key: cord-1016732-bg7w7k1k
authors: Vazquez, Rafael Ricardo Valdez; Gallardo-Rincón, Héctor; Lomelín-Gascon, Julieta; Ville Benavides, Rodrigo; Juárez, Linda Morales; Bello, Héctor Herrera; Castañeda, Lidia Moreno; Chavarria, Adrian Palacios; Castillo, Pablo Escalera; Gonzalez, Luis Esteban Ramirez; Avendaño, Mónica Arboleya; Berlanga, Santiago Treviño; Loza, Reyna Albertina Rosas; Wyssmann, Renate Victoria Álvarez; Lezama, Erika Salinas; Romero, Alonso Gutiérrez; Ortega, María Dolores Niembro; Acosta, Liudmila Villegas; Schotman, Ailyn Cendejas; Montoya, Jennifer Bertin; Rodriguez, Andrea Gonzalez; Ramos, Laura María Badel; Martinez-Juarez, Luis Alberto; Saucedo-Martínez, Rodrigo; Montoya, Alejandra; Tapia-Conyer, Roberto
title: Impact of preemptive hospitalization on health outcomes at the temporary COVID-19 hospital in Mexico City: a prospective observational study
date: 2021-08-27
journal: Ther Adv Infect Dis
DOI: 10.1177/20499361211040325
sha: ec10e050cfa1ac7de638dec103b12768817adf3c
doc_id: 1016732
cord_uid: bg7w7k1k

INTRODUCTION: In response to the evolution of the coronavirus disease 2019 (COVID-19) pandemic, the admission protocol for the temporary COVID-19 hospital in Mexico City has been updated to hospitalize patients preemptively with an oxygen saturation (SpO(2)) of >90%. METHODS: This prospective, observational, single-center study compared the progression and outcomes of patients who were preemptively hospitalized versus those who were hospitalized based on an SpO(2) ⩽90%. We recorded patient demographics, clinical characteristics, COVID-19 symptoms, and oxygen requirement at admission. We calculated the risk of disease progression and the benefit of preemptive hospitalization, stratified by CALL Score: age, lymphocyte count, and lactate dehydrogenase (<8 and ⩾8) at admission. RESULTS: Preemptive hospitalization significantly reduced the requirement for oxygen therapy (odds ratio 0.45, 95% confidence interval 0.31–0.66), admission to the intensive care unit (ICU) (0.37, 0.23–0.60), requirement for invasive mechanical ventilation (IMV) (0.40, 0.25–0.64), and mortality (0.22, 0.10–0.50). Stratification by CALL score at admission showed that the benefit of preemptive hospitalization remained significant for patients requiring oxygen therapy (0.51, 0.31–0.83), admission to the ICU (0.48, 0.27–0.86), and IMV (0.51, 0.28–0.92). Mortality risk remained significantly reduced (0.19, 0.07–0.48). CONCLUSION: Preemptive hospitalization reduced the rate of disease progression and may be beneficial for improving COVID-19 patient outcomes.

As of 20 May 2021, there have been over 163.8 million confirmed coronavirus disease 2019 (COVID-19) cases globally, of which more than 65.1 million cases have been detected in the Americas. 1 In Mexico, more than 2.3 million COVID-19 cases have been confirmed as of 20 May 2021, with more than 220,000 patient deaths reported due to Even though the pandemic has been ongoing since March 2020, there are still no established standards of care being applied across the globe. 3 At present, the Government of Mexico has applied pandemic management practices based on the recommendations of the World Health Organization (WHO). 3 The WHO approach is dependent on disease severity, with hospitalization generally reserved for severely ill patients; this has been recommended primarily to avoid overburdening healthcare systems. Venous thromboembolism prophylaxis and antithrombotic therapy are started for these patients, although this is dependent on contraindications.

To reduce the burden on healthcare facilities as well as mitigate the impact of the COVID-19 pandemic in Mexico City's metropolitan area, a synergistic public-private partnership among a group of foundations, the Government of Mexico City, and the National Autonomous University of Mexico, funded, designed, developed, and currently operate an intermediate-care, dedicated COVID-19 hospital in the heart of Mexico City. This was made possible by rapidly converting the largest convention center in Latin America into a temporary hospital along with the concomitant development of a referral network that comprises dedicated respiratory triage community centers and 40 federal and state primary care clinics and hospitals. The operations of the temporary COVID-19 hospital (TCH) include a streamlined process of admission, treatment, clinical monitoring, discharge, and household follow-up.

