a b s t r a c t

Importance: Initial guidelines recommended prompt endotracheal intubation rather than non-invasive ventila- tion (NIV) for COVID-19 patients requiring ventilator support. There is insufficient data comparing the impact of intubation versus NIV on patient-centered outcomes of these patients.

Objective: To compare all-cause 30-day mortality for hospitalized COVID-19 patients with respiratory failure who underwent intubation first, intubation after NIV, or NIV only.

Design: Retrospective study of patients admitted in March and April of 2020.

Setting: A teaching hospital in Brooklyn, New York City.

Participants: Adult COVID-19 confirmed patients who required ventilator support (non-invasive ventilation and/ or endotracheal intubation) at discretion of treating physician, were included.

Exposures: Patients were categorized into three exposure groups: intubation-first, intubation after NIV, or NIV-only. Primary outcome: 30-day all-cause mortality, a predetermined outcome measured by multivariable logistic regres- sion. Data are presented with medians and interquartile ranges, or percentages with 95% confidence intervals, for continuous and categorical variables, respectively. Covariates for the model were age, sex, qSOFA score >= 2, present- ing oxygen saturation, vasopressor use, and greater than three comorbidities. A secondary multivariable model com- pared mortality of all patients that received NIV (intubation after NIV and NIV-only) with the intubation-first group. Results: A total of 222 were enrolled. Overall mortality was 77.5% (95%CI, 72-83%). Mortality for intubation-first group was 82% (95%CI, 73-89%; 75/91), for Intubation after NIV was 84% (95%CI, 70-92%; 37/44), and for NIV- only was 69% (95%CI, 59-78%; 60/87). In multivariable analysis, NIV-only was associated with decreased all-cause mortality (odds ratio [OR]: 0.30, 95%CI, 0.13-0.69). No difference in mortality was observed between intubation- first and intubation after NIV. Secondary analysis found all patients who received NIV to have lower mortality than patients who were intubated only (OR: 0.44, 95%CI, 0.21-0.95).

Conclusions & Relevance: Utilization of NIV as the initial intervention in COVID-19 patients requiring ventilatory sup- port is associated with significant Survival benefit. For patients intubated after NIV, the mortality rate is not worse than those who undergo intubation as their initial intervention.

(C) 2021

1. Introduction

* Corresponding author at: 440 Lenox Rd, Suite 2M, Brooklyn, NY 11203, USA.

E-mail addresses: [email protected] (P. Daniel), [email protected] (M. Mecklenburg), [email protected] (C. Massiah), [email protected] (M.A. Joseph),

The high volume of critically ill patients suffering from the novel coro- navirus disease 2019 (COVID-19) has presented new clinical challenges. The reported mortality rates for COVID-19 Intensive Care Unit (ICU) pa- tients has ranged from 26% to 69% [1-5]. Respiratory failure is a frequent cause of mortality in COVID-19 victims [6]. A study on COVID-19 patients receiving non-invasive ventilation (NIV¹) and intubation found 28-day

[email protected] (S. Rosengarten), [email protected]

(R. Maini), [email protected] (J. Kim), [email protected] (A. Oomen), [email protected] (S. Zehtabchi).

¹ NIV refers to the use of ventilatory positive airway pressure through a mask as op- posed to an endotracheal tube

https://doi.org/10.1016/j.ajem.2021.01.068

0735-6757/(C) 2021

ventilatory support for ARDS, pneum”>mortality rates of 79% and 86%, respectively [6]. Many of the initial case series and descriptions of COVID-19 patients have characterized the lung damage from COVID-19 in terms of Acute Respiratory Distress Syn- drome (ARDS) [7,8]. ARDS can develop from a variety of etiologies caus- ing diffuse inflammation, increased pulmonary vascular permeability, and resulting loss of Gas exchange and hypoxemia [8]. ARDS has defined criteria measurable with radiographic and laboratory findings. COVID-19 patients who decompensate generally meet the criteria for ARDS [9]. Given COVID-19 is a novel pathogen with no data to base treatment rec- ommendation on, the basis for initial guidance in managing COVID-19 pa- tients with respiratory failure was mainly from ARDS studies.

