ABSTRACT
Background: SARS-CoV-2 antibody responses after COVID-19 vaccination are attenuated in people living with MS on high efficacy DMTs such as Fingolimod and Ocrelizumab. Uncertainties on how to manage vaccination schedule and DMT administration persist. Furthermore, data on effects of newer related DMTs like Siponimod and Ofatumumab are limited. Objective(s): We aimed to determine the seroprevalance of Spike antibody and the longevity of antibody mediatedimmune protection after COVID-19 vaccination in MS patients. Method(s): Spike IgG antibodies against Wuhan SARS CoV-2 were assessed in sera (n=520) of MS patients collected pre-vaccination (baseline n= 304), 1 month post second dose (n=172), 6 months post second dose (n=23) and 1 month post third dose (n=21). Demographic and clinical information including age, gender, DMT treatment and timing of COVID-19 vaccination were collected from 160 of these MS patients. Result(s): 151/172 sera at 1 month post second dose, 20/23 sera at 6 months post second dose, and 15/21 sera at 1 month post third dose were positive for Spike antibodies. Seropositive patients were treated on Alemtuzumab;n=3, Cladribine;n=32, Dimethyl fumarate;n=8, Fingolimod;n=16, IFN;n =4, Ocrelizumab;n=14, Ofatumumab;n=4, Natalizumab;n=11, Siponimod;n=1 and Teriflunomide;n=1. Out of the 21 patients who did not seroconvert at a month post second dose, treatment information was available in 12 patients. n=9 were treated by Ocrelizumab and n=2 were treated by Cladribine and n=1 was treated by Fingolimod, confirming certain DMTs prevent seroconversion. Out of the 151 patients that did seroconvert, 120 had titers that were comparable to controls (healthy general population) and 31 had reduced titres. Treatment information was available in 21/31 of these patients. Interestingly, 9/21 were on Ocrelizumab, 8/21 were on Fingolimod, 2/21 were on Ofatumumab, 1/21 was on Natalizumab and 1/21 was on Siponimod. This finding confirmed that certain DMTs such as Fingolimod, Ocrelizumab, Ofatumumab and Siponimod cause a reduction in post-vaccination Spike antibody titers in MS patients in comparison to general population. Expectedly, 304/304 sera were negative at baseline. Conclusion(s): Some High efficacy DMTs reduce Spike Ab titers or even prevent seroconversion. To maximize vaccine-mediated immune protection against COVID-19, timing of DMT administration and vaccine schedule may need intricate co-ordination in people living with MS.
ABSTRACT
Background: Current SARS-CoV-2 vaccines rely on protective immunity against early clade SARS-CoV-2 and have resulted in seroconversion in a subset of MS patients receiving immunosuppressive DMTs. However, it is unknown if SARS-CoV-2 spike antibodies afford immunity against emerging variants of concern, such as Delta and Omicron. Objective(s): To determine the binding of spike antibodies to early clade, Delta, and Omicron SARS-CoV-2 in patients with MS receiving different DMTs. Method(s): Spike antibody binding to early clade SARS-CoV-2, Delta and Omicron was assessed by flow cytometry using sera collected from 58 patients one month post second dose and one patient 1 month post third dose. All patients were previously determined to be seropositive against Wuhan (early clade spike). Clinical and demographic information including DMT treatment and vaccination timing was collected. Result(s): 53 patients were seropositive for Wuhan, Delta and Omicron spike antibodies. Wuhan Spike antibody titres were high at one month post second vaccination, whereas Delta and Omicron Spike antibody titres were significantly decreased. We observed a 70% and 93% decrease of in immunoreactivity to Delta and Omicron, respectively. Although ocrelizumab and fingolimod decrease Spike antibody titres after vaccination, they did not affect immunoreactivity to variants, in comparison to other DMTS. Conclusion(s): All 53 patients were able to generate a positive antibody response following vaccination. However, there was an observable decrease in the antibody titres and immunoreactivity to the Delta and Omicron variants, in comparison to Wuhan.