The TCH is dedicated to patients with a mild or moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and who require oxygen therapy. Admission is only by referral through our network of dedicated respiratory triage community centers, hospitals, and primary care centers. With a continually evolving pandemic and the steady release of newly emerging data related to this illness, it has been necessary to update and adapt the management and care protocols used in the TCH. Accordingly, the TCH protocol of referral and admission was revised to provide a preemptive approach to hospitalization for patients with COVID-19.

Preemptive hospitalization aims to prevent progression to severe disease, reduce the onset of complications, and improve patient outcomes. Furthermore, by ensuring a hospital stay during the period of contagion, this approach is likely to prevent spread in the community. Thus, rather than admitting patients with an oxygen saturation (SpO 2 ) level of ⩽90%, referred patients are now being admitted based on SpO 2 >90%, as measured by pulse oximetry. This SpO 2 level also takes into consideration the geographical and atmospheric factors of Mexico City due to its high altitude (approximately 2250 m above sea level). 4 In this prospective observational study, we report our analysis and outcomes of preemptive hospitalization of patients with COVID-19 who were referred and admitted to the TCH in Mexico City. Furthermore, we compare these patients against those who were admitted with an SpO 2 ⩽90% according to the previous protocol for referral to the TCH.

This prospective, observational, single-center study was conducted between 1 June 2020 and 6 November 2020 at the TCH in Mexico City. This study aimed to compare the progression and outcomes between patients who underwent preemptive hospitalization [hereafter known as the preemptive hospitalization (PH) group] and patients who did not undergo preemptive hospitalization [hereafter known as the non-preemptive hospitalization (NPH) group]. The objective was to compare hospitalized patients' characteristics and outcomes by stratifying both groups using a comorbidities, age, lymphocyte count, and lactate dehydrogenase (CALL) score cut-off of <8 and ⩾8 at admission, which represents a moderate risk of disease. 5 This study adhered to the Declaration of Helsinki as well as local laws and regulations. The need for informed consent was waived as the data were collected retrospectively and deidentified prior to analysis. The study protocol was approved by an independent ethical review board at the National Autonomous University of Mexico (FM/DI/099/ 2020).

The analysis included information from all men and non-pregnant women aged ⩾18 years, referred from community respiratory triage centers, with a confirmed COVID-19 diagnosis by polymerase chain reaction (PCR), who were admitted to the journals.sagepub.com/home/tai 3 TCH from 1 June 2020 and discharged by 6 November 2020, without a history of hospitalization for COVID-19, and who had known outcomes and complete laboratory data. We excluded information from those patients without an advance directive document that permitted transfer to the TCH, pregnant women, patients who refused the prescribed treatment, and those with incomplete outcome assessment data.

On admission, patients underwent a physical examination and routine laboratory tests, including hematology, blood chemistry, arterial blood gas analysis, D-dimer, and ferritin. 6 The triage screening of patients on arrival was conducted using the national early warning score (NEWS), a scoring method based on physiological parameters that allows the standardized assessment of acute-illness severity. 7 A green status (NEWS <5) indicates that patients are either provided with regular follow-up by a general practitioner, or, during the early stage of the disease, are hospitalized to prevent spread in the community. An orange status (NEWS 5 or 6) indicates the patient has symptoms of concern and requires a specialist's priority care. A red status (NEWS >6) indicates a severe condition, and patients are immediately provided with respiratory therapy and are either admitted for intensive care or counter-referred to another hospital.

The operational definition of preemptive hospitalization was based on the following criteria: COVID-19 diagnosis as confirmed by PCR and with an SpO 2 >90% as measured by pulse oximetry. Furthermore, the TCH also used the CALL score to predict the risk of progression in patients with COVID-19 pneumonia. 5 For this analysis, patients with a CALL score >8 were considered at higher risk of progression, and those with a CALL score <8 were deemed to have a lower risk of progression. The treatment prescribed for hospitalized patients at the TCH follows the Government of Mexico's recommendations and is focused on the control of comorbidities, oxygen therapy, anticoagulation, and immunomodulation. 3

We collected data from patient medical charts and the COVID360 Digital Health platform. We evaluated the following variables: demographics and clinical characteristics of patients at admission; respiratory status at admission [i.e. whether patients required supplemental oxygen, use of high-flow nasal cannula (HFNC), bilevel positive airway pressure (BiPAP), or invasive mechanical ventilation (IMV)]; treatment prescribed at admission; signs and symptoms at admission; and laboratory test results. We also routinely evaluated patients' NEWS, 7 CALL score, 5 and Charlson comorbidity index. 8 Hospitalization outcomes included the timing of symptom onset before admission, use of HFNC, admission to the intensive care unit (ICU), length of hospital stay, and clinical outcome.

