Predictors of ICU Admission in Adult Cancer Patients Presenting to the Emergency Department for COVID-19 Infection: A Retrospective Study

Abstract

Study Objective:

Adult cancer patients with COVID-19 were shown to be at higher risk of ICU admission. Previously published prediction models showed controversy and enforced the importance of heterogeneity among different populations studied. The aim of this study was to detect the predictors of ICU admission for adult COVID-19 patients with cancer who present to the emergency department (ED).

Methods:

Theis a retrospective cohort study. It was conducted on adult cancer patients older than 18 years who presented to the EDof the American University of Beirut MedicalCenter from February 21, 2020, till February 21, 2021, and were found to have COVID-19 infection. Relevant electronic data were extracted. The association between different variables and ICU admission was tested. Logistic regression was done to adjust for confounding variables. P value less than 0.05 was considered significant.

Results:

Eighty-nine distinct patients were included. About 37% were admitted to the ICU (n=33). Higher ICU admission was seen in patients who had received chemotherapy within one month, had a respiratory rate at triage > 22 breaths per minute, an oxygen saturation < 95%, and/or a higher CRP upon presentation to the ED. After adjusting for confounding variables only recent chemotherapy and higher respiratory rate at triage were significantly associated with ICU admission.

Conclusion:

Physicians need to be vigilant when taking care of covid infected oncology patients. Patients who are tachypneic at presentation and those who have had chemotherapy within one month are at high risk for ICU admission.

Background

One of the most vulnerable patients to critical illness from respiratory viral infections are cancer patients [1]. It is postulated that patients with cancer who are infected with the SARS-CoV-2 coronavirus may have worse outcomes than others [2]. Published work reported higher morbidity and mortality rates from COVID-19 among cancer patients compared to their cancer-free counterparts [2–6].

Admission to the Intensive care units (ICU) plays a significant role in the management of COVID-19 patients with some reports showing a reduced mortality rate among those admitted to critical units [7–9]. Several studies developed prediction models and risk scores of ICU admission in COVID-19. Nevertheless, these studies have shown various results that were sometimes controversial [10]. This controversy might be due to a composite of causes including methodological differences, regional care differences, SARS-CoV-2 variants, heterogeneity of the evaluated population, as well as the large heterogeneity embedded within cancer and COVID-19 diseases [10].

During the COVID-19 pandemic, emergency departments (EDs) have been on the frontlines, playing an essential role in detecting infected patients, providing urgent medical care [11], and deciding on the proper disposition of patients. Worldwide, these departments have been challenged and overwhelmed by the increasing number of Covid-19 cases. Consequently, it has been of utmost importance, in ED settings, to be able to predict which cancer patients with COVID-19 are at risk of deteriorating and having worse outcomes. The knowledge of these predictors can be used to assure a proper and timely risk stratification, adjusting management accordingly, avoiding ICU admission delay [12], and prioritizing the admission of more needy patients.

To our knowledge, there are no studies conducted in Lebanon that aim to determine the predictors of ICU admission in our cancer patient population with COVID-19. Therefore, the objective of the present study was to identify these predictors. In addition to that, we explored the impact of targeted COVID-19 drugs administered in the ED on COVID-19 ICU patients.

Methods

Study Design:

The present study is a retrospective cohort study conducted in the American University of Beirut Medical Center (AUBMC), a tertiary care academic hospital in Lebanon. The study enrolled all cancer patients who presented from February 21, 2020, till February 21, 2021, to the emergency department (ED) of AUBMC and were diagnosed with COVID-19 infection. The ED is run as a closed unit by onsite coverage of emergency medicine specialists 24-hr/7.

The study was approved by the Institutional Review Board (IRB) at AUBMC under the protocol number (BIO-2021-0015).

Participants:

Patients included were only adult (> 18 years old) cancer patients who presented to the ED of AUBMC from February 21, 2020, till February 21, 2021, and were found to have COVID-19 infection. Patients not fitting any of the above criteria, as well as those who presented dead on arrival to the ED were excluded.

We defined COVID-19 infection as a positive result of SARS-COV-2 nucleic acid RT-PCR test using the nasal swab samples.

Data Collection:

Eligible patients were identified through the electronic health system (Epic Systems, Verona, WI, USA). The patients’ charts were then reviewed by the research team members who entered the relevant data into REDCap, a free, secure, web-based platform designed to support data capture for research studies that is Health Insurance Portability and Accountability Act compliant.

The data collection form was divided into multiple sections. The first section encompassed the demographic and medical history of the patients. These were sex, date of birth, smoking status, medication, and comorbidities. It also included a subsection about the cancer history of the patient (type of cancer, its spread, and treatment modalities including chemotherapy and immunotherapy). The second section was about the details of the ED visit where the patient was confirmed to be COVID-19 infected. We collected information about vital signs, treatment given in the ED and ED disposition. Finally, the third section was about the patients’ hospital stay which included all complications (Sepsis, AKI, cardiac and respiratory complications like ARDS and PE.) along with the procedures done (central line or chest tube insertion, dialysis, tracheostomy) and hospital discharge date, and disposition. The data collection sheet is attached as an appendix.

