulmonary symptoms. Chest CT scan showed segmental consolidation with centrilobular nodular infiltration, ground glass opacifications in the inferior segment of the left upper and lower lobes, and left lung pleural thickening which was atypical for either COVID-19 infection or pneumocystis carinii pneumonia but his SARS-CoV-2 PCR result was positive and he received COVID-19 treatment. His symptoms recurred after a few months with the same chest CT findings and subsequent bronchoalveolar lavage revealed the presence of pneumocystis carinii infection. Consequently, he received cotrimoxazole which caused improvement in symptoms, nonetheless splenomegaly and anemia remained in his clinical and laboratory investigation. Accordingly, bone marrow study and flow cytometry was done and confirmed the previously undiagnosed hairy cell leukemia. This case accentuates the fact that when we face atypical clinical or paraclinical features in a COVID-19 patient, we should explore for coinfection or unknown underlying diseases.

Nationwide Implementation of Nonpharmaceutical Interventions During the Coronavirus Disease 2019 Pandemic Is Associated With Decreased Incidence of Pneumocystis jirovecii Pneumonia in Kidney Transplant Recipients.

This study aimed to investigate the impact of nationwide nonpharmaceutical interventions against coronavirus disease 2019 (COVID-19) on the incidence of Pneumocystis jirovecii pneumonia (PCP) in kidney transplant recipients. The monthly incidence of PCP during the COVID-19 period decreased significantly compared to that of the pre-COVID-19 period in kidney transplant recipients.

Concurrent Infection with SARS-CoV-2 and Pneumocystis jirovecii in Immunocompromised and Immunocompetent Individuals.

Coronavirus disease 2019 (COVID-19) may occur with concurrent infections caused by bacterial and fungal microorganisms. This systematic review evaluated studies reporting concomitant COVID-19 and Pneumocystis jirovecii pneumonia (PJP). We found 39 patients (74% male, median age: 56.8 (range: 11-83) years), including 66% immunosuppressed individuals (23% HIV-infected and 41% on long-term corticosteroid therapy). Patients were characteristically severely ill (mechanical ventilation: 70%), associated with 41% mortality. The median lymphocyte count was 527 cells/mm3 (range: 110-2200), and the median CD4+ T cell count was 206 cells/mm3 (range: 8-1021). We identified three patterns of concurrent COVID-19 and P. jirovecii infection. The first pattern (airway colonization with a low burden of P. jirovecii) does not seem to modify the COVID-19 course of illness. However, P. jirovecii superinfection, typically occurring weeks after COVID-19 diagnosis as a biphasic illness, and P. jirovecii coinfection characteristically results in progressive multilobar pneumonia, which is associated with poor outcomes. To support this categorization, we reported three patients with concurrent PJP and COVID-19 identified in our institution, presenting these clinical scenarios. The diagnosis of PJP requires a high index of suspicion, since clinical and radiological characteristics overlap with COVID-19. Observational studies are necessary to determine the PJP burden in patients with COVID-19 requiring hospitalization.

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.

Neumonía por SARS-CoV-2 asociado a coinfección por Pneumocystis jiroveciien paciente inmunocomprometido: a propósito de caso y revisión literatura

Resumen La neumonía por Pneumocystis jirovecii es una infección oportunista que se presenta habitualmente en pacientes con inmunodeficiencias graves adquiridas. Durante la actual contingencia en salud por la COVID-19 se ha incrementado la presencia de infección por este microorganismo fúngico en pacientes críticamente enfermos lo que aumenta el riesgo de desenlaces fatales. A continuación se presenta el caso de un hombre con neumonía grave por SARS-CoV-2, inmunosupresión por VIH y coinfección por P. jirovecii quien desarrolló síndrome de distrés respiratorio agudo requiriendo soporte ventilatorio mecánico invasivo con presión positiva. A pesar del manejo intrahospitalario recibido, terapia antibiótica y soporte ventilatorio el paciente presentó deterioro hemodinámico con inestabilidad falleciendo al día 20 de la hospitalización. Posteriormente se realiza una revisión bibliográfica de la literatura actual discutiendo aspectos como epidemiología, fisiopatología, diagnóstico oportuno, tratamiento entre la relación de P. jirovecii y SARS-CoV-2 en pacientes críticamente enfermos. Pneumocystis jirovecii pneumonia is an opportunistic infection that commonly occurs in patients with severe acquired immunodeficiencies. During the current health contingency the presence of infection and co-infection by P. jirovecii in critically ill patients, is apparently increasing altogether with the risk of fatal outcomes. The following is the case of a man with severe SARS-CoV-2 pneumonia, HIV immunosuppression and P. jirovecii coinfection who developed acute respiratory distress syndrome requiring invasive mechanical positive pressure ventilatory support. Despite the in-hospital management received, antibiotic therapy, and ventilatory support, the patient presented hemodynamic deterioration with instability, dying on day 20 of hospitalization. Subsequently, a bibliographic review of the current literature is carried out, discussing aspects such as epidemiology, pathophysiology, timely diagnosis, and treatment between the relationship of P. jirovecii and SARS-CoV-2 in critically ill patients.