• 1. Ventilatory support for ARDS, pneumonia, & COVID-19 patients

Much research over the past few years has focused on the question of appropriate ventilatory interventions for ARDS and pneumonia pa- tients. Late intubation has been associated with increased mortality [10]. NIV techniques such as continuous positive airway pressure (CPAP) and biphasic positive airway pressure (BiPAP) have been criti- cized in recent years as not applicable to use in ARDS [11]. Attempts to use NIV in ARDS patients, therefore delaying intubation, have shown Negative outcomes [12]. Similar to ARDS, the use of NIV in pandemic viral pneumonia is not recommended [13]. Studies show a higher mor- tality for NIV than invasive mechanical ventilation in patients with se- vere pneumonia, and over 90% of Middle East respiratory syndrome patients who initially received NIV eventually required intuba- tion [14,15].

Early guidance for respiratory support in COVID-19 recommended caution in the use of NIV [16] and noted that early intubation was preferable [17]. Later reports however, showed lower mortality for COVID-19 patients using NIV and high-flow nasal oxygen than with in- tubation [18]. Other authors have used a stepwise approach, advocating non-invasive ventilation or high flow nasal cannula oxygenation prior to intubation, in an effort to stave off need for it [19]. From an Infection control standpoint, studies show NIV disperses air from the lungs a meter from the device and droplets can remain suspended in room air for the duration of use [20-23]. This risk of aerosolization was an impor- tant consideration in the initial recommendations to avoid NIV [16,17] in order to protect the Healthcare staff.

• 1. Our experience

Beginning in March of 2020, as the COVID-19 pandemic was de- clared, a wave of patients in respiratory distress arrived in the emer- gency department at our academic medical center in Brooklyn, New York. Within days, hospital guidelines were established calling for early intubation over NIV. Our institution was following national [17] and international [16] COVID-19 guidelines based on studies of acute re- spiratory distress syndrome (ARDS) and around infection control con- cerns [20-23]. Notable among these COVID-19 victims were those with “silent hypoxia” who were also called “happy hypoxic” due to min- imal respiratory distress despite extremely low oxygen saturations measured by pulse oximetry [24]. Witnessing the deleterious effect of prolonged hypoxia on patients, aggressive management of hypoxia be- came a priority early on. Noting high mortality rates among intubated patients, some physicians elected to first initiate NIV, against hospital guidelines recommending prompt intubation. Initiation of NIV before endotracheal intubation became popular with anecdotal success.

Therefore, we designed this study to examine the outcome of pa- tients undergoing different initial methods of ventilator support in COVID-19 patients in respiratory distress.

1. Methods

Study Design: The study design is a retrospective cohort study of a sample of patients, age 18 or older, with COVID-19 confirmed by real-

time polymerase chain reaction between March 12th and April 13th, 2020. All these identified patients were followed up through May 12th, 2020, if they were still hospitalized. Patients were included if they required ventilatory support (intubation or NIV in the hospital) due to respiratory failure. Respiratory failure and initiation of ventila- tory support was determined by the treating physician. See Fig. 1 for an exclusion flowchart. The State University of New York - Downstate Health Sciences University (SUNY - Downstate) Institutional Review Board approved the study and waived the written informed consent requirement.

Study setting: The study was conducted at SUNY - Downstate, an ac- ademic medical center in Central Brooklyn, which was designated by the state authorities as a COVID-only center. The area of Central Brook- lyn is inhabited by a mostly under- or un-insured and underserved pop- ulation of African- and Caribbean-Americans.

Group Comparisons: Three categories defined the exposures in the primary analysis: those who were initially intubated (Intubation- First), those who were initially on NIV and did not require intubation (NIV-Only), and those who were initially on NIV and required subse- quent intubation (NIV-Intubation).

Outcome: The study outcome was all-cause in-hospital or 30-day mortality (whichever came first). The outcome was determined by reviewing the institutional electronic medical records (EMR).

Study Protocol: Data was collected and reviewed from EMR according to a set study protocol by a trained team of physicians and medical stu- dents. Patient confidentiality was protected by systematically de- identifying patients and storing patient data in a HIPAA-compliant, institution-managed network drive only accessible to those with an institution-associated account and permission given by the principal investigator.

NIV and intubation were defined as either an order or physician doc- umentation of the use of CPAP/BiPAP or endotracheal intubation. In cases of these interventions, when orders and physician documentation disagreed, written documentation was used for data entry. If an order regarding ventilatory intervention was found in the chart but no docu- mentation supported the order having been carried out, it was assumed such interventions were not performed. For the purposes of categoriz- ing exposure groups, we assumed that if NIV and intubation were or- dered on the same date, that NIV took place first. This assumption is based on the typical sequence of escalating interventions in the clinical setting, and an informal review of the data showing that nearly all of these patients remained intubated beyond the date of intubation, pre- cluding use of NIV. Patients intubated in the field were categorized in the Intubation-First group.

