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Biomechanical Dependence of SARS-CoV‑2 Infections
journal contributionposted on 2022-04-29, 21:05 authored by Alexandra Paul, Sachin Kumar, Tamer S. Kaoud, Madison R. Pickett, Amanda L. Bohanon, Janet Zoldan, Kevin N. Dalby, Sapun H. Parekh
Older people have been disproportionately vulnerable to the current SARS-CoV-2 pandemic, with an increased risk of severe complications and death compared to other age groups. A mix of underlying factors has been speculated to give rise to this differential infection outcome including changes in lung physiology, weakened immunity, and severe immune response. Our study focuses on the impact of biomechanical changes in lungs that occur as individuals age, that is, the stiffening of the lung parenchyma and increased matrix fiber density. We used hydrogels with an elastic modulus of 0.2 and 50 kPa and conventional tissue culture surfaces to investigate how infection rate changes with parenchymal tissue stiffness in lung epithelial cells challenged with SARS-CoV-2 Spike (S) protein pseudotyped lentiviruses. Further, we employed electrospun fiber matrices to isolate the effect of matrix density. Given the recent data highlighting the importance of alternative virulent strains, we included both the native strain identified in early 2020 and an early S protein variant (D614G) that was shown to increase the viral infectivity markedly. Our results show that cells on softer and sparser scaffolds, closer resembling younger lungs, exhibit higher infection rates by the WT and D614G variant. This suggests that natural changes in lung biomechanics do not increase the propensity for SARS-CoV-2 infection and that other factors, such as a weaker immune system, may contribute to increased disease burden in the elderly.
weaker immune systemviral infectivity markedlyrecent data highlightingparenchymal tissue stiffnessnative strain identifiedalternative virulent strainssevere immune responseprotein pseudotyped lentivirusesincreased disease burdeninfection rate changessevere complicationsprotein variantincreased risknatural changesbiomechanical changes2 infectionweakened immunityused hydrogelsstudy focusessparser scaffoldsresults showmay contributematrix densitylung physiologylung parenchymalung biomechanicsindividuals agegive riseelastic modulusdisproportionately vulnerabledeath comparedbiomechanical dependenceage groups50 kpa