Toshiki Kuno ORCID iD: 0000-0002-2487-8366

The Association of Interleukin-6 value, Interleukin inhibitors and Outcomes of

Patients with COVID-19 in New York City

Tetsuro Maeda, MD*,a Reiichiro Obata, MD*,a Dahlia Rizk DO, MPH,a Toshiki Kuno,
Accepted Article
MD, PhDa
a
Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth

Israel, NY, USA

*Drs. Maeda and Obata contributed equally to this article.

Conflict of interest: none

Short title: COVID-19, interleukin-6 and New York

Article word counts: 2,578 words

Address for correspondence:

Toshiki Kuno, MD, PhD, FESC, FSCAI

Department of Medicine, Icahn School of Medicine at Mount Sinai,

Mount Sinai Beth Israel

First Avenue, 16th street, New York, NY, 10003, USA

Phone: +1(212) 844-1808

E-mail: Toshiki.Kuno@mountsinai.org

Abstract

Background: Since cytokine release syndrome with elevation of interleukin-6 (IL-6) is

considered to be associated with severe cases of Coronavirus disease 2019 (COVID-19),

IL-6 inhibitors such as tocilizumab are expected to be effective for its treatment.

This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which
may lead to differences between this version and the Version of Record. Please cite this
article as doi: 10.1002/jmv.26365.

This article is protected by copyright. All rights reserved.

 Methods: This was a retrospective study using a consecutive cohort of 224 patients

hospitalized with COVID-19 in March 2020. Patients were divided into those admitted to

the intensive care unit (ICU group) and those not (no ICU group), and clinical data
Accepted Article
including usage of tocilizumab were compared. Correlation between IL-6 value and

tocilizumab use, as well as clinical outcomes were also investigated.

Results: The ICU group had higher rates of preexisting comorbidities such as

hypertension, diabetes and coronary disease, and higher IL-6 than no ICU group (all

P<0.05). Age, peak IL-6, and peak d-dimer were significant predictors of in-hospital

mortality (1.05 [1.01-1.09], P=0.012, 1.001 [1.000-1.002], P=0.002, 1.10 [1.03-1.18],

P=0.008). Receiver operating characteristics curve showed higher predictability of in-

hospital mortality with IL-6 at peak than others (area under curve; IL-6 at peak: 0.875

[0.87-0.942], IL-6 at admission: 0.794 [0.699-0.889], d-dimer at peak 0.787 [0.690-

0.883], d-dimer at admission 0.726 [0.625-0.827]). Incidence of fungal infections was

significantly higher in patients who were given tocilizumab than those who were not

(13.0% vs 1.1%, P<0.001). Notably, tocilizumab did not affect in-hospital mortality after

adjustment including IL-6 (OR [95% CI]: 1.00 [0.27-3.72, P=0.998]).

Conclusions: Age, peak IL-6, and peak d-dimer levels were significant predictors of in-

hospital mortality. Tocilizumab did not decrease in-hospital mortality in our cohort.

Keywords: COVID-19, New York, intensive care unit, invasive mechanical ventilation,

interleukin-6, tocilizumab

Introduction

Coronavirus disease 2019 (COVID-19) caused by a novel coronavirus, severe acute

respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally since December

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 2019 (1) and the World Health Organization declared COVID-19 to be a pandemic on

March 11, 2020 (2). The United States has the largest number of COVID-19 cases in the

world, with more than 1 million confirmed as of May 2, 2020, New York City being its
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epicenter. The total number of deaths has risen exponentially to 15,580, with 211,670

patients suffering from COVID-19 as of June 19, 2020 in New York City.

The clinical manifestations of COVID-19 range quite dramatically from no

symptoms whatsoever, to mild cough, and pneumonia, to acute respiratory distress

syndrome, and death (3, 4). Since cytokine release syndrome with elevation of

interleukin-6 (IL-6) is considered to be associated with severe cases of COVID-19, IL-6

inhibitors such as tocilizumab are expected to be effective for its treatment (5, 6). Despite

lack of proven clinical benefit, tocilizumab was used for selected patients with COVID-

19 at our institution usually early in the hospital course, with rationale that it may prevent

progression of disease.

