COVID-19 and fungal infections: Etiopathogenesis and therapeutic implications.
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ABSTRACT:
SUBMITTER: Chumbita M
PROVIDER: S-EPMC8683007 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Invasive fungal infections (IFIs) can complicate the clinical course of COVID-19 and are associated with a significant increase in mortality, especially in critically ill patients admitted to an intensive care unit (ICU). This narrative review concerns 4099 cases of IFIs in 58,784 COVID-19 patients involved in 168 studies. COVID-19-associated invasive pulmonary aspergillosis (CAPA) is a diagnostic challenge because its non-specific clinical/imaging features and the fact that the proposed clinically diagnostic algorithms do not really apply to COVID-19 patients. Forty-seven observational studies and 41 case reports have described a total of 478 CAPA cases that were mainly diagnosed on the basis of cultured respiratory specimens and/or biomarkers/molecular biology, usually without histopathological confirmation. Candidemia is a widely described secondary infection in critically ill patients undergoing prolonged hospitalisation, and the case reports and observational studies of 401 cases indicate high crude mortality rates of 56.1% and 74.8%, respectively. COVID-19 patients are often characterised by the presence of known risk factors for candidemia such as in-dwelling vascular catheters, mechanical ventilation, and broad-spectrum antibiotics. We also describe 3185 cases of mucormycosis (including 1549 cases of rhino-orbital mucormycosis (48.6%)), for which the main risk factor is a history of poorly controlled diabetes mellitus (>76%). Its diagnosis involves a histopathological examination of tissue biopsies, and its treatment requires anti-fungal therapy combined with aggressive surgical resection/debridement, but crude mortality rates are again high: 50.8% in case reports and 16% in observational studies. The presence of other secondary IFIs usually diagnosed in severely immunocompromised patients show that SARS-CoV-2 is capable of stunning the host immune system: 20 cases of Pneumocystis jirovecii pneumonia, 5 cases of cryptococcosis, 4 cases of histoplasmosis, 1 case of coccidioides infection, 1 case of pulmonary infection due to Fusarium spp., and 1 case of pulmonary infection due to Scedosporium.
| S-EPMC8620819 | biostudies-literature
Project description:Severe COVID-19 disease is associated with an increase in pro-inflammatory markers, such as IL-1, IL-6, and tumor necrosis alpha, less CD4 interferon-gamma expression, and fewer CD4 and CD8 cells, which increase the susceptibility to bacterial and fungal infections. One such opportunistic fungal infection is mucormycosis. Initially, it was debated whether a person taking immunosuppressants, such as corticosteroids, and monoclonal antibodies will be at higher risk for COVID-19 or whether the immunosuppresive state would cause a more severe COVID-19 disease. However, immunosuppressants are currently continued unless the patients are at greater risk of severe COVID-19 infection or are on high-dose corticosteroids therapy. As understood so far, COVID-19 infection may induce significant and persistent lymphopenia, which in turn increases the risk of opportunistic infections. It is also noted that 85% of the COVID-19 patients' laboratory findings showed lymphopenia. This means that patients with severe COVID-19 have markedly lower absolute number of T lymphocytes, CD4+T and CD8+ T cells and, since the lymphocytes play a major role in maintaining the immune homeostasis, the patients with COVID-19 are highly susceptible to fungal co-infections. This report is intended to raise awareness of the importance of early detection and treatment of mucormycosis and other fungal diseases, such as candidiasis, SARS-CoV-2-associated pulmonary aspergillosis, pneumocystis pneumonia and cryptococcal disease, in COVID-19 patients, to reduce the risk of mortality.
| S-EPMC8137279 | biostudies-literature
Project description:ObjectivesThis systematic review aims to summarize the mycological and clinical features of COVID-19-associated fungal infections (CAFIs) in Iran.MethodsPubMed, Web of Science, Scopus, Cochrane Library, SID, Magiran, IranDoc, and Google Scholar were searched for Persian and English articles published from January 1, 2020, to November 5, 2021, using a systematic search strategy. Studies on Iranian patients suffering from CAFIs were included in the review.ResultsTwenty-two studies comprising 169 patients were retrieved. Reported CAFIs included candidiasis (85, 50.30%), mucormycosis (35, 20.71%), aspergillosis (29, 17.16%), fusariosis (6, 3.55%), three cases caused by rare pathogens (Rhodotorula mucilaginosa, Diaporthe foeniculina, and Sarocladium kiliense) and 11 (6.51%) uncharacterized mold infections. The most common underlying diseases were diabetes (67/168, 39.88%), cardiovascular diseases (55/168, 32.74%), and hypertension (43/168, 25.59%). The use of antibiotics (111/124, 89.52%), corticosteroids (93/132, 70.44%), and mechanical ventilation (66, 51.16%) were the most common predisposing factors. Totally, 72 (50.35%) of 143 patients with CAFIs died (data were not available for 26 patients).ConclusionFungal infections are evident to be a complication of COVID-19 in Iran; thus, clinicians should consider them as a differential diagnosis, especially in patients with comorbidities and previous antibiotic or corticosteroid use.
