Project description:Coronavirus disease 2019 (COVID-19) can become complicated by secondary invasive fungal infections (IFIs), stemming primarily from severe lung damage and immunologic deficits associated with the virus or immunomodulatory therapy. Other risk factors include poorly controlled diabetes, structural lung disease and/or other comorbidities, and fungal colonization. Opportunistic IFI following severe respiratory viral illness has been increasingly recognized, most notably with severe influenza. There have been many reports of fungal infections associated with COVID-19, initially predominated by pulmonary aspergillosis, but with recent emergence of mucormycosis, candidiasis, and endemic mycoses. These infections can be challenging to diagnose and are associated with poor outcomes. The reported incidence of IFI has varied, often related to heterogeneity in patient populations, surveillance protocols, and definitions used for classification of fungal infections. Herein, we review IFI complicating COVID-19 and address knowledge gaps related to epidemiology, diagnosis, and management of COVID-19-associated fungal infections.
Project description:BackgroundThe incidence of infective endocarditis (IE) has increased in recent decades. Societal lockdown including reorganization of the healthcare system during the COVID-19 pandemic may influence the incidence of IE. This study sets out to investigate the incidence of IE during the Danish national lockdown.MethodsIn this nationwide cohort study, patients admitted with IE in either one of two periods A) A combined period of 1 January to 7 May for 2018 and 2019, or B) 1 January to 6 May 2020, were identified using Danish nationwide registries. Weekly incidence rates of IE admissions for the 2018/2019-period and 2020-period were computed and incidence rate ratios (IRR) for 2020-incidence vs 2018/2019-incidence were calculated using Poisson regression analysis.ResultsIn total, 208 (67.3% men, median age 74.1 years) and 429 (64.1% men, median age 72.7 years) patients were admitted with IE in 2020 and 2018/2019, respectively. No significant difference in incidence rates were found comparing the 2020-period and 2018/2019-period (IRR: 0.96 (95% CI: 0.82-1.14). The overall incidence rate pre-lockdown (week 1-10: 1 January to 11 March 2020) was 14.2 IE cases per 100,000 person years (95% CI: 12.0-16.9) as compared with 11.4 IE cases per 100,000 person years (95% CI: 9.1-14.1) during lockdown (week 11-18: 12 March to 6 May 2020) corresponding to an IRR of 0.80 (95% CI: 0.60-1.06) and thus no significant difference pre- versus post-lockdown.ConclusionIn this nationwide cohort study, no significant difference in the incidence of IE admissions during the national lockdown due to the COVID-19 pandemic was found.
Project description:Objective: To study the potential effect of COVID-19 on the endometrium of affected symptomatic women. Design: Preliminary study of the endometrial transcriptomes in women with COVID-19 through RNA sequencing. Setting: Hospital and university laboratories. Subjects: Women with COVID-19 lacking SARS-CoV-2 infection in endometrial tissue. Intervention/Exposure: Endometrial biopsy collection. Main outcomes measures: Endometrial gene expression and functional analysis of patients with COVID-19 versus uninfected individuals. Results: COVID-19 systemic disease alters endometrial gene expression in 75% of women, with patients exhibiting a preponderance of 163 up-regulated (e.g., UTS2, IFI6, IFIH1, BNIP3) and 72 down-regulated genes (e.g., CPZ, CDH3, IRF4) (FDR<0.05). A total of 161 dysregulated functions (36 up-regulated and 125 down-regulated) were typically enriched in COVID-19 endometria, including upregulation in pathways involved in response to virus and cytokine inflammation, highlighting upregulation of a COVID-19 response pathway. Conclusion: COVID-19 affects endometrial gene expression despite the absence of SARS-CoV-2 particles in endometrial tissues.
Project description:Persistent severe acute respiratory syndrome coronavirus 2 infection is difficult to treat. Here, we report a case of 5-month persistent coronavirus disease 2019 in an immunocompromised patient who was successfully treated with 30 consecutive days of remdesivir. Prolonged remdesivir infusion with concurrent cycle threshold monitoring might provide a potential solution to cure these patients with difficult-to-treat infections.
Project description:BackgroundTo investigate the CT imaging and clinical features of three atypical presentations of coronavirus disease 2019 (COVID-19), namely (1) asymptomatic, (2) CT imaging-negative, and (3) re-detectable positive (RP), during all disease stages.MethodsA consecutive cohort of 79 COVID-19 patients was retrospectively recruited from five independent institutions. For each presentation type, all patients were classified into atypical vs. typical groups (i.e., asymptomatic vs.symptomatic, CT imaging-negative vs. CT imaging-positive, and RP and non-RP,respectively). The chi-square test, Student's t test, and Kruskal-Wallis H test were performed to compare CT imaging and clinical features of atypical vs. typical patients for all three presentation categories.ResultsIn our COVID-19 cohort, we found 12.7% asymptomatic patients, 13.9% CT imaging-negative patients, and 8.9% RP patients. The asymptomatic patients had fewer hospitalization days (P=0.043), lower total scores for bilateral lung involvement (P< 0.001), and fewer ground-glass opacities (GGOs) in the peripheral area (P< 0.001) than symptomatic patients. The CT imaging-negative patients were younger (P=0.002), had a higher lymphocyte count (P=0.038), had a higher lymphocyte rate (P=0.008), and had more asymptomatic infections (P=0.002) than the CT imaging-positive patients. The RP patients with moderate COVID-19 had lower total scores of for bilateral lung involvement (P=0.030) and a smaller portion of the left lung affected (P=0.024) than non-RP patients. Compared to their first hospitalization, RP patients had a shorter hospitalization period (P< 0.001) and fewer days from the onset of illness to last RNA negative conversion (P< 0.001) at readmission.ConclusionsSignificant CT imaging and clinical feature differences were found between atypical and typical COVID-19 patients for all three atypical presentation categories investigated in this study, which may help provide complementary information for the effective management of COVID-19.