This study describes our experience in an academic medical center in downtown

Manhattan. We set out to have a better understanding of our COVID-19 admissions

including detailed baseline patient characteristics, clinical manifestations, and factors that

led to a need to escalate to intensive care units (ICUs). The ultimate goal was to

investigate potential correlation between IL-6 value and the impact of administration of

tocilizumab on clinical outcomes hospitalized patients with COVID-19 in New York

City.

Methods

This was a single-center retrospective cohort study. We obtained medical records for

hospitalized patients with laboratory confirmation of COVID-19 at Mount Sinai Beth

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 Israel, which is located in downtown Manhattan. The study protocol was approved by the

institutional review boards (#20-00436) and conducted in accordance with the principles

of the Declaration of Helsinki. Diagnosis of COVID-19 required nasopharyngeal swab

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for SARS-CoV-2 polymerase chain reaction testing. The pathogenic detection was

initially performed in Department of Health in New York City and LabCorp, and

transitioned into Mount Sinai Hospital’s internal laboratory thereafter. Patients who

presented to the hospital with respiratory symptoms or a viral prodrome were tested for

COVID-19 and evaluated for admission. Since very little was known about the disease,

decision to admit was largely provider-dependent, and not based on any specific

predetermined criteria.

Since the first hospitalized patient with COVID-19 was identified on March 13,

2020, a total of 224 consecutive patients with COVID-19 were hospitalized by March 31,

2020 and were included in our study. Mainly two authors (R.O. and T.M.) conducted a

retrospective review of electronic medical records for the patients’ demographics,

comorbidities, test results, in-hospital treatment and outcomes through May 2, 2020. The

collected data included the following: whether patients met criteria for systemic

inflammatory response syndrome (SIRS); whether patients met criteria for type 1 or type

2 myocardial infarction (7); quick sepsis-related organ failure assessment (qSOFA) score

(8); d-dimer and IL-6 values at admission and at peak; use of medications including

hydroxychloroquine, azithromycin, corticosteroids and tocilizumab; and characteristics of

the clinical course such as activation of rapid response team (RRT), length of hospital

stay, length of ICU stay, invasive mechanical ventilation, cardiopulmonary resuscitation

(CPR). Of note, radiographic findings were reviewed by attending radiologists. Our

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 institution initially used hydroxychloroquine for moderate cases, which was defined as

radiologic evidence of pneumonia or oxygen saturation of <94%. Completion of

hydroxychloroquine treatment was defined as receiving hydroxychloroquine for 5 days or

Accepted Article
being discharged alive from the hospital (9). Corticosteroids were usually given as

intravenous dexamethasone 20mg daily for 5 days followed by 10mg for 5 days.

Patients were divided into two groups: those who were admitted to the ICU

during the hospital course (ICU group, 25.4% [N=57]) and those who were not (no ICU

group, 75.6% [N=167]). Continuous variables were presented as mean ± standard

deviation or median [interquartile range], as appropriate for the data distribution;

categorical variables were expressed as percentages. The changes from baseline in

continuous variables were evaluated using Student’s t-test or Mann-Whitney U test; the χ2

or Fisher’s exact t-test was used for analyzing categorical variables. A multivariate

logistic regression model was constructed for predicting the incidence of invasive

mechanical ventilation and in-hospital mortality excluding patients who remained in the

hospital as of May 2, 2020. Considering the total number of invasive mechanical

ventilation (N=34) and death (N=40), three variables were chosen based on prior data.

The following covariates were entered for multivariate logistic regression analyses; age,

d-dimer, and IL-6. Age and d-dimer were recently reported as independent predictors for

mortality of COVID-19 patients (10). IL-6 was also considered a reflection of cytokine

release syndrome of COVID-19 (5). 149 patients (66.5%) had both d-dimer and IL-6

values reported. We entered age, d-dimer levels (at admission), and IL-6 levels (at

admission) for invasive mechanical ventilation and in-hospital mortality, or age, d-dimer

(at peak), IL-6 levels (at peak) for in-hospital mortality. Receiver operating characteristic

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 (ROC) curve to estimate in-hospital mortality with d-dimer (at admission and at peak) as

well as IL-6 (at admission and at peak) was also created. Additionally, we also analyzed

effect of tocilizumab, an IL-6 inhibitor which was used in our hospital during the study
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period, using inverse probability weighted analysis. To estimate a propensity score for the

use of tocilizumab, the following covariates were entered: age, d-dimer and IL-6 at

admission, and use of invasive mechanical ventilation. To estimate the effect of

tocilizumab on in-hospital mortality, inverse probability weighted analysis was performed

for adjustment. All statistical calculations and analyses were performed using SPSS

(version 24, SPSS, Chicago, IL, USA), with p-values <0.05 considered statistically

significant.