| S-EPMC9273100 | biostudies-literature
Project description:The coagulopathy of COVID-19 is characterised by significantly elevated D Dimer and fibrinogen, mild thrombocytopenia and a mildly prolonged PT/APTT. A high incidence of thrombotic complications occurs despite standard thromboprophylaxis. The evidence to date supports immunothrombosis as the underlying mechanism for this coagulopathy which is triggered by a hyperinflammatory response and endotheliopathy. A hypercoagulable state results from endothelial damage/activation, complement activation, platelet hyperactivity, release of Extracellular Neutrophil Traps, activation of the coagulation system and a "hypofibrinolytic" state. Significant cross-talk occurs between the innate/adaptive immune system, endothelium and the coagulation system. D dimer has been shown to be the most reliable predictor of disease severity, thrombosis, and overall survival. In this context, targeting pathways upstream of coagulation using novel or repurposed drugs alone or in combination with other anti-thrombotic agents may be a rational approach to prevent the mortality/morbidity due to COVID-19 associated coagulopathy.
| S-EPMC8596655 | biostudies-literature
Project description:The SARS-CoV-2 virus invades and replicates within host cells by "hijacking" biomolecular machinery, gaining control of the microtubule cytoskeleton. After attaching to membrane receptors and entering cells, the SARS-CoV-2 virus co-opts the dynamic intra-cellular cytoskeletal network of microtubules, actin, and the microtubule-organizing center, enabling three factors that lead to clinical pathology: (1) viral load due to intra-cellular trafficking, (2) cell-to-cell spread by filopodia, and (3) immune dysfunction, ranging from hyper-inflammatory cytokine storm to ineffective or absent response. These factors all depend directly on microtubules and the microtubule-organizing center, as do cell functions such as mitosis and immune cell movement. Here we consider how the SARS-CoV-2 virus may "hijack" cytoskeletal functions by docking inside the microtubule-organizing center's centriole "barrels", enabling certain interactions between the virus's positively charged spike ("S") proteins and negatively charged C-termini of the microtubules that the centriole comprises, somewhat like fingers on a keyboard. This points to the potential benefit of therapies aimed not directly at the virus but at the microtubules and microtubule-organizing center of the host cell on which the virus depends. These therapies could range from anti-microtubule drugs to low-intensity ultrasound (megahertz mechanical vibrations) externally applied to the vagus nerve at the neck and/or to the spleen (since both are involved in mediating inflammatory response). Given that ultrasound imaging machines suitable for vagal/splenic ultrasound are available for clinical trials in every hospital, we recommend an alternative therapeutic approach for COVID-19 based on addressing and normalizing the host cell microtubules and microtubule-organizing centers co-opted by the SARS-CoV-2 virus.
| S-EPMC9225596 | biostudies-literature
Project description:This study systematically reviewed fungal-bacterial co-infections and super-infections among hospitalized COVID-19 patients. A PRISMA systematic search was conducted. On September 2022, Medline, PubMed, Google Scholar, PsychINFO, Wiley Online Library, NATURE, and CINAHL databases were searched for all relevant articles published in English. All articles that exclusively reported the presence of fungal-bacterial co-infections and super-infections among hospitalized COVID-19 patients were included. Seven databases produced 6937 articles as a result of the literature search. Twenty-four articles met the inclusion criteria and were included in the final analysis. The total number of samples across the studies was 10,834, with a total of 1243 (11.5%) patients admitted to the intensive care unit (ICU). Of these patients, 535 underwent mechanical ventilation (4.9%), 2386 (22.0%) were male, and 597 (5.5%) died. Furthermore, hospitalized COVID-19 patients have a somewhat high rate (23.5%) of fungal-bacterial co-infections and super-infections. Moreover, for SARS-CoV-2 patients who have a chest X-ray that suggests a bacterial infection, who require immediate ICU admission, or who have a seriously immunocompromised condition, empiric antibiotic therapy should be taken into consideration. Additionally, the prevalence of co-infections and super-infections among hospitalized COVID-19 patients may have an impact on diagnosis and treatment. It is crucial to check for fungal and bacterial co-infections and super-infections in COVID-19 patients.