ABSTRACT
Background: COVID-19 vaccination induces protective Spike antibodies. Some responses are attenuated in people with multiple sclerosis (MS) on high efficacy disease-modifying therapies (DMT).Whether antibodies afford immunity against emerging SARS-CoV-2 Variants of Concern (VoC) such as Delta and Omicron is unknown. Aim(s): To assess the longevity and breadth of Spike antibody in MS patients after COVID-19 vaccination. Objective(s): To determine seroconversion and antibody binding toVoC Spike. Method(s): Spike antibodies to Clade A SARS-CoV-2 were assessed in 535 MS sera at baseline (n=292), 1 (n=141) and 6 month (n=67) post-second dose, and 1 month post-third dose (n=35), and 489 health worker controls. When known, COVID- 19 vaccines were BNT162b2 (n= 489 controls, n=108 MS patients) and ChAdOx1-S (n=37).Spike antibody binding to VoC Delta and Omicron BA1 was assessed in 68 sera 1 month post-second dose. Demographic and DMT information was available in 269 patients. Result(s): 123/141 sera at 1 month post-second dose, 66/67 at 6 months post-second dose, and 26/35 at 1 month post-third dose were positive for Spike antibodies.Patients who did not seroconvert at 1 and 6 month post-second and 1 month post-third dose (n=28) were treated with ocrelizumab (n=22), cladribine (n=1), fingolimod (n=4), and siponimod (n=1). At 1 month post-second dose, the median and IQR Spike antibody levels were 67,224+/- 101,251 in the seroconverted MS group compared to 145,510+/- 99,669 in controls (n=489). When patient sera were assessed for binding to Clade A Spike, and VoC Delta and Omicron BA1 Spikes, most sera were able to bind the three different Spike antigens (n=61). However, Spike antibody immunoreactivity was decreased by 70% against Delta Spike and 90% for Omicron BA1 Spike compared to the original clade A Spike.As observed for Clade A Spike antibody, DMTs, such as ocrelizumab, fingolimod, and ofatumumab, decreased the antibody binding to Delta and Omicron Spike. Still, the pattern of antibody recognition was similar between the three Spikes and all DMTs analysed, i.e. alemtuzumab, natalizumab, teriflunomide, and interferons. Our data suggest that, irrespectively of DMTs, antibodies generated after vaccination did not bind Spike from recent VoCs to the same extent as the original Spike used in COVID-19 vaccines. Conclusion(s): Some DMTs reduce Spike antibody titres or prevent seroconversion. The sequence of Spike used in the first generation of vaccines may need to be updated for emerging VoC.
ABSTRACT
BACKGROUND: Crises and disasters disproportionally impact people with chronic health conditions such as multiple sclerosis (MS). OBJECTIVE: To assess the impact of the COVID-19 pandemic and the Australian Black Summer Bushfires on health behaviours in people with MS. METHODS: People with MS, carers, healthcare and advocacy professionals were recruited online between May-July 2020 for an online survey and telephone interviews. RESULTS: Survey items relating to health behaviours were completed by 113 people with MS, and 18 people with MS, 4 MS advocates, 5 healthcare professionals, and 2 carers were interviewed. The bushfires affected 34.5% and the pandemic affected 74.3% of survey participants with MS. The pandemic and bushfires caused a decrease in physical activity in 53.8% and 55.3% of participants respectively, as well as increases in unhealthy eating (43.6% and 24.3% respectively) and alcohol consumption (35.4% and 10.5% respectively), and a decrease in typical sleeping patterns (40.5% and 39.5% respectively). Conversely, 27.5% of participants reported an increase in physical activity during the pandemic. Interview data detailed the circumstances and motivations for changes in health behaviours, as well as consequences, including reduced mobility, fitness, mood disturbances, and weight gain. CONCLUSION: There is a need to increase support and health promotion for people with MS to maintain or initiate positive health behaviours, especially in times of adversity.