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3.
Lancet Infect Dis ; 2022 Apr 04.
Article in English | MEDLINE | ID: covidwho-1773856

ABSTRACT

COVID-19-associated pulmonary mucormycosis (CAPM) remains an underdiagnosed entity. Using a modified Delphi method, we have formulated a consensus statement for the diagnosis and management of CAPM. We selected 26 experts from various disciplines who are involved in managing CAPM. Three rounds of the Delphi process were held to reach consensus (≥70% agreement or disagreement) or dissensus. A consensus was achieved for 84 of the 89 statements. Pulmonary mucormycosis occurring within 3 months of COVID-19 diagnosis was labelled CAPM and classified further as proven, probable, and possible. We recommend flexible bronchoscopy to enable early diagnosis. The experts proposed definitions to categorise dual infections with aspergillosis and mucormycosis in patients with COVID-19. We recommend liposomal amphotericin B (5 mg/kg per day) and early surgery as central to the management of mucormycosis in patients with COVID-19. We recommend response assessment at 4-6 weeks using clinical and imaging parameters. Posaconazole or isavuconazole was recommended as maintenance therapy following initial response, but no consensus was reached for the duration of treatment. In patients with stable or progressive disease, the experts recommended salvage therapy with posaconazole or isavuconazole. CAPM is a rare but under-reported complication of COVID-19. Although we have proposed recommendations for defining, diagnosing, and managing CAPM, more extensive research is required.

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5.
Indian J Crit Care Med ; 26(3): 403-404, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1742858

ABSTRACT

Muthu V, Sehgal IS, Dhooria S, Prasad KT, Aggarwal AN, Agarwal R. Corticosteroids for Non-severe COVID-19: Primum Non Nocere. Indian J Crit Care Med 2022;26(3):403-404.

8.
Mycopathologia ; 187(1): 31-37, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1588765

ABSTRACT

Literature on COVID-19-associated pulmonary mucormycosis (CAPM) is sparse. Pulmonary artery pseudoaneurysm (PAP) is an uncommon complication of pulmonary mucormycosis (PM), and rarely reported in CAPM. Herein, we report five cases of CAPM with PAP managed at our center and perform a systematic review of the literature. We diagnosed PM in those with clinico-radiological suspicion and confirmed it by microbiology or histopathology. We encountered five cases of CAPM with PAP (size ranged from 1 × 0.8 cm to ~ 4.9 × 4.8 cm). All subjects had diabetes and were aged 55-62 years (75% men). In two cases, COVID-19 and mucormycosis were diagnosed simultaneously, while in three others, COVID-19 preceded PM. One subject who underwent surgery survived, while all others died (80% mortality). From our systematic review, we identified one additional case of CAPM with PAP in a transplant recipient. CAPM with PAP is rare with high mortality. Early diagnosis and multimodality management are imperative to improve outcomes.


Subject(s)
Aneurysm, False , COVID-19 , Mucormycosis , Aneurysm, False/diagnosis , Aneurysm, False/etiology , Female , Humans , Male , Mucormycosis/complications , Mucormycosis/diagnosis , Pulmonary Artery/diagnostic imaging , SARS-CoV-2
11.
Mycoses ; 65(1): 120-127, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1501485

ABSTRACT

BACKGROUND: Whether dysregulated iron metabolism is associated with COVID-19-associated mucormycosis (CAM) remains unknown. Herein, we compare the serum iron indices in COVID-19 subjects with and without mucormycosis. METHODS: We conducted a case-control study enrolling COVID-19 participants with and without mucormycosis. We compared the baseline serum iron indices (iron, ferritin, total iron-binding capacity [TIBC], unsaturated iron-binding capacity and percentage transferrin saturation) between CAM cases and COVID-19 controls. Additionally, we performed a multivariate logistic regression analysis to assess whether any iron indices are associated with CAM. RESULTS: We enrolled 28 CAM cases (mean age 53.6 years old; 78.6% men) and 26 controls (mean age 57.2 years old; 73.1% men). Rhino-orbital (±cerebral) mucormycosis (85.7%) was the most clinical presentation. Diabetes mellitus was more frequent in the cases than controls (75% vs. 42.3%; p = .015). Hypoxaemia during COVID-19 illness was more common in controls than cases. The mean serum iron values (33 vs. 45 µg/dl, p = .03) and TIBC (166.6 vs. 201.6 µg/dl, p = .003) were significantly lower in CAM cases than controls. On multivariate analysis, we found a lower TIBC (odds ratio [OR] 0.97; 95% confidence interval [CI], 0.95-0.99) and diabetes mellitus (OR 5.23; 95% CI, 1.21-22.68) to be independently associated with CAM after adjusting for serum iron, ferritin and glucocorticoid therapy. The case fatality rate of CAM was 73.9%. The iron indices were not significantly different between CAM survivors and non-survivors. CONCLUSIONS: The CAM is associated with lower TIBC levels than COVID-19 subjects without mucormycosis, suggesting dysregulated iron metabolism in its pathogenesis. Further studies are required to confirm our preliminary observations.