Results

2.1 Characteristics Of Patients Who Required Intubation In The Ed

There were 11 patients intubated in the ED (12.4%). There was no significant difference in gender, age, smoking status, and presence of comorbidities between patients who were endotracheal intubated in the ED and those who were not. The average age of intubated patients was 66.7 years (± 10.2) and were mainly males (81.8%).

For vital signs, patients who were intubated in the ED had significantly more low oxygen saturation level at triage < 95 mmHg (81.8% vs 34.6%, p = .006), tachypnea with a RR > 22 breaths/minute (72.7% vs 8%, p < .001), or tachycardia (HR > 100 beats/minute) (81.8% vs 43.6%, p = .018).

Patients who were intubated were more on Ivermectin (36.4% vs 11.5%, p = .051), vasopressors (54.5% vs 1.3%, p < .001), or anticoagulants (81.8% vs 42.3%, p = .014). Intubated patients were less on antibiotics (9.1% vs 53.8%, p = .005). The CRP level was significantly higher in intubated patients (187.5 ± 93.3 vs 85.5 ± 74.6, p < .001).

2.2 Characteristics Of Patients Who Had Respiratory Complications

About 30 patients developed respiratory complications (33.7%) including pneumothorax, acute respiratory distress syndrome, and respiratory failure. However, patients with respiratory complications or not didn’t show significant differences in terms of gender, age, smoking status, or presence of comorbidities.

For vital signs, patients with respiratory complications had significantly lower oxygen saturation level at triage < 95 mmHg (56.7% vs 32.2%, p = .026) or tachypnea RR > 22 (35.7% vs 6.9%, p = .001).

Patients with respiratory complications were significantly more on Tocilizumab (20% vs 3.4%, p = .016), steroids (76.7% vs 45.8%, p = .005) or anticoagulants (66.7% vs 37.3%, p = .009). They had significantly elevated CRP level (132.8 ± 94.2 vs 82.6 ± 74.5, p = .011). They were also more admitted to the ICU (75.8% vs 13.6%, p < .001) and more died (23.3% vs 1.7%, p = .002).

Discussion

In the present study, chemotherapy within one month, a respiratory rate at triage > 22 breaths per minute, an oxygen saturation < 95%, and a higher CRP were shown to be significantly associated with ICU admission for cancer patients who present to the ED with Covid-19 infection. Out of these, after multivariate analysis, only high respiratory rate and recent chemotherapy were top predictors of ICU admission. We didn’t find significant associations between any of the demographic variables of our included sample and the risk of ICU admission.

The significance of our study is that it focuses on cancer outpatients who present to the emergency department for COVID-19 infection which might aid ED staff with a better specific assessment and management of the patients they encounter. Furthermore, to the best of our knowledge, this is the first study done in Lebanon to evaluate the morbidity of COVID-19 in cancer patients and given the fact of heterogeneity of Coronavirus and cancer diseases among geographical regions, this might be of use to ensure an optimal practice tailored to this specific population.

Studies that evaluated the role of recent chemotherapy on covid-19 outcomes have shown controversial results. Zhang et al. showed that rates of severe respiratory COVID-19 were associated with recent chemotherapy [13]. On the contrary, Jee et al found that cytotoxic chemotherapy administered between 90 and 14 days before testing positive for covid-19 have no increased HR for ICU admission[14]; a finding that is consistent with previous data[15, 16]. This controversy in results may be explained by the high heterogeneity of chemotherapy drugs which differ in terms of their mechanisms. Interestingly, some agents were found to have anti cytokine storm effects. Among these drugs which have shown promise in patients with COVID-19 were the Janus kinase (JAK) inhibitors and Bruton’s tyrosine kinase (BTK) inhibitors [17, 18]. These antineoplastic drugs revealed the ability to  prevent the cytokine storm generation thus suppressing the immune system response along with multiple organ failure[19]. Another explanation of the contradictory results regarding chemotherapy could possibly be due to different study models that have not accounted for factors that may affect the results[14].

As we have previously mentioned, presenting to the ED with a respiratory rate exceeding 22 breaths per minute was a top predictor for ICU admission. Since COVID-19 has the potential to affect the respiratory system[20], it sounds rational to suggest that changes in resting respiratory rate might occur in the early stages of infection[21]. Respiratory rate changes is an important marker often preceding major complications, including respiratory depression, and failure[22]. High respiratory rates displayed the ability to predict most of in-hospital cardiac arrests as well as admission to the  intensive care unit[23]. When compared to heart rate, respiratory rate is found to be a better indicator of the patient’s stability[24]. Furthermore, Subbe et. al showed that respiratory rate is superior not only to pulse rate but also to both blood pressure in detecting high-risk patient groups[25].

