key: cord-0753714-qqkyxtkt
authors: Raheja, Hitesh; Chukwuka, Nnamdi; Agarwal, Chirag; Sharma, Dikshya; Munoz-Martinez, Alejandro; Fogel, Joshua; Khalid, Mazin; Hashmi, Arsalan Talib; Ehrlich, Samantha; Waheed, Maham Akbar; Siddiqui, Sabah; de Brito Gomes, Bruno Augusto; Aslam, Awais; Gualan, Carlos Jose Merino; Aftab, Iqra; Tiwari, Aparna; Singh, Sehajpareet; Pouching, Kristal; Somal, Navjot; Shani, Jacob; Rojas-Marte, Geurys R
title: Should COVID-19 Patients > 75 Years be Ventilated? An Outcome Study
date: 2021-02-12
journal: QJM
DOI: 10.1093/qjmed/hcab029
sha: f3305a505594e7c34cb200603d073ebd017bdb4a
doc_id: 753714
cord_uid: qqkyxtkt

BACKGROUND: Elderly patients with COVID-19 disease are at increased risk for adverse outcomes. Current data regarding disease characteristics and outcomes in this population is limited. AIM: To delineate the adverse factors associated with outcomes of COVID- 19 patients ≥75 years of age. DESIGN: Retrospective cohort study. METHODS: Patients were classified into mild/moderate, severe/very severe, and critical disease (intubated) based on oxygen requirements. The primary outcome was in-hospital mortality. RESULTS: 355 patients aged ≥75 years hospitalized with COVID-19 between March 19(th) and April 25(th), 2020 were included. Mean age was 84.3 years. One-third of the patients developed critical disease. Mean length of stay was 7.10 days. Vasopressors were required in 27%, with the highest frequency in the critical disease group (74.1%). Overall mortality was 57.2%, with a significant difference between severity groups (mild/moderate disease : 17.4%, severe/very severe disease : 71.3%, critical disease: 94.9%, p < 0.001). Increased age, dementia, and severe/very severe and critical disease groups were each significantly associated with increased odds for mortality while diarrhea was associated with decreased odds for mortality (OR : 0.12, 95% CI : 0.02-0.60, p < 0.05)]. None of the cardiovascular comorbidities were significantly associated with mortality. CONCLUSION: Age and dementia are associated with increased odds for mortality in patients ≥75 years of age hospitalized with COVID-19. Those who require intubation have the greatest odds for mortality. Diarrhea as a presenting symptom was associated with lower odds for mortality.

As of early January 2021, the coronavirus (SARS-CoV-2) pandemic remains a public health crisis, affecting more than 84 million people globally and 20 million in the United States (US) alone. 1 Presentations range from an asymptomatic course to severe inflammatory reaction resulting in acute respiratory distress syndrome (ARDS) and multi-organ dysfunction. 2 Older age, obesity, and other comorbid conditions are associated with higher rates of COVID-19 mortality. 3, 4 The Centers for Disease Control and Prevention (CDC) reports that although individuals older than age 65 comprise 17% of the total US population, they account for 31% of COVID-19 infections, 45% of hospitalizations, 53% of intensive care unit (ICU) admissions, and 80% of deaths. 5 Similarly, a report from the Chinese Center for Disease Control and Prevention evaluating more than 72,000 cases of COVID-19 reported an overall case fatality rate (CFR) of 2.3%. In contrast, the CFR was 8% in 70-79-year-olds and 14.8% in those ≥80 years old. 6 A Chinese study of 201 patients found that older age is associated with a greater risk of developing ARDS and of death. 7

Elderly patients may have one or more pre-existing medical conditions, which places them at increased risk for developing severe forms of COVID-19 and even of dying from the disease.

Physiological changes that accompany aging, including altered immune response and multiple age-related comorbidities (e.g., dementia), are associated with poorer outcomes in older patients. 8 Very few studies have focused on the characteristics and outcomes of COVID-19 infection in the elderly in the US; hence, data in this regard are limited. This retrospective single-center study aims to delineate the characteristics, risk factors, and outcomes among patients aged ≥75 years hospitalized with COVID-19.

A single-center, retrospective, observational analysis was performed at Maimonides Medical Center, a 711-bed tertiary care teaching hospital in New York City. The Maimonides Medical Center Institutional Review Board approved the study, qualified it as minimal risk research, and waived the need for informed consent.

We analyzed the clinical and demographic characteristics and outcomes of patients aged ≥75 years admitted to Maimonides Medical Center with COVID-19 between March 19 th and April 25 th , 2020.

The method for diagnosis of SARS-CoV-2 infection was real-time reverse transcriptionpolymerase chain reaction (RT-PCR) testing of a nasopharyngeal sample. All patients included in this study presented to our emergency department (ED) with either symptoms suggestive of COVID-19 infection or had a history of exposure to a person with known COVID-19 infection.

Those who presented with symptoms and had a positive result as outpatient, were re-tested in our emergency department to confirm COVID-19 infection. Patients who died within one day of being admitted or during their ED stay prior to being admitted were excluded. Patients seen in the ED or outpatient clinics that did not require hospitalization were also excluded.

