Hospitalized patients with X-linked disease and infected with SARS-CoV-2 in Brazil: A serial case report from the first two years of the pandemic

Abstract

We described the characteristics of 18 patients with coronavirus disease (COVID)-19 and X-linked disorders in a cohort of 2,066,678 Brazilian patients hospitalized due to COVID-19. The patients were diagnosed with Hemophilia B (one patient), Klinefelter syndrome [eight patients– three deaths occurred, one unrelated to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection], and Turner syndrome (nine patients– two patients died). Half of the patients with X-linked disorders and COVID-19 (9/18) were male, the age varied from 1 to 71 years, and most patients were White (9/12; six patients had missing data). The most common symptoms were cough (13/17; one patient had missing data) and fever (12/16; two patients had missing data), whereas the most common comorbidities were diabetes mellitus (3/11; seven patients had missing data) and cardiopathy (2/12; six patients had missing data). Nearly half of the patients needed intensive care unit (8/17; one patient had missing data), and a quarter required invasive mechanical ventilation (4/16; two patients had missing data). Our study accounted for a total of five deaths, one unrelated to COVID-19. There may be several reasons for the low number of X-linked patients found in our data, such as limited access to genetic diagnosis tools causing underdiagnosis and a lack of knowledge by health professionals to identify the necessity of a genetic diagnosis or even forgetting to fill in the Brazilian database for hospitalization due to severe acute respiratory syndrome.

1. Introduction

Coronavirus disease (COVID)-19 seems to affect more vulnerable individuals disproportionately. For instance, few reports observed an enhanced burden on individuals with genetic conditions such as Down syndrome [1,2]. Besides that, other individuals with genetic syndromes, especially those related to X-linked disorders, might also be affected by COVID-19, such as Klinefelter syndrome, Turner syndrome, and even Hemophilia B.

In the literature, one study evaluated COVID-19 in patients with Klinefelter syndrome, and another study hypothesized COVID-19 in a patient with Klinefelter syndrome and pulmonary symptoms. However, the COVID-19 diagnostic tests were negative two times [3,4], and to the best of our knowledge, no study has evaluated patients with Turner syndrome or Hemophilia B regarding the COVID-19 diagnosis and its evolution. Thus, this study aimed to describe the epidemiological and clinical characteristics and outcomes of patients with COVID-19 and X-linked disorders in a cohort of 2,066,678 Brazilian patients hospitalized due to a severe acute respiratory syndrome caused by COVID-19 during the first two years of the COVID-19 pandemic.

2. Methods

We performed an epidemiological study in Brazil using the data from OpenDataSUS (https://opendatasus.saude.gov.br/), which is a Brazilian open dataset comprising demographic and clinical features of patients hospitalized due to severe acute respiratory infection, which included the severe acute respiratory syndrome caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (COVID-19) (Fig. 1 ).

Fig. 1.

Data acquisition of the hospitalized patients with X-linked diseases infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Brazil during the first two years of the coronavirus disease (COVID)-19 pandemic (December 29, 2019, to March 20, 2022). We presented the total number of patients affected by severe acute respiratory syndrome and the exclusion criteria. Moreover, we presented the frequency of the diseases according to our data. We presented the data as the number of patients and their percentage. ∗, Adenovirus, Metapneumovirus, Rhinovirus, Parainfluenza (1, 2, 3, and 4), and Respiratory Syncytial Virus.

The data collection was between December 29, 2019 and March 20, 2022. From the original dataset, we selected those patients who had X-linked diseases and were infected with SARS-CoV-2.

We described the following features of these patients: the place of residence (State and Federal District and residence in urban, peri-urban, or rural areas), sex (male and female), age at hospitalization (years old, y.o.; and grouped as follow: 0–12 years, 13–24 years, 25–60 years, 61–72 years, 73–85 years, and +85 years), race (White, Black, indigenous, multiracial background– Pardos/mixed-race individuals, and Asian), clinical signs (fever, cough, sore throat, dyspnea, respiratory distress, peripheral capillary oxygen saturation (SpO₂) below 95%, diarrhea, vomit, abdominal pain, fatigue, loss of smell, loss of taste, and other clinical signs), comorbidities (cardiopathy, diabetes mellitus, neurological disorder, kidney disease, obesity, hematological disorder, Down syndrome, hepatic disorder, asthma, chronic lung disease, and immunosuppressive disease), need for intensive care unit, need for ventilatory support and type of ventilatory support (if any), vaccination status against the SARS-CoV-2 infection, discharge criterium, and outcomes (clinical recovery or death).

