Despite antifungal treatment, chronic pulmonary aspergillosis (CPA) is associated with substantial morbidity and mortality. We conducted a systematic review and meta-analysis to evaluate rates of mortality and its predictors in CPA. A systematic literature search was conducted across MEDLINE (PubMed), Scopus, Embase, and Web of Science to identify studies in English, reporting mortality in CPA, from database inception to Aug 15, 2023. We included clinical studies, observational studies, controlled trials, and abstracts. Case reports, animal studies, letters, news, and literature reviews were excluded. Authors of studies published since 2016 were also contacted to obtain anonymised individual patient data (IPD); for other studies, summary estimates were extracted. Subgroup analysis was done for differences in overall 1-year and 5-year mortality, data source, study design, risk of bias, country, Human Development Index, age groups, and the underlying lung disease. We used random-effects meta-analyses to estimate pooled mortality rates. Subgroup analyses and meta-regression were done to explore sources of heterogeneity. One-stage meta-analysis with a stratified Cox proportional hazards model was used to estimate the univariable and hazards for mortality, adjusting for age, sex, type of CPA, treatment, and underlying pulmonary comorbidities. This study was registered with PROSPERO (CRD42023453447). We included 79 studies involving 8778 patients in the overall pooled analysis and 15 studies involving 1859 patients in the IPD meta-analysis. Pooled mortality (from 70 studies) was estimated at 27% overall (95% CI 22-32; I² =95·4%), 15% at 1 year (11-19; I² =91·6%), and 32% at 5 years (25-39; I² =94·3%). Overall mortality in patients with CPA with pulmonary tuberculosis as the predominant predisposing condition was 25% (16-35; I² =87·5%; 20 studies) and with chronic obstructive pulmonary disease was 35% (22-49; I² =89·7%; 14 studies). Mortality in cohorts of patients who underwent surgical resection was low at 3% (2-4). In the multivariable analysis, among predisposing respiratory conditions, pulmonary tuberculosis history had the lowest mortality hazard (relative to an absence of the disease at baseline), whereas worse outcomes were seen with underlying malignancy; subacute invasive pulmonary aspergillosis and chronic cavitary pulmonary aspergillosis subtypes of CPA were also significantly associated with increased mortality relative to simple aspergilloma on multivariable analysis. Mortality hazard increased by 25% with each decade of age (adjusted hazard ratio 1·25 [95% CI 1·14-1·36], p<0·0001). CPA is associated with substantial mortality. Advancing age, CPA subtype, and underlying comorbidities are important predictors of mortality. Future studies should focus on identifying appropriate treatment strategies tailored to different risk groups. None.

Infrared thermal screening, via the use of handheld non-contact infrared thermometers (NCITs) and thermal scanners, has been widely implemented all over the world. We performed a systematic review and meta-analysis to investigate its diagnostic accuracy for the detection of fever. We searched PubMed, Embase, the Cochrane Library, medRxiv, bioRxiv, ClinicalTrials.gov, COVID-19 Open Research Dataset, COVID-19 research database, Epistemonikos, EPPI-Centre, World Health Organization International Clinical Trials Registry Platform, Scopus and Web of Science databases for studies where a non-contact infrared device was used to detect fever against a reference standard of conventional thermometers. Forest plots and Hierarchical Summary Receiver Operating Characteristics curves were used to describe the pooled summary estimates of sensitivity, specificity and diagnostic odds ratio. From a total of 1063 results, 30 studies were included in the qualitative synthesis, of which 19 were included in the meta-analysis. The pooled sensitivity and specificity were 0.808 (95%CI 0.656–0.903) and 0.920 (95%CI 0.769–0.975), respectively, for the NCITs (using forehead as the site of measurement), and 0.818 (95%CI 0.758–0.866) and 0.923 (95%CI 0.823–0.969), respectively, for thermal scanners. The sensitivity of NCITs increased on use of rectal temperature as the reference. The sensitivity of thermal scanners decreased in a disease outbreak/pandemic setting. Changes approaching statistical significance were also observed on the exclusion of neonates from the analysis. Thermal screening had a low positive predictive value, especially at the initial stage of an outbreak, whereas the negative predictive value (NPV) continued to be high even at later stages. Thermal screening has reasonable diagnostic accuracy in the detection of fever, although it may vary with changes in subject characteristics, setting, index test and the reference standard used. Thermal screening has a good NPV even during a pandemic. The policymakers must take into consideration the factors surrounding the screening strategy while forming ad-hoc guidelines.

