Disentangling the dynamical underpinnings of differences in SARS-CoV-2 pathology using within-host ecological models
Fig 2
Dynamics of SARS-CoV-2 showing the hypothesized trajectory of viral load in the respiratory tract (bottom panel) for males (blue) and females (red). The top panel broadly maps a set of potential immune responses, roughly corresponding to recently described immunotypes [5]: Detecting and responding early (e.g., via early activation of type I Interferons) leading to early resolution, a delayed but ultimately successful response (e.g., via moderate Type 1 T cell activation), or an aberrant response resulting in hyperactivation (e.g., cytokine storms and exhaustion of lymphocytes) and the most severe forms of disease. Hosts of different sexes or ages might differ in propensity to follow the possible trajectories suggested in the top panel. For example, strong early detection and response in females or younger individuals (purple arrow labeled 1) could result in lower early viral loads. Despite delayed control, males or older individuals might still be able to regain the lost ground by successful development of cellular immunity (purple arrow labeled 2); if this response is greater for greater viral loads, this could ultimately result in similar scales of viral load in both slow and fast responding individuals around the peak of viral load. Finally, exhaustion/hyperactivation (of adaptive and innate arms of the immune system, respectively), potentially shaped by events early during infection (“path dependence,” such as failure of early interferon defenses or by comorbidities), could result in slower clearance in males or older individuals (purple arrow labeled 3 would correspond to females/younger individuals).