We presented the data as a serial case report (Table 1 ), and we used absolute frequencies. In addition, we presented the complete information of the Brazilian patients hospitalized due to severe acute respiratory syndrome during the SARS-CoV-2 infection (Table 2, Table 3 ). We used absolute and relative frequencies. To calculate the relative frequency, we excluded the individuals without the data imputation into the dataset; in this case, we considered only the patients with complete data imputation for each marker.

Table 1.

Description of the demographic, clinical markers, and outcomes of hospitalized patients with X-linked diseases severely infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Brazil during the first two years of the coronavirus disease (COVID)-19 pandemic.

Markera,b	Hemophilia B	Klinefelter syndrome								Turner syndrome
		P1	P2	P3	P4	P5	P6	P7	P8	P1	P2	P3	P4	P5	P6	P6	P8	P9
State and Federal District	RJ	CE	SP	SP	SP	SP	SC	SP	SP	GO	FD	RJ	CE	CE	PA	BA	PR	PR
Sex	M	M	M	M	M	M	M	M	M	F	F	F	F	F	F	F	F	F
Age (years)	10	20	27	71	31	35	42	35	39	20	38	1	30	15	24	2	17	41
Racec	NI	NI	White	White	White	White	White	White	NI	White	Pardo	White	White	NI	Pardo	Pardo	NI	NI
Place of residence	Urban	Urban	NI	Urban	Urban	Urban	NI	Urban	Urban	NI	Urban	Urban	Urban	NI	Urban	NI	Urban	Urban
Clinical signs
Fever	No	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	No	NI	NI	Yes	Yes	No
Cough	No	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes	Yes	Yes	Yes	NI	No	No	Yes	Yes
Sore throat	No	NI	Yes	No	No	No	Yes	Yes	No	Yes	No	No	NI	NI	No	No	No	NI
Dyspnea	No	NI	Yes	No	No	Yes	No	Yes	Yes	Yes	Yes	Yes	NI	NI	Yes	No	No	Yes
Respiratory distress	No	NI	Yes	Yes	No	Yes	No	Yes	No	Yes	No	No	NI	NI	No	No	No	Yes
SpO2 below 95%	No	NI	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	No	Yes	Yes	NI	Yes	No	No	Yes
Diarrhea	No	NI	NI	No	No	No	No	No	No	NI	No	No	NI	NI	No	Yes	Yes	NI
Vomit	No	NI	NI	No	No	Yes	No	Yes	No	NI	No	No	NI	NI	No	Yes	No	NI
Abdominal pain	No	No	No	No	No	Yes	No	No	No	No	No	No	No	No	No	Yes	No	No
Fatigue	No	No	No	No	No	Yes	No	Yes	Yes	No	No	No	No	No	No	No	Yes	Yes
Loss of smell	No	No	No	No	No	No	No	No	No	No	No	No	No	No	No	No	No	No
Loss of taste	No	No	No	No	No	No	No	No	No	No	No	No	No	No	Yes	No	No	No
Other clinical signs	Yes	Yes	NI	No	No	NI	Yes	Yes	No	Yes	Yes	No	NI	Yes	No	NI	Yes	Yes
Comorbidities
Cardiopathy	No	NI	NI	No	No	No	No	No	No	Yes	No	No	NI	NI	NI	NI	No	Yes
Diabetes mellitus	No	NI	NI	No	No	No	No	Yes	No	Yes	Yes	No	NI	NI	NI	NI	No	NI
Neurological disorder	No	NI	NI	No	Yes	No	No	Yes	No	NI	No	No	NI	NI	NI	NI	No	NI
Kidney disease	No	NI	NI	No	No	No	No	No	No	NI	No	No	NI	NI	NI	Yes	No	NI
Obesity	No	NI	NI	No	No	No	No	No	No	NI	No	No	NI	NI	NI	NI	No	NI
Intensive care unit	Yes	No	No	Yes	Yes	Yes	No	Yes	No	No	No	Yes	No	No	No	NI	Yes	Yes
Ventilatory support
None	Yes	No	No	No	No	No	No	No	No	No	Yes	Yes	Yes	NI	Yes	NI	No	No
Non-invasive	No	Yes	Yes	No	Yes	No	No	No	Yes	Yes	No	No	No	NI	No	NI	Yes	No
Invasive	No	No	No	Yes	No	Yes	No	Yes	No	No	No	No	No	NI	No	NI	No	Yes
Outcomes	Cured	Cured	Death	Deathd	Cured	Cured	Cured	Death	Cured	Cured	Cured	Cured	Cured	Cured	Death	NI	Cured	Death
COVID-19 vaccination	No	No	No	No	Yes	No	No	No	NI	No	No	No	No	No	No	No	Yes	No

