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Analysis of measles-mumps-rubella (MMR) titers of recovered COVID-19 patients

Citation

Gold, Jeffrey et al. (2020), Analysis of measles-mumps-rubella (MMR) titers of recovered COVID-19 patients, Dryad, Dataset, https://doi.org/10.5061/dryad.jsxksn077

Abstract

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 < .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.

Methods

Study Design. 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%).

Symptoms Score Calculations. 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.

Severity Levels. 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.