Adult Patients with confirmed COVID-19 N = 572

Patients tested for COVID-19 N = 684

Patients requiring ventilatory support N = 222

NIV-Only N = 87

Intubation-First N = 44

Intubation-First N = 91

Fig. 1. Exclusion flowchart.

All demographic variables were collected from EMR demographic data. Older age, Black race, and male sex have all been correlated with increased mortality among COVID-19 patients [2,4,25]. The data to cal- culate qSOFA and SpO₂ were collected from EMR records of arrival vital signs and mental status. Higher mortality is seen in patients with

Table 1

Baseline characteristics of the study Cohort

COVID-19 Patient Characteristics and Conditions Characteristics N = 222 (%, or IQR*

for continuous variables)

95% Confidence Interval

a qSOFA score of two or greater; this is validated for hospital and ED pa- tients with infectious symptoms [26,27]. Lower SpO2 is correlated with	Exposure Intubation First	91 (41%)	(0.34, 0.48)
increased mortality in COVID-19 patients [28]. Separately, the first re-	NIV to intubation	44 (20%)	(0.15, 0.26)
corded ratio of arterial oxygen to the fraction of inspired oxygen (P/F	NIV Only	87 (39%)	(0.33, 0.46)

ratio) was collected from the EMR. Pressor use, associated with shock, at any time during the patients’ hospital stay was assessed from their Medication orders.

Comorbidities were collected from patients’ ICD-10 codes as re- corded in the EMR. medical comorbidities included hypertension, dia- betes mellitus, congestive heart failure, coronary artery disease, chronic pulmonary disease, chronic kidney disease, Immunocompro- mised patients (due to HIV or other reasons), cancer, and obesity (body mass index [BMI] >=30). Each comorbidity was assigned a score of 1, and if 3 or more the comorbidities were present, a patient was cat- egorized as >=3 comorbidities for analysis. These comorbidities have been found at higher rates in COVID-19 patients than in the general population [29]. Comorbidities including obesity, diabetes, coronary ar- tery disease, and hypertension are also associated with increased mor- tality [30,31], and likelihood of having been intubated [2,31], among COVID-19 patients. Mental status on presentation and body mass index (BMI), both components of other variables, were also collected for bivariate analysis.

Statistical analysis: Data are presented with medians and interquar-

tile ranges, or percentages with 95% confidence intervals, for continuous and categorical variables respectively. Case-wise deletion was used to handle missing data. Bivariate analysis was carried out using a chi- square test to assess the association of categorical variables with mortal- ity. Continuous variables were analyzed using a Kruskal-Wallis H test. Multivariable logistic regression was used to establish the odds of mor- tality. The variables included in the regression model were chosen based on previous literature or if they reached a p value of <0.1 in the bivariate analysis [32]. The association of each variable with the study outcome is reported with odds ratio (OR) and 95% confidence interval (CI). Patients who were intubated first were the reference group for both models.

We established significance of the model at the 0.05 ? level. Statisti- cal analysis was carried out using SAS 9.4.

1. Results

During the study period, a total of 574 patients tested positive for COVID-19. Of these patients, 222 adult patients met the inclusion criteria (respiratory failure requiring ventilatory support in the

-hospital). All but one of the included patients had a disposition (discharged alive or died) by the end of the follow-up period. The over- all mortality was 77.5% (95%CI, 72-83%). Mortality for Intubation-First group was 82% (95%CI, 73-89%; 75/91), for NIV-Intubation was 84% (95%CI, 70-92%; 37/44), and for NIV-Only was 69% (95%CI, 59-78%;

60/87). The baseline characteristics of the study cohort are listed in Table 1. The most common comorbidities were hypertension, diabetes, and asthma.

Table 2 presents the characteristics of the cohort categorized by the exposure group. Age, mental status, vasopressor use, diabetes, obesity, and presenting SpO₂ varied by exposure group. The P/F ratio was re- corded for 140 patients; the median value was 138 (IQR, 74-241).