P, Patient; RJ, Rio de Janeiro; CE, Ceará; SP, São Paulo; SC, Santa Catarina; GO, Goiás; FD, Federal District; PA, Pará; BA, Bahia; PR, Paraná; M, male; F, female; NI, not informed; SpO₂, peripheral capillary oxygen saturation.

^aThe following comorbidities were not described in the patients enrolled in the study: hematological disorder, Down syndrome, hepatic disorder, asthma, chronic lung disease, and immunosuppressive disease.

^bAll patients had a laboratory finding as discharge criterium.

^cPardos = Multiracial background/Mixed-race.

^dDeath was not related to the severe acute respiratory syndrome. Cured = the patient was considered clinically recovered. The data collection comprised the period between December 29, 2019, and March 20, 2022.

Table 2.

States and Federal District of Brazil where the patients were notified due to hospitalization by severe acute respiratory syndrome during the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection [coronavirus disease (COVID)-2019].

State and Federal District	N (%)a
Acre	4901 (0.2%)
Alagoas	22,746 (1.1%)
Amazonas	41,765 (2.1%)
Amapá	6296 (0.3%)
Bahia	77,528 (3.9%)
Ceará	72,624 (3.6%)
Federal District	46,823 (2.3%)
Espírito Santo	15,911 (0.8%)
Goiás	77,280 (3.9%)
Maranhão	23,203 (1.2%)
Minas Gerais	198,628 (9.9%)
Mato Grosso do Sul	34,238 (1.7%)
Mato Grosso	46,771 (2.3%)
Pará	51,456 (2.6%)
Paraíba	30,179 (1.5%)
Pernambuco	53,151 (2.6%)
Piauí	24,028 (1.2%)
Paraná	133,913 (6.7%)
Rio de Janeiro	188,849 (9.4%)
Rio Grande do Norte	20,581 (1.0%)
Rondônia	16,837 (0.8%)
Roraima	4739 (0.2%)
Rio Grande do Sul	122,638 (6.1%)
Santa Catarina	81,682 (4.1%)
Sergipe	19,614 (1.0%)
São Paulo	578,890 (28.8%)
Tocantins	11,407 (0.6%)

The data collection comprised the period between December 29, 2019, and March 20, 2022.

%, percentage; N, number of individuals.

^aIn the table, we presented the information for all the hospitalized patients in Brazil.

Table 3.

Description of the demographic, clinical markers, and outcomes of hospitalized Brazilian patients due to severe acute respiratory syndrome during the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection [coronavirus disease (COVID)-2019].

