The flow chart for study selection (according to PRISMA statement) is shown in the Fig. 1.
Our search retrieved 525 articles; after removing duplicates and screening from title and abstract, we assessed 140 full-text articles for eligibility. Of these, 18 articles [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28] met the eligibility criteria. Most of the data were collected during the first pandemic wave, with database lock set in April 2020 , May 2020 [14, 18, 22, 24], June 2020 [13, 15, 16, 19, 21], whereas data of the remaining studies were collected until September 2020 [26, 27], October 2020 , December 2020 [17, 25], February 2021 [12, 28], April 2021 .
Data were collected in different sites in Iran (three articles) [14, 15, 24] and United States (two articles) [18, 23]; two articles included data from different countries of Latin America  and North America . The remaining articles were from Austria , Brazil , Chile , Czechia , France , Italy , Netherland , Poland , Saudi Arabia , Spain , Turkey . Three articles included also data of 20 patients with neuromyelitis optica spectrum disorder that were removed from further analysis [11, 19].
Characteristics of participants
The pooled cohort consisted in 5634 patients. Their mean pooled age was 41.8 years and there were 1590 out of 5568 (28.6%) males (no data on sex ratio was reported in one article including 66 patients ). The Table 1 shows the main characteristics of included studies. Out of 5634 patients, 3968 (70.4%) received a COVID-19 diagnosis as confirmed at a positive reverse transcriptase polymerase chain reaction (RT-PCR) on nasal and/or pharyngeal swabs, whereas the remaining 1666 (29.6%) were suspected cases on the basis of clinical symptoms and signs.
Selected articles reported 111 deaths in 5634 patients with suspected or confirmed COVID-19, yielding a CDR of 1.97% (95% CIs 1.61–2.33). Overall, 873 patients required hospitalization, yielding a hospitalization rate of 15.5% (95% CIs 14.6–16.4).
Lethality of COVID-19 in patients with MS
The estimated SLR was 1.24 (95% CIs 1.01–1.48) after indirect standardization using time- and country-restricted data of general population. Most of the reference data were accessible on the detailed surveillance data at the WHO website [11, 13, 16, 17, 19,20,21,22, 26,27,28], whereas age-specific CFRs for Iran and Saudi Arabia were not available; therefore, we used data from Eastern Mediterranean Region as reference information [12, 14, 15, 24]. Reference data for articles conducted in United States [18, 23] and North America  were available at the Centers for Disease Control and Prevention (CDC) website (https://www.cdc.gov/coronavirus/2019-nCoV/index.html).
The leave-one-out sensitivity analysis confirmed that this estimate did not change substantially even after iteratively removing one study at a time, thus indicating that the pooled result was not driven by any single study (see Table 2).
The Fig. 2 shows changes over time of the age-standardized SLR using the distribution of case-fatality rates by age; except for the first few months of the COVID-19 pandemic, the estimated SLR was steadily above 1.00, indicating an increased risk of death attributable to COVID-19 in patients with MS as compared to general population.