Multivariable Analysis: In the multivariable adjusted logistic regres- sion model, we found a 70% reduction in odds of mortality among COVID-19 patients who received NIV only (OR 0.30, 95% CI 0.13-0.69) compared to those who received intubation without NIV. No association was found for those who were intubated after initial therapy with NIV, as compared to those intubated without prior NIV (Table 3).

Age 69.5 (62-78) (67.2, 70.5)

Sex

Male 129 (58%) (0.51, 0.65)

Female 93 (42%) (0.35, 0.49)

Race/Ethnicity

Black/African American 194 (87%) 0.82, 0.91)

White 12 (5%) 0.02, 0.09)

Hispanic 1 (<1%) 0.0001, 0.02)

Asian 1 (<1%) 0.0001, 0.02)

Undisclosed/Unknown 14 (6%) 0.03, 0.10)

BMI

BMI continuous 29.39 (25.5-33) (29.4, 31.4)

BMI >= 30 83 (44%) (0.37, 0.51)

Symptoms

SpO2 <= 90 98 (46%) (0.41, 0.55)

ED SpO2 91 (86-97) (88.4, 90.9)

Fever >=100.4 78 (36%) (0.30, 0.42)

qSOFA >=2 58 (26%) (0.21, 0.33)

Altered Mental Status 77 (35%) (0.28, 0.41)

Pressor Use 74 (33%) (0.27, 0.40)

Comorbidities

Diabetes 136 (61%) (0.55, 0.68)

Hypertension 169 (76%) (0.71, 0.82)

Coronary Artery Disease 37 (17%) (0.12, 0.22)

Asthma 22 (44%) (0.30, 0.58)

COPD 23 (43) (0.29,0.56)

Any Pulmonary Disease 52 (27%) (0.21, 0.34)

>= 3 Comorbidities 125 (56%) (0.50, 0.63)

*Interquartile range values (IQR) are medians (IQR)

+ Missing values for BMI variables, Fever, qSOFA >=2, >=3 comorbidities, Coronary Artery Dis- ease, Asthma, COPD_Emphysema & SpO2

*Comorbidities included hypertension, diabetes, congestive heart failure, coronary artery disease, chronic pulmonary disease, kidney disease, HIV, immunocompromised from an- other etiology, cancer, or obesity (BMI >= 30).

- Abbreviations: NIV: Non-invasive ventilation; IQR: Inter-quartile range; SPO2: Pulse Oxymetry; qSOFA: quick Sepsis Related Organ Failure Assessment; BMI: Body Mass Index.

Of all 131 patients receiving NIV as initial ventilatory support, 44 (33.6%) required intubation after NIV treatment failed. Secondary anal- ysis (data not shown) found no difference in crude mortality for pa- tients who received NIV as an initial intervention, as compared to those who were intubated without NIV. In the secondary multivariable adjusted logistic regression model, we found 66% reduced odds of mor- tality among COVID-19 patients who received NIV initially (OR 0.44, 95% CI 0.21-0.95) compared to those who received intubation without NIV.

1. Discussion

This study compared - all-cause 30-day mortality for hospitalized COVID-19 patients with respiratory failure who underwent intubation without prior NIV, intubation after NIV, or NIV alone. Our analysis of a sample of 222 COVID-19 adult inpatients at a teaching hospital in Brooklyn, New York found that utilization of NIV as the first step of the ventilatory support, was associated with improved survival. Our study also revealed that the mortality rate in patients who were intubated first was similar to mortality rates in patients who were intubated after an initial attempt of NIV. In the setting of initial NIV fail- ing the patient, the risk of death would be the same as for those who are

Table 2

Patient characteristics stratified by ventilatory support method

Table 3

Adjusted Odds Ratios for Mortality among select COVID-19 Patient Characteristics and Conditions

Variables Exposure Groups Stratified

Variables	Adjusted Odds Ratio, 95% CI	P-value*
Intubation-first	1.00	-
NIV-only	0.30	0.004
	(0.13, 0.69)
NIV-intubation	1.39	0.58
	(0.44, 4.39)
Age	1.06	<0.001
	(1.03, 1.09)
Male gender	1.18	0.67
	(0.55, 2.53
>= 3 Comorbidities	1.28	0.51
	(0.61, 2.68)
SpO2 <= 90	1.34	0.43
	(0.64, 2.81)
qSOFA >= 2	1.67	0.28
	(0.66, 4.22)
Pressor Use	1.92	0.21
	(0.70, 5.28)

