1. Introduction
A myriad of publications addressing COVID-19 and its impact on acute and chronic neurological disorders have been published in the last few months. Special interest has arisen in chronic demyelinating disorders, such as Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorders (NMOSD), mainly due to immunotherapy and increased risk of infections (Brownlee et al., 2020). In MS, a multicentric study led by the Italian program for COVID-19 infection in multiple sclerosis, including 238 symptomatic patients (57 had positive RT-PCR) from 38 centers, seems to reassure that most patients (96%) developed a mild disease. Unfortunately, 5 patients died, all of them with EDSS ≥ 6.52. An observational study including 8 patients from North America, also highlights the importance of EDSS in the risk of fatal outcome (Bowen et al., 2020). A more recent multicentric study, including 347 patients from the Covisep French registry, showed that 21% of the patients at least required hospitalization, while 12 patients (3.5%) died. Multivariate analyses determined that EDSS, age and obesity were independent risk factors for hospitalization or more severe COVID-19, while no association between disease-modifying therapy exposure and COVID-19 severity was observed (Louapre et al., 2020). In NMOSD fewer articles have been published, also suggesting a similar rate of infection compared to the general population (Sahraian et al., 2020).
On May 16th, our group published a first report addressing the impact of COVID-19 using an online survey completed by 280 patients, highlighting the relevance of early communication for infection prevention measures, and social impact of telemedicine and remote-working. Main results included a high percentage of patients under disease-modifying therapy (95%), a high percentage of patients reporting at least one comorbidity (60%), 75% stated to be remote working/studying since early March, and 8% declared to be unemployed. Three patients were confirmed with COVID-19, with no fatal outcomes (Ciampi et al., 2020). Unfortunately, over 100 days after the first patient was confirmed in Chile, things have dramatically changed. The number of cases and deaths due to COVID-19 has exponentially increased, with over 300,000 patients diagnosed (1.6% of the total population) and over 6500 deaths (2.2%) (MINSAL, 2020). Therefore, a second online questionnaire was distributed among MS and NMOSD treating neurologists throughout the country in order to assess a national representation of the impact of COVID-19 in their patients’ lives, and to improve and update the recommendations given to patients and caregivers, in the event of a confirmed infection. Patients under regular clinical care had already given written informed consent approved by the local Ethics Committee. Also, before survey completion, patients were asked to agree on an online informed consent. A total of 409 surveys from 9 centers have been completed, 71% women, mean age 41 years, 98% with MS, and 88% receiving immunotherapy. Most prevalent self-reported comorbidities were being overweight/obese (17%), current smoking (14%), insulin resistance/type 2 diabetes (9%), thyroid disorders (8%) and hypertension (8%). Remote working-studying remains high (74%), but unemployment has risen to 10%. Compared to our previous study, a similar proportion of patients (16%) reported having any symptom suggestive of COVID-19 (Table 1 ). Eighteen patients have been diagnosed with COVID-19 (14 RRMS, 4 NMOSD), 12 women (67%), median age of 32.5 years (range 17–61), median disease duration of 7 years (range 0.3–12) and median EDSS of 1.0 (0–6.0). No progressive MS patient has yet been infected. All patients had at least one comorbidity, and all were receiving immunotherapy. No changes in disease-modifying therapy were suggested in 11 patients, while 6 patients required transient suspension, and one patient required stress dose steroids. Five patients (28%, 3/5 men) required hospitalization, while one patient (NMOSD, male, EDSS 6.0, with hypertension and type 2 diabetes), required invasive mechanical ventilation, and had a fatal outcome due to critical illness polyneuromyopathy and secondary bacterial infection (Table 2 ).
Table 1.
