key: cord-0758198-q8940i7k authors: Demonbreun, Alexis R.; Velez, Matthew P.; Saber, Rana; Ryan, Daniel T.; Sancilio, Amelia; McDade, Thomas W.; McNally, Elizabeth M. title: mRNA intramuscular vaccination produces a robust IgG antibody response in advanced neuromuscular disease date: 2021-11-19 journal: Neuromuscul Disord DOI: 10.1016/j.nmd.2021.11.006 sha: 8e66325ca5701e7b2d5c66cab64f1ee0912eb669 doc_id: 758198 cord_uid: q8940i7k SARS-CoV-2 vaccines protect against symptomatic and severe COVID-19. The BNT162b2/Pfizer and mRNA-1273/Moderna vaccines represent new vaccine technology relying on administration of mRNA encoding SARS-CoV-2 viral spike protein encased in lipid nanoparticles. The vaccines are administered as two doses into muscle, which elicits a strong response, typically within 14 days after the second dose. Neuromuscular diseases are characterized by the progressive loss of muscle and are often treated with chronic glucocorticoid steroids, both of which may contribute to a blunted immune response to vaccination. Herein, we measured IgG antibody content and neutralizing antibody response after mRNA COVID-19 vaccination in non-ambulatory neuromuscular disease patients. After two doses of mRNA COVID-19 vaccine, median anti-receptor binding domain IgG and percent surrogate viral neutralization in non-ambulatory neuromuscular disease samples were significantly elevated similar to healthy vaccinated controls. As in healthy controls, COVID-19 vaccines produce greater antibody levels compared to those with a history of outpatient COVID-19 infection. This data documents that non-ambulatory neuromuscular disease patients respond well to two doses of mRNA COVID-19 vaccine despite low muscle mass and even chronic steroid use. Highlights (each to be no more than 85 characters including spaces):  Robust IgG response after COVID-19 vaccination in non-ambulatory NMD patients  Accompanying surrogate neutralization after COVID-19 vaccination in NMD patients  Steroid use does not strongly inhibit COVID-19 vaccination response in NMD patients predictive of COVID-19 protection [1] . All research activities were implemented under protocols approved by the institutional review board at Northwestern University (#STU00212457 and #STU00212472). Participants provided e-consent and completed an online questionnaire regarding health, COVID-19 viral status, and COVID-19 vaccination status. Participants were mailed a dried blood spot (DBS) kit, instructed to self-collect DBS 14 days after receiving vaccine dose two and return by mail. Results were compared to a similarly conducted community-based survey, Screening for Coronavirus Antibodies in Neighborhoods (SCAN), which measured antibody response after COVID-19 viral infection (COVID-19+) or after administration of vaccine dose two [2, 3] . The anti-RBD (receptor binding domain) IgG enzyme-linked immunosorbent assay (ELISA) protocol was performed as described [4, 5] . Anti-RBD IgG concentration was calculated from the 4PL regression of the CR3022 calibration curve [4, 5] . The surrogate virus neutralization protocol was performed as described [6] . Percent surrogate neutralization = 100 x 1 -(sample mean fluorescence intensity (MFI) /negative control MFI). Samples were evaluated in duplicate and reported as the average. Fourteen participants (13 advanced non-ambulatory NMD patients and one ambulatory carrier) were monitored for IgG response after vaccination. Results were compared to healthy community-derived controls. As a third comparator, IgG levels were measured in unvaccinated non-NMD participants who had a history of outpatient COVID-19 infection. Table 1 describes the NMD cohort; 8 of 14 were taking chronic steroids in a wide range of doses and frequency, and none reported previous COVID-19 infection. Advanced NMD patients have little intact muscle mass, yet these individuals responded well to two doses of mRNA vaccines. Although longitudinal health data is not yet available, the near-term vaccine response suggests a comparable response to that seen in healthy community controls and supports it is reasonable to expect similar protection. The presence of a normal immune response to mRNA vaccination indicates the non-muscle components as being more critical for immune response to these novel vaccines. The study is limited by its small size and self-report nature of vaccination and health history. Although immunosuppression, including glucocorticoid use is known to lower the humoral vaccine response [7] , in our small study we did not observe chronic glucocorticoid steroid use as strongly interfering with vaccine response. The number of participants taking glucocorticoids, combined with the wide range of dose and dosing schedules, does not allow us to draw any conclusions regarding the amount of steroid use and vaccine response. It is possible that those taking chronic daily steroids may have lower vaccine response, but further study is needed to confirm this. Supported by the National Science Foundation 2035114, NIH 3UL1TR001422-06S4, Northwestern University Office of Research, and a generous gift from Dr. Andrew Senyei and Noni Senyei. The funding sources had no role in the study design, data collection, analysis, interpretation, or writing of the report. Thomas McDade has a financial interest in EnMed Microanalytics, a company that specializes in laboratory testing of dried blood spot samples. All other authors declare no conflicts of interest. LGMD, limb girdle muscular dystrophy; SMA, spinal muscular atrophy. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection Patterns and persistence of SARS-CoV-2 IgG antibodies in Chicago to monitor COVID-19 exposure Comparison of IgG and neutralizing antibody responses after one or two doses of COVID-19 mRNA vaccine in previously infected and uninfected individuals A serological assay to detect SARS-CoV-2 seroconversion in humans High seroprevalence for SARS-CoV-2 among household members of essential workers detected using a dried blood spot assay A surrogate virus neutralization test to quantify antibody-mediated inhibition of SARS-CoV-2 in finger stick dried blood spot samples Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2 : A Prospective Cohort Study The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.