Learning from past failures: Challenges with monoclonal antibody therapies for COVID-19

Abstract

COVID-19, the disease caused by infection with SARS-CoV-2, requires urgent development of therapeutic interventions. Due to their safety, specificity, and potential for rapid advancement into the clinic, monoclonal antibodies (mAbs) represent a highly promising class of antiviral or anti-inflammatory agents. Herein, by analyzing prior efforts to advance antiviral mAbs for other acute respiratory infections (ARIs), we highlight the challenges faced by mAb-based immunotherapies for COVID-19. We present evidence supporting early intervention immediately following a positive diagnosis via inhaled delivery of mAbs with vibrating mesh nebulizers as a promising approach for the treatment of COVID-19.

Graphical abstract

Fig. 1

Infection and spread of SARS-CoV GFP in WD-HAE cultures over time after apical or basolateral inoculation. HAE were inoculated via the apical (left: A, C, E, G) or basolateral (right: B, D, F, and H) compartments with SARS-CoV GFP and GFP-positive cells and assessed over time. Apical inoculation resulted in significant numbers of GFP-positive cells at 40 h post-infection (C), with extensive spread of infection by 90 h post-infection (G). In contrast, basolateral inoculation resulted in a low proportion of cells positive for GFP only at 68 h post-infection (F). These images are representative of duplicate cultures from at least three different patient sets. Original magnification, 10×. Image reproduced from [41].

Fig. 2

Preferential apical infection and shedding of progeny viruses in the respiratory tract. SARS-CoV-2 deposited in the upper respiratory tract can diffuse through airway mucus and internalize into airway epithelial cells by binding to ACE2. The red X's indicate that SARS-CoV-2 does not typically spread from an infected cell laterally to a neighboring cell or through shedding into the basal compartment. Instead, SARS-CoV-2 is preferentially shed from infected cells from the apical side, back into the airway fluids, in which it diffuses to the apical face of neighboring cells, interacting with ACE2 and initiating the process of cellular entry. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)