Intubation-first NIV-Only NIV-intubation

N = 91

(41%)

N = 87

(39%)

N = 44

(20%)

P-value

N = 222 (% with 95% CI or Median with IQR)

Age (Median)	67 (60-76)	67 (65-82)	69 (58-75)	0.004
Male gender	55 (60)	51 (59)	23 (52)	0.66
	(0.50, 0.71)	(0.48, 0.69)	(0.37, 0.68)
Black/African	80 (88)	72 (83)	42 (95)	0.12
American race	(0.79, 0.94)	(0.73, 0.90)	(0.85, 0.99)
SpO2 < 90.5	37 (41)	37 (45)	24 (62)	0.15
	(0.33, 0.55)	(0.34, 0.57)	(0.45, 0.77)
Temperature >= 100.4	35 (38)	25 (29)	18 (41)	0.23
Triage SpO2	(0.30, 0.51) 93 (87-97)	(0.20, 0.40) 91.5 (86-96)	(0.26, 0.57) 88 (81-94)	0.008

(Median)

qSOFA >= 2	29 (32)	21 (24)	8 (18)	0.21
	(0.22, 0.42)	(0.16, 0.35)	(0.08, 0.33)
Altered Mental	40 (44)	27 (31)	10 (23)	0.03
Status	(0.34, 0.54)	(0.22, 0.41)	(0.13, 0.37)
Pressor Use	50 (55)	2 (2)	22 (50)	<0.0001
	(0.45, 0.65)	(0.014, 0.80)	(0.36, 0.64)
BMI (Median)	30 (26-35)	28 (25-30)	31 (27-34)	0.09
Diabetes	49 (54)	52 (60)	35 (80)	0.02
	(0.43, 0.64)	(0.49, 0.70)	(0.68, 0.91)
Hypertension	65 (71)	71 (83)	33 (77)	0.28
	(0.62, 0.81)	(0.73, 0.90)	(0.64, 0.89)
Coronary Artery	10 (12)	20 (23)	7 (16)	0.14
Disease	(0.04, 0.19)	(0.14, 0.32)	(0.05, 0.27)
Asthma	8 (36)	11 (58)	3 (33)	0.30
	(0.36, 0.80)	(0.30, 0.64)	(0.16, 0.56)
COPD/Emphysema	8 (35)	10 (53)	5 (42)	0.51
	(0.15, 0.54)	(0.30, 0.75)	(0.14, 0.70)
Any Pulmonary	19 (25)	24 (31)	9 (25)	0.68
Disease	(0.15, 0.35)	(0.05, 0.21)	(0.11, 0.39)
>= 3 Comorbidities	48 (53)	49 (56)	28 (63)	0.49
	(0.42, 0.63)	(0.45, 0.67)	(0.48, 0.78)
BMI >= 30	38 (50)	25 (32)	20 (56)	0.03
	(0.38, 0.62)	(0.22, 0.44)	(0.38, 0.72)
Mortality	75 (82)	60 (69)	37 (84)	0.0501
	(0.73, 0.90)	(0.58, 0.78)	(0.70, 0.93)

intubated first. Other similar studies show initiating NIV prior to intuba- tion is presenting with some success [23,24,26]. In contrast to data from ARDS studies, particularly those looking at ICU patients with severe ARDS [33], using NIV as the first step did not increase mortality of the patients reviewed in our study [12].

This study contributes to the body of evidence suggesting that COVID-19 patients may respond differently to NIV than patients suffering from ARDS or severe viral pneumonia [9,34]. In this light, the interchangeability of clinical guidance for these three groups needs to be re-evaluated. If NIV prior to intubation is not significantly associated with an increased risk of mortality, as our results indicate, then it may be clinically prudent to use intubation as a last resort, as has been sug- gested [35]. Furthermore, there were significantly lower odds of mortal- ity for patients who only receive NIV. More research is needed to determine which subset of patients may indeed benefit from intubation, and when it should be performed.

Treatment measures at the individual level must also weigh the risks to the overall response in a disaster. Respiratory support that further spreads infection to staff and patients will increase the number of vic- tims with COVID-19 while decreasing the number of healthcare staff available to manage the event. Clinicians can attempt to mitigate this with the use of helmet ventilators, negative pressure rooms, and appro- priate PPE for hospital staff.