Results

Among 224 patients, the mean age was 63±17 and 56.7% were male. 35.9% were

Caucasian, 19.5% were African American and notably, 44.7% were Hispanic. Regarding

other demographics of interest, 4.5% were undomiciled, and 93.7% had health insurance

including Medicare (49.3%) and Medicaid (35.4%).

Table 1 shows detailed baseline characteristics. The ICU group had significantly

lower oxygen saturation level (94% [88, 96] versus 96% [94, 98], P<0.001), higher SIRS

and qSOFA criteria met, and were more likely to have hypertension, diabetes mellitus and

coronary artery disease compared to the no ICU group.

Table 2 describes baseline laboratory, electrocardiogram and chest X-ray findings.

The ICU group had a significantly higher white blood cell count, neutrophil count,

glucose levels, blood urea nitrogen, creatinine, lactate dehydrogenase, and d-dimer

compared to the no ICU group (all P<0.05). The ICU group also had significantly higher

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 value of brain natriuretic peptide and inflammatory markers such as C-reactive protein,

procalcitonin, ferritin and IL-6 (all P<0.05). Electrocardiograms significantly more

frequently showed ST elevation in the ICU group compared to the no ICU group (5.3%
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versus 0.0%, P=0.003). Chest X-ray significantly more frequently showed multifocal

pneumonia in the ICU group compared to the no ICU group (73.2% versus 51.9%,

P=0.005). Interestingly, there was a very low rate of lobular consolidation observed

among the study cohort (0.9%).

Table 3 shows in-hospital treatment and outcomes. 57.9% of the ICU group was

initially admitted to the ICU and the rest of those patients were transferred from a general

medicine floor. RRT was activated for 5.8% of the total study cohort. Regarding

treatment, 84.4% of patients received hydroxychloroquine (with completion rate of

94.2%), and 62.1% of patients received azithromycin with higher proportions in the ICU

group. In addition, corticosteroids were given to more than half of the ICU group.

Tocilizumab was given to more than a quarter of the ICU group and 10.3% of the total

cohort. Notably, 59.6% of patients in the ICU group required mechanical ventilation

(15.2% of the total cohort). CPR was performed in 5.4% of the total cohort with a

shockable rhythm (1 out of 12 CPR, 8.3%), and death rate for that group was 100% (age:

70 [60, 76]). In the ICU group, 55.4% of patients died, which was 18.2% of the total

cohort (age: 73 [67, 81]).

With a multivariate logistic regression model, age (odds ratio (OR) [95%

confidential interval (CI)]: 1.04 [1.00-1.70], P=0.05) and IL-6 (at admission) (OR

[95%CI]: 1.006 [1.003-1.009], P<0.001) were significant predictors of the use of invasive

mechanical ventilation, but d-dimer (at peak) was not (OR [95% CI]: 1.00 [0.87-1.15]).

This article is protected by copyright. All rights reserved.

 Notably, age and IL-6 (at admission) were significant predictors of in-hospital death (OR

[95%CI]: 1.05 [1.01-1.09], P=0.007, 1.002 [1.000-1.003], P=0.018), but d-dimer (at

admission) was not (OR [95% CI]: 1.07 [0.95-1.19], P=0.28). In contrast, age, IL-6 (at
Accepted Article
peak) and d-dimer (at peak) were significant predictors of in-hospital death (1.05 [1.01-

1.09], P=0.012, 1.001 [1.000-1.002], P=0.002, 1.10 [1.03-1.18], P=0.008, respectively).

ROC curve (Figure 1) showed higher predictability of in-hospital mortality with

IL-6 at peak than others (area under curve; IL-6 at peak: 0.875 [0.87-0.942], IL-6 at

admission: 0.794 [0.699-0.889], d-dimer at peak 0.787 [0.690-0.883], d-dimer at

admission 0.726 [0.625-0.827]).