Marker	N (%)a
Sex (Male)	1,111,978/2,006,382 (55.4%)
Age
0–12 years old	32,502/2,006,678 (1.6%)
13–24 years old	40,874/2,006,678 (2.0%)
25–60 years old	1,010,158/2,006,678 (50.3%)
61–72 years old	459,770/2,006,678 (22.9%)
73–85 years old	347,196/2,006,678 (17.3%)
+85 years old	116,178/2,006,678 (5.8%)
Race
White	842,158/1,632,352 (51.6%)
Black	85,342/1,632,352 (5.2%)
Asian	19,793/1,632,352 (1.2%)
Pardos (Multiracial Background/Mixed-race)	681,025/1,632,352 (41.7%)
Indigenous people	4034/1,632,352 (0.2%)
Place of residence
Urban	1,671,912/1,768,058 (94.5%)
Peri-urban	6397/1,768,058 (0.4%)
Rural	89,749/1,768,058 (5.1%)
Clinical signs
Fever	1,132,152/1,665,358 (68.0%)
Cough	1,374,493/1,734,451 (79.2%)
Sore throat	351,544/1,387,130 (25.3%)
Dyspnea	1,405,464/1,745,348 (80.5%)
Respiratory distress	1,110,341/1,602,043 (69.3%)
SpO2 below 95%	1,254,900/1,665,314 (75.4%)
Diarrhea	260,435/1,363,345 (19.1%)
Vomit	159,497/1,333,372 (12.0%)
Abdominal pain	102,892/1,132,589 (9.1%)
Fatigue	440,850/1,209,823 (36.4%)
Loss of smell	171,697/1,148,336 (15.0%)
Loss of taste	174,143/1,146,346 (15.2%)
Other clinical signs	657,444/1,379,464 (47.7%)
Comorbidities
Cardiopathy	621,817/1,500,354 (41.4%)
Hematological disorder	12,340/1,255,230 (1.0%)
Down syndrome	5323/1,254,575 (0.4%)
Hepatic disorder	14,593/1,253,269 (1.2%)
Asthma	47,817/1,265,658 (3.8%)
Diabetes mellitus	443,963/1,430,921 (31.0%)
Neurological disorder	65,684/1,273,274 (5.2%)
Chronic lung disease	60,658/1,272,248 (4.8%)
Immunosuppressive disease	42,379/1,262,127 (3.4%)
Kidney disease	64,604/1,271,166 (5.1%)
Obesity	161,120/1,297,089 (12.4%)
Any (at least one comorbidity)	1,132,933/1,676,208 (67.6%)
Intensive care unit (Yes)	650,591/1,727,332 (37.7%)
Ventilatory support
None	356,328/1,705,493 (20.9%)
Non-invasive	997,945/1,705,493 (58.5%)
Invasive	351,220/1,705,493 (20.6%)
Outcomes
Cured (Clinically recovered)	1,214,267/1,851,592 (65.6%)
Death	632,101/1,851,592 (34.1%)
Death was not associated with the COVID-19	5224/1,851,592 (0.3%)
Discharge criterium
Laboratorial	1,777,722/1,956,853 (90.8%)
Clinical	179,131/1,956,853 (9.2%)
COVID-19 vaccination (Yes)	296,762/741,879 (40.0%)

%, percentage; N, number of individuals; SpO₂, peripheral capillary oxygen saturation. The data collection comprised the period between December 29, 2019, and March 20, 2022.

^aThe denominator was not equal for all markers because we included only the individuals with the data imputation in the dataset for each marker.

The data used in our study were made publicly available, not containing consent-free personal data since it did not present any risk to the research participants. The study was approved by the Ethics Committee of the Universidade São Francisco no 36628020.0.0000.5514 on February 27, 2022.

3. Results

We enrolled 18 patients who were diagnosed with COVID-19 and X-linked diseases, such as Hemophilia B (one patient), Klinefelter syndrome (eight patients), and Turner syndrome (nine patients) (Fig. 1).

The patient with Hemophilia B was originally from Rio de Janeiro and was ten y.o.; lived in an urban area, and did not receive the vaccine against the SARS-CoV-2. The patient did not present any common COVID-19 symptoms, such as fever, cough, or dyspnea, and did not have any comorbidity, such as diabetes mellitus, cardiopathy, or obesity. However, the patient needed an intensive care unit treatment without the need for ventilatory support. The patient was cured at the end of the hospitalization (Table 1).

Most of the patients diagnosed with Klinefelter syndrome were from São Paulo (6/8) state. Their age ranged from 20 to 71 years; they were White (6/6; two patients had missing data) and lived in an urban area (6/6; two patients had missing data). The most common symptoms were fever (7/8), cough (7/8), respiratory distress (4/7; one patient had missing data), and SpO₂ below 95% (6/7; one patient had missing data). Only two patients reported comorbidities; one reported diabetes mellitus, and the other reported diabetes mellitus and a neurological disorder. Four patients were hospitalized in the intensive care unit; however, three needed invasive mechanical ventilation, and four needed non-invasive mechanical ventilation. In this group, three deaths occurred, one unrelated to SARS-CoV-2 infection. One patient received the vaccine against SARS-CoV-2 (Table 1).

Among the patients with Turner syndrome, the age ranged from one to 41 years; most patients lived in urban areas (6/6; three patients had missing data) and were White (3/6) or Pardos (3/6)– three patients had missing data for race. Most of the patients with Turner syndrome presented with fever (5/7; two patients had missing data), cough (6/8; one patient had missing data), dyspnea (5/7; two patients had missing data), and SpO₂ below 95% (5/8; one patient had missing data); and reported several comorbidities, such as diabetes mellitus (2/4; five patients had missing data), cardiopathy (2/5; four patients had missing data), and kidney disorder (1/4; five patients had missing data). A total of three patients needed intensive care unit care, one needed invasive mechanical ventilation, and two needed non-invasive mechanical ventilation. Two patients died, and one received the vaccine against SARS-CoV-2 (Table 1).

