The hydrodynamic force acting on a rigid spherical particle translating with arbitrary time-dependent motion in a time-dependent flowing fluid is calculated to O(Re) for small but finite values of the Reynolds number, Re, based on the particle's slip velocity relative to the uniform flow. The corresponding expression for an arbitrarily shaped rigid particle is evaluated for the case when the timescale of variation of the particle's slip velocity is much greater than the diffusive scale, a2/v, where a is the characteristic particle dimension and v is the kinematic viscosity of the fluid. It is found that the expression for the hydrodynamic force is not simply an additive combination of the results from unsteady Stokes flow and steady Oseen flow and that the temporal decay to steady state for small but finite Re is always faster than the t-f behaviour of unsteady Stokes flow. For example, when the particle accelerates from rest the temporal approach to steady state scales as r2.

SARS-CoV-2 infection results in viral burden in the respiratory tract, enabling transmission and leading to substantial lung pathology. The 1212C2 fully human monoclonal antibody was derived from an IgM memory B cell of a COVID-19 patient, has high affinity for the Spike protein Receptor Binding Domain, neutralizes SARS-CoV-2 and exhibits in vivo prophylactic and therapeutic activity in hamsters when delivered intraperitoneally, reducing upper and lower respiratory viral burden and lung pathology. Inhalation of nebulized 1212C2 at levels as low as 0.6mg/kg, corresponding to 0.03mg/kg of lung deposited dose, reduced viral burden below the detection limit, and mitigated lung pathology. The therapeutic efficacy of an exceedingly low-dose of inhaled 1212C2 supports the rationale for local lung delivery for dose-sparing benefits as compared to the conventional parenteral route of administration. These results suggest clinical development of 1212C2 formulated and delivered via inhalation for the treatment of SARS-CoV-2 infection should be considered.

SARS-CoV-2 infection results in viral burden in the upper and lower respiratory tract, enabling transmission and often leading to substantial lung pathology. Delivering the antiviral treatment directly to the lungs has the potential to improve lung bioavailability and dosing efficiency. As the SARS-CoV-2 Receptor Binding Domain (RBD) of the Spike (S) is increasingly deemed to be a clinically validated target, RBD-specific B cells were isolated from patients following SARS-CoV-2 infection to derive a panel of fully human monoclonal antibodies (hmAbs) that potently neutralize SARS-CoV-2. The most potent hmAb, 1212C2 was derived from an IgM memory B cell, has high affinity for SARS-CoV-2 RBD which enables its direct inhibition of RBD binding to ACE2. The 1212C2 hmAb exhibits in vivo prophylactic and therapeutic activity against SARS-CoV-2 in hamsters when delivered intraperitoneally, achieving a meaningful reduction in upper and lower respiratory viral burden and lung pathology. Furthermore, liquid nebulized inhale treatment of SARS-CoV-2 infected hamsters with as low as 0.6 mg/kg of inhaled dose, corresponding to approximately 0.03 mg/kg of lung deposited dose, mediated a reduction in respiratory viral burden that is below the detection limit, and mitigated lung pathology. The therapeutic efficacy achieved at an exceedingly low-dose of inhaled 1212C2 supports the rationale for local lung delivery and achieving dose-sparing benefits as compared to the conventional parenteral route of administration. Taken together, these results warrant an accelerated clinical development of 1212C2 hmAb formulated and delivered via inhalation for the prevention and treatment of SARS-CoV-2 infection.

No abstract

The hydrodynamic force on a body that undergoes translational acceleration in an unbounded fluid at low Reynolds number is considered. The results extend the prior analysis of Lovalenti and Brady [to appear in J. Fluid Mech. (1993)] for rigid particles to drops and bubbles. Similar behavior is shown in that, with the inclusion of convective inertia, the long-time temporal decay of the force (or the approach to steady state) at finite Reynolds number is faster than the t-1 2 predicted by the unsteady Stokes equations.