Summary: Objectives: Patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications like invasive aspergillosis. Our study evaluates coronavirus disease 19 (COVID‐19) associated invasive aspergillosis at a single centre in Cologne, Germany.Methods: A retrospective chart review of all patients with COVID‐19 associated ARDS admitted to the medical or surgical intensive care unit at the University Hospital of Cologne, Cologne, Germany.Results: COVID‐19 associated invasive pulmonary aspergillosis was found in five of 19 consecutive critically ill patients with moderate to severe ARDS.Conclusion: Clinicians caring for patients with ARDS due to COVID‐19 should consider invasive pulmonary aspergillosis and subject respiratory samples to comprehensive analysis to detect co‐infection.

Tuberculosis (TB) is one of the ten leading causes of death worldwide (1). In Germany and other highly developed countries, however, TB occurs relatively seldom and can almost always be treated successfully. The rarity of TB means that not all...

Innate immunity triggers responsible for viral control or hyperinflammation in COVID‐19 are largely unknown. Here we show that the SARS‐CoV‐2 spike protein (S‐protein) primes inflammasome formation and release of mature interleukin‐1β (IL‐1β) in macrophages derived from COVID‐19 patients but not in macrophages from healthy SARS‐CoV‐2 naïve individuals. Furthermore, longitudinal analyses reveal robust S‐protein‐driven inflammasome activation in macrophages isolated from convalescent COVID‐19 patients, which correlates with distinct epigenetic and gene expression signatures suggesting innate immune memory after recovery from COVID‐19. Importantly, we show that S‐protein‐driven IL‐1β secretion from patient‐derived macrophages requires non‐specific monocyte pre‐activation in vivo to trigger NLRP3‐inflammasome signaling. Our findings reveal that SARS‐CoV‐2 infection causes profound and long‐lived reprogramming of macrophages resulting in augmented immunogenicity of the SARS‐CoV‐2 S‐protein, a major vaccine antigen and potent driver of adaptive and innate immune signaling.

Summary: WhiB‐like proteins of actinomycetes are known to co‐ordinate iron‐sulfur (Fe‐S) clusters and are believed to have regulatory functions in many essential bacterial processes. The systematic determination of the genome sequences of mycobacteriophages has revealed the presence of several whiB‐like genes in these viruses. Here we focussed on the WhiB‐like protein of mycobacteriophage TM4, WhiBTM4. We provide evidence that this viral protein is capable of co‐ordinating a Fe‐S cluster. The UV‐visible absorption spectra obtained from freshly purified and reconstituted WhiBTM4 were consistent with the presence of an oxygen sensitive [2Fe‐2S] cluster. Expression of WhiBTM4 in the mycobacterial host led to hindered septation resembling a WhiB2 knockout phenotype whereas basal expression of WhiBTM4 led to superinfection exclusion. The quantification of mRNA‐levels during phage infection showed that whiBTM4 is a highly transcribed early phage gene and a dominant negative regulator of WhiB2. Strikingly, both apo‐WhiB2 of Mycobacterium tuberculosis and apo‐WhiBTM4 were capable of binding to the conserved promoter region upstream of the whiB2 gene indicating that WhiB2 regulates its own synthesis which is inhibited in the presence of WhiBTM4. Thus, we provide substantial evidence supporting the hypothesis of viral and bacterial WhiB proteins being important Fe‐S containing transcriptional regulators with DNA‐binding capability.

Corticosteroids are host-directed drugs with proven beneficial effect on survival of tuberculosis (TB) patients, but their precise mechanisms of action in this disease remain largely unknown. Here we show that corticosteroids such as dexamethasone inhibit necrotic cell death of cells infected with Mycobacterium tuberculosis (Mtb) by facilitating mitogen-activated protein kinase phosphatase 1 (MKP-1)-dependent dephosphorylation of p38 MAPK. Characterization of infected mixed lineage kinase domain-like (MLKL) and tumor necrosis factor receptor 1 (TNFR1) knockout cells show that the underlying mechanism is independent from TNFα-signaling and necroptosis. Our results link corticosteroid function and p38 MAPK inhibition to abrogation of necrotic cell death mediated by mitochondrial membrane permeability transition, and open new avenues for research on novel host-directed therapies (HDT).