We summarized the outcomes of the hospitalized patients with X-linked disease and infected with SARS-CoV-2, included in the serial case report, in Fig. 2 .

Fig. 2.

Summary of the outcomes of the hospitalized patients with X-linked disease and infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [coronavirus disease (COVID)-2019] in Brazil included in the serial case report.

We also presented the distribution of the hospitalized Brazilian patients (all) due to severe acute respiratory syndrome during the SARS-CoV-2 infection in Table 2; significant number of patients were notified in São Paulo (578,890 individuals; 28.8%), Minas Gerais (198,268 individuals; 9.9%), and Rio de Janeiro (188,849 individuals; 9.4%) states (Table 2).

In addition, we presented the epidemiological data of all Brazilian patients hospitalized due to severe acute respiratory syndrome during the SARS-CoV-2 infection in Table 3. To note, we had a higher number of male patients (1,111,978 individuals; 55.4%), aged between 25 and 60 years (1,010,158 individuals; 50.3%), from White race (842,158 individuals; 51.6%), and who lived in urban places (1,671,912 individuals; 94.5%). The most common clinical signs were dyspnea (1,405,464 individuals; 80.5%), cough (1,374,493 individuals; 79.2%), and SpO₂ below 95% (1,254,900 individuals; 75.4%) (Table 3). Also, the main comorbidities in our epidemiologic study were cardiopathy (621,817 individuals; 41.4%), diabetes mellitus (443,963 individuals; 31.0%), and obesity (161,120 individuals; 12.4%); interestingly, 1,132,933 individuals (67.6%) had at least one comorbidity (Table 3).

Among the Brazilian patients hospitalized due to severe acute respiratory syndrome during the SARS-CoV-2 infection, 650,591 patients (37.7%) were hospitalized in intensive care units, 351,220 (20.6%) received invasive mechanical ventilation, and 997,945 (58.5%) received non-invasive mechanical ventilation (Table 3). In addition, we observed 632,101 (34.1%) deaths due to COVID-19 and 5224 (0.3%) deaths not related to the SARS-CoV-2 infection (Table 3). In Brazil, the main criterion for hospital discharge was the laboratory findings (1,777,722 individuals; 90.8%), and during the study period, only 296,762 (40.0%) patients received the vaccination against the SARS-CoV-2 (Table 3).

4. Discussion

In our epidemiologic study, we described the prevalence of the X-linked disorders among those hospitalized due to the infection by SARS-CoV-2 in Brazil– 1:100,000, 1:140,000, and 1:1,100,000 inhabitants for Turner syndrome, Klinefelter syndrome, and Hemophilia B, respectively.

In our study, we described only 18 patients with COVID-19 and X-linked disorders in a cohort of 2,066,678 Brazilian patients hospitalized due to COVID-19. We could not affirm that the X-linked disorders were associated with an increased risk of death in our serial case report. Furthermore, the number of patients diagnosed with X-linked diseases among those hospitalized due to COVID-19 cannot represent a real case scenario, and perhaps several patients remained without a diagnosis. Also, as reported by Qian et al. (2023), it is essential to know more about the impact of COVID-19 among those with Klinefelter syndrome [5] and those with similar genetic conditions (e.g., Turner syndrome and Hemophilia B).

A previous study on patients affected by X-linked diseases reported only 12 patients with Klinefelter syndrome and COVID-19 [4]. Aliberti et al. (2022) performed a retrospective self-administered questionnaire in Italy, which included 120 patients with Klinefelter syndrome; interestingly, only 12 patients had COVID-19, and none needed hospitalization or received oxygen therapy [4]. This demonstrated that the extra X chromosome might be associated with a better clinical outcome. The most common symptoms of the patients with Klinefelter syndrome and COVID-19 included in the study by Aliberti et al. (2022) were migraine (33.3%), anosmia (loss of taste) (25.0%), fever (16.7%), and respiratory symptoms (16.7%). This clinical presentation was different from that of ours. In our cohort, the most common symptoms in patients with Klinefelter syndrome and COVID-19 were fever, cough, and SpO₂ below 95%, which can be explained by more severe clinical presentation in our epidemiologic study that included two deaths related to SARS-CoV-2 infection.