It is certain that vital signs play a fundamental role in getting an overall idea of a patient’s status. Oxygen saturation compared to the invasive arterial blood-gas measurement serves as a more accessible indicator for oxygenation[26]for triage purposes. From what we observed in the univariate analysis of this study, an oxygen saturation< 95% at presentation to ED was significantly associated with admission to ICU. Akhavan et al found that a lower ambulatory oxygen saturation was strongly correlated with requiring high oxygen supplementation and mechanical ventilation among admitted ED covid-19 patients[27].Severe respiratory failure and death associated with coronavirus infection may be the result of damaged alveoli and edema formation, which hinders the lung’s ability to oxygenate blood, as reflected in reduced oxygen saturation[28, 29].

Our results regarding CRP were consistent with Wang et al findings. Higher CRP levels were associated with aggravated COVID-19 cases, and these levels occurred before disease progression[30]. C-reactive protein is a well-known marker of systemic inflammation and severe infection[31]. In COVID-19 infection, CRP was established as an independent outcome predictor as well as an independent discriminator of severity of disease[32-35]. As a matter of fact,  high levels of CRP were considered the most important predictor of  COVID-19 severity in oncology patients[36]. Still, it’s good to keep in mind, especially when looking at the multivariate analysis of our study, that high CRP do commonly occur in oncology patients, which implies that it might be questionable whether or not it should be considered to be an independent prognostic factor in cancer COVID-19 patients[37].

As in other studies, Remdesivir displayed potential benefits in terms of reducing the risk of ICU admission in our study. When given alone to cancer patients with covid-19, this drug was associated with a reduced 30-day all-cause mortality(aOR, 0.41; 95% CI: 0.17–0.99)[38]. This nucleotide analog ribonucleic acid (RNA) polymerase inhibitor has shown promising results. In a cohort of severe COVID-19 patients clinical improvement was observed in 68% of 53 patients[39]. In a double-blind, randomized, placebo-controlled trial in hospitalized adults with Covid-19,  intravenous Remdesivir was shown to significantly speed the time to improvement versus placebo (p < 0.001)[40].Moreover, the fact that Remdesivir usage in treating outpatients with mild to moderate covid-19 was given approval by the US Food and Drug Administration is an additional verification of its efficacy[41].

While the literature suggests that early antibiotic administration in Covid-19 has no impact on mortality rates[42]and can actually increase the risk of adverse outcomes[43], we found that it is significantly associated with lower risk of ICU admission of infected cancer patients. To clear up this issue and draw definitive conclusions, large multi-centric studies are urgently required[44].

Large multi-centered studies are also needed to investigate the impact of other treatments including Tocilizumab and steroids on the morbidity and mortality of cancer patients with covid-19. While limited evidence is available on treatment with tocilizumab for COVID-19[45], data on steroids impact is conflicting[38, 46]. In our study population, these drugs were given by ED physicians to patients who are deemed sicker. We presume that this is the explanation for these treatment options to be associated with increased ICU admission.

Limitations:

The present study had several limitations and should be interpreted cautiously. The first limitation is the small sample size included and the retrospective nature of our study that was done in a single tertiary care center. However, AUBMC has the largest cancer center in Lebanon for oncology patients and treats patients from all over the MENA region. Another limitation is the evolving nature of the virus and its variants, and the discovery of new effective treatment methods along with vaccination that would affect our observations.

Conclusion

In conclusion, we have explored several factors that would aid in the early prognosis of cancer patients with COVID-19 infection. We found that patients who have received chemotherapy within one month of the infection, and/or whose respiratory rate at triage exceeds 22 breaths per minute are significantly at greater risk of requiring an ICU admission.Higher CRP levels were associated with aggravated COVID-19 cases. Remdesivir displayed potential benefits in terms of reducing the risk of ICU admission in our study.Early antibiotic administration was significantly associated with lower risk of ICU admission of infected cancer patients. ED physicians should be vigilant when treating oncology patients infected with covid and should look for predictors of disease progression and ICU admission and start prompt therapy early on.

Declarations

Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Conflicts of interest/Competing interests:  The authors have no conflicts of interest to declare.

Availability of Data and material: No

Code availability: NA

Author contributions: Imad El Majzoub and Tharwat El Zahran were responsible for the study concept, intellectual expert contribution, and design. Nour Kalot and Natalie Estelly collected the data. Malak Khalifeh performed all statistical analysis. Nour Kalot, Nathalie, and Malak Khalifeh drafted the manuscript.Tharwat El Zahran guided the analysis part, revised the whole manuscript, and supervised the whole study. Imad El Majzoub revised the manuscript and supervised the whole study

Ethics approval: This observational study was approved by the Institutional Review Board (IRB) at AUBMC under the protocol number (BIO-2021-0015).

Consent to participate: A waiver of consent was obtained given the retrospective nature of our study.

Consent to publish: A waiver of consent was obtained given the retrospective nature of our study.

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Appendix

Appendix is not available with this version.