Factors associated with death among postpartum women with COVID-19: a Brazilian population-based study

Objective: to identify the factors associated with death due to COVID-19 among Brazilian postpartum women in the first five months of the pandemic and five subsequent months, and describe the sociodemographic and clinical characteristics of postpartum women who developed the disease. Method: cross-sectional population-based study using a secondary database available in the Sistema de Informação de Vigilância Epidemiológica da Gripe -SIVEP-Gripe (Influenza Epidemiological Surveillance Information System), Brazilian Ministry of Health. A total of 869 postpartum women were included, and the analysis considered the first five months of the pandemic and subsequent five months. Association between the variables of interest and outcome (death due to COVID-19/cure) was investigated using logistic regression. Results: most participants were aged between 20 and 34, of mixed race or Caucasian, and lived in the urban/peri-urban area. The proportion of deaths was 20.2% in the first period and 11.2% in the second. The likelihood of death increased in both periods due to the presence of respiratory signs and symptoms: dyspnea, respiratory distress, and oxygen saturation below 95%, in addition to the need for ventilatory support and intensive care. Conclusion: the proportion of deaths among postpartum women was high and decreased in the second period under study. Respiratory signs and symptoms, mechanical ventilation, and intensive care were associated with death in both periods.


Introduction
COVID-19 has impacted nations differently depending on each country's economic, social, and political context (1) .
However, the occurrence of this disease in the pregnancypuerperal cycle has resulted in adverse outcomes not only in low-income countries, with restricted resources and precarious health systems, but also in developed and well-structured countries with traditionally low maternal mortality rates (2) . Hence, the pandemic has evidenced an important crisis in the health field in different contexts while revealing the relevance of health workers in general, though of nurses in particular; the competencies of nurses are essential at all levels of healthcare services (3) .
From 2020 onwards, the United States presented the highest rates of Covid-19 worldwide due to three overlapping epidemic waves. Brazil, the United Kingdom, Italy, and Spain stood out as they presented a similar pattern of high incidence and mortality; in Brazil, the disease evolved heterogeneously both between and within states. In 2020, Brazil totaled 7,714,819 cases and 195,742 deaths over the 44 epidemiological weeks.
An unequal pattern was also verified in the distribution of more complex health services and quality care (4) . with systemic and/or gastrointestinal symptoms (5) . The most common clinical repercussions for the population, in general, include difficulty breathing or increased respiratory rate, oxygen saturation below 95%, and the worsening of underlying diseases and hypotension (6)(7) ; one in six infected people develop the severe form of the disease (8-9) . However, thus far, there is not a study specifically describing how the disease progresses among postpartum women.
At the beginning of the pandemic, pregnant and postpartum women did not seem to be any more vulnerable to the severe form of the disease than the population in general (10)(11) . However, more recently, recommendations were revised based on studies reporting that pregnancy and postpartum may represent additional risks to mothers and infants (7,(12)(13) , probably because of the physiological changes inherent to pregnancy. Immunodeficiency, increased susceptibility to respiratory pathogens, and changes in organic responses to viral infections (14)(15)(16)(17) result in a greater risk of invasive ventilation and admittance into an Intensive Care Unit (ICU) (18)(19) , and even death (2) .
A Swedish report showed that the maternal group was five times more likely to be admitted to an ICU than non-pregnant women, though the risk of death was the same for both groups (20) . In comparison, a Brazilian study found that postpartum women were two times and half times more likely to experience adverse effects than pregnant women (21) . For this reason, pregnant and postpartum women infected with COVID-19 up to two weeks postpartum deserve special attention, as do women who experienced a miscarriage or fetal loss (7) .
Brazil, a country that usually presents high maternal mortality rates, has witnessed an increase in the number of deaths during the pregnant-puerperal cycle since the beginning of the COVID-19 pandemic (15) , surpassing other countries, as international reports show (22)(23)(24)(25) . However, research usually addresses pregnant women, and few studies focus on the clinical outcome of the SARS-CoV-2 during postpartum to contribute to therapeutic and preventive decisions directed to this group.
Understanding how COVID-19 progresses specifically among postpartum women is a gap this study is intended to fill in by achieving the following objectives: 1 -identify the factors associated with death due to COVID-19 among

Study design
This is a cross-sectional, population-based study.

