Reportsof COVID-19-associated mucormycosis have been increasing in frequency since early 2021, particularly among patients with uncontrolled diabetes. Patients with diabetes and hyperglycaemia often have an inflammatory state that could be potentiated by the activation of antiviral immunity to SARS-CoV2, which might favour secondary infections. In this Review, we analysed 80 published and unpublished cases of COVID-19-associated mucormycosis. Uncontrolled diabetes, as well as systemic corticosteroid treatment, were present in most patients with COVID-19associated mucormycosis, and rhino-orbital cerebral mucormycosis was the most frequent disease. Mortality was high at 49%, which was particularly due to patients with pulmonary or disseminated mucormycosis or cerebral involvement. Furthermore, a substantial proportion of patients who survived had life-changing morbidities (eg, loss of vision in 46% of survivors). Our Review indicates that COVID-19-associated mucormycosis is associated with high morbidity and mortality. Diagnosis of pulmonary mucormycosis is particularly challenging, and might be frequently missed in India.

Background Invasive aspergillosis is a well‐known complication of severe influenza pneumonia with acute respiratory distress syndrome (ARDS). However, recent studies are reporting emergence of aspergillosis in severe COVID‐19 pneumonia, named as COVID‐19 associated aspergillosis (CAPA). Methods A retrospective observational study was conducted in patients with severe COVID‐19 pneumonia from February 2020‐ April 2020. Patients’ ≥18 years of age with clinical features and abnormal chest imaging with confirmed COVID‐19 by RT‐PCR for SARS‐Cov‐2 were included. CAPA was diagnosed based on clinical parameters, radiological findings and mycological data. Data were recorded on a structured proforma and descriptive analysis was performed using Stata ver 12.1. Results A total of 147 patients with confirmed COVID‐19 and 23 (15.6%) patients requiring ICU admission were identified. Aspergillus species were isolated from tracheal aspirates of nine (39.1%) patients and of these five patients (21.7%) were diagnosed with CAPA and four (17.4%) had Aspergillus colonization. The mean age of patients with CAPA was 69 years (Median age: 71, IQR: 24, Range: 51 – 85) and 3/5 patients were male. The most frequent co‐morbid was diabetes mellitus (4/5). The overall fatality rate of COVID‐19 patients with aspergillosis was 44% (4/9). The cause of death was ARDS in all 3 patients with CAPA and the median length of stay was 16 days (IQR: 10; Range 6‐35 days). Conclusion This study highlights the need for comparative studies to establish whether there is an association of aspergillosis and COVID‐19 and the need for screening for fungal infections in severe COVID‐19 patients with certain risk factors.

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Adverse outcomes in coronavirus infection disease-19 patients are not always due to the direct effects of the viral infection, but often due to bacterial coinfection. However, the risk factors for such bacterial coinfection are hitherto unknown. A case-control study was conducted to determine risk factors for bacterial infection in moderate to critical COVID-19. Out of a total of 50 cases and 50 controls, the proportion of cases with severe/critical disease at presentation was 80% in cases compared to 30% in controls (p < 0.001). The predominant site was hospital-acquired pneumonia (72%) and the majority were Gram-negative organisms (82%). The overall mortality was 30%, with comparatively higher mortality among cases (42% vs. 18%; p = 0.009). There was no difference between procalcitonin levels in both groups (p = 0.883). In multivariable logistic regression analysis, significant independent association was found with severe/critical COVID-19 at presentation (AOR: 4.42 times; 95% CI: 1.63-11.9) and use of steroids (AOR: 4.60; 95% CI: 1.24-17.05). Notably, 64% of controls were administered antibiotics despite the absence of bacterial coinfection or secondary infection. Risk factors for bacterial infections in moderate to critically ill patients with COVID-19 include critical illness at presentation and use of steroids. There is widespread empiric antibiotic utilization in those without bacterial infection.

Protection against Mycobacterium tuberculosis infection is dependent on T cell and macrophage activation regulated by cytokines. Cytokines and chemokines produced at disease sites may be released into circulation. Data available on circulating cytokines in tuberculosis (TB) is mostly on pulmonary TB (PTB) with limited information on extrapulmonary disease (EPul‐TB). We measured interferon‐gamma (IFN‐γ), interkeukin‐10 (IL‐10), CXCL9 and CCL2 in sera of patients (n = 80) including; PTB (n = 42), EPul‐TB (n = 38) and BCG vaccinated healthy endemic controls (EC, n = 42). EPul‐TB patients comprised those with less severe (LNTB) or severe (SevTB) disease. Serum IFN‐γ, IL‐10 and CXCL9 levels were significantly greater while CCL2 was reduced in TB patients as compared with EC. IFN‐γ was significantly greater in PTB as compared with LNTB (P = 0.002) and SevTB (P = 0.029). CXCL9 was greater in PTB as compared with LNTB (P = 0.009). In contrast, CCL2 levels were reduced in PTB as compared with LNTB (P = 0.021) and SevTB (P = 0.024). A Spearman’s rank correlation analysis determined a positive association between IFN‐γ and IL‐10 (rho = 0.473, P = 0.002) and IFN‐γ and CXCL9 (rho = 0.403, P = 0.008) in the PTB group. However, in SevTB, only IFN‐γ and CXCL9 were positively associated (rho = 0.529, P = 0.016). Systemic levels of cytokines are reflective of local responses at disease sites. Therefore, our data suggests that in PTB increased IFN‐γ and CXCL9 balanced by IL‐10 may result in a more effective cell mediated response in the host. However, elevated inflammatory chemokines CXCL9 and CCL2 in severe EPul‐TB without concomitant down modulatory cytokines may exacerbate disease related pathology and hamper restriction of M. tuberculosis infection.