Factors associated with COVID-19 severity among Brazilian pregnant adolescents: a population-based study

Abstract Objective: to identify the factors associated with need for intensive care unit admission of Brazilian pregnant adolescents with COVID-19. Method: population-based non-concurrent cohort study using secondary databases. Brazilian pregnant adolescents who had laboratory confirmation of SARS-CoV-2 by RT-PCR, between March 14, 2020 and April 11, 2021 were included in the study. Statistical analysis using the Poisson multiple regression model, estimating the relative risk and respective 95% confidence intervals, with values of p <0.05 considered significant. Results: in total, 282 pregnant women were included in the study, with median age of 17 years, most with brown skin, in the third trimester of pregnancy, and living in urban or peri-urban areas. The intensive care unit admission rate was 14.5%, associated with living in the Southeast region of Brazil (RR=5.03, 95%CI=1.78-14.24, p=0.002), oxygen saturation below 95% (RR=2.62, 95%CI=1.17-5.87, p=0.019), and having some comorbidity (RR=2.05, 95%CI=1.01-4.16, p=0.047). Conclusion: the intensive care unit admission rate was high among Brazilian pregnant adolescents and was associated with living in the Southeast region of Brazil, having some comorbidity and/or presenting low oxygen saturation.


Introduction
The COVID-19 pandemic has caused different impacts on the health of populations. Studies show that children and adolescents develop mild symptoms of the disease, with infrequent admission, intensive care, and oxygen support, and these cases are related to the presence of prior diseases. The hypotheses for a milder disease response in this population group include the strength of the innate immune response, a higher proportion of immunological factors to fight the virus, a lower prevalence of associated comorbidities, close proximity to the Coronavirus family in this age group, and increased colonization of the mucosa by other viruses and bacteria, which could limit colonization by SARS-CoV-2 (1) .
However, when an adolescent becomes pregnant, the progress of COVID-19 tends to be more serious, since the gestational period is characterized by hormonal changes, decreased lung capacity due to the uterus during pregnancy, and a suppressed immune systemaspects that make women more vulnerable to viral infections and related complications (2)(3)(4)(5) .
A systematic review conducted in the first months of the pandemic showed that pregnant women with COVID-19 have rapidly progressive complications, sometimes associated with comorbidities, leading to a high rate of cesarean deliveries, justified by the worsening of the non-reassuring maternal or fetal status, secondary to worsening of the woman's clinical status (6) .
Studies report fever, cough, pneumonia, myalgia, fatigue, abdominal pain, and diarrhea as the most recurrent symptoms in pregnant women with and gestational diabetes,hypothyroidism and hypertension as the most commonly associated comorbidities (1) . The outcomes found include higher rates of miscarriage, thyroid disease, coagulopathies, preeclampsia, eclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome, cesarean delivery, preterm birth, need for intensive care unit (ICU) admission, endometritis and/or puerperal sepsis, multiple organ failure, fetal distress and/or low birth weight, pneumonia, and other severe neonatal conditions, asphyxia, and maternal and perinatal death.
The maternal mortality ratio estimated for Brazil was 73.8 (2020) and 107.8 (2021) deaths per 100,000 live births, partially resulting from the COVID-19 pandemic (11) , since the lethality rate of the disease among pregnant and postpartum women was 11.7%, while in the general population, 2.8% (12) .
Considering the important effect of COVID-19 on pregnant women and the need for a better understanding of its evolution in different populations and that, so far, no systematic review is available about the evolution of the disease in pregnant adolescents, this study aims to identify the factors associated with need for intensive care unit admission in Brazilian pregnant adolescents with COVID-19. The study hypothesis is that unfavorable sociodemographic conditions, the presence of comorbidities, and the number of clinical signs and symptoms are associated with the need for ICU admission in the studied group.

Study design
This is a population-based non-concurrent cohort study.

Population and sample
This study included Brazilian pregnant adolescents aged 10 to 19 years reported in SIVEP-Gripe from March 14, 2020 to April 11, 2021April 11, , totaling 46 epidemiological weeks: weeks 11 to 53 in 2020April 11, and 1 to 4 in 2021 with laboratory confirmation of SARS-CoV-2 by RT-PCR and records of disease progress (ICU admission: yes, no

Data collection
This study used the secondary database of the

Study variables
The outcome variable was the need for ICU admission (yes, no) of pregnant adolescents with confirmed diagnosis of COVID-19. The independent variables were: • Sociodemographic aspects: age in years of pregnant adolescents (11)(12)(13)(14)(15)(16)(17)(18)(19) Considering that any event must be reported in the SIVEP-Gripe system, this variable was analyzed in a dichotomous manner, with ignored cases (blank) considered as "no" clinical signs and symptoms.
Considering that any event must be reported in the SIVEP-Gripe system, this variable was analyzed in a dichotomous manner, with ignored cases (blank) considered as "no" comorbidity.

