Background. Infectivity, genomic variability, and symptomatic diversity of the SARS-CoV-2 virus represents a persistent challenge in the treatment of acute and long COVID-19 diseases. A direct consequence of pervasive ACE-2 receptors susceptible to the virion’s spike protein, disease trajectories commence as upper respiratory infection migrating into bronchia (presenting coughing, dyspnea, and fever), followed by viremic infection and circulatory distress from inflammation of visceral epithelium and vascular endothelia, decreased blood perfusion, and hypoxia. Severe cases include hyperinflammation, cytokine storms, and multisystem inflammatory syndrome with lung and nerve damage, and chronic cognitive deficits. Method. This paper (Part I) considers the requirements for treating acute and chronic COVID-19 with deep-tissue photobiomodulation (PBM) of sinuses, lungs and other ACE-2 populated organs using transdermal and transcranial light as a primary therapeutic modality. Analysis. A detailed analysis of optics, biophysics, numerical simulations, and quantum photochemistry for non-invasive deep tissue PBM of SARS-CoV-2 infected organs was performed including optical design, photonic control, irradiance, fluence, modulation, and protocols. Results. Analysis concludes large-area 3D bendable LED pads are best suited for deep-tissue PBM to transdermally treat whole-organ infection of the lungs, sinuses, abdominal cavity (and to transcranially treat long-COVID). Robotic laser scanning represents another viable option for deep-tissue PBM provided the optical angle of incidence is minimal. Penetration depth depends on wavelength (not optical power) with red (635nm) and NIR (850nm) shown to adequately penetrate through cutaneious tissue and parietal fascia into viscera. Conclusions. Red and NIR LEDs with average pulsed irradiances of 8.5 and 13.5 mW/cm2 respectively deliver hands-free whole-organ deep-tissue doses of between 0.5 to 4.0 J/cm2 in 60 min sessions from a surface dose of Pl/A = 40 J/cm2 depending on tissue transmission coefficients Yx at depth x>6mm. The designed photonic PBM system performs algorithmic variable frequency pulsed protocols covering up to 1,200 cm2. Duty factor control limits skin temperatures below 43°C irrespective of pulse modulating frequency. A mechanistic model for deep-tissue PBM, phenomenologically consistent with biophysics, photon penetration studies, COVID disease trajectories, and patient recovery profiles is presented. Part II details various acute and chronic case studies and positive outcomes thereof confirming PBM as a efficacious modality for COVID-19.