Risk factors for pulmonary mucormycosis in subjects with diabetes mellitus-A case-control study.

BACKGROUND: Factors associated with pulmonary mucormycosis (PM) among subjects with diabetes mellitus (DM) remain unclear. Following the coronavirus disease (COVID-19)-associated mucormycosis outbreak in India, specific environmental exposures (especially cattle dung exposure) were proposed as possible aetiology. We hypothesized that environmental factors are associated with PM. We compared subjects with DM with (cases) and without PM (controls). METHODS: In this case-control study, for each PM case, we included five unmatched diabetic controls (hospital [n = 2], community [n = 3]) without PM. We collected information on demography, COVID-19 infection, glycated haemoglobin% (HbA1c), the type of house (pucca vs. kutcha) where the participants reside, and other environmental factors. The primary exposure tested was cattle dung exposure (CDE; using cattle dung cakes as fuel or cattle handling). We performed a multivariate logistic regression to explore factors associated with PM and report the association as an adjusted odds ratio (OR) with 95% confidence intervals (CI). RESULTS: We enrolled 39 PM cases and 199 controls (hospital [n = 80], community [n = 119]). CDE (OR 0.68, 95% CI [0.14-3.31]; p = 0.63) was not associated with increased PM in DM. We found male sex (OR 4.07, 95% CI [1.16-14.31]), higher HbA1c (OR 1.51, 95% CI [1.18-16.32]), COVID-19 (OR 28.25, 95% CI [7.02-113.6]) and residence at kutcha house (OR 4.84, 95% CI [1.33-17.52]) associated with PM. CONCLUSION: Cattle dung exposure was not associated with PM in subjects with DM. Instead, male sex, poor glycaemic control, COVID-19 and the type of housing were associated with pulmonary mucormycosis.

Doffing Corridor: Establishing Expedited High-Volume Doffing With Exposure Reduction to Contaminated Personal Protective Equipment (PPE) in a COVID-19 Hospital in India.

Background Considering the virulent nature of the COVID-19, the safety of healthcare workers (HCW) became a challenge for hospital administrators. Wearing a personal protective equipment (PPE) kit, called donning, which can be easily done by the help of another staff. But correctly removing the infectious PPE kit (doffing) was a challenge. The increased number of HCWs for COVID-19 patient care raised the opportunity to develop an innovative method for the smooth doffing of PPEs. Objective We aimed to design and establish an innovative PPE doffing corridor in a tertiary care COVID-19 hospital during the pandemic in India with a heavy doffing rate and minimize the COVID-19 virus spread among healthcare workers. Methodology A prospective, observational cohort study at the COVID-19 hospital, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, was conducted from July 19, 2020, to March 30, 2021. The time taken for PPE doffing process of HCWs was observed and compared between the doffing room and doffing corridor. The data was collected by a public health nursing officer using Epicollect5 mobile software and Google forms. The following parameters, like grade of satisfaction, time and volume of doffing, the errors in the steps of doffing, rate of infection, were compared between the doffing corridor and the doffing room. The statistical analysis was done by the use of SPSS software. Result 'Doffing corridor' decreased the overall doffing time by 50% compared to the initial doffing room. The doffing corridor solved the purpose of accommodating more HCWs for PPE doffing and an overall saving of 50% time. Fifty-one percent of HCWs rated the satisfaction rate as Good in the grading scale. The errors in the steps of doffing that occurred in the doffing process were comparatively lesser in the doffing corridor. The HCWs who doffed in the doffing corridor were three times less likely to get self-infection than the conventional doffing room. Conclusion Since COVID-19 was a new pandemic, the healthcare organizations focused on innovations to combat the spread of virus. One of these was an innovative doffing corridor to expedite the doffing process and decrease the exposure time to the contaminated items. The doffing corridor process can be considered at a high-interest rate to any hospital dealing with infectious disease, with high working satisfaction, less exposure to the contagion, and less risk of infection.

Treatment of pulmonary mucormycosis with adjunctive nebulized amphotericin B (MUCONAB trial): Results of an open-label randomized controlled trial.

