Abstract
This cohort study assesses a group of patients with multiple sclerosis in Amsterdam, the Netherlands, for SARS-CoV-2 antibodies to quantify asymptomatic infections and immunological response to COVID-19.
Various cohorts of patients with multiple sclerosis (MS) and COVID-19 have been described. So far, limited information is available regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in patients with MS. The objective of this study was to test for SARS-CoV-2 antibodies in a large MS cohort to evaluate asymptomatic infections and immunological responses to COVID-19.
Methods
This is a prospective cohort study conducted at the MS Center Amsterdam in Amsterdam, the Netherlands. On July 31, 2020, all adult patients with a current diagnosis of MS who had visited the MS Center Amsterdam in the past 2 years were invited to participate. The database was closed on December 18, 2020. The study was approved by the Medical Ethical Committee of the VU University Medical Center, and all patients provided written informed consent. The STROBE reporting guideline was followed.
Blood samples were drawn for SARS-CoV-2 antibody measurements with a total antibody assay with 98.1% sensitivity and 99.5% specificity.1 Signals were quantified as normalized optical density (nOD) units, ranging from low (0.1-1.0 nOD) to high (>1.0 nOD). In the week following blood sampling, patients filled in digital questionnaires regarding their characteristics, current MS complaints, and COVID-19 symptoms. Other MS-specific data were retrieved from the medical files. Groups were compared with the Mann-Whitney U test (for continuous data) or the Pearson χ2 test (categorical data). The level of significance was set at .05, and SPSS version 26.0 (IBM) was used for data analysis.
Results
A total of 1778 patients were contacted, and 546 patients were included (mean [SD] age, 46.9 [12.1] years; 388 women [71.1%]). Additional baseline characteristics are described in the Table. In 64 patients (11.7%), SARS-CoV-2 antibodies were detected. Thirty-five patients experienced COVID-19, as established by polymerase chain reaction (PCR) testing (Figure, A). Of the patients positive by PCR, 4 (11%) tested negative for SARS-CoV-2 antibodies.
Table. Baseline and COVID-19 Characteristics.
| Characteristic | Patients, No. (%) | ||
|---|---|---|---|
| Total (N = 546) | SARS-CoV-2 antibody positive (n = 64) | SARS-CoV-2 antibody negative (n = 482) | |
| Age, mean (SD), y | 46.9 (12.1) | 46.3 (12.6) | 46.9 (12.1) |
| Women | 388 (71.1) | 43 (67.2) | 345 (71.6) |
| Men | 158 (28.9) | 21 (32.8) | 137 (28.4) |
| Weight, mean (SD), kga | 75.4 (25.1) | 74.2 (12.7) | 75.6 (26.4) |
| Years since diagnosis, median (interquartile range) | 12 (6-18) | 11 (5-21) | 12 (6-17) |
| SARS-CoV-2 polymerase chain reaction test performed, No. | 148 | 38 | 110 |
| Positive | 35 (23.6) | 31 (82.6) | 4 (3.6) |
| Negative | 113 (76.4) | 7 (18.4) | 106 (96.4) |
Abbreviation: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Not all answers were complete.
Figure. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Response in Patients With Multiple Sclerosis With Positive Results on Polymerase Chain Reaction (PCR) and Antibody Testing.
A, Time between the positive PCR (at month 0) and the SARS-CoV-2 total antibody test. In 4 patients, no SARS-CoV-2 antibodies could be detected. None were lymphopenic (<1000 cells per microliter; to convert to cells × 109 per liter, multiply by 0.001) in testing in the 2 months prior to the start of COVID-19 complaints. The patient taking ocrelizumab was B-cell depleted prior to COVID-19 and had received 4 cycles of ocrelizumab. B, SARS-CoV-2 antibody response in patients with positive results on PCR and/or antibody testing who were receiving different disease-modifying therapies. The maximum response that could be measured was 2.5 normalized optical density (nOD) units, with a cutoff of 0.1 for seropositivity. The 2 patients treated with alemtuzumab received their last course 43 and 29 months prior to SARS-CoV-2 antibody sampling, respectively. One patient with an autologous stem cell transplant (aSCT) was treated 10 months prior to SARS-CoV-2 antibody sampling.
Nine patients who were antibody positive (14%) did not experience any symptoms suggestive of COVID-19. The most frequently reported symptom in those positive for SARS-CoV-2 antibodies was a loss of taste and/or smell (30 of 64 patients [47%]), while only 14 of 482 patients (2.9%) without SARS-CoV-2 antibodies reported these symptoms. To our knowledge, there were no COVID-19 fatalities in this MS population.
Of all 546 patients, 405 (74.2%) were receiving disease-modifying therapy. In these, SARS-CoV-2 antibodies were less prevalent in patients using injectable drugs (interferon β and glatiramer acetate) than patients with other treatments (3 of 69 [4%] vs 44 of 336 [13.1%]; P = .04).
The median SARS-CoV-2 antibody response in patients treated with ocrelizumab was lower in comparison with other patients (0.2 [interquartile range, 0.1-0.4] nOD vs 2.5 [interquartile range, 0.6-2.5] nOD; P < .001; Figure, B). All patients taking ocrelizumab were B-cell depleted, as measured at a median (range) of 2.5 (0-41) days before the antibody response was measured. None of these patients experienced hypogammaglobulinemia at that time.
Discussion
In this study, we found a lower SARS-CoV-2 antibody response in patients with MS who were depleted of B cells. Case reports2,3,4 have described patients with MS and neuromyelitis optica treated with anti-CD20 therapies who did not develop detectable SARS-CoV-2 antibodies after PCR-confirmed COVID-19. Furthermore, in a retrospective cohort,5 SARS-CoV-2 antibodies were less prevalent in patients with MS and suspected COVID-19 who were treated with ocrelizumab.
This cohort study showed that 14% of patients with MS and COVID-19 were asymptomatic for COVID-19, which is comparable with a reported 17% in the general population.6 Because patients may have been more willing to participate in this study after experiencing symptoms fitting COVID-19, the percentage of patients who were asymptomatic might be an underrepresentation.
A limitation of our study is the relatively low percentage of patients who were SARS-CoV-2 positive. Still, we were able to show a lower antibody response in patients depleted of B cells.
Conclusions
In conclusion, our data imply that B-cell depletion could influence SARS-CoV-2 antibody production in patients with MS. This holds important consequences for humoral immunity after COVID-19 infection and possibly vaccination.
References
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