There are practical concerns of ventilator availability unrelated to pulmonary management that affect the level of respiratory support

used in COVID-19 patients. In the setting of a national deficit of ventila- tors, NIV is an alternative treatment option to conserve ventilators [36]. Furthermore, the staff needed to manage a ventilated patient is a great strain on a system that is faced with Staffing shortages at baseline. The overall response of the COVID-19 disaster depends on not wasting valu- able resources such as ventilators and critical care staff on patients who clinically do not require them for survival.

• 1. Limitations

While Brooklyn has been one of the epicenters of the global COVID- 19 pandemic, our cohort mostly consists of African-American and Caribbean-American population with high prevalence of comorbidities. Therefore, our findings may not be generalizable to some other parts of the United States or to global populations at large. Older average age to- gether with high prevalence of comorbidities, particularly diabetes, obe- sity, and asthma, are likely contributors to the high mortality rates seen in our study population. These mortality rates do, however, appear to be in line with those seen in intubated patients at other New York City area hospitals [37], although higher than seen in other New York City studies [2]. The Severity of disease in our sample maybe further described by the median P/F ratio which, if discussed in terms of ARDS, falls into the cat- egory of moderate ARDS [38]. The P/F ratio as a data point has limita- tions in our study however, as this retrospective study could only use one snippet of a dynamic marker.

The statistical significance of our results may be affected by a rela- tively small sample size. Despite the high volume of COVID-19 patients presenting at our hospital, the limited timeframe available to capture data and the necessary filtering of patients to obtain the appropriate sample curtailed our sample size. Our smaller sample precluded the use of matching and sub-group analysis. Larger future studies may find a significant difference in mortality with regard to the use of NIV prior to intubation. We were able to follow almost all patients through their hospitalization course (via the EMR) as only one patient remained hospitalized after thirty days. We were unable to account for patients who may have died after discharge within 30 days if their death was not recorded in the EMR.

There are a number of limitations which affect our ability to address in closer detail the respiratory interventions in question. CPAP and BiPAP orders were not differentiated in our EMR, and so NIV has here been defined as the broad category encompassing both of these modal- ities. We hope that future studies may be able to provide a closer anal- ysis of differences in outcomes between these two modalities. Likewise, while the EMR can show that patients were intubated in the hospital, we were unable to assess whether any of these patients had

previously been intubated or given CPAP (EMS in our study area typi- cally do not have access to BiPAP) by EMS prior to arrival. There are, es- pecially with a disease where best practices are still being established, many possible variations in clinical care by physician which may be re- lated to both ventilatory management decisions and outcomes. Other issues not related to clinical course, including institutional protocols and crowding of the intensive care unit. It is difficult to assess how these limitations may impact the results of our study, but a future study examining patient outcomes as they vary by vent settings, lung compliance, physician, unit, or hospital, may help to clarify these variations.

The data for time of ventilatory interventions were collected from the orders placed in the EMR. It is likely, especially given the strains placed on hospital staff in the context of pandemic conditions, that the ordered times do not accurately reflect the time of the intervention. For this reason, we cannot directly speak to the use of “early” intubation, and instead can only discuss the sequence of ventilatory interventions. We attempted to introduce appropriate covariates into our model to account for factors which may affect both mortality and the type of re- spiratory intervention a patient receives. The decision to choose inva- sive versus non-invasive ventilation is a complex one which heavily relies on clinical judgement based on consideration of many factors. Some of these confounders might not have been accounted for in our analysis and the potential for residual confounding exists. The chosen covariates themselves are subject to the limitations of retrospective data collection. A qSOFA score is calculated based on respiratory rate, systolic blood pressure, and mental status. Respiratory rate, in particu- lar, may be incorrectly recorded in the EMR, especially in high-volume situations like those into which the patients in this study arrived at the hospital. Pulse oximetry readings vary depending on patient and equipment use characteristics, and whether a patient is receiving oxy- gen supplementation, factors for which we were unable to account for due to limitations of documentation. Some of the patients in our sample arrived at the hospital already intubated, and some arrived with CPAP already provided by emergency medical services. Future studies exam- ining the ratio of arterial oxygen to the fraction of inspired oxygen may

get a better approximation of patient severity on presentation.

