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Download fileBiomechanical Dependence of SARS-CoV‑2 Infections
journal contribution
posted 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. ParekhOlder
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.
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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