Subject(s)
COVID-19 , Ferritins/blood , Iron/blood , Mucormycosis , COVID-19/complications , Case-Control Studies , Diabetes Mellitus/epidemiology , Female , Humans , Male , Middle Aged , Mucormycosis/epidemiology
12.
PLoS One ; 16(10): e0259006, 2021.
Article in English | MEDLINE | ID: covidwho-1480463

ABSTRACT

OBJECTIVE: The proportion of COVID-19 patients having active pulmonary tuberculosis, and its impact on COVID-19 related patient outcomes, is not clear. We conducted this systematic review to evaluate the proportion of patients with active pulmonary tuberculosis among COVID-19 patients, and to assess if comorbid pulmonary tuberculosis worsens clinical outcomes in these patients. METHODS: We queried the PubMed and Embase databases for studies providing data on (a) proportion of COVID-19 patients with active pulmonary tuberculosis or (b) severe disease, hospitalization, or mortality among COVID-19 patients with and without active pulmonary tuberculosis. We calculated the proportion of tuberculosis patients, and the relative risk (RR) for each reported outcome of interest. We used random-effects models to summarize our data. RESULTS: We retrieved 3,375 citations, and included 43 studies, in our review. The pooled estimate for proportion of active pulmonary tuberculosis was 1.07% (95% CI 0.81%-1.36%). COVID-19 patients with tuberculosis had a higher risk of mortality (summary RR 1.93, 95% CI 1.56-2.39, from 17 studies) and for severe COVID-19 disease (summary RR 1.46, 95% CI 1.05-2.02, from 20 studies), but not for hospitalization (summary RR 1.86, 95% CI 0.91-3.81, from four studies), as compared to COVID-19 patients without tuberculosis. CONCLUSION: Active pulmonary tuberculosis is relatively common among COVID-19 patients and increases the risk of severe COVID-19 and COVID-19-related mortality.


Subject(s)
COVID-19/mortality , Hospitalization , SARS-CoV-2 , Tuberculosis, Pulmonary/mortality , Humans , Risk Factors , Tuberculosis, Pulmonary/virology
13.
Curr Opin Pulm Med ; 28(2): 84-92, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1470189

ABSTRACT

PURPOSE OF REVIEW: Asthma and chronic obstructive pulmonary disease (COPD) are widely prevalent disorders, and important contributors to morbidity and mortality, in both developing and developed countries. It is conjectured that these obstructive lung diseases may have had more deleterious effects in developing nations during the 2019 coronavirus disease (COVID-19) pandemic. We provide an evidence-based perspective on the relationship between asthma/COPD prevalence and COVID-19 burden, and the impact of comorbid asthma/COPD on selected COVID-19 outcomes and healthcare utilization, with special reference to developing countries. RECENT FINDINGS: Developing countries with higher COPD (but not asthma) prevalence appear to have higher COVID-19 related mortality. Patients with asthma (but not COPD) in developing countries may be less likely to acquire COVID-19. Published literature suggests that the overall impact of comorbid asthma or COPD on adverse COVID-19 outcomes may be broadly similar between developed and developing nations. SUMMARY: There is paucity of information on interaction between asthma/COPD and COVID-19 in developing countries. Limited data suggest minor differences between developed and developing nations. In view of inadequacies in healthcare preparedness and delivery in several developing countries, there is a need to generate quality evidence to assess impact of obstructive lung diseases and COVID-19 on each other.


