Pulmonary infection characteristics leading to respiratory failure, a modelling approach

How an infection propagates inside the lung is not well understood. Capturing its dynamics might help to understand how pathologies such as COVID19 can lead to rapid airways inflammation and respiratory failure. We hypothesized that respiratory failure might result from the interaction between the propagation of the infection from airway to airway (inner contagiousness) and the pathogen virulence. We develop a mathematical model of the infection and inflammation of the proximal lung (511 susceptible airways) by a generic pathogen that propagates from neighbor to neighbor between the airways. The degree of respiratory failure is evaluated by computing the mean number of infected airways (NI) and the mean drop in oxygen transfer to blood (DOx), assuming no compensation from patient ventilation. We simulated 840 idealized patients, covering 3 different degrees of virulence (Cured (C), Aseptic (A) and Septic (S) outcomes) and 14 degrees of contagiousness (1<=c<=14, arbitrary units). When virulence increases, the pathogens remain longer in the airways, increasing the propagation probability: NI(C)=51, DOx(C)=8.9%;NI(A)=410, DOx(A)=47.2%;NI(S)=511, DOx(S)=55.5%. For low contagiousness, c=1, NI(C)=1.6, DOx(C)=2.2%;NI(A)=132, DOx(A)=25.8%. However, NI(S)=511 and DOx(S)=52.2%. High contagiousness, c=14, leads to a large propagation whatever the virulence (NI(S/A)=511 and DOx(S/A)=57.5%;NI(C)=428 and DOx(C)=38.6%). Medium virulence and contagiousness also lead to a large propagation: for c=7, NI(A)=508, DOx=52.5%. Residence time of pathogens and inner contagiousness are interacting factors that might bring high NI and DOx. This interaction might be a core determinant of potential respiratory failure.

Structure Elucidation of the spiro-Polyketide Svalbardine B from the Arctic Fungal Endophyte Poaceicola sp. E1PB with Support from Extensive ESI-MSn Interpretation.

Svalbardines A and B (1 and 2) and annularin K (3) were isolated from cultures of Poaceicola sp. E1PB, an endophyte isolated from the petals of Papaver dahlianum from Svalbard, Norway. Svalbardine A (1) is a pyrano[3,2-c]chromen-4-one, a new analogue of citromycetin. Svalbardine B (2) displays an unprecedented carbon skeleton based on a 5'-benzyl-spiro[chroman-3,7'-isochromene]-4,8'-dione core. Annularin K (3) is a hydroxylated derivative of annularin D. The structure of these new polyketides, along with those of known compounds 4-6, was established by spectrometric analysis, including extensive ESI-CID-MSn processing in the case of svalbardine B (2).