Could an Unrelated Live Attenuated Vaccine Serve as a Preventive Measure To Dampen Septic Inflammation Associated with COVID-19 Infection?

Abstract

We propose the concept that administration of an unrelated live attenuated vaccine, such as MMR (measles, mumps, rubella), could serve as a preventive measure against the worst sequelae of coronavirus disease 2019 (COVID-19). There is mounting evidence that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing "trained" nonspecific innate immune cells for improved host responses against subsequent infections. Mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis. Vaccination with MMR in immunocompetent individuals has no contraindications and may be especially effective for health care workers who can easily be exposed to COVID-19. Following the lead of other countries conducting clinical trials with the live attenuated Mycobacterium bovis BCG (BCG) vaccine under a similar concept, a clinical trial with MMR in high-risk populations may provide a "low-risk-high-reward" preventive measure in saving lives during this unprecedented COVID-19 pandemic.

Keywords: COVID-19; MMR; clinical trial; inflammation; live attenuated vaccines; myeloid-derived suppressor cells; sepsis; trained innate immunity.

FIG 1

Protection against lethal polymicrobial-community-mediated sepsis by vaccination with an avirulent yeast strain. Mice were vaccinated intraperitoneally with avirulent (live attenuated) Candida dubliniensis (Cd) followed by a lethal challenge with Candida albicans and Staphylococcus aureus (Ca/Sa) intraperitoneally 14 days later. Survival data are shown for 8 independent experiments performed with groups of 10 mice each. The inset shows sepsis scoring during the observation period after lethal challenge. Animals were monitored daily using a modified mouse clinical assessment score for sepsis (M-CASS) scoring system that included fur aspect, posture, activity, and chest and eyelid movement. Animals with a combined daily score of 8+ were humanely euthanized. Data were statistically analyzed using the Mantel-Cox log rank test (survival curves) and two-way analysis of variance (ANOVA) with Bonferroni post hoc tests (sepsis scoring) (****, P < 0.0001). SEM, standard errors of the means.