Table I.

Projected IR-dependent COVID-19 phenotypes

Characteristic	Phenotype 1	Phenotype 2	Phenotype 3
Pre–COVID-19 IC-IF state∗	IChigh-IFlow	IChigh-IFlow	IClow-IFhigh
SARS-CoV-2–induced IClow-IFhigh∗ state	Resistance to induction	Susceptibility to induction	Susceptibility to induction
Corollaries of pre–COVID-19 IC-IF state†
Longevity‡	Survival advantage	Survival advantage	Survival disadvantage
Influenza infection severity§	Asymptomatic or mild	Moderate	Severe
AIDS resistance¶	High	Moderate	Low
Corollaries of pre–COVID-19 plus SARS-CoV-2–induced IC-IF states#
Resistance to progressive COVID-19#	High	Moderate	Low
Survival#	Pre–COVID-19 survival advantage preserved	Pre–COVID-19 survival advantage lost	Additive survival disadvantage
Sex bias††	Females		Males

^∗IC-IF (immunocompetence-inflammation) states: IC^high-IF^low signifies superior IR; IC^low-IF^high signifies a deficit in IR. In patients with COVID-19, phenotype 1 is defined by a pre–COVID-19 IC^high-IF^low state and resistance to induction of an IC^low-IF^high state in response to SARS-CoV-2–associated antigenic stimulation; phenotype 2 is defined by a pre–COVID-19 IC^high-IF^low state and susceptibility to induction of an IC^low-IF^high state in response to SARS-CoV-2–associated antigenic stimulation, and phenotype 3 is defined by a pre-COVID-19 IC^low-IF^high state and susceptibility to induction of an IC^low-IF^high state in response to SARS-CoV-2–associated antigenic stimulation. Corollaries (longevity, influenza infection severity, and AIDS risk) associated with pre–COVID-19 IC-IF states are contrasted with corollaries of pre–COVID-19 plus SARS-CoV-2–induced IC-IF states.

^†Evaluated in non-COVID-19 cohorts.

^‡Evaluated in the non–COVID-19 HIV-seronegative, Offspring cohort of the FHS; survival advantage and disadvantage signify lower and higher hazards of mortality over 9 y, respectively.

^§Evaluated in non-COVID-19 HIV-seronegative, influenza infection challenge and natural influenza infection cohorts.

^¶Evaluated in a non–COVID-19 HIV infection natural history cohort.

^#Evaluated in a COVID-19 cohort; survival advantage and disadvantage signify lower and higher hazards of mortality, respectively, during COVID-19. Additive survival disadvantage refers to the combined effects of pre–COVID-19 IC^low-IF^high state and the unique infection-induced IC^low-IF^high state induced in patients with COVID-19.

^††Evaluated in non-COVID-19 cohorts and a COVID-19 cohort.