Patients who were given tocilizumab (N=23) versus those who were not (N=201)

were also compared. Those who were given tocilizumab, compared to those who were

not, had higher proportion of ICU level of care (70.0% versus 20.3%, P<0.001) and

invasive mechanical ventilation (45.4% versus 11.9%, P<0.001), and had relatively

higher in-hospital mortality rates (33.3% versus 16.6%, P=0.058). Interestingly, incidence

of fungal infections was significantly higher in patients who were given tocilizumab

compared to those who were not (13.0% vs 1.1%, P<0.001). Also of interest, tocilizumab

did not affect in-hospital mortality after adjustment including IL-6 (OR [95% CI]: 1.00

[0.27-3.72, P=0.998]).

Discussion

The salient findings of this cohort study are the following: 1) Patients who were admitted

to the ICU had 55.4% of mortality rate, and the death rate of those who had CPR was

100%; 2) Age, IL-6 at peak, and d-dimer at peak were significant predictors of in-hospital

death; 3) IL-6 at peak and d-dimer at peak were better predictors than IL-6 at admission

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 and d-dimer at admission for in-hospital death; 4) incidence of fungal infections was

significantly higher in patients who were given tocilizumab than who were not; and 5)

tocilizumab did not show a decreased risk of in-hospital mortality after inverse
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probability weighted analysis.

New York City is the epicenter of COVID-19 crisis in the US (11). Mount Sinai

Beth Israel hospital has served the community of Lower Manhattan through numerous

crises such as 9/11 and the blackout, as well as hurricanes Irene and Sandy (12, 13), and

now is serving our community during this rapidly evolving COVID-19 pandemic. While

case rates have come down significantly in NYC in June, our hospital at its peak quickly

evolved to a nearly 90% COVID positive patient census in just a few short weeks, and

expanded its volume and ICU capacity during this time to meet the needs of our

community. Our study describes the diversity of COVID-19 patient characteristics in

New York City. Notably, we included variables such as homelessness, insurance status

(which may be a surrogate for access to healthcare), and race/ethnicity. Patients who

needed ICU admission in our study were likely to have similar comorbidities to those

described in prior studies (14). Our data showed that those who were admitted to the ICU

had higher metrics for SIRS, qSOFA score, lactate dehydrogenase, d-dimer, as well as

higher inflammatory markers such as C-reactive protein, procalcitonin, ferritin and IL-6.

Hydroxychloroquine and azithromycin were utilized, although both drugs were in

short supply citywide due to rapid expansion of usage (9). Some of those who were

initiated on one or both of these medications needed discontinuation of

hydroxychloroquine due to prolonged QTc (15, 16). Despite this, our study showed high

completion rates of hydroxychloroquine. Hydroxychloroquine and azithromycin were not

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 used as of June 21, 2020, however, due to emerging evidence of the negative trial (17).

We demonstrated that age and IL-6 levels were independent predictors of invasive

mechanical ventilation and death due to COVID-19. These variables may be useful to
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identify patients who are more likely to benefit from frequent monitoring since

respiratory failure from COVID-19 was found to have the potential to progress very

rapidly (18). Visitor restriction was applied during the pandemic per state and local

mandates to avoid spread of disease, which may have contributed to delayed recognition

of progression of patients’ condition as often families can help detect variability from

their baseline (19). Since medical resources may be strained during a crisis, this

prediction model might be valuable to distribute to medical personnel and help

understand who should be monitored in more acute settings with potentially higher

staffing ratios and monitoring levels.

Age and IL-6 at peak, as well as d-dimer at peak were demonstrated to be

independent predictors of in-hospital mortality, but not d-dimer at admission. Previous

data showed that age and d-dimer were predictors of in-hospital mortality (10). However,

the study did not include IL-6 as a covariate. ROC curve also showed higher

predictability of IL-6 at peak and d-dimer at peak than IL-6 at admission or d-dimer at

admission for in-hospital mortality. A recent study noted that patients with COVID-19

who received tocilizumab had a higher IL-6 value 12-48 hours after tocilizumab

administration than those who survived (20). Serial measurements of IL-6 and d-dimer

might be necessary to predict in-hospital death. Although the peak values would not be

immediately be known on admission, identifying patients who are more likely to have

poor outcomes would still be helpful to make reasonable clinical decisions. These values

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 which predict higher mortality may be helpful in guiding clinical decision making in

advanced disease. In addition, our data suggest that checking IL-6 value until it is peaked

may be of value in managing patients with COVID-19.

