Complications in hospitalized patients with SARS-CoV2 infection.

OBJECTIVES: The present study aimed to assess the prevalence of complications during hospitalization in patients diagnosed with COVID-19, as well as the association with mortality and prognosis. METHODS: A retrospective cohort study involved 306 patients admitted to a COVID ward and ICU aged 18 years or older with confirmed SARS-CoV2 infection admitted to a Brazilian Tertiary Hospital. Demographic, clinical, biochemical, radiological and outcome data were collected from the patients' charts. RESULTS: According to the data analyzed during hospitalization, 230 (75.2%) patients developed complications, 281 (91.8%) patients had comorbidities and 169 (55.2%) patients died. There are no differences regarding the sex of the patients. The most prevalent complication was ventilator-associated pneumonia, present in 130 (42.5%) patients, followed by acute kidney injury or chronic kidney disease requiring hemodialysis, presented by 100 (32.7%) patients. The calculation of the relative risk of death according to the occurrence of complications showed p<0.0001 for acute renal failure, p<0.0001 for orotracheal intubation and p=0.0434 for acute myocardial infarction. CONCLUSION: The relative risk of death in COVID-19 is significant, showing an increase in relation to age, length of hospital stay and complications. Prevention, early diagnosis and appropriate treatment are essential to reduce the mortality rate in patients with SARS-CoV-2 infection.


INTRODUCTION
The resulting complications of SARS-CoV-2 infection account for about 20% of hospital admissions [1]. And among those hospitalized, 25% become critical patients, requiring admission to an intensive care unit [2]. The most common complications are related to the respiratory, neurological and cardiovascular systems, in addition to secondary infections [3][4][5][6][7][8].
Complications due to COVID-19 are frequently observed in the intensive care environment, and are considered a risk factor for increased mortality [9]. In addition to pulmonary complications, other systems can also be affected, such as the cardiovascular, immunological, hematopoietic, gastrointestinal and neurological systems, which can result in single or multiple organ failure and disseminated intravascular coagulation [10].
Severe SARS-CoV-2 infection is characterized by numerous dependent pathways triggered by hypercytokinemia, especially IL-6 and TNF-alpha, leading to systemic inflammation, hypercoagulability, and multiple organ dysfunction, which results in an unfavorable prognosis [11]. Although the virus mainly affects the respiratory system, extrapulmonary involvement appears to be an important contributor to its lethality and morbidity. Endocrine, metabolic and electrolyte disturbances caused by COVID-19 have been described [12].
Retrospective studies have described variable mortality in relation to pulmonary complications related to SARS-CoV-2 [13]. However, death can occur from numerous conditions, including cardiovascular and neurological complications [14]. Many complications are underdiagnosed in environments with limited resources due to hemodynamic instability of many patients, which makes it impossible to perform imaging tests and the short hospital stay due to death [7].
This study retrospectively analyzed in a cohort of critically ill patients with confirmed COVID-19 infection admitted to a Brazilian University Hospital the prevalence of complications related to this pathology during admission and hospitalization. patients were hospitalized with a positive diagnosis for SARS-CoV-2 and over 18 years of age in the period from July 2020 to August 2021. 2 patients had insufficient data for the study. 308 patients had complete data. 2 patients were excluded due to pregnancyrelated body changes. 306 patients were included in the study.
Results are presented as mean ± standard deviation (SD) for normally distributed data and as median and interquartile range for non-normally distributed data.
Proportion tests were used for the variables analyzed, as well as relative risk calculation.
All tests were performed in Microsoft Excel for Mac, version 16.58.

RESULTS
A total of 306 patients were evaluated, of which 141 (46.1%) were female. The

DISCUSSION
In the present study, 306 Brazilian patients admitted to a tertiary hospital with confirmed SARS-CoV-2 infection were retrospectively evaluated. We observed a relatively high prevalence of complications during their stay in this hospital (75.2%).
Similar outcomes and prognosis (age, days of hospitalization, orotracheal intubation, death) were observed between male and female patients. We also observed an increase in the death rate in relation to complications.
The prevalence of comorbidity in our study differs from previously published data, as some studies reported a prevalence of less than 50% of comorbidity in patients with COVID-19 [15][16][17]. According to our data Docherty et al. also reported a higher prevalence of comorbidity (77.5%) in patients with COVID-19 in a mixed series (ICU and general ward) [18]. Our study, in line with previous work, includes patients in the general ward and critically ill patients with SARS-CoV-2.
Our data suggest a predominance of orotracheal intubation in patients affected by SARS-CoV-2. According to our data, one study observed the need for orotracheal intubation in 98.11% of patients [19]. In fact, the severity of COVID-19 disease has already been associated with the need for mechanical ventilation [20], and the presence of complications appears to contribute to ICU admission [21].  [16,[22][23]. A recent study indicated that orotracheal intubation is significantly associated with complications [24].
In our series, up to 83.7% of patients used invasive mechanical ventilation during hospitalization, which could partially explain the acquired complications. In agreement with this suspicion, pneumonia associated with mechanical ventilation (with germ isolation) was the most frequent complication in relation to the pulmonary system.
In our study, the second most prevalent complication was acute renal failure (or chronic kidney disease) requiring hemodialysis, in line with previously published data [11,23,[25][26]. In addition, our data confirmed the association between acute kidney failure/chronic kidney disease (requiring hemodialysis) and mortality in COVID-19 (p<0.001). Studies point to higher mortality and worse prognosis [27][28][29].
The prevalence of neurological complications in our study differs from previously published data, as some studies reported a prevalence of 62.7% in hospitalized patients [30]. Our study, in contrast to previous publications, evaluated critically ill patients, many of whom were uncooperative or had a lowered level of consciousness at hospital admission and/or remained bedridden during the entire stay (impossible to carry out more complex exams).
As for complications of the cardiovascular system, when we evaluated pulmonary thromboembolism in relation to the outcome, we obtained a significant p (p=0.0170). In our study, the prevalence was relatively low (4.6%), however, it is believed that this value is underestimated because the hemodynamic instability of most of our patients made it impossible to travel to carry out confirmatory tests. In contrast to our study, pulmonary thromboembolism has been a much-cited complication [4,31].
Another complication of the cardiovascular system with a significant p in relation to the outcome was acute myocardial infarction (p=0.0382), however, this pathology has a  [32].
Our data confirmed the relative risk of death according to the occurrence of some complications such as orotracheal intubation (p<0.0001), acute renal failure (p<0.0001) and acute myocardial infarction (p=0.0434). Many studies have observed a relationship between complications and mortality [4,15,21,30,[33][34][35], no studies were found to contradict this statement.
The main strength of this study is the confirmation of SARS-CoV-2 in all included patients, in addition, it covers patients admitted to a sickbed and intensive care unit for COVID-19. This study has limitations, we have limited information about the date of onset of complications and the general condition of patients at hospital admission.
Many patients were admitted in poor general condition, which limited the performance of bedside exams due to the lack of transport conditions for more complex and evidentiary exams for some pathologies.

DECLARATION OF INTEREST
The authors report no conflicts of interest in this work.