BACKGROUND: The role of nebulized amphotericin B (NAB) in managing pulmonary mucormycosis (PM) is unknown. METHODS: In this open-label trial, we randomized PM subjects to receive either intravenous liposomal amphotericin B (control arm, 3-5 mg/kg/day) alone or along with nebulized amphotericin B deoxycholate (NAB, 10 mg twice a day, every alternate day). The primary outcomes were: (1) overall response ('success' [complete or partial response] or 'failure' [stable disease, progressive disease, or death]) at 6 weeks; and (2) the proportion of subjects with adverse events (AE). The key secondary outcome was 90-day mortality. We performed a modified intention-to-treat (mITT) analysis where we included only subjects receiving at least a single dose of NAB. RESULTS: Fifteen and 17 subjects were randomized to the control and NAB arms; two died before the first dose of NAB. Finally, we included 30 subjects (15 in each arm; mean age 49.8 years; 80% men) for the mITT analysis. Diabetes mellitus (n = 27; 16/27 were COVID-19-associated PM) was the most common predisposing factor. The overall treatment success was not significantly different between the control and the NAB arms (71.4% vs. 53.3%; p = .45). Twenty-nine subjects experienced any AE, but none discontinued treatment. The 90-day mortality was not significantly different between the control (28.6%) and NAB arm (53.3%; p = .26). CONCLUSION: Adjunctive NAB was safe but did not improve overall response at 6 weeks. A different dosing schedule or nebulized liposomal amphotericin B may still need evaluation. More research is needed to explore other treatment options for PM.

CT findings in sequel of COVID-19 pneumonia and its complications.

A significant number of patients after initial recovery from COVID-19 continue to experience lingering symptoms of the disease that may last for weeks or even months. Lungs being the most commonly affected organ by COVID-19, bear the major brunt of the disease and thus it is imperative to be aware of the evolution of the pulmonary parenchymal changes over time. CT chest is the imaging modality of choice to evaluate post-COVID lungs. Persistent ground-glass opacities, septal thickening, parenchymal bands, crazy-paving, traction bronchiectasis and consolidation constitute the commonly encountered imaging patterns seen on CT in post-COVID-19 lungs. Few vulnerable patients can develop lung fibrosis and show honeycombing on CT. Additionally, many complications like superadded infections (bacterial and fungal), pulmonary thromboembolism and pseudoaneurysm formation are also being reported. In the present pictorial review, we have tried to show the entire CT spectrum of sequelae of COVID-19 pneumonia and commonly associated infections and vascular complications.

Serum glucose-regulated protein 78 (GRP78) levels in COVID-19-associated mucormycosis: results of a case–control study

Background In experimental models, the expression of glucose-regulated protein 78 (GRP78) in endothelial cells played a role in the pathogenesis of mucormycosis. However, the role of GRP78 in COVID-19-associated mucormycosis (CAM) has not been studied. We hypothesized that serum GRP78 levels are elevated in subjects with CAM. Objective To compare the serum GRP78 levels in subjects with CAM and COVID-19 controls without mucormycosis. Design And Setting We performed a hospital-based, case–control study between 1 April 2021 and 31 May 2021. Participants We enrolled 24 subjects each of CAM and COVID-19 subjects without mucormycosis. We also measured serum GRP78 levels in ten healthy controls. Exposure The primary exposure studied was serum GRP78 concentration, estimated using a commercially available ELISA kit in stored serum samples. Results We found the mean ± standard deviation (SD) serum GRP78 levels significantly higher (p = 0.0001) among the CAM (374.3 ± 127.3 pg/mL) than the COVID-19 (246.4 ± 67.0 pg/mL) controls. The proportion of subjects with an abnormal GRP78 level (> mean [184.8 pg/mL] plus two SD [23.2 pg/mL] of GRP78 from healthy participants) was 87.5% and 45.8% in the CAM group and COVID-19 controls, respectively. Serum GRP78 level was independently associated with CAM (odds ratio 1.011;95% confidence interval [1.002–1.019]) after adjusting for diabetes mellitus and hypoxemia during acute COVID-19. Conclusion Serum GRP78 levels were significantly higher in CAM than in COVID-19 controls. Further studies are required to the role of GRP78 in the pathogenesis of CAM. Supplementary Information The online version contains supplementary material available at 10.1007/s11046-022-00645-6.

Serum glucose-regulated protein 78 (GRP78) levels in COVID-19-associated mucormycosis: results of a case-control study.