Study's variables
The outcome variable is death due to COVID-19 (death-cure). The independent variables were: •

Data analysis
Initially, a descriptive analysis of the variables concerning sociodemographic data, infection, comorbidities, and respiratory and clinical signs and symptoms at the time the disease and its progression were reported. Next, the association between the variables of interest and the outcome was investigated using logistic regression, estimating odds ratios and respective 95% confidence intervals; the significance level was set at p<0.05. Only comorbidities with a proportion higher than 1.0% were included in the analysis, and clinical signs and symptoms were analyzed considering the total number presented in both epidemiological weeks: 13 th -32 nd and 33 rd -53 rd . No data imputation methods were used, even for variables with more than 20% of missing data, such as race and nosocomial cases.
The analysis was performed using SPSS v.21.0.

Ethical aspects
Ethical guidelines were complied with according to  (32) .
Note that the database used is publicly available and does not report the names of the participants, and there is no possibility to individually identify any of the participants so that anonymity is ensured. Thus, since this study used a publicly available database, there was no need to be submitted to an Institutional Review Board.

Results
Sociodemographic characteristics and those concerning the infection of postpartum women are presented in Table   1.  immunodeficiency, and nephropathy. Hematologic diseases also reached a proportion above 1.0%, but only in the group within the 33 rd -53 rd weeks. Table 2 presents the participants' comorbidities. Both groups presented a proportion above 1.0% of the following comorbidities: heart disease, diabetes, obesity, asthma,        period as the number of clinical symptoms increased.
Regarding sociodemographic aspects in the first period, an association was found between being 35 years old or older and death, while in the second period, Afro-descendant women were more likely to die than Caucasians as well as those living in the Northeast, compared to the women living in the South.
The COVID-19 pandemic reached Brazil while the country was still struggling with an exponentially high maternal mortality rate (14) . Additionally, the government did not implement a universal testing policy for the obstetric population; only women with symptoms were than the total of deaths due to COVID-19 reported in the same period worldwide (14) . Another Brazilian study found a risk 2.4 times greater of postpartum women experiencing adverse effects than pregnant women (21) .
The highest proportion of deaths among postpartum women was reported in the first period, i.e., in the first months of the pandemic when there was little knowledge about managing the disease. However, despite the important decrease in the number of deaths in the subsequent period, mortality was still high. Hence, considering the entire period under study, the proportion of deaths among postpartum women only was higher than that reported by another Brazilian study, which found a mortality rate of 12.7% between February and June 2020 (14) . This difference may be due to the fact that the database is continually updated, and the outcomes may be reported at any time, whenever there is a closure for cases.
The high proportion of deaths in the postpartum period may be associated with some factors, among which structural deficiencies in Brazilian maternity hospitals; lack of physical, human, and material resources; lack of resources to manage critical and emergency care; and a lack of beds in ICUs, among other barriers impeding access to health care (21,33) . Additional aggravating factors include a decrease in the number of prenatal consultations and routine exams after the pandemic, increased social vulnerability, and the fact that the population relaxed social isolation measures prematurely (21) .
The likelihood of death among postpartum women increased in both periods when individuals presented dyspnea, respiratory distress, or oxygen saturation below 95%. Uterine growth during pregnancy by itself is an obstacle to the normal process of maternal ventilation, which increases oxygen demand, and thus, as the uterus expands, the diaphragm is displaced so that dyspnea and respiratory distress are expected (11) . In the puerperium, physiological adaptations are complex and characterized by involutive phenomena that occur gradually. Therefore, it is necessary to pay attention to respiratory symptomatology in the postpartum and, whenever symptoms are outside normal parameters, they should be rapidly acknowledged for the condition to be timely reversed.
A meta-analysis addressing seven studies established that the most prevalent symptom associated with ICU admittance among COVID-19 patients, and consequently, with the severity of the condition, was dyspnea. Dyspnea increased 6.6 times the likelihood of individuals being admitted to an ICU compared to those without symptoms.
The conclusion was that respiratory distress and dyspnea predicted a severe disease progression (34) . week postpartum, compared to non-pregnant women (2) .
The same was evidenced by an American analysis with 400,000 women who tested positive for COVID-19 and a retrospective multi-center case-control study, in which pregnant women were more likely to be admitted to an ICU, require mechanical ventilation, intubation, and die (18,35) .
In the first epidemiological period addressed in this study, the need for ICU admittance and ventilatory support In a case series that included pregnant women and women in the immediate postpartum, maternal death occurred in 15% of the patients admitted in an ICU due to COVID-19 (PCR confirmed cases) and 25% of those who required invasive mechanical ventilation. The conclusion was that pregnant and postpartum women with COVID-19 admitted to an ICU are at increased risk to die, even when they present no comorbidities (36) . In the initial months of the pandemic, 53 women (i.e., pregnant, non-pregnant, and postpartum women) admitted to a Swedish public health  (20) . Note that one of this study's findings cannot be explained: in the first period, the number of clinical signs and symptoms was a protective factor against death among postpartum women diagnosed with COVID-19.
A late pregnancy, traditionally defined as a pregnancy that occurs at the age of 35 or later, is usually considered a risk pregnancy due to the possibility of comorbidities such as hypertension and diabetes (37) , diseases associated with COVID-19 (38) . Hence, future studies can be designed to confirm whether the association between death due to COVID-19 and late postpartum, found in the first period, is an independent event.

