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.

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.

Role of MRI in the Evaluation of Pulmonary Sequel Following COVID-19 Acute Respiratory Distress Syndrome (ARDS).

To evaluate the role of magnetic resonance imaging (MRI) chest as an alternative modality to CT chest for follow-up of patients recovered from severe COVID-19 acute respiratory distress syndrome (ARDS). A total of 25 subjects (16 [64%] men; mean age 54.84 years ± 12.35) who survived COVID-19 ARDS and fulfilled the inclusion criteria were enrolled prospectively. All the patients underwent CT and MRI chest (on the same day) at 6-weeks after discharge. MRI chest was acquired on 1.5T MRI using HASTE, BLADE, VIBE, STIR, and TRUFI sequences and evaluated for recognition of GGOs, consolidation, reticulations/septal thickening, parenchymal bands, and bronchial dilatation with CT chest as the gold standard. The differences were assessed by independent-sample t-test and Mann-Whitney U test. P-value of less than 0.05 was taken significant. There was a strong agreement (k = 0.8-1, P<0.01) between CT and MRI chest. On CT, the common manifestations were: GGOs (n=24, 96%), septal thickening/reticulations (n=24, 96%), bronchial dilatation (n=16, 64%), parenchymal bands (n=14, 56%), pleural thickening (n=8, 32%), consolidation (n=4, 16%) and crazy-paving (n=4, 16%). T2W HASTE, T2W BLADE, and T1 VIBE sequences showed 100% (95% CI, 40-100) sensitivity and 100% (95% CI, 3-100) specificity for detecting GGOs, septal thickening/reticulations, pleural thickening, consolidation, and crazy-paving. The overall sensitivity of MRI for detection of bronchial dilatation and parenchymal bands were 88.9% (95% CI, 77-100) and 92.9% (95% CI, 66-100), respectively; and specificity was 100% (95% CI, 29-100) for both findings. MRI chest, being radiation-free imaging modality can act as an alternative to CT chest in the evaluation of lung changes in patients recovered from COVID-19 pneumonia.

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.

Ultra-Low Dose CT Chest in Acute COVID-19 Pneumonia: A Pilot Study from India.

The rapid increase in the number of CT acquisitions during the COVID-19 pandemic raised concerns about increased radiation exposure to patients and the resultant radiation-induced health risks. It prompted researchers to explore newer CT techniques like ultra-low dose CT (ULDCT), which could improve patient safety. Our aim was to study the utility of ultra-low dose CT (ULDCT) chest in the evaluation of acute COVID-19 pneumonia with standard-dose CT (SDCT) chest as a reference standard. This was a prospective study approved by the institutional review board. 60 RT-PCR positive COVID-19 patients with valid indication for CT chest underwent SDCT and ULDCT. ULDCT and SDCT were compared in terms of objective (noise and signal-to-noise ratio) and subjective (noise, sharpness, artifacts and diagnostic confidence) image quality, various imaging patterns of COVID-19, CT severity score and effective radiation dose. The sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy of ULDCT for detecting lung lesions were calculated by taking SDCT as a reference standard. The mean age of subjects was 47.2 ± 10.7 years, with 66.67% being men. 90% of ULDCT scans showed no/minimal noise and sharp images, while 93.33% had image quality of high diagnostic confidence. The major imaging findings detected by SDCT were GGOs (90%), consolidation (76.67%), septal thickening (60%), linear opacities (33.33%), crazy-paving pattern (33.33%), nodules (30%), pleural thickening (30%), lymphadenopathy (30%) and pleural effusion (23.33%). Sensitivity, specificity and diagnostic accuracy of ULDCT for detecting most of the imaging patterns were 100% (p < 0.001); except for GGOs (sensitivity: 92.59%, specificity: 100%, diagnostic accuracy: 93.33%), consolidation (sensitivity: 100%, specificity: 71.43%, diagnostic accuracy: 93.33%) and linear opacity (sensitivity: 90.00%, specificity: 100%, diagnostic accuracy: 96.67%). CT severity score (range: 15-25) showed 100% concordance on SDCT and ULDCT, while effective radiation dose was 4.93 ± 1.11 mSv and 0.26 ± 0.024 mSv, respectively. A dose reduction of 94.38 ± 1.7% was achieved with ULDCT. Compared to SDCT, ULDCT chest yielded images of reasonable and comparable diagnostic quality with the advantage of significantly reduced radiation dose; thus, it can be a good alternative to SDCT in the evaluation of COVID-19 pneumonia.

A Delphi consensus statement for the management of post-COVID interstitial lung disease.