Project description:The catastrophic outbreak of coronavirus disease 2019 (COVID-19) is currently a public emergency. Adult-onset Still's disease (AOSD) is an autoinflammatory disease characterized by life-threatening complications. Systemic hyperinflammation and cytokine storm play a critical role in the pathogenesis of both COVID-19 and AOSD. We aimed to compare the similarities and differences focusing on ferritin and cytokine levels between severe COVID-19 and active AOSD. A literature search was performed using the databases PubMed, EMBASE, and Web of Science to collect the levels of cytokine including IL-1β, IL-6, IL-18, TNF-α, IL-10, and ferritin in severe COVID-19 patients. After extracting available data of indicators of interest, we acquired these statistics with a single-arm meta-analysis. Furthermore, a comparison was conducted between 52 patients with active AOSD in our center and severe COVID-19 patients from databases. The levels of IL-6 and IL-10 were higher in severe COVID-19 compared with those in active AOSD. There were no significant differences on the cytokine of IL-1β and TNF-α. Fold changes of IL-18 were defined as the mean expression level ratio of severe COVID-19 to healthy controls in the COVID-19 study and active AOSD to healthy controls in our study, individually. Although the fold change of IL-18 in patients with AOSD was significantly higher than patients with severe COVID-19 (fold change: 594.00 vs 2.17), there was no statistical comparability. In addition, the level of ferritin was higher in active AOSD in comparison with severe COVID-19. Our findings suggest that severe COVID-19 and active AOSD have differences in cytokine panel and ferritin level, indicating the pathogenic role of ferritin in overwhelming inflammation. And it paves the way to make efficacy therapeutic strategy targeting the hyperinflammatory process in COVID-19 according to AOSD management, especially in severe COVID-19.
Project description:Coronavirus disease 2019 (COVID-19) is an infection caused by the novel coronavirus severe acute respiratory coronavirus 2 (SARS-CoV-2). The infection manifests as a mild flu to severe acute respiratory infection. The World Health Organization (WHO) declared COVID-19 as a global pandemic on March 11, 2020. The disease spreads by droplet infection from person to person. Early diagnosis is the key for prompt management of cases and control of the spread of the virus. Currently, the laboratory diagnosis of SARS-CoV-2 is based on nucleic acid amplification tests (NAAT) like real-time reverse transcriptase (RT-PCR). Various genes like E, N, S, ORF and RdRp are targeted as a part of screening and confirmation of cases. Furthermore, nucleic acid sequencing may be done for the identification of mutation in the genome of SARS-CoV-2. The development of serological assays and point of care molecular test will further intensify the diagnostic modalities of SARS-CoV-2.
Project description:The purpose of this study was to identify miRNAs that were dysregulated after the onset of COVID-19 and thus potentially be used for risk stratification (i.e., mortality). Therefore, we conducted a multi-center, retrospective longitudinal cohort study enrolling 142 patients with laboratory-confirmed SARS-CoV-2 infection who presented to two Canadian hospitals from May 2020 – December 2020 along with a cohort of 27 SARS-CoV-2 patients with mild upper respiratory tract symptoms and 69 SARS-CoV-2-negative patients from the ICU. Blood was biobanked from SARS-CoV-2 positive patients in the emergency department (mild), ward (moderate) or intensive care unit (severe). Assessment of miRNA expression and co-regulatory network generation revealed significant transcriptome dyregulation in pateints with severe COVID-19 that was largely different from SARS-CoV-2 negative patients in the ICU.
Project description:The novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2 is an international public health emergency. Until now, the intermediate host and mechanisms of the interspecies jump of this virus are unknown. Phylogenetic analysis of all available bat CoV complete genomes was performed to analyze the relationships between bat CoV and SARS-CoV-2. To suggest a possible intermediate host, another phylogenetic reconstruction of CoV genomes obtained from animals that were hypothetically commercialized in the Chinese markets was also carried out. Moreover, mutation analysis was executed to suggest genomic regions that may have permitted the adaptation of SARS-CoV-2 to the human host. The phylogenetic analysis demonstrated that SARS-CoV-2 formed a cluster with the bat CoV isolate RaTG13. Possible CoV interspecies jumps among bat isolates were also observed. The phylogenetic tree reconstructed from CoV strains belonging to different animals demonstrated that SARS-CoV-2, bat RaTG13, and pangolin CoV genomes formed a monophyletic cluster, demonstrating that pangolins may be suggested as SARS-CoV-2 intermediate hosts. Three AA substitutions localized in the S1 portion of the S gene were observed, some of which have been correlated to structural modifications of the S protein which may facilitate SARS-CoV-2 tropism to human cells. Our analysis shows the tight relationship between SARS-CoV-2 and bat SARS-like strains. It also hypothesizes that pangolins might have been possible intermediate hosts of the infection. Some of the observed AA substitutions in the S-binding protein may serve as possible adaptation mutations in humans but more studies are needed to elucidate their function.