Demographic | Disease-related | ||
---|---|---|---|
Sex N(%) female: male | 290 (71):118(29) | Diagnosis | N (%) |
Age mean+SD (range) | 41.2 + 11.4(17–81) | MS | 400(98) |
Health Insurance N(%) public:private:other | 77(19)/325(79)/7(2) | NMOSD | 5(1) |
Current pregnancy N(%) | 3(1) | Other | 4(1) |
Current treatment | N (%) | Self-reported comorbidities | N (%) |
Any DMT | 360(88) | Overweight/obese | 70(17) |
Interferon beta | 47(11) | Current smoking | 57(14) |
Glatiramer acetate | 16(4) | Insulin resistance/type 2 diabetes | 36(9) |
Teriflunomide | 20(5) | Thyroid disorder | 32(8) |
Dimethyl fumarate | 17(4) | Hypertension | 32(8) |
Fingolimod | 118(29) | Other autoimmune disease | 36(9) |
Cladribine | 17(4) | Dyslipidemia | 25(6) |
Natalizumab | 12(3) | Asthma/COPD | 20(5) |
Ocrelizumab | 77(19) | Mood disorder | 5(1) |
Rituximab | 16(4) | Cancer | 4(1) |
Alemtuzumab | 17(4) | Cardiac disease | 3(1) |
Azathioprine | 1(0) | Epilepsy | 3(1) |
Mycophenolate | 2(1) | Another comorbidity | 12(3) |
No immunotherapy | 49(12) | No comorbidity | 159(39) |
Social Information | N (%) | COVID-19 | N (%) |
Medical leave due to MS | 12(3) | Any symptom suggestive of COVID-19 | 65(16) |
Medical leave du to other diagnosis | 16(4) | Headache | 35(54) |
Unemployed | 41(10) | Sore throat | 33(52) |
Homesteader/Home keeper | 42(10) | Cough | 28(44) |
Full-time student | 11(3) | Malaise | 26(40) |
Part-time student | 1(0) | Diarrhea | 21(33) |
Retired due to MS | 33(8) | Fever | 12(19) |
Retired due to age | 8(2) | Dyspnea | 11(17) |
Full-time job | 200(49) | Anosmia | 6(9) |
Part-time job | 45(11) | Nasal congestion | 2(3) |
Remote working/studying | 303(74) | Eye infection | 1(2) |
In-office working/studying | 45(11) | Measures taken after symptom onset | |
Mixed remote and in-office | 61(15) | Stayed at home | 42(65) |
Visited Emergency Room | 6(9) | ||
Consulted treating neurologist | 8(13) | ||
Consulted another doctor | 9(14) | ||
COVID-19 test | 14(22) | ||
Required hospitalization | 5(8) |
DMT disease-modifying therapy, MS multiple sclerosis, NMOSD Neuromyelitis Optica Spectrum Disorders, COPD chronic obstructive pulmonary disease.
Table 2.
Patient | RT-PCR | Sex | Age (years) | Diagnosis | Disease Duration (years) | EDSS | Comorbidities | DMT | DMT modification or interruption | Hospitalization | IMV | COVID-19 symptoms and Follow-up | Outcome |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | positive | male | 30 | RRMS | 6 | 1 | insulin resistance, hypothyroidism | ocrelizumab | no change - last infusion 10 days before symptoms onset | yes | no | bilateral pneumonia, readmission due to Adenovirus pneumonia | full recovery |
2 | positive | female | 23 | RRMS | 8 | 1 | insulin resistance | dimethyl fumarate | suspended for 35 days until clinical recovery | yes | no | bilateral pneumonia | full recovery |
3 | positive | female | 24 | RRMS | 9 | 1 | migraine, depression, insulin resistance | fingolimod | suspended for 21 days until clinical recovery | yes | no | myalgias and fever | full recovery |
4 | positive | male | 61 | NMOSD-AQP4 | 0.3 | 6 | hypertension, type 2 diabetes | prednisone | steroid stress dose | yes | yes | bilateral pneumonia, tracheostomy | fatal |
5 | positive | female | 54 | NMOSD-AQP4 | 12 | 3 | insulin resistance, pernicious anemia, osteoarthritis | mycophenolate | no change | no | no | anosmia | full recovery |
6 | positive | female | 29 | RRMS | 7 | 1 | hypothyroidism | fingolimod | suspended for 5 days until clinical recovery | no | no | myalgias and fever | full recovery |
7 | not performed - close contact with positive PCR, positive IgM | female | 23 | RRMS | 2.5 | 1 | obesity | dimethyl fumarate | no change | no | no | myalgias and fever | full recovery |
8 | positive | male | 55 | RRMS | 7 | 1 | depression | teriflunomide | suspended for 7 days until clinical recovery | no | no | myalgias and fever, recovering at home | full recovery |
9 | positive | female | 57 | RRMS | 7 | 4 | anxiety, type 2 diabetes | fingolimod | no change | no | no | sore throat, headache, mild dyspnea | full recovery |
10 | positive | male | 17 | RRMS | 2 | 0 | asthma | fingolimod | no change | no | no | asymptomatic | full recovery |
11 | not performed - close contact with positive PCR | female | 28 | NMOSD | 3 | 2.5 | obesity | mycophenolate | no change | no | no | anosmia, fever and diarrhea | full recovery |
12 | not performed - close contact with positive PCR, positive IgG | female | 44 | RRMS | 6 | 3 | depression, cutaneous amyloidosis | natalizumab | last dose 4 months prior infection - waiting for switching to cladribine | no | no | anosmia, diarrhea, fever | full recovery |