Afro-descendant postpartum women living in the
Northeast were more likely to die. A potential explanation is that social and racial inequality found among Brazilian regions is mainly related to difficult access to health services, which may predict worse outcomes for COVID-19 patients (39)(40) . At the base of these disparities are historically structural and social factors that the pandemic made even more apparent and the weakness of the health system, especially regarding the women's health care structure (41) .
Regarding comorbidities, comparing the second to the first period, there were at least twice as many cases of obesity and asthma. This change in profile may result from improved reporting, with a consequent decrease in missing data. Perhaps scientific evidence indicating the importance of these comorbidities in influencing the severe form of COVID-19 (42)(43) encouraged improved reporting.
This study's limitations include using a secondary database that contained information that depended on health workers' reports, i.e., there were missing data impossible to recover. Additionally, because the database is continually updated and data were collected near the last epidemiological week included in the study, some deaths probably were not reported in time, resulting in some level of underestimation. Note, however, that pending cases were excluded to improve data consistency.
On the other hand, it is worth noting that a populationbased dataset from a continent-spanning country was used, and data accumulated for a period that may be considered too long, that is, from March 2020 to January

2021.
Considering this study's results and the fact that nurses provide direct assistance in maternity hospitals and Primary Health Care units, it is essential that nurses monitor postpartum women for respiratory symptomatology via telehealth or face-to-face consultations, promoting rapid testing when necessary, and avoiding delays in implementing the appropriate protocol whenever COVID-19 is confirmed. This procedure will interrupt the transmission chain, minimize the worsening of cases, and consequently decrease the need for ventilatory support and ICU admittance, thus, contributing to decreasing maternal mortality.

Conclusion
Despite the decrease observed in the second epidemiological period, the proportion of deaths among postpartum women was high. In general, considering both the periods, the factors associated with death were related to respiratory signs and symptoms: dyspnea, respiratory distress, and oxygen saturation below 95%.
In addition, an association was found between mechanical ventilation and ICU and the progression of cases. As for sociodemographic aspects, being older, Afro-descendant, and living in the Northeast was associated with deaths.