Disease severity was determined by the amount of oxygen supplementation required throughout the patient's hospital course. Mild disease severity was defined as an oxygen saturation level >95% on room air. Moderate disease severity was defined as requiring oxygen supplementation via nasal cannula at rates of up to 5 L/min to maintain an oxygen saturation level of ≥95%. Severe disease was defined as any patient with SARS-CoV-2 infection requiring oxygen supplementation via face mask at rates up to 10 L/min to maintain an oxygen saturation level of ≥95%. The disease was considered very severe when requiring oxygen supplementation via non-rebreather mask or highflow nasal cannula (HFNC) to maintain an oxygen saturation level of ≥95%. The disease was deemed critical when intubation and mechanical ventilation were required.

Data collected included patient demographics, presenting symptoms, comorbidities, home medications, initial vital signs upon admission, pertinent laboratory results, treatment received for COVID-19, complications, and outcomes, including mortality and length of hospital stay (LOS).

The primary outcome was in-hospital mortality, described as death in hospital following the diagnosis of COVID-19. The secondary outcome was LOS.

Descriptive statistics of mean and standard deviation were used to describe continuous variables, 

There were 355 patients included in the study. The mean age was 84.3 years, and almost half were female. Two-thirds were Caucasian and 7.6% were Hispanic. Hypertension (78.6%), diabetes mellitus (33.8%), heart failure (26.2%), and coronary artery disease (26.2%) were the most common comorbidities. There were 15.8% that were obese. Shortness of breath (58.9%), fever (49.9%), and cough (41.1%) were the most common presenting symptoms. Table 1 shows the baseline characteristics. Table 2 shows management and outcome variables. There were 33% that were intubated and 27% required vasopressors, with the highest frequency for vasopressors in the critical disease severity group (74%). There were 10.1% that received hemodialysis and 9.9% received blood transfusions.

More than two-thirds received hydroxychloroquine (69.9%) and/or azithromycin (72.7%).

Prophylactic antibiotics were administered to 76.1%.

There were 10.1% diagnosed with bacteremia/fungemia, while <1% had either a cerebrovascular accident or deep venous thrombosis. No statistical difference was found in the occurrence of deep vein thrombosis/pulmonary embolism or cerebrovascular accident based on disease severity.

Bacteremia/fungemia were seen more often in patients with critical disease severity (19.8%).

The overall mortality rate was 57.2%, with a significant difference between severity groups.

Patients with mild/moderate disease had mortality of 17.4%, those with severe/very severe disease had mortality of 71.3%, and those with critical disease had the highest mortality of 94.9% (p<0.001). The mean LOS was 7.10 days. This varied from 4.77 days in patients with mild/moderate disease, 5.92 days for those with severe/very severe disease, to 9.1 days for those with critical disease (p<0.001). Table 3 shows comparisons between patients with and without dementia. Those with dementia were older, had less diabetes, more severe/very severe disease, and less critical disease (i.e., intubated). Those with dementia had a greater percentage for mortality than those without dementia (p=0.003). There was no difference for LOS between those with and without dementia.

Both severe/very severe disease (p<0.001) and critical disease (p<0.001) were each significantly associated with increased odds for mortality. Critical disease was significantly associated with increased LOS. Table 4 shows linear regression analyses for LOS. In the multivariate analysis, female gender, cough, severe/very severe disease, hemodialysis, blood transfusion, steroid use, prophylactic anticoagulation, therapeutic anticoagulation, vitamin C, tocilizumab, and antibiotics for suspected bacterial infection were each significantly associated with increased LOS. None of the comorbidities, vital signs, laboratory values, and complication variables were significantly associated with LOS. Table 5 shows logistic regression analyses for mortality. In the multivariate analysis, increased age, dementia, severe/very severe and critical disease were each significantly associated with increased odds for mortality. Conversely, diarrhea was significantly associated with decreased odds for mortality. None of the vital signs, laboratory values, treatment management, and complication variables were significantly associated with mortality.

The current COVID-19 pandemic has affected the older population most severely. To our knowledge, this study represents the largest US analysis focusing on elderly patients hospitalized with COVID-19. Our findings indicate that even in very elderly patients that older age is associated with increased mortality. This corroborates previous studies that suggest that advancing age is a risk factor for increased mortality in COVID-19 infection. [9] [10] [11] [12] The overall mortality in our cohort was 57.2%. However, this percentage significantly varied among disease severity levels where mild to moderate disease had mortality of 17.4% while critical disease had mortality of 94.9%. Other studies report COVID-19 mortality rates for older patients ranging from 20% to 97%. 9, 11, 13 This broad variation in mortality rates depends significantly on admission criteria, disease severity and age cutoffs of the patients included in the individual studies. As our study included only inpatients, we anticipated higher mortality rates than other studies that included outpatients or patients who were seen in the emergency department and discharged. Intubated patients (critical disease group) in our study had the highest mortality rate.