The predominance of hypoxemia and respiratory failure in patients hospitalized with severe COVID-19 poses a challenge to physicians car- ing for these patients. Our study is highly relevant to the current climate as it examines the association of different ventilatory support modalities to a patient-centered outcome (mortality). Ultimately, randomized con- trolled trials comparing these ventilatory support mechanisms should shed light on the definitive management of respiratory failure in COVID-19 patients.

1. Conclusion

Utilizing NIV as an initial therapy in COVID-19 patients requiring ventilatory support is associated with significant survival benefit. For failed NIV treatment, patients’ mortality rate is not worse than for those who undergo intubation first.

Declaration of Competing Interest

None.

Acknowledgements

We would like to acknowledge the contributions through data collection.

of:

• Alvin Oomen, 4th year Medical Student, SUNY Downstate Health Sci- ences University, Brooklyn, NY, USA, [email protected]
• Jessica Delahanty, 4th year Medical Student, SUNY Downstate Health Sciences University, Brooklyn, NY, USA, jessica.delahanty@downstate. edu

As well as the following for their contribution to framing and discus- sion of on-the-ground.

treatments in the ED:

• Surriya Ahmad, MD, SUNY Downstate Health Sciences University, Brooklyn, NY, USA, [email protected]

References

1. Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington state. JAMA. 2020 Apr 28;323(16):1612-4. https:// doi.org/10.1001/jama.2020.4326 Published online March 19.
2. Goyal P, Choi JJ, Pinheiro LC, et al. Clinical characteristics of Covid-19 in New York City. N Engl J Med. 2020 Apr;17.
3. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323 (11):1061-9.
4. Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 Patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020;323(16):1574-81. https://doi.org/10.1001/jama.2020.5394 Pub- lished online April 06.
5. Bhatraju PK, Ghassemieh BJ, Nichols M, et al. Covid-19 in critically ill Patients in the Seattle region - case series. N Engl J Med. 2020 Mar 30. https://doi.org/10.1056/ NEJMoa2004500.
6. Yang Xiaobo, et al. Clinical course and outcomes of critically ill patients with SARS- CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine. 2020;8(5):P475-481 May 01, 2020; Pub- lished:February 24.
7. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506.
8. The ARDS Definition Task Force*. Acute respiratory distress syndrome: The Berlin definition. JAMA. 2012;307(23):2526-33.
9. Marini JJ, Gattinoni L. management of COVID-19 respiratory distress. JAMA. 2020; 323(22):2329-30. https://doi.org/10.1001/jama.2020.6825 Published online April 24.
10. Kangelaris KN, Ware LB, Wang CY, et al. Timing of intubation and clinical outcomes in adults with acute respiratory distress syndrome. Crit Care Med. 2016;44(1): 120-9.
11. Nava S, Hill N. Non-invasive ventilation in acute respiratory failure. Lancet. 2009 Jul 18;374(9685):250-9.
12. Garpestad E, Schumaker G, Hill NS. Noninvasive ventilation for acute respiratory dis- tress syndrome: breaking down the final frontier? Crit Care Med. 2007 Jan;35(1): 288-90.
13. Rochwerg B, et al. Official ERS/ATS clinical practice guidelines: noninvasive ventila- tion for acute respiratory failure. European Respiratory Journal. 2017;50 (2):1602426.
14. Valley TS, Walkey AJ, Lindenauer PK, Wiener RS, Cooke CR. Association between noninvasive ventilation and mortality among older Patients with pneumonia. Crit Care Med. 2017;45(3):e246-54.
15. Alraddadi BM, Qushmaq I, Al-Hameed FM, et al. Noninvasive ventilation in critically ill patients with the Middle East respiratory syndrome. Influenza Other Respi Vi- ruses. 2019;13(4):382-90.
16. Clinical management of severe acute respiratory infection when COVID-19 is suspected. World Health Organization. Available at https://www.who.int/ publications-detail/clinical-management-of-severe-acute-respiratory-infection- when-novel-coronavirus-(ncov)-infection-is-suspected. Accessed May 8th, 2020.
17. COVID-19 treatment guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treat- ment Guidelines. National Institutes of Health. Available at https://www.covid1 9treatmentguidelines.nih.gov/. Accessed May 8th, 2020.
18. Wang K, Zhao W, Li J, et al. The experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of Chongqing, China. Ann Intensive Care. 2020;10:37.
19. Sun Q, Qiu H, Huang M, Yang Y. Lower mortality of COVID-19 by early recognition and intervention: experience from Jiangsu Province. Ann Intensive Care. 2020;10

(1):33 Published 2020 Mar 18.