Subject(s)
Asthma , COVID-19 , Pulmonary Disease, Chronic Obstructive , Asthma/epidemiology , Developing Countries , Humans , Pulmonary Disease, Chronic Obstructive/epidemiology , SARS-CoV-2
14.
Respir Care ; 66(12): 1912-1923, 2021 12.
Article in English | MEDLINE | ID: covidwho-1444437

ABSTRACT

BACKGROUND: We conducted this systematic review to evaluate whether asthma increases the risk of severe disease and adverse outcomes among subjects with COVID-19. METHODS: We queried the PubMed and Embase databases for studies indexed through December 2020. We included studies providing data on severe disease, hospitalization, ICU care, need for mechanical ventilation, or mortality among subjects with COVID-19 with and without asthma. We calculated the relative risk for each reported outcome of interest and used random effects modeling to summarize the data. RESULTS: We retrieved 1,832 citations, and included 90 studies, in our review. Most publications reported data retrieved from electronic records of retrospective subject cohorts. Only 25 studies were judged to be of high quality. Subjects with asthma and COVID-19 had a marginally higher risk of hospitalization (summary relative risk 1.13, 95% CI 1.03-1.24) but not for severe disease (summary relative risk 1.17, 95% CI 0.62-2.20), ICU admission (summary relative risk 1.13, 95% CI 0.96-1.32), mechanical ventilation (summary relative risk 1.05, 95% CI 0.85-1.29), or mortality (summary relative risk 0.92, 95% CI 0.82-1.04) as compared to subjects with COVID-19 without asthma. CONCLUSIONS: Comorbid asthma increases risk of COVID-19-related hospitalization but not severe disease or other adverse outcomes in subjects with COVID-19.


Subject(s)
Asthma , COVID-19 , Asthma/complications , Hospitalization , Humans , Respiration, Artificial , Retrospective Studies , SARS-CoV-2
15.
Emerg Infect Dis ; 27(9): 2349-2359, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1406812

ABSTRACT

During September-December 2020, we conducted a multicenter retrospective study across India to evaluate epidemiology and outcomes among cases of coronavirus disease (COVID-19)-associated mucormycosis (CAM). Among 287 mucormycosis patients, 187 (65.2%) had CAM; CAM prevalence was 0.27% among hospitalized COVID-19 patients. We noted a 2.1-fold rise in mucormycosis during the study period compared with September-December 2019. Uncontrolled diabetes mellitus was the most common underlying disease among CAM and non-CAM patients. COVID-19 was the only underlying disease in 32.6% of CAM patients. COVID-19-related hypoxemia and improper glucocorticoid use independently were associated with CAM. The mucormycosis case-fatality rate at 12 weeks was 45.7% but was similar for CAM and non-CAM patients. Age, rhino-orbital-cerebral involvement, and intensive care unit admission were associated with increased mortality rates; sequential antifungal drug treatment improved mucormycosis survival. The COVID-19 pandemic has led to increases in mucormycosis in India, partly from inappropriate glucocorticoid use.


Subject(s)
COVID-19 , Mucormycosis , Antifungal Agents/therapeutic use , Humans , India/epidemiology , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Mucormycosis/epidemiology , Pandemics , Retrospective Studies , SARS-CoV-2
17.
Mycoses ; 64(10): 1291-1297, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1367354

ABSTRACT

BACKGROUND: The enormous increase in COVID-19-associated mucormycosis (CAM) in India lacks an explanation. Zinc supplementation during COVID-19 management is speculated as a contributor to mucormycosis. We conducted an experimental and clinical study to explore the association of zinc and mucormycosis. METHODS: We inoculated pure isolates of Rhizopus arrhizus obtained from subjects with CAM on dichloran rose Bengal chloramphenicol (DRBC) agar enriched with (three different concentrations) and without zinc. At 24 h, we counted the viable colonies and measured the dry weight of colonies at 24, 48 and 72 h. We also compared the clinical features and serum zinc levels in 29 CAM cases and 28 COVID-19 subjects without mucormycosis (controls). RESULTS: We tested eight isolates of R arrhizus and noted a visible increase in growth in zinc-enriched media. A viable count percentage showed a significantly increased growth in four of the eight isolates in zinc-augmented DRBC agar. A time- and concentration-dependent increase in the mean fungal biomass with zinc was observed in all three isolates tested. We enrolled 29 cases of CAM and 28 controls. The mean serum zinc concentration was below the reference range in all the subjects and was not significantly different between the cases and controls. CONCLUSIONS: Half of the R arrhizus isolates grew better with zinc enrichment in vitro. However, our study does not conclusively support the hypothesis that zinc supplementation contributed to the pathogenesis of mucormycosis. More data, both in vitro and in vivo, may resolve the role of zinc in the pathogenesis of CAM.