In a case report by Lagha et al. (2022) [3], an individual with Klinefelter syndrome presented to the hospital with dyspnea, acute chest pain, fever, tachycardia, tachypnea, cyanosis, and SpO₂ of 87%. COVID-19 was one of the main hypotheses. However, the results of the real-time polymerase chain reaction were negative twice. The authors suspected a pulmonary embolism since the Wells score was intermediate (4.5). The hypothesis was confirmed by the computed tomography of the chest [3].

We hypothesized that the main factors that could be associated with the low frequency of X-linked diseases in patients hospitalized due to COVID-19 in Brazil were as follows: i) limited access to diagnostic tools, mainly the genetics ones; ii) possible underdiagnosis associated with less severe symptoms for some genetic syndromes, such as the Klinefelter and Turner syndromes; iii) lack of knowledge by the health professionals to identify the necessity of a genetic diagnosis, since in Brazil we have a precarious training in genetic conditions for all health professionals, especially physicians; and iv) errors in the inclusion of data into the dataset (e.g., we observed the inclusion of several terminologies, such as genetic disease, chromosomal disorder, and chromosomal error, which could be better explored to classify the patients better). In Brazil, we can describe where we went wrong in the management of patients during the pandemic [6]; and further studies should be done to better understand the COVID-19 pandemic, mainly its impact on those with rare conditions.

4.1. Limitations

We used a public dataset and we did not have access the original data. Some epidemiological data were not imputed into the dataset for all patients, or there might even be errors in the imputation, which might have reduced the study power. There is evidence of underreporting of COVID-19 in Brazil, and since we did not have access to the original data, we could not control for this study's bias. We only evaluated the hospitalized patients with X-linked diseases. Thus, we cannot conclude anything regarding the impact of COVID-19 on those patients who did not need hospitalization. There might have been underreporting of X-linked diseases in the dataset, and we did not have access to the prevalence of X-linked disorders in Brazil before the COVID-19 pandemic. Since this is a serial case report, we only described the clinical presentation of COVID-19 in those with X-linked disorders. We could not describe any causality or the association between the diagnoses of X-linked disorders and the outcomes, since we did not have the statistical power and the study was not designed for that.

5. Conclusion

In our study, those with X-linked disorders [Hemophilia B (one patient), Klinefelter syndrome (eight patients), and Turner syndrome (nine patients)] accounted for a clinical profile in which symptoms such as fever and cough, and comorbidities such as diabetes mellitus and cardiopathy were more prevalent when compared with the other types of symptoms and comorbidities in patients. Moreover, the need for intensive care units and invasive mechanical ventilation occurred in 8/17 (47.1%; one patient had missing data) and 4/16 (25.0%; two patients had missing data) of patients, respectively. Our study accounted for a total of five deaths [Klinefelter syndrome (three deaths occurred, one unrelated to SARS-CoV-2 infection), and Turner syndrome (two deaths)]. Those with genetic conditions might experience COVID-19 differently; besides, Brazil might have an underdiagnosis of X-linked diseases, or even those with this genetic condition may have difficulty seeking healthcare, thus harming patients with both COVID-19 and X-linked diseases.

Funding

[MNB] Fundação de Amparo à Pesquisa do Estado de São Paulo (Foundation for Research Support of the State of São Paulo, Brazil; no 2022/05810-7).

Ethics approval

The data used in this study were made publicly available, not containing consent-free personal data since it did not present risks to the research participants. The study was approved by the Ethics Committee of the Universidade São Francisco no 36628020.0.0000.5514 on February 27, 2022.

Consent to participate

Not required.

Consent for publication

The authors have approved the manuscript and agreed with the submission.

Data and material availability

We accessed the data in OpenDataSUS (https://opendatasus.saude.gov.br/) between December 29, 2019, and March 20, 2022.

Code availability

Not required.

Authors’ contributions

All the authors contributed equally to this study.

FALM– made substantial contributions to the study conception and design; and performed the acquisition, analysis, and interpretation of data for the work. MNB, NMSS, and FALM– drafted the work and revised it critically for important intellectual content. MNB, NMSS, and FALM– gave the final approval for the version to be published.

Conflicts of interest

The authors have no conflicts of interest.