Impact of ICU saturation on hospital mortality from COVID-19 in a secondary care center in Iztapalapa, Mexico City

INTRODUCTION: A saturated intensive care unit (ICU) setting and socioeconomic factors such as higher poverty rates have been associated with increased rates of in-hospital mortality in COVID-19 patients. Mexico City has become the national epicenter of the pandemic, with Mexico’s highest death toll. Iztapalapa is the delegation with the highest population density and the most notorious conditions of marginalization in Mexico City. We describe the clinical characteristics and risk factors associated with mortality in 164 patients who received care in a hospital ward setting due to ICU saturation in a hospital in Iztapalapa, Mexico City. MATERIALS AND METHODS: In this retrospective cohort study, data from conrmed COVID-19 patients hospitalized between April 1, 2020 and May 31, 2020 were collected. Patients were categorized into different subgroups: alive vs. deceased and intubated vs. nonintubated for analysis between groups. A p-value <0.05 was considered statistically signicant. RESULTS: In this setting, 67% of the patients required mechanical ventilation, and 32.3% needed vasopressor support, with an in-hospital mortality of 68.3%. The most common complications during hospitalization were acute kidney injury (36%) and acute respiratory distress syndrome (34.8%). We observed similar factors associated with death as previous studies: male sex, older age, comorbidities, laboratory values indicating increased inammatory/organ failure markers, and severe disease at admission. Additionally, we found that routine use of intravenous antibiotics was associated with a higher rate of in-hospital mortality (RR 3.45, 95% CI 1.69-7.06, p <0.001).

accumulated COVID-19 con rmed cases of 91,112 had been reported, with 66,373 recovered cases and 5,670 deaths, a fatality rate of 6.2%. At the time of writing, 2,496 active cases had been reported in the second week of March 2021. [4] Prevalent socioeconomic factors such as higher poverty rates, high public transportation use, lack of health insurance, poor formal education level, and overcrowded housing (and other factors that preclude social distancing and preventive measures) are associated with an increased rate of in-hospital mortality in COVID-19 patients. [2] As the principal tertiary centers for COVID-19 treatment in the metropolitan area of Mexico City reached ICU bed saturation, most Iztapalapa populations with severe or critical COVID-19 receive attention in units with minimal ICU bed availability, such as our center. This study describes the clinical characteristics and risk factors associated with mortality of adults with con rmed SARS-CoV-2 pneumonia who received care in a hospital-ward setting due to ICU saturation in a hospital in Mexico City.

2.1.-Study design and setting
This was a retrospective cohort study at a hospital in the Iztapalapa Delegation of Mexico City, Mexico. Our hospital has served as a pandemic hospital since March 2020. During the study period, the ICU bed capacity was only seven beds, but the hospital wards' capacity was expanded from 36 to 72 beds (all equipped for invasive mechanical ventilation).
We conducted the study in line with the Declaration of Helsinki. The Institutional Ethics Committee approved the study protocol and waived the requirement for written informed consent due to the study's minimal risk to participants. Privacy and personally identi able information of the patients were protected, and data collection did not harm the patients.

Study population
We enrolled patients who had been diagnosed with COVID-19 pneumonia and were hospitalized in the internal medicine department of our hospital between April 1st, 2020, and May 31st, 2020. The inclusion criteria were as follows: (1) patients over 18 years old; (2) patients with COVID-19 con rmed by real-time reverse transcription-polymerase chain reaction (PCR); (3) patients treated only by the internal medicine department medical team; and (4) patients discharged from the hospital due to death or clinical improvement. Exclusion criteria: (1) pregnant patients, (2) patients treated only in the emergency department and intensive care unit, (3) patients referred from other medical units with mechanical ventilation and/or vasopressor support, and (4) those with incomplete data.
Any suspected case with respiratory distress (>30 breaths/minute) or oxygen saturation lower than <90% at room air was hospitalized.

2.3.-Data collection
Patients' clinical, demographic, radiologic, and laboratory feature data with treatments and hospitalization days were extracted from medical records and collected in a database.

2.4.-Variables
The study's primary outcome was in-hospital mortality, de ned as documented death from any cause during hospitalization. The secondary outcome was the use of mechanical ventilation during hospitalization. Patients were further categorized into different subgroups: alive vs. deceased and intubated vs. nonintubated patients.

2.5.-Statistical analysis
The analyses were computed using IBM SPSS Statistics 22 Regarding data distribution, continuous data are presented as the mean and standard deviation (SD) or median and interquartile range (IQR). Categorical data are reported as frequencies and percentages. Variables were compared between groups using Student's t-test or a Mann-Whitney U test if numeric or a chi-squared test if categorical. Analysis of risk factors for in-hospital mortality was performed between the groups. A p-value <0.05 was considered statistically signi cant.
When comparing surviving vs deceased groups, dyspnea (73% in the survivor group vs. 83% in deceased group, p 0.02) and cyanosis (1.9% vs. 11.6%, p 0.03) were more frequently observed in deceased patients. Comparing the intubated vs. nonintubated groups, cyanosis (p 0.03) was associated with the requirement of mechanical ventilation.