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Previous studies have speculated that IL-6 inhibitors such as tocilizumab may

reduce mortality especially if given earlier in the clinical course (21, 22), and have shown

that IL-6 can be elevated following administration of tocilizumab (23). Tocilizumab was

used in selected cases in our cohort, especially among the ICU group (24). Our study

demonstrated that a high IL-6 level is associated with death. However, our study revealed

that tocilizumab did not reduce the risk of in-hospital mortality with inverse probability

weighted analysis including adjustment of IL-6 with the incremental finding of fungal

infections.

There are several limitations in our study. First, this study was conducted in a

single hospital with relatively small sample size. Although we did attempt rigorous

adjustment, we could not eliminate unadjusted confounders. For example, corticosteroids

were given to the majority of the ICU group, and its relationship to tocilizumab remains

unclear. Although corticosteroids were often discontinued if the patient was subsequently

given tocilizumab to avoid profound immunosuppression, it may have caused more

infectious complications than tocilizumab alone would have. It also remains unclear how

fungal infections were treated in patients who received tocilizumab and how antifungal

treatment would have influenced mortality. Data regarding the timing of tocilizumab

administration (whether it was given in the ICU or in the general medicine floor) were

not available or consistent given its lack of treatment guidelines, and therefore could not

be incorporated into the analysis. Further accumulation of data such as ongoing

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 randomized controlled trials is needed to confirm our findings (25).

In conclusion, we reported detailed description of clinical characteristics,

especially ICU versus no ICU admission in the diverse multicultural urban city of New
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York. Age and IL-6 at peak, d-dimer at peak were significant predictors of in-hospital

death. Incidence of fungal infections was significantly higher in patients who were given

tocilizumab during hospital course than those who were not. Tocilizumab did not

decrease risk of in-hospital mortality after adjustment.

Figure Legends

Figure 1: Receiver operating characteristics curve, IL-6 versus d-dimer to predict in-

hospital mortality

IL-6: interleukin-6, ROC: receiver operating characteristics

This article is protected by copyright. All rights reserved.

Accepted Article

Patients or the public WERE NOT involved in the design, or conduct, or reporting, or

dissemination plans of our research

Funding: none

Disclosure: none

Acknowledgements: none

Author Contributions: RO, TM, DR, TK had full access to all the data in the study and
take responsibility for the integrity of the data and accuracy of the data analysis.
Study concept and design: RO, TK
Data Curation: RO, TM
Acquisition, analysis, or interpretation of data: RO, TM, DR, TK

This article is protected by copyright. All rights reserved.

 Drafting of the manuscript: TK
Critical revision of the manuscript for important intellectual content: RO, TM, DR, TK
Statistical analysis: TK
Administrative, technical, or material support: DR
Accepted Article
Study supervision: TK, DR
Data Availability Statement

Research data are not shared.

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Table 1: Baseline characteristics at admission; ICU group versus no ICU group

ICU group No ICU group P value

N=57 N=167
Age 67 [58, 76] 65 [51, 77] 0.32
Male 54.4% (31/57) 57.5% (96/167) 0.68
BMI 27.2 [24.1, 31.8] 28.9 [24.7, 2.3] 0.33

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 Race White 33.3% (19/57) White 36.8% (60/163) 0.95
black 19.3% (11/57) Black 19.6% (32/163)
Asian 14.0% (8/57) Asian 11.7% (19/163)
other 33.3% (19/57) Other 31.9% (52/163)
Hispanic 41.1% (23/56) 46.0% (75/163) 0.52
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Insurance 93.0% (53/57) 94.0% (156/166) 0.79
Medicare 59.6% (34/57) 45.8% (76/166) 0.071
Medicaid 36.8% (21/57) 34.9% (58/166) 0.80
Undomiciled 3.6% (2/56) 4.8% (8/167) 0.70
Symptoms
Fever 60.7% (34/56) 67.3% (111/165) 0.37
Myalgia 14.3% (8/56) 16.8% (28/167) 0.66
Chest pain 8.9% (5/56) 21.0% (35/167) 0.042
Malaise 26.8% (15/56) 28.1% (47/167) 0.84
Sore throat 1.8% (1/56) 9.0% (15/167) 0.071
Runny nose 5.4% (3/56) 8.4% (14/166) 0.45
Shortness of breath 66.1% (37/56) 58.7% (98/167) 0.33
Cough 71.4% (40/56) 70.1% (118/167) 0.91
Sputum 21.1% (12/57) 20.4% (34/167) 0.91
Abdominal pain 5.4% (3/56) 11.4% (19/167) 0.19
Nausea/Vomit 26.8% (15/56) 26.3% (44/167) 0.95
Diarrhea 16.1% (9/56) 27.5% (46/167) 0.085
Black diarrhea 0.0% (0/34) 3.4% (3/88) 0.28
Dysgeusia 0.0% (0/56) 0.6% (1/167) 0.56
Initial Vital Signs
Temperature (℃) 36.9 [36.3, 37.6] 36.7 [36.2, 37.6] 0.51
Heart rate (beat/min.) 102 [89.5, 111] 95.0 [81, 110] 0.057
SBP (mmHg) 133 [121, 151] 133 [116, 150] 0.48
DBP (mmHg) 75 [65, 86.5] 78 [68, 88] 0.44
MAP (mmHg) 93.8 [87.7, 105] 96.7 [86.5, 108] 0.62
RR (/min.) 22 [18, 25.0] 20 [18, 23] 0.043
SpO2 (%) at room air 94 [88, 96] 96 [94, 98] <0.001
SIRS 2 [1, 2] 1 [0, 2] 0.005
qSOFA score 1 [0, 1] 0 [0, 1] 0.016
Altered Mental Status 16.4% (9/55) 8.4% (14/167) 0.092
Aspirin 39.3% (22/56) 22.2% (37/167) 0.012