The sample size considered all patients admitted to the TCH who met the inclusion criteria during the study period. For descriptive group comparisons, we used a two-sided Student's t-test or the Wilcoxon rank-sum test for quantitative variables and Fisher's exact test or chi-square test for categorical variables, depending on the variable distribution.

To evaluate the impact of preemptive hospitalization on patient outcomes we used a multiple logistic regression model and adjusted by sex, age, diabetes, hypertension, obesity, prior dexamethasone use, D-dimer levels, and ferritin levels to control for differences between groups at the time of hospitalization admission. We also stratified patients by risk of progression using the CALL score at admission (<8 points and ⩾8 points). We reported odds ratios (ORs) with 95% confidence intervals (CIs) for different hospitalization outcomes and a p-value of <0.05 was considered statistically significant. Statistical analysis was conducted using STATA version 15 (StataCorp LLC, Texas, USA) and R package version 1.3.1073.

A total of 2265 patients were included, of which 1988 were preemptively hospitalized (SpO 2 >90%), and 277 were hospitalized (SpO 2 ⩽90%).

In the PH group, there were significantly more women (53.1% versus 38.6%; p < 0.0001) and patients were significantly younger (median age 48 versus 53 years; p < 0.0001) compared with the NPH group (Table 1) . 

Patients with a CALL score ⩾8 were at a significantly greater risk of disease progression, requiring HFNC, admission to ICU, requiring IMV, (Table 6) . Among patients at high risk of progression of disease severity (CALL score ⩾8), preemptive hospitalization reduced the likelihood of death by 81% (OR 0.19, 95% CI 0.07-0.48). In patients with a lower risk of progression (CALL score <8), the likelihood of requiring IMV was reduced by 69% (adjusted OR 0.31, 95% CI 0.12-0.80), the likelihood of requiring HFNC was reduced by 54% (adjusted OR 0.46, 95% CI 0.23-0.91), and the likelihood of admission to ICU decreased by 72% (adjusted OR 0.28, 95% CI 0.10-0.73).

This prospective observational study aimed to evaluate the importance of preemptive hospitalization by comparing patients with an SpO 2 >90% with those who were previously admitted with an SpO 2 ⩽90% according to the previous referral protocol. During this study, 2265 patients were referred to the TCH from our dedicated respiratory triage community centers. Overall, most patients were middle-aged with approximately 20% of patients older than 60 years. The most common comorbidities were diabetes mellitus and hypertension; however, over two-thirds of patients were classified as either overweight or obese.

As expected, the PH group had a significantly shorter mean time from onset of symptoms to admission than the NPH group (7.3 versus 8.6 days; p < 0.0001). Patients in the PH group presented with significantly fewer severe respiratory symptoms, as shown by fewer patients needing oxygen supplementation by simple nasal cannula, simple mask, reservoir mask, or HFNC. No patient in the PH group required the use of IMV at admission. Furthermore, predictive markers associated with poor outcomes, [9] [10] [11] [12] such as LDH, D-dimer, and ferritin levels, were all abnormal and at significantly higher levels in a larger proportion of patients in the NPH group compared with the PH group. Notably, the main difference between the groups in terms of risk factors for progression was that a significantly higher proportion of patients in the NPH group were aged 60 years or older, had a high Charlson comorbidity index score, had diabetes mellitus or hypertension, and had higher CALL scores compared with the PH group at admission (all p < 0.0001). This is consistent with previous findings in Mexico where it has been reported that patients with COVID-19 and comorbidities such as hypertension, diabetes mellitus, and obesity are associated with worse outcomes. 13 Interestingly, it was shown in a Swiss tertiary care setting that disease progression was not significantly affected by the presence of comorbidities or by age, with these parameters providing little prognostic information. However, the small sample size as well as an older cohort (median of 67 years) in that study may have masked some associations. Finally, our study also reports that thrombotic and inflammatory markers are prognostic characteristics of poorer outcomes, which has also been reported in several other studies. 10, 14, 15 Treatment administered in the TCH follows the recommendations of the Government of Mexico, 3 which is based on the recommendations provided by the WHO. Although significantly more patients in the PH group had received treatment before admission, no significant differences were observed between groups regarding the types of treatments received before admission. Of note, over 35% of patients, most of whom were in the PH group, had previously been treated with steroids. This is not consistent with the current recommendations, which state that steroids should only be prescribed under careful supervision in an in-hospital setting and for no longer than 10 days. 3 Although there is a biological rationale for offlabel steroid treatment during this pandemic, patients are at an increased risk of drug-drug interactions, especially patients with high-risk comorbidities. 16, 17 As such, it is unknown if prior steroid treatment had any effect on patient outcomes once admitted to the TCH.

