Background The incidence of secondary pulmonary infections is not well described in hospitalized COVID-19 patients. Understanding the incidence of secondary pulmonary infections and the associated bacterial and fungal microorganisms identified can improve patient outcomes. Objective This narrative review aims to determine the incidence of secondary bacterial and fungal pulmonary infections in hospitalized COVID-19 patients, and describe the bacterial and fungal microorganisms identified. Method We perform a literature search and select articles with confirmed diagnoses of secondary bacterial and fungal pulmonary infections that occur 48 h after admission, using respiratory tract cultures in hospitalized adult COVID-19 patients. We exclude articles involving co-infections defined as infections diagnosed at the time of admission by non-SARS-CoV-2 viruses, bacteria, and fungal microorganisms. Results The incidence of secondary pulmonary infections is low at 16% (4.8-42.8%) for bacterial infections and lower for fungal infections at 6.3% (0.9-33.3%) in hospitalized COVID-19 patients. Secondary pulmonary infections are predominantly seen in critically ill hospitalized COVID-19 patients. The most common bacterial microorganisms identified in the respiratory tract cultures are Pseudomonas aeruginosa, Klebsiella species, Staphylococcus aureus, Escherichia coli, and Stenotrophomonas maltophilia. Aspergillus fumigatus is the most common microorganism identified to cause secondary fungal pulmonary infections. Other rare opportunistic infection reported such as PJP is mostly confined to small case series and case reports. The overall time to diagnose secondary bacterial and fungal pulmonary infections is 10 days (2-21 days) from initial hospitalization and 9 days (4-18 days) after ICU admission. The use of antibiotics is high at 60-100% involving the studies included in our review. Conclusion The widespread use of empirical antibiotics during the current pandemic may contribute to the development of multidrug-resistant microorganisms, and antimicrobial stewardship programs are required for minimizing and de-escalating antibiotics. Due to the variation in definition across most studies, a large, well-designed study is required to determine the incidence, risk factors, and outcomes of secondary pulmonary infections in hospitalized COVID-19 patients.
Background COVID-19-associated pulmonary aspergillosis (CAPA) is defined as invasive pulmonary aspergillosis occurring in COVID-19 patients. Objective The purpose of this review is to discuss the incidence, characteristics, diagnostic criteria, biomarkers, and outcomes of hospitalized patients diagnosed with CAPA. Methods A literature search was performed through Pubmed and Web of Science databases for articles published up to March 20th, 2021. Results In 1,421 COVID-19 patients, the overall CAPA incidence was 13.5% (ranging 2.5-35.0%). The majority required invasive mechanical ventilation (IMV). The time to CAPA diagnosis from illness onset varied between 8.0-16.0 days. However, the time to CAPA diagnosis from ICU admission and IMV initiation ranged between 4.0-15.0 days and 3.0-8.0 days. The most common diagnostic criteria were the modified AspICU-Dutch/Belgian Mycosis Study Group and IAPA-Verweij et al. 77.6% of patients had positive lower respiratory tract cultures, other fungal biomarkers of BAL and serum galactomannan were positive in 45.3% and 18.2% of patients. The CAPA mortality rate was high at 48.4%, despite the widespread use of antifungals. Lengthy hospital and ICU LOS ranging between 16.0-37.5 days and 10.5-37.0 days were observed. CAPA patients had prolonged IMV duration of 13.0-20.0 days. Conclusion The true incidence of CAPA likely remains unknown as the diagnosis is limited by the lack of standardized diagnostic criteria that rely solely on microbiological data with direct or indirect detection of Aspergillus in respiratory specimens, particularly in clinical conditions with a low pretest probability. A well-designed, multi-center study to determine the optimal diagnostic approach for CAPA is required.
Purpose Invasive pulmonary aspergillosis has been increasingly recognized in COVID-19 patients, termed COVID-19-associate pulmonary aspergillosis (CAPA). Our meta-analysis aims to assess the clinical characteristics and outcomes of patients diagnosed with CAPA compared to those without CAPA. Methods We searched the Pubmed, Cochrane Library, SCOPUS, and Web of Science databases for studies published between January 1, 2020 and August 1, 2021, containing comparative data of patients diagnosed with CAPA and those without CAPA. Results Eight cohort studies involving 729 critically ill COVID-19 patients with comparative data were included. CAPA patients were older (mean age 66.58 vs. 59.25 years; P = 0.007) and had underlying chronic obstructive pulmonary disease (COPD) (13.7 vs. 6.1%; OR 2.75; P = 0.05). No differences in gender, body mass index (BMI), and comorbidities of diabetes and cancer were observed. CAPA patients were more likely to receive long-term corticosteroid treatment (15.0 vs. 5.3%; OR 3.53; P = 0.03). CAPA patients had greater severity of illness based on sequential organ failure assessment (SOFA) score with a higher all-cause in-hospital mortality rate (42.6 vs. 26.5%; OR 3.39; P < 0.001) and earlier ICU admission from illness onset (mean 11.00 vs. 12.00 days; P = 0.003). ICU length of stay (LOS), invasive mechanical ventilation (IMV) duration, the requirement of inotropic support and renal replacement therapy were comparable between the two groups. Conclusions CAPA patients are typically older with underlying COPD and received long-term corticosteroid treatment. Furthermore, CAPA is associated with higher SOFA scores, mortality, and earlier onset of ICU admission from illness onset.
