| Abstract | Imunološka obrana oboljelog u infekciji SARS-CoV-2 virusom važan je čimbenik u razvoju kliničke slike i krajnjeg ishoda infekcije, stoga su bolesnici s multiplom sklerozom skupina od posebnog značenja s obzirom na to da lijekovi za liječenje multiple skleroze na različite načine interferiraju s imunološkim sustavom.
Cilj predloženog istraživanja bio je utvrditi povezanost terapije interferonom kod bolesnika s multiplom sklerozom s asimptomatskom COVID-19 infekcijom, poremećajem okusa u COVID19 infekciji, post-COVID sindromom i pojavom COVID-19 infekcije nakon cijepljenja te ih usporediti s utjecajem ostalih terapijskih opcija za multiplu sklerozu. Uključeno je ukupno sto
ispitanika. Podaci su analizirani pomoću Hi-kvadrat testa, Fisherovog egzaktnog testa, Waldovog testa tipa III i procjene omjera izgleda uz 95 %-tne Waldove intervale pouzdanosti. Značajnom se pokazala povezanost terapije interferonom i asimptomatske COVID-19 infekcije (p = 0,0015), post-COVID sindroma (p < 0,0001), kognitivnih smetnji (p = 0,0002) i umora (p = 0,0025) u post-COVID sindromu, poremećaja okusa u COVID-19 infekciji (p < 0,0001) i COVID-19 infekcija nakon cijepljenja (p = 0,0002). Nije se pokazala značajnom veza interferona i trajanja kognitivnih smetnji i umora u post-COVID sindromu te veza spola i poremećaja okusa u COVID-19 infekciji.
Rezultati sugeriraju protektivan utjecaj terapije interferonom na ishode COVID-19 infekcije. |
| Abstract (english) | The immune response of a patient infected with the SARS-CoV-2 virus is, along with age, sex, comorbidities and response to the vaccine, an important factor in the development of the clinical picture and the outcome of the infection. Patients with multiple sclerosis are emphasized as a group of special importance, considering that different disease modifying treatments used to treat multiple sclerosis interfere with the immune system in different ways. Interferons are cytokines isolated from human blood and have the ability to inhibit virus replication, inhibit tumor growth and influence the immune system. The mode of action of interferon beta in multiple sclerosis is complex and not fully understood so far. An in vitro study showed that the application of IFN-α or IFN-β can reduce the titer of SARS-CoV-2 virus in cells and that they have the highest potency against SARS-CoV-2 virus in the form of antigen expression and reduction of viral load. Clinical data support the positive effect of subcutaneous and inhaled IFN in combination with other drugs on survival rate, reduction of infection symptoms and reduction of hospitalization days. A meta-analysis of clinical studies showed that IFN-β treatment reduced the risk of treatment of COVID-19 infection in the intensive care unit by 42% and increased the discharge rate 3.05 times, but additional confirmation of effectiveness is needed. Patients with multiple sclerosis, compared to the general population, have a significantly higher risk of infections in general, of serious infections, as well as of more severe clinical outcomes of the COVID-19 infection, but, for now, with the incompletely clarified effect of immunomodulating and immunosuppressive MS therapies on clinical outcomes of COVID-19 infection. According to current knowledge, patients with multiple sclerosis who were treated with fingolimod, ocrelizumab, rituximab and ofatumumab have a higher susceptibility to COVID-19 infection, a higher risk of a more severe clinical picture and a higher risk of complications of COVID-19 infection, while those treated with interferon β and glatiramer acetate have the lowest risk of infection. The positive effect of interferon in patients
with multiple sclerosis is known to reduce the level of cytokines IL6, IL-1 β and TNFα (participating in the pathophysiology of COVID-19 infection) within 24-48 hours after the injection
of interferon β. Anti-CD20 therapy partially attenuates the formation of antibodies after vaccination against the SARS-CoV-2 virus, while with interferon there is normal seroconversion after vaccination, but data on reinfections in patients with multiple sclerosis are scarce. The sequelae of the COVID-19 infection in which interferons play a role, the post-COVID syndrome, and taste disorders in patients with MS have also been insufficiently investigated.
Aim of this study was to determine the association of interferon therapy in patients with multiple sclerosis with clinical outcomes of coronavirus infection and the occurrence of coronavirus infection after vaccination, and to compare the obtained results with other therapeutic options for the treatment of multiple sclerosis. The associations between interferon therapy and asymptomatic COVID-19 infection, taste disturbances in coronavirus infection, post-COVID syndrome, and the
occurrence of coronavirus infection after vaccination were analysed.
Material and methods: The subjects were patients with multiple sclerosis from the Neurology Department of Sestre milosrdnice University Hospital Center, who had recovered from the coronavirus infection and had been vaccinated with the SARS-CoV-2 virus vaccine. The subjects were divided into two groups: a group of 50 patients with multiple sclerosis treated with interferons and another group of 50 patients with multiple sclerosis treated with other therapies that modify the course of multiple sclerosis. All subjects answered a paper questionnaire, the data on the degree of disability and the type of multiple sclerosis were obtained from the hospital electronic database, and the subjective taste disorder present at the time of answering the questionnaire was objectified with validated Burghart strips. The research is based on the assumption that interferon could affect the clinical picture, post-COVID syndrome and taste disturbances in coronavirus infection. Data on the clinical picture of acute coronavirus infection, the occurrence and duration of post-COVID syndrome, fatigue and cognitive impairment in post-COVID syndrome, and the number of postvaccination coronavirus infections were collected. Data were analyzed using the Chi-square test, Fisher's exact test, Wald type III test, and odds ratio estimation with 95% Wald confidence intervals.
Results: The association between interferon therapy and asymptomatic COVID-19 infection was significant (p=0.0015), as well as the association between interferon therapy and post-COVID syndrome (p<0.0001), but also individually cognitive disorders (p=0.0002) and fatigue (p=0.0025) as part of the post-COVID syndrome. The association between interferon and the duration of cognitive impairment and fatigue in the post-COVID syndrome was not found to be significant.
The association between taste disorders in COVID-19 infection and interferon therapy was found to be significant (p<0.0001), while the association between gender and taste disorders in COVID19 infection was not significant. The association between interferon and COVID-19 infection after vaccination was found to be significant (p=0.0002).
Conclusion: This study showed that interferon therapy in patients with multiple sclerosis is associated with asymptomatic COVID-19 infection, taste disturbance in COVID-19 infection, post-COVID syndrome, cognitive impairment and fatigue in post-COVID syndrome, and COVID19 infection after vaccination suggesting a protective effect of interferon therapy on the outcomes of COVID-19 infection. |
