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Few studies have evaluated the outcomes of COVID-19 in individuals with Down syndrome (DS), which indicated a higher association between DS and longer hospitalisation time, COVID-19 severity and mortality rate.1–8 From these studies, four out of five have presented a small cohort with less than 40 individuals with DS and COVID-19,1–4 except one report that has included 750 individuals.5 Thus, the real effect of COVID-19 in individuals with DS is not entirely clear, and it would be important to know it, mainly for its importance as a risk factor for death. In this context, we compared the case fatality rate, the need for mechanical ventilation (MV) and the need for intensive care unit (ICU) hospitalisation between hospitalised individuals with DS infected by SARS-CoV-2 and hospitalised individuals without DS also infected by SARS-CoV-2, using a Brazilian public dataset.
We retrieved the data from the Brazilian Ministry of Health platform (https://opendatasus.saude.gov.br/) that included epidemiological data for severe acute respiratory infection (SARI) in Brazil, including the cases of severe acute respiratory syndrome (SARS) due to the COVID-19. Among a total of 3 117 562 individuals with SARI, representing 2 years of COVID-19 pandemic in Brazil, 5152 individuals were identified as individuals with DS and were positive for SARS-CoV-2 RT-PCR (G1). In addition, the second group of individuals was enrolled, including individuals without DS and also infected by SARS-CoV-2 (G2). For the last group, the exclusion criteria were based on the absence of DS. For both groups, we excluded the individuals without confirmation of the SARS-CoV-2 infection or individuals without the information for outcome (death or clinical recovery) and comorbidities status to prove the DS diagnosis. Thus, it was set in two groups of study, those hospitalised individuals without DS (G2) and those hospitalised individuals with DS (G1). Both groups were positive for RT-PCR SARS-CoV-2. We enrolled 1 493 385 individuals in the G2 after exclusion criteria (figure 1).
We calculated relative risk (RR) and 95% CI for the case fatality rate, need for MV and need for ICU among G1 and G2 regarding only those who required hospitalisation. We assumed an alpha error of <0.05. We did the statistical analysis in the Statistical Package for the Social Sciences (IBM SPSS Statistics for Macintosh, V.27.0). We draw the figures 2 and 3 using GraphPad Prism V.9.0.0 for Mac, GraphPad Software, San Diego, California USA, www.graphpad.com.
We observed a higher case fatality rate in individuals from G1 (42.3% vs 35.5%; RR=1.193; 95% CI=1.156 to 1.232) when compared with G2 (figure 2; online supplemental table 1). The case fatality rate was also higher in individuals from G1 without MV support (21.0% vs 15.5%; RR=1.361; 95% CI=1.184 to 1.564) or who received non-invasive MV (29.8% vs 24.7%; RR=1.205; 95% CI=1.135 to 1.279) when compared with G2 (figure 2; online supplemental table 3). No differences in case fatality rate between the groups occurred regarding the invasive MV status (77.2% vs 78.6%; RR=0.982; 95% CI=0.954 to 1.010) (figure 2; online supplemental table 3). Individuals from G1 were more frequently associated with need of ICU hospitalisation (47.4% vs 39.0%; RR=1.216; 95% CI=1.180 to 1.253) (online supplemental table 1) and invasive MV (29.6% vs 22.2%; RR=1.180; 95% CI=1.144 to 1.218) (online supplemental table 2) when compared with G2. We also presented the descriptive data for demographic features and comorbidities of hospitalised individuals infected with SARS-CoV-2 who presented SARS regarding the DS diagnosis in table 1. Finally, we presented the distribution of the individuals during the study period in figure 3.
To the best of our knowledge, our study evaluated the largest number of individuals with DS and COVID-19.1–8 Also, our and previous studies have observed a high case fatality rate among individuals with DS and COVID-19, regardless of the need for MV, demonstrating that those patients might be more susceptible to SARS-CoV-2 clinical complications. Four out of the five studies have analysed the risk for death in individuals with DS and positive for COVID-19, and different risks were observed in each one as a 24-fold increase,2 10-fold increase1 and 2.5-fold5 mortality rate. In contrast, one study has observed a similar case fatality rate among individuals with DS and COVID-19 when compared with other individuals positive for SARS-CoV-2 infection.4 Moreover, four out of five studies have presented the case fatality rate with a wide range of confidence intervals, except Huls et al 5 due to the larger sample size. Although our RR for death risk was relatively small compared with other studies, the CI range was shorter, reflecting our sample size statistical power and, maybe, a real-life scenario.
The significant need for ICU among individuals with DS and COVID-19 has also been observed in one previous study,5 indicating the presence of a more severe clinical condition in these individuals. In the same way, the significant need for invasive MV in individuals with DS, similar to one previous study,4 reflects the severe clinical condition of these individuals. In addition, the absence of a higher case fatality rate among individuals with DS who required invasive MV compared with those without DS can reflect the adjustments performed during the invasive MV that controlled the clinical manifestations equally and demonstrated equal success independently of DS diagnosis.
Curiously, as discussed by Illouz and collaborators, the extra chromosome 21, observed in individuals with DS, can alter the expression levels of several genes related to the immune response as an amyloid-beta precursor protein, synaptojanin-1, intersectin-1 and transmembrane protease serine 2, facilitating the SARS-CoV-2 infection.3
As explained before, individuals with DS are more susceptible to worse outcomes, and due to that, they should be considered an important risk population for severe COVID-19. Several specialised measures should be taken to explain how to use facial masks, sanitise hands properly and the importance of social isolation, not only for individuals but also for their families, once most of these individuals are dependent on their family members. In addition, individuals with DS have presented the type 1 interferon gene constitutively activated, being one of the factors associated with a worse vaccine response in this group.3 Thus, individuals with DS should be a priority group in the COVID-19 vaccination plan to mitigate the enhanced death risk and, consequently, worse vaccine immune response.
In conclusion, individuals with DS presented a more severe impact of the SARS-CoV-2 infection, with enhanced case fatality rate, the need for MV, and ICU hospitalisation; thus, specialised care should be directed to this group as well as priority in the vaccination plan.
Patient consent for publication
Camila Vantini Capasso Palamim (firstname.lastname@example.org; ORCID: 0000-0001-6825-1154) to collaborate with the data collection. The authors, mainly FALM, who coordinated the study, thank Professor Carmen Silvia Bertuzzo, who collaborated with interpreting the findings and is the mother of a person with Down syndrome. Also, Professor Carmen Sílvia Bertuzzo dedicated her life to studying genetic conditions such as Down syndrome and guided Professor FALM during his postgraduate studies.
Handling editor Tahir S Pillay.
MNB, JRLF and FALM contributed equally.
Contributors All authors have approved the manuscript and agreed with its submission to the journal. Also, all authors wrote and revised the manuscript.
Funding (MNB) Fundação de Amparo à Pesquisa do Estado de São Paulo (The São Paulo Research Foundation; FAPESP: #2021/05810-7).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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