Although there is substantial heterogeneity in COVID-19 symptomatology, the most common symptoms reported at the TCH were headache, cough, myalgia, fever, and pharyngodynia, which is in line with the existing literature. 18, 19 In our study, patients in the NPH group, who were more likely to present with disease progression, frequently reported headache, myalgia, and arthralgia in addition to cough and fever. Of note, specific symptoms such as loss of a patient's sense of smell and taste were only reported in approximately 20% of patients, without any differences between the groups.

Patients in each group were stratified by CALL score at admission, which is a risk factor scoring system based on a patient's age, presence of comorbidities, lymphocyte count, and serum LDH levels. These characteristics have previously been identified as risk factors that are associated with poor prognosis at an early stage of disease. 12, 20 It has been shown that the CALL score is an accurate and easy to use model for predicting the risk of progression in patients with COVID-19. 5,21 Therefore, we evaluated the effect preemptive hospitalization had on patient outcomes when stratifying patients by CALL score. In patients at a higher risk of disease progression (CALL score ⩾8), there were significantly fewer patients requiring HFNC (23.2% versus 44.2%), admission to the ICU (11.9% versus 23.9%) or IMV (11.9% versus 22.5%) when compared with patients who were not preemptively hospitalized.

When stratifying by a CALL score of <8 (low risk of progression) and ⩾8 (high risk of progression), preemptive hospitalization reduced the likelihood of death by 94% and 81%, respectively. Furthermore, preemptive hospitalization reduced the likelihood of requiring IMV (69% and 49%), HFNC (54% and 49%), or admission to the ICU (72% and 52%), respectively. These findings show that preemptive hospitalization prevented progression to a more severe form of disease compared with patients who were not preemptively

hospitalized. An additional benefit of preemptive hospitalization may be a reduction in community and household contagiousness.

The study's main limitations are the observational, single-center, retrospective study design, the heterogeneous population, and possible selection bias.

Preemptive hospitalization, based on SpO 2 , may result in a lower rate of progression to severe disease and may be beneficial for improving outcomes in patients with COVID-19. In addition, our results show that it is important to triage patients by CALL score at admission as those with a CALL score ⩾8 are more likely to require HFNC or IMV, be admitted to the ICU, and have a higher mortality risk.

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All authors conceived of and designed the study. HGR, JLG, RSM, LAMJ, and LMJ acquired and interpreted the data. HGR, JLG, LMJ, LAMJ, and RTC drafted the manuscript; acquired, analyzed, and interpreted the data; contributed to writing the sections of the manuscript dealing with data analysis; and revised the manuscript for important intellectual content. All authors read and approved the final version to be published and agree to be accountable for all aspects of the work.

The Carlos Slim Foundation funded this study. The funding source was involved in the design of 

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors would like to thank Keyra Martinez Dunn and James Graham of Edanz for providing medical writing support, which was funded by the Carlos Slim Foundation.

Héctor Gallardo-Rincón https://orcid.org/ 0000-0002-0811-4606Rodrigo Ville Benavides https://orcid.org/0000-0003-2158-831XLuis Alberto Martinez-Juarez https://orcid. org/0000-0001-7550-7867

The data that support the findings of this study will be made available on reasonable request to the corresponding author.

Supplemental material for this article is available online.