| S-EPMC10299597 | biostudies-literature
Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis.SummaryThe pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions. The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients' clinical outcomes and prognosis. Key Messages: The objective of this article is to explore and comment on the potential role of the promising immunomodulatory therapies using pharmacological and nonpharmacological approaches to overcome the dysregulated proinflammatory response in COVID-19.
| S-EPMC7360507 | biostudies-literature
Project description:The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has profoundly impacted all fields of medicine. Infection with SARS-CoV-2 and the resulting coronavirus of 2019 (COVID-19) syndrome has multiorgan effects. The pandemic has united researchers from bench to bedside in attempts to understand the pathophysiology of the disease and define optimal treatment strategies. Cardiovascular disease is highly prevalent and a leading cause of death across gender, race, and ethnic groups. As the pandemic spreads, there is increasing concern about the cardiovascular effects of the viral infection and the interaction of infection with existing cardiovascular disease. Additionally, there are concerns about the cardiac effects of the numerous treatment agents under study. It will be essential for cardiologists to understand the interplay between underlying cardiac comorbidities, acute cardiovascular effects of COVID-19 disease, and adverse effects of new treatments. Here we describe emerging evidence of the epidemiology of SARS-CoV-2 infection and underlying cardiovascular disease, the evidence for direct myocardial injury in SARS-CoV-2 infection, the specific presentations of cardiovascular involvement by SARS-CoV-2, and the cardiac effects of emerging treatments.
| S-EPMC7292941 | biostudies-literature
Project description:Mesenchymal stromal cells (MSCs) constitute a heterogeneous population of stromal cells with immunomodulatory and regenerative properties that support their therapeutic use. MSCs isolated from many tissue sources replicate vigorously in vitro and maintain their main biological properties allowing their widespread clinical application. To date, most MSC-based preclinical and clinical trials targeted immune-mediated and inflammatory diseases. Nevertheless, MSCs have antiviral properties and have been used in the treatment of various viral infections in the last years. Here, we revised in detail the biological properties of MSCs and their preclinical and clinical applications in viral diseases, including the disease caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection (COVID-19). Notably, rapidly increasing numbers of MSC-based therapies for COVID-19 have recently been reported. MSCs are theoretically capable of reducing inflammation and promote lung regeneration in severe COVID-19 patients. We critically discuss the rationale, advantages and disadvantages of MSC-based therapies for viral infections and also specifically for COVID-19 and point out some directions in this field. Finally, we argue that MSC-based therapy may be a promising therapeutic strategy for severe COVID-19 and other emergent respiratory tract viral infections, beyond the viral infection diseases in which MSCs have already been clinically applied. Graphical Abstract.
| S-EPMC7476649 | biostudies-literature
Project description:Background: Invasive Fungal Infections (IFI) are emergent complications of COVID-19. In this study, we aim to describe the prevalence, related factors, and outcomes of IFI in critical COVID-19 patients. Methods: We conducted a nested case-control study of all COVID-19 patients in the intensive care unit (ICU) who developed any IFI and matched age and sex controls for comparison (1:1) to evaluate IFI-related factors. Descriptive and comparative analyses were made, and the risk factors for IFI were compared versus controls. Results: We found an overall IFI prevalence of 9.3% in COVID-19 patients in the ICU, 5.6% in COVID-19-associated pulmonary aspergillosis (CAPA), and 2.5% in invasive candidiasis (IC). IFI patients had higher SOFA scores, increased frequency of vasopressor use, myocardial injury, and more empirical antibiotic use. CAPA was classified as possible in 68% and 32% as probable by ECMM/ISHAM consensus criteria, and 57.5% of mortality was found. Candidemia was more frequent for C. parapsilosis Fluconazole resistant outbreak early in the pandemic, with a mortality of 28%. Factors related to IFI in multivariable analysis were SOFA score > 2 (aOR 5.1, 95% CI 1.5-16.8, p = 0.007) and empiric antibiotics for COVID-19 (aOR 30, 95% CI 10.2-87.6, p = <0.01). Conclusions: We found a 9.3% prevalence of IFIs in critically ill patients with COVID-19 in a single center in Mexico; factors related to IFI were associated with higher SOFA scores and empiric antibiotic use for COVID-19. CAPA is the most frequent type of IFI. We did not find a mortality difference.
| S-EPMC10219464 | biostudies-literature