DOI: 10.5061/dryad.jsxksn077
title: Analysis of measles-mumps-rubella (MMR) titers of recovered COVID-19 patients

description: The measles-mumps-rubella (MMR) vaccine has been theorized to provide
 protection against COVID-19. Our aim was to determine whether any MMR IgG
 titers are inversely correlated with severity in recovered COVID-19
 patients previously vaccinated with MMR II. We divided 80 subjects into
 two groups, comparing MMR titers to recent COVID-19 severity. The MMR II
 group consisted of 50 subjects who would primarily have MMR antibodies
 from the MMR II vaccine, and a comparison group of 30 subjects who would
 primarily have MMR antibodies from sources other than MMR II, including
 prior measles, mumps, and/or rubella illnesses. There was a significant
 inverse correlation (rs = -0.71, P &lt; .001) between mumps titers and
 COVID-19 severity within the MMR II group. There were no correlations
 between mumps titers and severity in the comparison group, between mumps
 titers and age in the MMRII group, or between severity and measles or
 rubella titers in either group. Within the MMR II group: mumps titers of
 134 to 300 AU/ml (n=8) were only found in those who were functionally
 immune or asymptomatic; all with mild symptoms had mumps titers below 134
 AU/ml (n=17); all with moderate symptoms had mumps titers below 75 AU/ml
 (n=11); all who had been hospitalized and required oxygen had mumps titers
 below 32 AU/ml (n=5). Our results demonstrate that there is a significant
 inverse correlation between mumps titers from MMR II and COVID-19
 severity.
description: <b>Study Design.</b> MMR IgG titers were measured in
 80 adults consented to join our study. All were born in the United States
 and over 18 years of age. Applicants (n=568) were screened using a
 HIPAA-compliant online form in which informed consent was obtained,
 approved by our Investigational Review Board (Integrity IRB Protocol ID:
 40005). Subjects were chosen from applicants who responded to online
 advertisements that we ran seeking recovered COVID-19 patients for this
 study. Each applicant was required to upload documentation of their
 COVID-19 medical history including COVID-19 test results and
 hospitalization records, as well as completing an in-depth online survey
 in which they provided details related to their COVID-19 symptoms and
 outcomes on a HIPAA-compliant form. Follow-up was done as necessary to
 verify the information provided to ensure each subject met the study
 criteria. Subjects in the study were selected in the order that they
 applied, if they matched criteria for either the MMR II group or the
 comparison group, until all 80 subjects had been selected and tested.
 Review of applicants stopped once 80 subjects had been selected. The
 selection and titer test process ran from May 12, 2020 through August 26,
 2020. A small stipend to help defray costs was available to subjects. We
 divided subjects into two groups. The first group was
 the MMR II group which consisted of 50 subjects (mean age, 30.6 [SD, 7.6],
 33 women, 17 men) whose only likely source of MMR antibodies would be from
 the MMR II vaccine. Of these, 40 had previously tested COVID-19 positive
 with symptoms ranging from asymptomatic to requiring a ventilator, and 10
 subjects were functionally immune (COVID-19 negative despite strong
 COVID-19 exposure). Functionally immune subjects had several days of close
 contact with someone who was symptomatic and who had tested positive for
 COVID-19, without either person social distancing or wearing masks.
 Despite the extensive contact, the functionally immune subjects tested
 negative for COVID-19 and never exhibited symptoms. Each person in the MMR
 II group was U.S. born and either: born on or after December 1, 1978,
 meaning they would have received their first vaccination after the MMR II
 vaccine was launched; or if born on or after December 1, 1973 but before
 December 1, 1978, specifically documented one or more MMR II
 vaccinations. The remaining 30 subjects (mean age, 57.4
 [SD, 7.8], 18 women, 12 men) made up the comparison group, all of whom
 tested positive for COVID-19 and were born before December 1, 1976. All
 subjects in the comparison group were born at least several years before
 the MMR II vaccine was launched, and none had any record of ever receiving
 an MMR II vaccination or booster. The age disparity between the MMR II
 group and the comparison group was purposeful, which is why we utilized a
 comparison group, not a control group. Age differentiation was the only
 way to accurately separate people who definitively had prior MMR II
 vaccinations from those who had not. Mumps, measles,
 and rubella IgG titers were measured by Quest Diagnostics using LIAISON
 analyzers with chemiluminescence immunoassay (CLIA) technology for the
 qualitative determination of IgG antibodies in human serum specimens. The
 method for qualitative determination of specific IgG to each virus was an
 indirect CLIA. The principal components of each test were magnetic
 particles (solid phase) coated with recombinant antigen and a conjugate of
 mouse monoclonal antibody to human IgG linked to an isoluminol derivative
 (isoluminol-antibody conjugate). During the first incubation, antibodies
 to the virus being tested present in the calibrators, specimens or
 controls would bind to the solid phase. During the second incubation, the
 antibody conjugate would react with each virus IgG already bound to the
 solid phase. After each incubation, the unbound material was removed with
 a wash cycle. Subsequently, the starter reagents were added and a flash
 chemiluminescence reaction was thus induced. The chemiluminescent signal,
 and hence the amount of isoluminol-antibody conjugate, was measured by a
 photomultiplier as relative light units (RLU) and was indicative of the
 presence of IgG in calibrators, specimens, or controls. Diagnostic
 sensitivities were: measles 94.7% (95% C.I.: 91.7-96.9%), mumps 98.5% (95%
 C.I.: 96.5-99.5%), rubella 100% (95% C.I.: 99.3-100%). Diagnostic
 specificities were: measles 97.4% (95% C.I.:94.1-99.2%), mumps 98.2% (95%
 C.I.: 94.8-99.6%), rubella 100% (95% C.I: 97.0-100%).
 <b>Symptoms Score Calculations.</b> Each subject
 began with a score of zero, then points were added. One point each:
 COVID-19 positive, dry cough, sore throat, slight shortness of breath,
 headache, confusion, muscle aches/pain, fever over 101° F, nausea and/or
 vomiting, or diarrhea. Two points each: severe difficulty breathing, chest
 pain, or sudden loss of sense of smell/taste. Five points each: subject
 was hospitalized, required supplemental oxygen, or was intubated on a
 ventilator. <b>Severity Levels.</b> Five
 severity levels were designated based upon symptoms scores. “Functionally
 Immune” had a symptom score of 0. “Asymptomatic” had a score of 1, i.e.,
 those who were COVID-19 positive but had no symptoms. “Mild” were those
 with scores ranging from 2 to 10. “Moderate” were those with scores from
 11 to 20. “Severe” were those with scores from 21 to 30.