Background The clinical features and outcomes of mechanically ventilated patients with COVID-19 infection who develop a pneumothorax has not been rigorously described or compared to those who do not develop a pneumothorax. Purpose To determine the incidence, clinical characteristics, and outcomes of critically ill patients with COVID-19 infection who developed pneumothorax. In addition, we compared the clinical characteristics and outcomes of mechanically ventilated patients who developed a pneumothorax with those who did not develop a pneumothorax. Methods This study was a multicenter retrospective analysis of all adult critically ill patients with COVID-19 infection who were admitted to intensive care units in 4 tertiary care centers in the United States. Results A total of 842 critically ill patients with COVID-19 infection were analyzed, out of which 594 (71%) were mechanically ventilated. The overall incidence of pneumothorax was 83/842 (10%), and 80/594 (13%) in those who were mechanically ventilated. As compared to mechanically ventilated patients in the non-pneumothorax group, mechanically ventilated patients in the pneumothorax group had worse respiratory parameters at the time of intubation (mean PaO 2 :FiO 2 ratio 105 vs 150, P<0.001 and static respiratory system compliance: 30ml/cmH 2 O vs 39ml/cmH 2 O, P=0.01) and significantly higher in-hospital mortality (63% vs 49%, P=0.04). Conclusion The overall incidence of pneumothorax mechanically ventilated patients with COVID-19 infection was 13%. Mechanically ventilated patients with COVID-19 infection who developed pneumothorax had worse gas exchange and respiratory mechanics at the time of intubation and had a higher mortality compared to those who did not develop pneumothorax.
Background COVID-19-related pleural effusions are frequently described during the ongoing pandemic. Objectives We described the incidence, characteristics, and outcomes of COVID-19-related pleural effusions based on the current evidence available in the literature. Methods We searched MEDLINE, Pubmed, and Google Scholar databases using keywords of “coronavirus disease 2019 (COVID-19),” “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),” “pleural effusion,” “pleural fluid,” and “pleura” from January 1 st , 2020 to January 31 st , 2021. Results The incidence of pleural effusions was low at 7.3% among the 47 observational studies. Pleural effusions were commonly observed in critically ill patients and had Multisystem Inflammatory Syndrome (MIS). COVID-19-related pleural effusions were identified 5-7 days and 11 days, after hospital admission and onset of COVD-19 symptoms. The characteristic findings of pleural fluid were exudative, lymphocytic or neutrophilic-predominant pleural fluid with markedly elevated lactate dehydrogenase (LDH) levels and pleural fluid to serum LDH ratio. Conclusion A well-designed study is required to assess the significance of COVID-19-related pleural effusions during this current pandemic.
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.
Multiple observational studies have described the similarities between COVID-19 pneumonia and organizing pneumonia (OP). These two entities clinically manifest with mild and subacute respiratory symptoms, often with a delayed diagnosis due to the atypical ARDS and silent hypoxemia presentation. Radiological features are often indistinguishable between the two. With the increase in antemortem lung biopsies and autopsies being performed, more histopathological findings of OP and its variant, acute fibrinous and organizing pneumonia (AFOP), are being diagnosed. These entities are known complications of viral infections as a delayed immunological process, explaining the favorable response to corticosteroids. Clinicians should be vigilant to diagnose this under-recognized entity of secondary OP in people with COVID-19 when clinical deterioration occurs, especially with compatible radiologic findings and recent cessation of corticosteroids. Despite the proven benefits of corticosteroids in treating COVID-19, treatment approaches can be more effective as OP often requires higher doses and a more prolonged therapy duration for remission and preventing relapses. The purpose of our narrative review is to compare the similarities between COVID-19 pneumonia and OP, emphasizing the clinical, radiological, and histopathological features based on the evidence available in the literature.
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