Subject(s)
COVID-19/epidemiology , Mucormycosis/epidemiology , Rhizopus oryzae/growth & development , Zinc Compounds/adverse effects , Zinc Compounds/metabolism , COVID-19/pathology , Case-Control Studies , Female , Humans , India/epidemiology , Male , Middle Aged , Mucormycosis/mortality , Mucormycosis/pathology , Rhizopus oryzae/isolation & purification , SARS-CoV-2/isolation & purification , Zinc Compounds/therapeutic use
18.
Mycopathologia ; 186(6): 739-754, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1366388

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has led to a concerning resurgence of mucormycosis. More than 47,000 cases of mucormycosis were reported in three months from India. We update our systematic review on COVID-19-associated mucormycosis (CAM) till June 21st, 2021, comparing cases reported from India and elsewhere. We included individual patient details of 275 cases of CAM, of which 233 were reported from India and 42 from the rest of the world. Diabetes mellitus was the most common underlying risk factor for CAM in India than in other countries. The fatality rate of cases reported from India (36.5%) was less than the globally reported cases (61.9%), probably due to the predominance of rhino-orbital mucormycosis. On a multivariate analysis, we found that pulmonary or disseminated mucormycosis cases and admission to the intensive care unit were associated with increased mortality, while combination medical therapy improved survival. The paucity of pulmonary and disseminated mucormycosis cases from India suggests that these cases were either not diagnosed or reported, further supported by a trend of search data from the Google search engine. In this review, we discuss the factors explaining the substantial rise in cases of CAM. We also propose a hypothetical model describing the epidemiologic triad of CAM.


Subject(s)
COVID-19 , Diabetes Mellitus , Mucormycosis , Humans , India/epidemiology , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Mucormycosis/epidemiology , Risk Factors , SARS-CoV-2
19.
Mycoses ; 64(9): 1028-1037, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1270864

ABSTRACT

Reports are increasing on the emergence of COVID-19-associated mucormycosis (CAM) globally, driven particularly by low- and middle-income countries. The recent unprecedented surge of CAM in India has drawn worldwide attention. More than 28,252 mucormycosis cases are counted and India is the first country where mucormycosis has been declared a notifiable disease. However, misconception of management, diagnosing and treating this infection continue to occur. Thus, European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) felt the need to address clinical management of CAM in low- and middle-income countries. This article provides a comprehensive document to help clinicians in managing this infection. Uncontrolled diabetes mellitus and inappropriate (high dose or not indicated) corticosteroid use are the major predisposing factors for this surge. High counts of Mucorales spores in both the indoor and outdoor environments, and the immunosuppressive impact of COVID-19 patients as well as immunotherapy are possible additional factors. Furthermore, a hyperglycaemic state leads to an increased expression of glucose regulated protein (GRP- 78) in endothelial cells that may help the entry of Mucorales into tissues. Rhino-orbital mucormycosis is the most common presentation followed by pulmonary mucormycosis. Recommendations are focused on the early suspicion of the disease and confirmation of diagnosis. Regarding management, glycaemic control, elimination of corticosteroid therapy, extensive surgical debridement and antifungal therapy are the standards for proper care. Due to limited availability of amphotericin B formulations during the present epidemic, alternative antifungal therapies are also discussed.


Subject(s)
Antifungal Agents/standards , Antifungal Agents/therapeutic use , COVID-19/complications , Intensive Care Units/standards , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Mucormycosis/physiopathology , Adult , Aged , Aged, 80 and over , COVID-19/microbiology , Female , Humans , Male , Middle Aged , Practice Guidelines as Topic , SARS-CoV-2
20.
Emerg Infect Dis ; 27(9): 2349-2359, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1259328

ABSTRACT

During September-December 2020, we conducted a multicenter retrospective study across India to evaluate epidemiology and outcomes among cases of coronavirus disease (COVID-19)-associated mucormycosis (CAM). Among 287 mucormycosis patients, 187 (65.2%) had CAM; CAM prevalence was 0.27% among hospitalized COVID-19 patients. We noted a 2.1-fold rise in mucormycosis during the study period compared with September-December 2019. Uncontrolled diabetes mellitus was the most common underlying disease among CAM and non-CAM patients. COVID-19 was the only underlying disease in 32.6% of CAM patients. COVID-19-related hypoxemia and improper glucocorticoid use independently were associated with CAM. The mucormycosis case-fatality rate at 12 weeks was 45.7% but was similar for CAM and non-CAM patients. Age, rhino-orbital-cerebral involvement, and intensive care unit admission were associated with increased mortality rates; sequential antifungal drug treatment improved mucormycosis survival. The COVID-19 pandemic has led to increases in mucormycosis in India, partly from inappropriate glucocorticoid use.


Subject(s)
COVID-19 , Mucormycosis , Antifungal Agents/therapeutic use , Humans , India/epidemiology , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Mucormycosis/epidemiology , Pandemics , Retrospective Studies , SARS-CoV-2
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