13 | positive | male | 40 | NMOSD-MOG | 0.6 | 2.5 | depression | azathioprine | suspension for 1 month | yes | no | myalgia, fever and sore throat, dyspnea, suspected bacterial sobreinfection, received tocilizumab | full recovery |
14 | positive | female | 52 | RRMS | 8 | 1 | depression, obesity, hypertension, insulin resistance | teriflunomide | no change | no | no | dry cough | full recovery |
15 | positive | female | 31 | RRMS | 3 | 2 | hypothyroidism | fingolimod | no change | no | no | asymptomatic | full recovery |
16 | positive, IgG positive | female | 34 | RRMS | 7 | 1 | secondary thyroiditis | alemtuzumab | no change - last dose October 2018 | no | no | myalgia, headache, anosmia | recovering at home |
17 | positive | male | 36 | RRMS | 4 | 2 | migraine, depression | interferon beta 1a IM | no change | no | no | myalgia, rhinorrhea, anosmia | recovering at home |
18 | not performed, negative IgG | female | 31 | RRMS | 14 | 1 | migraine | alemtuzumab 4 doses, ocrelizumab | no change - last infusion 2 months before symptom onset | no | no | fever, myalgia, headache, anosmia | recovering at home |
RT-PCR: real-time polymerase chain reaction; RRMS relapsing-remitting multiple sclerosis; NMOSD Neuromyelitis Optica Spectrum Disorder; AQP4 aquaporin 4; MOG myelin oligodendrocyte glycoprotein; EDSS expanded disability status scale, DMT disease modifying therapy, IMV invasive mechanical ventilation.
The sustained worsening of the COVID-19 pandemic in our country warrants an urgent need in maintaining fluid communication with our patients. Although this is a small study in a country with an estimated prevalence of 13.4 per 100,000 habitants (Fernández, 2008), we achieved a representative 16% of the estimated total MS population of 2546 patients. We noticed a possible impact of comorbidities, age, male gender and higher EDSS in the outcome of COVID-19 severe acute respiratory syndrome, with no clear relationship with any specific disease-modifying therapy. Nonetheless, the small sample size of this case series is a major limitation for further conclusions. Results from large multicentric databases such as the Italian (Sormani, 2020) and French (Louapre et al., 2020) registries will better elucidate the real influence of these variables on COVID-19 outcomes.
The results from this survey has also impacted our clinical practice and we have changed the way our MS program works. We have implemented telemedicine consultations in over 80% of our routine or emergent visits, infusions have been postponed and rescheduled to an outpatient clinic infusion center, physical therapy, neurocognitive rehabilitation and psychological support access have decreased and efforts are being made in order to maintain the standard clinical care for our MS-NMOSD community.
Maintaining the connection between the different MS groups at national and international levels will be essential to delineate future directions regarding the changes that COVID-19 is generating in the care of our patients.
Declaration of Competing Interest
EC received the ECTRIMS Clinical Fellowship (2013–2014), ECTRIMS travel grant awards, and academic travel support from Novartis, Genzyme, Merck, Biogen and Roche, has been a member of advisory boards at Genzyme, Biogen, Merck and Novartis, has received sub-investigator fees from the ISS “Social Cognition in MS” project at Teva. RUSM received academic travel support from Novartis, Genzyme, Merck, Biogen andRoche, has been a member of advisory boards at Genzyme, Biogen, Merck and Novartis. BS received academic travel support from Novartis, Teva, Merck and Biogen RF received academic travel support from Genzyme, Biogen, Merck, Novartis, Roche, Teva and speaker compensations from Teva and Biogen. PG nothing to disclose CN received academic travel support from Biogen, Genzyme, Novartis and Merck JMT nothing to disclose RT received academic travel support from Biogen, Roche, Teva, Sanofi, Novaris and Merck JP received academic travel support from Biogen, Novartis, Genzyme, Merck and Roche FS nothing to disclose MJC nothing to disclose CC received academic travel support from Novartis, Genzyme, Merck, Biogen and Roche, has been a member of advisory boards at Genzyme, Biogen, Merck and Novartis, has received PI fees from the ISS “Social Cognition in MS” project at Teva.
Acknowledgments
Funding
No funding was received for this study
Acknowledgements
We thank our MS care team, our patients, and their families, and Nicole Ciampi for contributing to the development of this information.
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