Chronic pulmonary aspergillosis (CPA) may be confused with, or a coinfection of, pulmonary tuberculosis (PTB), or may manifest itself after completion of antituberculous therapy (ATT). Literature searches were conducted on PubMed. The selected studies stated the timing of CPA diagnosis with respect to PTB. The key assumptions for estimating the annual incidence, annual deaths, and 5-year-period prevalence related to CPA were: of the clinically diagnosed PTB patients , 19% of those HIV-negative had CPA and 7% of HIV-positive patients had CPA; the percentage of patients presenting in the first year after PTB diagnosis or developing CPA as ATT finished was 10%; the annual rate of development of CPA from 2–5 years after PTB diagnosis was 1.5%; and the mortality of CPA was 20% in year 1 and 7.5% thereafter to year 5. In India, the annual incidence of CPA arising in PTB patients in 2019 was estimated to be 363 601 cases (range 254 521 - 472 682) and 42 766 deaths (range 29 936–55 595) — 10.5% of total PTB deaths. The 5-year-period prevalence of CPA was estimated at 1 575 716 , with an additional 100 715 deaths' total range of deaths 100 436– 186 525) annually. The revised estimation indicates a substantial unmet need for better diagnosis of CPA as part of a complex PTB-related respiratory morbidity burden.

To elucidate the molecular mechanisms that manifest lung abnormalities during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, we performed whole-transcriptome sequencing of lung autopsies from 31 patients with severe COVID-19 and ten uninfected controls. Using metatranscriptomics, we identified the existence of two distinct molecular signatures of lethal COVID-19. The dominant ‘classical’ signature (n=23) showed upregulation of the unfolded protein response, steroid biosynthesis and complement activation, supported by massive metabolic reprogramming leading to characteristic lung damage. The rarer signature (n=8) that potentially represents ‘cytokine release syndrome’ (CRS) showed upregulation of cytokines such as IL1 and CCL19, but absence of complement activation. We found that a majority of patients cleared SARS-CoV-2 infection, but they suffered from acute dysbiosis with characteristic enrichment of opportunistic pathogens such as Staphylococcus cohnii in ‘classical’ patients and Pasteurella multocida in CRS patients. Our results suggest two distinct models of lung pathology in severe COVID-19 patients, which can be identified through complement activation, presence of specific cytokines and characteristic microbiome. These findings can be used to design personalized therapy using in silico identified drug molecules or in mitigating specific secondary infections.

Background: The diagnosis of CPA relies on the detection of the IgG Aspergillus antibody, which is not freely available, especially in resource-poor settings. Point-of-care tests like LDBio Aspergillus ICT lateral flow assay, evaluated in only a few studies, have shown promising results for the diagnosis of CPA. However, no study has compared the diagnostic performances of LDBio LFA in setting of tuberculosis endemic countries and have compared it with that of IgG Aspergillus. Objectives: This study aimed to evaluate the diagnostic performances of LDBio LFA in CPA and compare it with existing the diagnostic algorithm utilising ImmunoCAP IgG Aspergillus. Methods: Serial patients presenting with respiratory symptoms (cough, haemoptysis, fever, etc.) for >4 weeks were screened for eligibility. Relevant investigations, including direct microscopy and culture of respiratory secretions, IgG Aspergillus, chest imaging, etc., were done according to existing algorithm. Serums of all patients were tested by LDBio LFA and IgG Aspergillus (ImmunoCAP Asp IgG) and their diagnostic performances were compared. Results: A total of 174 patients were included in the study with ~66.7% patients having past history of tuberculosis. A diagnosis of CPA was made in 74 (42.5%) of patients. The estimated sensitivity and specificity of LDBio LFA was 67.6% (95% CI: 55.7–78%) and 81% (95% CI: 71.9–88.2%), respectively, which increased to 73.3% (95% CI: 60.3–83.9%) and 83.9% (95% CI: 71.7–92.4%), respectively, in patients with a past history of tuberculosis. The sensitivity and specificity of IgG Aspergillus was 82.4% (95% CI: 71.8–90.3%) and 82% (95% CI: 73.1–89%); 86.7% (95% CI: 75.4–94.1%) and 80.4% (95% CI: 67.6–89.8%), in the whole group and those with past history of tuberculosis, respectively. Conclusions: LDBio LFA is a point-of-care test with reasonable sensitivity and specificity. However, further tests may have to be done to rule-in or rule-out the diagnosis of CPA in the appropriate setting.

India continues to battle the second wave of COVID-19 and has recently reported the highest number of cases ever in a single day from a country. As severe COVID-19 continues to claim thousands of lives in this country, there has also been a recent spate of COVID-19-associated mucormycosis (CAM) cases which have garnered attention globally. More than 14 000 cases of CAM have been reported from all over India with many states resorting to declaration of an epidemic as well as making it a notifiable disease. ¹ We wish to elaborate on the evolving situation of CAM in India with special attention to the association of mucormycosis with COVID-19, the pathophysiological basis for CAM, likely reasons for preponderance of CAM in India as well as the core management issues.