Risk factors for death
We summarize the analysis of risk factors for in-hospital mortality in Table 5

Discussion
In this study, among patients with con rmed COVID-19 pneumonia who presented during the initial phase of the COVID-19 outbreak in a hospital in the Iztapalapa delegation of Mexico City, in-hospital mortality was 68.3%, which was higher than that found in previous studies. [1,[6][7][8][9][10][11][12] The hospitalization criteria in our hospital may be the cause for this nding. As discussed previously, a considerable number of severely ill or oxygen-dependent patients were hospitalized. Thus, our cohort might represent more severe COVID-19 patients. In this setting of ICU bed unavailability, 67% of the patients hospitalized in a hospital ward required mechanical ventilation, and 32.3% needed vasopressor support.
This study shows the problem of health system saturation and ICU resource rationing during the COVID-19 pandemic. These results were similar to those observed during the pandemic's initial surge in several countries, where over 50% of the critically ill patients who required ICU care died in general hospital wards due to resource constraints. [13] This investigation showed similar factors associated with death as previous studies. Some comorbidities (such as diabetes mellitus), male sex, older age, increased in ammatory markers, and laboratory values indicating organ failure were associated with a higher rate of in-hospital mortality. [6][7][8][10][11] In this study, we found that routine use of intravenous antibiotics was associated with a higher rate of inhospital mortality and the need for mechanical ventilation. COVID-19 may mimic bacterial pneumonia, and therefore, antibiotics for possible bacterial coinfections are frequently administered.
[14] Langford et al. reported a more frequent unnecessary antibiotic prescription in patients with COVID-19 in the rst six months of the global pandemic, mainly due to suspected bacterial coinfections. Despite frequent antibiotic prescriptions, the prevalence of bacterial coinfection and secondary infection in patients hospitalized with COVID-19 was relatively low at 3.5% and 14.3%, respectively. [15] Studies about the impact of early antibiotic therapy on mortality or critical complications in COVID-19 patients are limited. Buetti et al. reported that early administered antibiotics do not appear to signi cantly impact mortality or delay hospital-acquired infections in critically ill patients. [14] In respiratory viral infection, an altered innate immune function exists in pulmonary tissue due to respiratory viral infection; macrophages are overwhelmed by the increased burden of apoptotic cells and become limited in their capacity to phagocytose bacteria as a result of increasing bacterial growth. Additionally, the initial immune response to a viral lung infection modi es the respiratory tract microbiome, which can, in turn, undermine immune defenses against infectious pathogens. Other inciting mechanisms following viral illnesses include altered epithelial cells that disrupt mucociliary clearance and mucus thickening, impairing immune cell movement. In the speci c setting of SARS-CoV-2 infection, uid-and pus-lled pulmonary alveoli create a nutritive environment for bacteria such as P. aeruginosa and S. aureus. [16] Nosocomial and ventilator-associated pneumonia associated with multidrug-resistant P. aeruginosa, Acinetobacter baumanii, and K. pneumoniae is common in our center. We did not have microbiology laboratory analyses during the study period in our hospital, so bacterial infections in these patients were unknown. To our knowledge, this is the rst research study in which early antibiotic intravenous therapy was associated with higher in-hospital mortality and an increased need for mechanical ventilation in COVID-19 patients. The use of routine intravenous antibiotics, generally broad-spectrum antibiotics, could modify the respiratory tract microbiome. This altered microbiome with impaired immune cells due to SARS-CoV-2 infection could trigger multidrug-resistant pulmonary infections, impacting patient survival.
Respiratory failure is the leading cause of mortality in patients with COVID-19.
[17] Myocardial injury, kidney or liver injury, and multiorgan dysfunction are among the other complications leading to death.
[18] There are several pathways leading to SARS-CoV-2-related death: those directly attributed to viral infection, those in which the infection partially contributed to the cause of death, and those unrelated to it. In this study, most complications were directly related to SARS-CoV-2. [19] In a large retrospective cohort study in the United States, risk factors associated with mortality were similar to those identi ed in our study. Nevertheless, due to the low in-hospital mortality and lower mechanical ventilation use reported, COVID-19 patients present a higher prevalence of acute complications such as ARDS, AKI, and shock.
[20] Regarding Mexico, Olivas Martinez et al. reported in a prospective cohort study the same patterns for risk factors for death as our study and showed how lack of ICU bed availability increased patient mortality. The limitation reported in this extensive study was that a considerable percentage of the patients were transferred to other hospitals due to clinical improvement, clinical deterioration, and saturation of critical care areas, so some clinical outcomes were unknown. [1] With the ndings of previous studies and our results, our group rightfully concluded that in-hospital mortality is associated with a clear pattern. We can expect an increased incidence of acute complications, need for critical care, and higher mortality in a COVID patient with the following risk factors: male sex, older age, presence of comorbidities, laboratory values indicating increased in ammatory/organ failure markers, and severe disease at admission.
In addition to our best efforts, this cohort had the limitation of a small sample size. The population was limited to the Iztapalapa delegation in Mexico City. Extrapolating these ndings to other areas in Mexico (with different population densities and ICU bed availability) could be inaccurate.

Conclusions
Patients hospitalized due to COVID-19 pneumonia in a saturated ICU setting had higher mortality than in other studies reported globally. Expanding bed capacity in hospital wards could help mitigate hospital saturation during the COVID-19 pandemic. Nevertheless, a hospital with a low ICU bed capacity could not provide a better outcome for these patients, who had higher mechanical ventilation or vasopressor support requirements. This study reports a critical situation of hospital area overcrowding, elucidating this situation during the COVID-19 pandemic to inform strategies in resource-limited medical units.

Declarations FUNDING CONSIDERATIONS
This study did not bene t from any funding organization in the public or commercial.

CONFLICT OF INTEREST
None.
AUTHOR'S CONTRIBUTIONS JM Alanís-Naranjo wrote the initial draft of the manuscript. VM Anguiano-Alvarez, and EF Hammeken-Larrondo contributed to reviewing the manuscript. All authors played a signi cant role in editing this research article.

ETHICAL CONSIDERATIONS
The Institutional Ethics Committee approved the study protocol (CEI-1-2021, 501-010-01-21). Privacy and personally identi able information of the patients were protected, and data collection did not harm the patients.          Figure 1 Flowchart of the study design. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. PCR, polymerase chain reaction. IMV, invasive mechanical ventilation.