The mortality rate was similar to the 97% mortality rate found in the subgroup of older COVID-19 patients who required intubation in another study. 13 This was likely due to a more severe disease process in these patients leading to severe respiratory distress rather than intubation itself and its complications. Hence, the decision to intubate in this elderly population should be individualized based on the overall clinical picture as would be done in non-COVID patients.

Cardiovascular comorbidities are associated with worse outcomes in COVID-19 patients. 9, [14] [15] [16] [17] [18] As expected in a study focused on older patients, a higher percentage of hypertension, atrial fibrillation, coronary artery disease, heart failure, and cerebrovascular disease were found in our study as compared to reports that included younger patients. 13, 19 However, we did not find any association for any of these comorbidities with mortality.

COVID-19 patients with dementia had a higher mortality rate than those patients without dementia. This contrasts with a study on elderly patients hospitalized with COVID-19 that included 44% of patients with dementia. Although there was a numerically higher mortality in patients with dementia (27% vs 20%), this was not statistically significant. 20 In a report from Italy of 627 COVID-19 patients admitted to a geriatric service, patients with dementia had a mortality rate of 62% as compared to 26% in those without the disease. 21 However, there was a difference in age between the groups of 13.7 years which was statistically significant and could have accounted for the difference in mortality. Interestingly, even though our study showed dementia to be associated with higher mortality, less patients with dementia were in the critical disease severity group. This could possibly be explained by a higher proportion of demented patients undergoing palliative care and refusing aggressive interventions that would include intubation.

In our cohort, obesity was not associated with mortality. In contrast, a recent study in general population found that obesity was associated with higher mortality. 10 It is possible that effect of obesity differs by age group where the elderly that are obese are not associated with mortality.

Studies report the incidence rate of diarrhea in COVID-19 patients to range from 2-50%. 22-24 We found diarrhea as a presenting symptom in 6.8% of patients, and its presence was associated with decreased mortality. In a previous study by our group, diarrhea was associated with lower mortality in COVID-19 patients with high oxygen requirements. 25 In contrast, another report found COVID-19 patients with diarrhea, nausea, and vomiting to be more likely to develop ARDS requiring mechanical ventilation as compared to patients without gastrointestinal symptoms. 26 https://mc.manuscriptcentral.com/qjm Our study has some limitations. First, we did not collect data on certain atypical symptoms, such as delirium and altered mental status, which may be particularly relevant in the older population.

Second, we have no follow-up data on discharged patients to determine post-discharge mortality and readmission rates. However, our focus was to characterize hospitalized patients and determine their outcomes. Third, we did not include information regarding goals of care, which is of paramount importance in the very elderly, especially with a disease process as lethal as COVID-19. Although our study is one of the largest analyses to date focusing on the very elderly, further research is needed in this population to address these topics.

Age and dementia are important risk factors for mortality in patients ≥75 years of age hospitalized with COVID-19. Patients who require intubation have the greatest odds for dying. Patients who reported diarrhea as a presenting symptom had lower mortality than those who did not.

Furthermore, although cardiovascular comorbidities are more frequent in the older population, these comorbidities were not associated with mortality in our study. Note: M=mean, SD=standard deviation. Sample size for continuous variables less than 355 are: Systolic blood pressure (n=353), Diastolic blood pressure (n=353), Heart rate (n=352), Oxygen saturation (n=351), and Respiratory rate (n=353). Sample size for categorical variables missing are: Obesity (n=54), Hypertension (n=1), Diabetes mellitus (n=1), Cerebrovascular accident (n=1), Atrial fibrillation (n=1), Heart failure (n=24), Chronic obstructive pulmonary disease (n=1), Chronic kidney disease (n=2), Asthma (n=1), Deep vein thrombosis/pulmonary embolism (n=2), Coronary artery disease (n=1), Cancer (n=1), Dementia (n=1), Fever (n=2), Cough (n=3), Anosmia (n=3), Ageusia (n=2), Myalgia (n=3), Nausea (n=2), Vomiting (n=3), Diarrhea (n=2), Shortness of breath (n=2), and Chest pain (n=2). 

Clinical characteristics of hospitalized patients with SARS-CoV-2 infection: A single arm meta-analysis

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington state

Severe outcomes among patients with Coronavirus disease 2019 (COVID-19) -United States

Characteristics of and important lessons from the Coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 314 cases from the Chinese center for disease control and prevention: Summary of a report

Risk factors for mortality in 244 older adults with COVID-19 in Wuhan, China: A retrospective study

Risk factors influencing the prognosis of elderly patients infected with COVID-19: a clinical retrospective study in Wuhan

Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area

Risk factors for predicting mortality in elderly patients with COVID-19: A review of clinical data in China

Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study

Analysis of death risk factors among 200 COVID-19 patients in Wuhan, China: A hospital-based case-cohort study

Sample size for continuous variables less than 355 are: White blood cell (n=351)

Sample size for categorical variables missing are: Vasopressor (n=6)

Comparison between groups reports percentages only for cases analyzed and does not include missing cases. Prophylactic anticoagulation included Lovenox 40 mg (n=34, 9.6%) Lovenox 60 mg (n=73, 20.6%), Heparin (n=71, 20.0%), and Low dose apixaban (n=54, 15.2%)