IMAGE: Macrophage differentiation from M0 to M1 or M2 is complex.
Introduction:
In the literature on atherosclerosis, they confuse the “foam cell” defined by strong staining for Oil Red O; ie., M2 Lipid Body positive (LB+) foamy macrophages, as mediating the deregulated inflammation. But these cells are anti-inflammatory. Instead it is the M1-like LB- foamy macrophages which when exhibiting immunosenescence (failed lytic release of HERV-K102 particles) mediate atherosclerosis. Since they upregulate ACE1 with activation, this may contribute to hypertension. During a response to viral infection (or even inhaled corticosteroids), the blood pressure will elevate slowly over the 6 days (to about 140 mm Hg systolic) and on the 6th day there will be a rapid drop over several hours to near normal due to the lytic release of the HERV-K102 particles on day 6. Presumably if the particles are not released, then hypertension continues and unfortunately the virus gets the advantage. This may be why hypertension is a ‘risk factor’ for COVID-19 severity, ie., it indicates the presence of immunosenescence/ failed trained innate immunity.
The same failure to lytically release HERV-K102 particles from sebocytes (specialized M1-like foamy macrophages in sebaceous glands lining the skin or mucosa such as in the nasopharynx and oral cavities) leads to acne. Melnick argues all anti-acne treatments re-establish the function of p53 needed for apoptosis. Hence, these anti-acne treatments are expected to ‘reverse immunosenescence’ the critical risk factor for COVID-19 severity.
“Several drugs that are often used in dermatology are among the potentially useful treatments: ivermectin, antiandrogenic agents, melatonin, and the antimalarial drugs chloroquine and hydroxychloroquine.”
Ortega-Peña M, González-Cuevas R. Familiar Dermatologic Drugs as Therapies for COVID-19. Actas Dermosifiliogr (Engl Ed). 2021 Feb;112(2):118-126. English, Spanish. doi: 10.1016/j.ad.2020.09.004.
Here is a ppt presentation PDF to explain the rationale for why anti-acne drugs and others may be useful in combatting COVID-19.