INTRODUCTION: As millions of people worldwide recover from COVID-19, a substantial proportion continue to have persistent symptoms, pulmonary function abnormalities, and radiological findings suggestive of post-COVID interstitial lung disease (ILD). To date, there is limited scientific evidence on the management of post-COVID ILD, necessitating a consensus-based approach. AREAS COVERED: A panel of experts in pulmonology and thoracic radiology was constituted. Key questions regarding the management of post-COVID ILD were identified. A search was performed on PubMed and EMBASE and updated till 1 March 2022. The relevant literature regarding the epidemiology, pathophysiology, diagnosis and treatment of post-COVID ILD was summarized. Subsequently, suggestions regarding the management of these patients were framed, and a consensus was obtained using the Delphi approach. Those suggestions which were approved by over 80% of the panelists were accepted. The final document was approved by all panel members. EXPERT OPINION: Dedicated facilities should be established for the care of patients with post-COVID ILD. Symptom screening, pulmonary function testing, and thoracic imaging have a role in the diagnosis. The pharmacologic and non-pharmacologic options for the management of post-COVID ILD are discussed. Further research into the pathophysiology and management of post-COVID ILD will improve our understanding of this condition.

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.

A multicenter survey study of antifibrotic use for symptomatic patients with post-COVID-19 interstitial lung abnormalities.

Background: Little data exist on antifibrotic drugs for treating symptomatic patients with persistent interstitial lung abnormalities in the postacute phase of coronavirus disease 2019 (COVID-19). Herein, we describe the physician practices of prescribing pirfenidone and nintedanib for these patients and the physician-assessed response. Materials and Methods: This was a multicenter, retrospective survey study of subjects administered pirfenidone or nintedanib for post-COVID-19 interstitial lung abnormalities. Data on the demographic details, comorbidities, abnormalities on the computed tomography (CT) of the chest, treatment, antifibrotic drug use, and physician-assessed response were collected on a standard case record pro forma. We explored physician practices of prescribing antifibrotics (primary objective) and the physician-assessed response (secondary objective). Results: We included 142 subjects (mean age, 55.9 years; 16.2% women) at eight centers. The most common abnormalities on CT chest included ground glass opacities (75.7%), consolidation (49.5%), reticulation (43.9%), and parenchymal bands (16.8%). Of the 5701 patients discharged after hospitalization at six centers, 115 (2.0%) received antifibrotics. The drugs were prescribed an average of 26 days after symptom onset. One hundred and sixteen subjects were administered pirfenidone; 11 (9.5%) received the full dose (2400 mg/day). Thirty subjects were prescribed nintedanib; 23 (76.7%) received the full dose (300 mg/day). Of 76 subjects with available information, 27 (35.6%) and 26 (34.2%) had significant or partial radiologic improvement, respectively, according to the physician's assessment. Conclusions: Antifibrotic agents were administered to a minority of patients discharged after recovery from acute COVID-19 pneumonia. Larger, randomized studies on the efficacy and safety of these agents are 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.

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.

Impact of Asthma on Severity and Outcomes in COVID-19.

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.

The Conundrum of 'Long-COVID-19': A Narrative Review.

COVID-19 is an ongoing pandemic with many challenges that are now extending to its intriguing long-term sequel. 'Long-COVID-19' is a term given to the lingering or protracted illness that patients of COVID-19 continue to experience even in their post-recovery phase. It is also being called 'post-acute COVID-19', 'ongoing symptomatic COVID-19', 'chronic COVID-19', 'post COVID-19 syndrome', and 'long-haul COVID-19'. Fatigue, dyspnea, cough, headache, brain fog, anosmia, and dysgeusia are common symptoms seen in Long-COVID-19, but more varied and debilitating injuries involving pulmonary, cardiovascular, cutaneous, musculoskeletal and neuropsychiatric systems are also being reported. With the data on Long-COVID-19 still emerging, the present review aims to highlight its epidemiology, protean clinical manifestations, risk predictors, and management strategies. With the re-emergence of new waves of SARS-CoV-2 infection, Long-COVID-19 is expected to produce another public health crisis on the heels of current pandemic. Thus, it becomes imperative to emphasize this condition and disseminate its awareness to medical professionals, patients, the public, and policymakers alike to prepare and augment health care facilities for continued surveillance of these patients. Further research comprising cataloging of symptoms, longer-ranging observational studies, and clinical trials are necessary to evaluate long-term consequences of COVID-19, and it warrants setting-up of dedicated, post-COVID care, multi-disciplinary clinics, and rehabilitation centers.