1. Hui DS, Chow BK, Lo T, et al. Exhaled air dispersion during noninvasive ventilation via helmets and a total facemask. Chest. 2015;147(5):1336-43.
2. Simonds AK, Hanak A, Chatwin M, et al. Evaluation of droplet dispersion during non- invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic influenza and other airborne infections. Health Technol Assess. 2010 Oct;14(46):131-72.
3. World Health Organization 2020. Infection prevention and control during health care when novel coronavirus (nCoV) infection is suspected: interim guidance. World Health Organization 2020. Date accessed: April 14, 2020.
4. Tran K, Cimon K, Severn M, Pessoa-Silva CL, Conly J. Aerosol generating procedures and risk of transmission of acute Respiratory infections to Healthcare workers: a sys- tematic review. PLoS One. 2012;7(4):e35797.
5. Levitan R. The Infection That’s Silently Killing Coronavirus Patients. The New York Times. 2020 Apr 20.
6. Wadhera RK, Wadhera P, Gaba P, et al. Variation in COVID-19 hospitalizations and deaths across New York City boroughs. JAMA. 2020;323(21):2192-5. https://doi. org/10.1001/jama.2020.7197 Published online April 29.
7. Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of clinical criteria for Sepsis: for the third international consensus definitions for Sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):762-74.
8. Freund Y, Lemachatti N, Krastinova E, et al. Prognostic accuracy of Sepsis-3 criteria for in-hospital mortality among Patients with suspected infection presenting to the emergency department. JAMA. 2017;317(3):301-8.
9. Xie J, Covassin N, Fan Z, et al. Association Between Hypoxemia and Mortality in Pa- tients With COVID-19. Mayo Clin Proc. 2020;95(6):1138-47. https://doi.org/10. 1016/j.mayocp.2020.04.006 [published online ahead of print, 2020].
10. Killerby ME, Link-Gelles R, Haight SC, et al. Characteristics associated with hospital- ization among Patients with COVID-19 — metropolitan Atlanta, Georgia, March- April 2020. MMWR Morb Mortal Wkly Rep. 2020;69:790-4.
11. Guan WJ, Liang WH, Zhao Y, et al. Comorbidity and its impact on 1590 patients with Covid-19 in China: A Nationwide Analysis published online ahead of print. Eur Respir J. 2020;2020:2000547.
12. Nakeshbandi M, Maini R, Daniel P, et al. The impact of obesity on COVID-19 compli- cations: a retrospective cohort study. Int J Obes (Lond). 2020;44:1832-7. https://doi. org/10.1038/s41366-020-0648-x.
13. Vittinghoff E, Glidden DV, Shiboski SC, et al. Regression methods in biostatistics: Lin- ear, logistic, survival, and repeated measures models. New York: Springer; 2015.
14. Bellani G, Laffey JG, Pham T, LUNG SAFE Investigators; ESICM Trials Group, et al. Noninvasive ventilation of Patients with acute respiratory distress syndrome. In- sights from the LUNG SAFE study. Am J Respir Crit Care Med. 2017 Jan 1;195(1): 67-77.
15. Bartosch J. UChicago medicine doctors see ‘truly remarkable’ success using ventilator alternatives to treat COVID-19. U Chicago Medicine Forefront. 2020 Apr 22https:// www.uchicagomedicine.org/forefront/coronavirus-disease-covid-19/uchicago- medicine-doctors-see-truly-remarkable-success-using-ventilator-alternatives-to- treat-covid19. (Online publication, accessed April 30, 2020).
16. Tobin MJ. Basing respiratory management of Coronavirus on physiological princi- ples. Am J Respir Crit Care Med. 2020 Jun 1;201(11):1319-20. https://doi.org/10. 1164/rccm.202004-1076ED.
17. Ranney ML, Griffeth V, Jha AK. Critical supply shortages - The need for ventilators and Personal protective equipment during the Covid-19 pandemic. N Engl J Med. 2020 Apr 30;382(18):e41.
18. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidi- ties, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. JAMA. 2020;323(20):2052-9. https://doi.org/10.1001/jama.2020. 6775 Published online April 22.
19. Horovitz JH, Carrico CJ, Shires GT. Pulmonary response to Major injury. Arch Surg. 1974 Mar;108(3):349-55.