Can I go back to work? A case of persistent SARS-CoV-2 with advanced untreated HIV infection.

We describe the case of a 30-year-old care home employee diagnosed with COVID-19 and acute untreated HIV-1. He was unable to return to work for 119 days due to concerns over transmission risk as his SARS-CoV-2 PCR remained detectable. This highlights the uncertainty in interpreting SARS-CoV-2 PCR results post-infection in acute untreated HIV.

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.

No Change of Pneumocystis jirovecii Pneumonia after the COVID-19 Pandemic: Multicenter Time-Series Analyses.

Consolidated infection control measures imposed by the government and hospitals during COVID-19 pandemic resulted in a sharp decline of respiratory viruses. Based on the issue of whether Pneumocystis jirovecii could be transmitted by airborne and acquired from the environment, we assessed changes in P. jirovecii pneumonia (PCP) cases in a hospital setting before and after COVID-19. We retrospectively collected data of PCP-confirmed inpatients aged ≥18 years (N = 2922) in four university-affiliated hospitals between January 2015 and June 2021. The index and intervention dates were defined as the first time of P. jirovecii diagnosis and January 2020, respectively. We predicted PCP cases for post-COVID-19 and obtained the difference (residuals) between forecasted and observed cases using the autoregressive integrated moving average (ARIMA) and the Bayesian structural time-series (BSTS) models. Overall, the average of observed PCP cases per month in each year were 36.1 and 47.3 for pre- and post-COVID-19, respectively. The estimate for residuals in the ARIMA model was not significantly different in the total PCP-confirmed inpatients (7.4%, p = 0.765). The forecasted PCP cases by the BSTS model were not significantly different from the observed cases in the post-COVID-19 (-0.6%, 95% credible interval; -9.6~9.1%, p = 0.450). The unprecedented strict non-pharmacological interventions did not affect PCP cases.

COVID-19-associated opportunistic infections: a snapshot on the current reports.

Treatment of the novel Coronavirus Disease 2019 (COVID-19) remains a complicated challenge, especially among patients with severe disease. In recent studies, immunosuppressive therapy has shown promising results for control of the cytokine storm syndrome (CSS) in severe cases of COVID-19. However, it is well documented that immunosuppressive agents (e.g., corticosteroids and cytokine blockers) increase the risk of opportunistic infections. On the other hand, several opportunistic infections were reported in COVID-19 patients, including Aspergillus spp., Candida spp., Cryptococcus neoformans, Pneumocystis jiroveci (carinii), mucormycosis, Cytomegalovirus (CMV), Herpes simplex virus (HSV), Strongyloides stercoralis, Mycobacterium tuberculosis, and Toxoplasma gondii. This review is a snapshot about the main opportunistic infections that reported among COVID-19 patients. As such, we summarized information about the main immunosuppressive agents that were used in recent clinical trials for COVID-19 patients and the risk of opportunistic infections following these treatments. We also discussed about the main challenges regarding diagnosis and treatment of COVID-19-associated opportunistic infections (CAOIs).

Pneumocystis pneumonia in the COVID-19 pandemic era: similarities and challenges.

The clinical picture of the fungal disease, Pneumocystis pneumonia, resembles the course of coronavirus disease 2019 (COVID-19), presenting a diagnostic challenge in the pandemic era. We discuss the concern of Pneumocystis jirovecii and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coinfection, their similarities, and the impact of immunosuppression, with a suggested diagnostic pathway for their suspected coinfection.

Detection of Pneumocystis jirovecii in Patients with Severe COVID-19: Diagnostic and Therapeutic Challenges.

Cases of Pneumocystis jirovecii pneumonia (PCP) in patients suffering from COVID-19 were described in patients with various comorbidities and outcomes. The diagnosis of PCP in these patients is difficult due to clinical and radiological similarities. We carried out this study in order to better describe potentially at-risk patients and their outcomes. We retrospectively analyzed all patients with a P. jirovecii PCR performed in bronchoalveolar lavage fluid, tracheal aspirate, or sputum within a month after the COVID-19 diagnosis. Fifty-seven patients with COVID-19 infection were tested for P. jirovecii. Among 57 patients with COVID-19, four patients had a concomitant positive P. jirovecii PCR. These four patients were elderly with a mean age of 78. Two patients were immunocompromised, and the two others presented only diabetes mellitus. Three patients presented an ARDS requiring transfer to the ICU and mechanical ventilation. All patients presented lymphocytopenia. Three patients had probable PCP, and one had proven PCP. All patients died within two months after hospital admission. These co-infections are rare but severe, therefore, PCP should be considered in case of worsening of the condition of patients with severe COVID-19.