BACKGROUND: In experimental models, the expression of glucose-regulated protein 78 (GRP78) in endothelial cells played a role in the pathogenesis of mucormycosis. However, the role of GRP78 in COVID-19-associated mucormycosis (CAM) has not been studied. We hypothesized that serum GRP78 levels are elevated in subjects with CAM. OBJECTIVE: To compare the serum GRP78 levels in subjects with CAM and COVID-19 controls without mucormycosis. DESIGN AND SETTING: We performed a hospital-based, case-control study between 1 April 2021 and 31 May 2021. PARTICIPANTS: We enrolled 24 subjects each of CAM and COVID-19 subjects without mucormycosis. We also measured serum GRP78 levels in ten healthy controls. EXPOSURE: The primary exposure studied was serum GRP78 concentration, estimated using a commercially available ELISA kit in stored serum samples. RESULTS: We found the mean ± standard deviation (SD) serum GRP78 levels significantly higher (p = 0.0001) among the CAM (374.3 ± 127.3 pg/mL) than the COVID-19 (246.4 ± 67.0 pg/mL) controls. The proportion of subjects with an abnormal GRP78 level (> mean [184.8 pg/mL] plus two SD [23.2 pg/mL] of GRP78 from healthy participants) was 87.5% and 45.8% in the CAM group and COVID-19 controls, respectively. Serum GRP78 level was independently associated with CAM (odds ratio 1.011; 95% confidence interval [1.002-1.019]) after adjusting for diabetes mellitus and hypoxemia during acute COVID-19. CONCLUSION: Serum GRP78 levels were significantly higher in CAM than in COVID-19 controls. Further studies are required to the role of GRP78 in the pathogenesis of CAM.

Could cattle dung burning have contributed to the epidemic of COVID-19-associated mucormycosis in India? Results of an experimental aero-mycological study.

BACKGROUND: Several hypotheses have been proposed for explaining the outbreak of coronavirus disease 2019 (COVID-19)-associated mucormycosis in India, including the burning of cattle dung cakes, though no study has yet been conducted to support this claim. METHODS: We conducted an aero-mycological study to evaluate whether Mucorales in the air increased during or after burning cattle dung cakes. We further compared the growth of Mucorales in the indoor air samples from houses with and without cattle. We also cultured fresh and dried cattle dung and soil samples for Mucorales. RESULTS: We noted no significant difference in the proportion of air samples growing Mucorales during (4/22 [18.2%]) and after (3/2 [13.6%]) cattle dung burning than that collected immediately before (4/22 [18.2%]). Mucorales were isolated in 15.4% of the indoor air samples obtained from different houses (both rural and urban); the proportion of samples growing Mucorales was not significantly different in households with and without cattle. We also observed growth of Mucorales in 6 of the 8 [75%] fresh and 3 of the 6 [50%] dried dung samples. The most common Mucorales isolated from soil and dung samples was Lichtheimia corymbifera, while Rhizopus arrhizus was the most common species isolated from indoor air samples. CONCLUSIONS: We found no significant increase in the proportion of air samples growing Mucorales during or after burning cattle dung cake than that before. It seems unlikely that cattle dung burning contributes to the occurrence of mucormycosis.

A 63-year-old man with hypoxemia and shock after initial recovery from COVID-19 pneumonia.

A 63-year-old man presented with fever and breathlessness during the coronavirus disease 2019 (COVID-19) pandemic. He was diagnosed to have severe COVID-19 pneumonia. He was treated with oxygen, noninvasive ventilation, and glucocorticoids. He improved over 5 weeks and was shifted out of the intensive care unit. Subsequently, he experienced worsening during hospitalization with refractory hypoxemia and shock and finally succumbed to his illness. An autopsy was performed. Herein, we have presented a clinical discussion on the possible causes of the patient's fatal outcome followed by the autopsy findings.

Definition, diagnosis, and management of COVID-19-associated pulmonary mucormycosis: Delphi consensus statement from the Fungal Infection Study Forum and Academy of Pulmonary Sciences, India.

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.

Corticosteroids for Non-severe COVID-19: Primum Non Nocere.

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.

Serum iron indices in COVID-19-associated mucormycosis: A case-control study.

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.

Active pulmonary tuberculosis and coronavirus disease 2019: A systematic review and meta-analysis.

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.