Data analysis
First, data were analyzed by descriptive statistics.  (13) .
Then, as the database used in this study can be accessed by the general public, it did not contain the names of participants or any other information allowing individual identification of the participants; therefore, anonymity was guaranteed and this study did not have to be submitted to the Research Ethics Committee for evaluation.

Discussion
This study aimed to identify factors associated with COVID-19 severity in Brazilian pregnant adolescents requiring ICU admission, found that living in the Southeast region, having oxygen saturation below 95%, and presenting some comorbidity increased the risk of ICU admission by five times, two and a half times, and two times, respectively. The ICU admission rate was high (14.5%).
A study conducted in Brazil in 2020 assessed pregnant women regardless of age, who needed to be hospitalized due to SARS by COVID-19 and, therefore, with some severity; it found that most women lived in the Southeast region of the country, and the authors associate this finding with the fact that the first cases of the disease were reported in this region, specifically in the states of São Paulo and Rio de Janeiro (14) .
Regarding the risk of ICU admission according to the region of the country, the North region was selected as a reference, as it has the lowest proportion of hospitalizations. Compared to it, the risk of ICU admission was higher in the Southeast region, a result that should be considered with caution for two main reasons: the large extension of the confidence interval obtained and, due to the large territorial extension of the country, the pandemic evolved with distinct temporality. However, the fact that data collection included cases reported over a long period can minimize this effect. in the Southeast region (15) .
Among the signs and symptoms presented by pregnant adolescents, oxygen saturation below 95% was an independent risk factor for ICU admission, which agrees with the finding of another Brazilian study (14) which assessed pregnant women with progression to death. An American study explains that in COVID-19, silent hypoxia occurs in the early stages of the disease, so that the patient may not have difficulty breathing.
It happens because the air sacs in the lungs collapse rather than being filled with fluid or pus, which results in reduced oxygen levels but still has the ability to expel carbon dioxide (CO2). On the other hand, when symptoms of shortness of breath begin, the disease is already in its moderate to advanced levels (16) . Therefore, this sign must be carefully investigated when the first symptoms of the disease appear, especially because they are related to disease worsening.
In our study, just under half of pregnant adolescents with COVID-19 had some comorbidity, and this condition doubled the risk of needing an ICU admission. Asthma and heart disease were the most frequent, and were the same comorbidities found in other national studies with pregnant women (14,17) , who also mentioned other diseases, such as diabetes, hypertension, and obesity. In Canada, a study with adult and pediatric patients diagnosed with COVID-19, with 1.1% of these pregnant women hospitalized in the ICU of 32 hospitals during the first half of 2020, identified the most common comorbidities were chronic arterial hypertension, diabetes, and chronic cardiovascular disease (18) . A systematic review that included more than 190 studies compared pregnant and non-pregnant women and showed the presence of comorbidity is a risk factor for worse outcomes among pregnant women (19) . Brazilian states (17,21) . Studies conducted in Brazil (21)(22) www.eerp.usp.br/rlae 9 Duarte BK, Parenti ABH, Jamas MT, Nunes HRC, Parada CMGL.
showed that black and brown population were more negatively affected by the pandemic, as well as people of lower social class and education, and these groups showed a stronger need to go out to work, and then, they were infected on the job or public transport, since activities performed outside the home increased the contact with other people, making social isolation difficult and favoring virus transmission (21) . It is evident that health determinants must be at the core of policies addressing COVID-19, since the disease does not affect all the population the same way.
Also, most pregnant adolescents who needed ICU admission were in the third trimester of pregnancy (64.6%), which can be attributed to the physiological changes of this period and be related to complications at delivery, in postpartum, and with the neonate. The same findings were observed in a study conducted in Iran (23) , in which 62.5% of hospitalized women were in the third trimester of pregnancy. Brazilian studies often identified the occurrence of COVID-19 in the third trimester of pregnancy, with this rate ranging from 45.8% to 66.7% of pregnant women (14,17) . Of the signs and symptoms observed in national and international studies (14,17,(24)(25) , pregnant adolescents had a higher frequency of fever and cough. Because these symptoms are common and unspecific, extensive testing of this population is required for notification and early treatment of the disease, especially during the flu season.
Since pregnant adolescents with COVID-19 can progress to severe disease, potentially requiring ICU admission, and that such care still presents weaknesses, it is necessary to organize and prepare professionals from the entire maternal and child health care network to ensure the best care, particularly nurses, for their important role in prenatal, birth and postpartum care, and for acting as key agents of comprehensive care, present at all levels of health care (26)(27) .
Finally, the study limitations refer to the fact that it was conducted with a secondary database, which makes it impossible to use some variables of low quality, as well as the possibility of under-recording of cases, both limitations related to reduced sample. On the other hand, the fact that it is a national bank in a country with continental dimensions, such as Brazil, is a positive aspect to be highlighted.

Conclusion
This study identified a higher rate of ICU admission among pregnant adolescents living in the Southeast region who presented oxygen saturation below 95% and prior comorbidities. A high prevalence of comorbidities and ICU admission was found in the study sample.
Then, careful prenatal follow-up is required, also for the identification of comorbidities in pregnant adolescents with COVID-19.