Anticoagulation 17.9% (10/56) 8.4% (14/167) 0.048

ACEI 17.9% (10/56) 16.8% (28/167) 0.85
ARB 19.6% (11/56) 16.9% (28/166) 0.64
ACEI or ARB 37.5% (21/56) 33.5% (56/167) 0.59
Steroid use at home 1.8% (1/57) 1.8% (3/166) 0.98
Comorbidities

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 Hypertension 73.7% (42/57) 54.5% (91/167) <0.001
Hyperlipidemia 49.1% (28/57) 38.3% (64/167) 0.15
DM 45.6% (26/57) 28.1% (47/167) 0.015
DM with insulin 15.8% (9/57) 6.6% (11/167) 0.035
COPD 5.3% (3/57) 7.8% (13/167) 0.52
Accepted Article
Asthma 7.0% (4/57) 11.4% (19/167) 0.35
CVA 8.8% (5/57) 6.0% (10/167) 0.47
PVD 7.0% (4/57) 6.0% (10/167) 0.78
Dialysis 5.3% (3/57) 2.4% (4/167) 0.28
Cirrhosis 1.8% (1/57) 2.4% (4/167) 078
CAD 31.6% (18/57) 16.2% (27/167) 0.012
Previous PCI 24.6% (14/57) 8.4% (14/167) 0.001
Previous CABG 10.5% (6/57) 3.0% (5/167)
0.023
Previous PE/DVT 8.8% (5/57) 4.8% (8/167) 0.27
History of AF 12.3% (7/57) 7.2% (12/167) 0.23
Previous CHF 16.1% (9/56) 11.4% (19/167) 0.36
History of cancer 8.8% (5/57) 7.2% (12/167) 0.70
Active cancer 1.8% (1/57) 0.6% (1/165) 0.43
History of transplant 1.8% (1/57) 0.6% (1/167) 0.42
HIV 5.3% (3/57) 6.0% (10/167) 0.84
Dementia 7.0% (4/57) 9.0% (15/167) 0.65

Schizophrenia 1.8% (1/57) 1.8% (3/167) 0.98

Other psychiatry 17.5% (10/57) 16.4% (27/165) 0.84

diseases
Smoker 0.20
Current smoker 5.5% (3/55) 2.5% (4/163)
Former smoker 32.7% (18/55) 23.9% (39/163)

Abbreviation: ICU; intensive care unit, BMI; body mass index, SBP; systolic blood
pressure, DBP; diastolic blood pressure, MAP; mean arterial pressure, RR; respiratory
rate, SIRS; systematic inflammatory response syndrome, qSOFA; quick sepsis related
organ failure assessment, ACEI; angiotensin converting enzyme inhibitor, ARB;
angiotensin Ⅱ receptor blocker, DM; diabetes mellitus, COPD; chronic obstructive
pulmonary disease, CVA; cerebrovascular accident, PVD; peripheral vascular disease,
CKD; chronic kidney disease, CAD; coronary artery disease, PCI; percutaneous coronary
intervention, CABG; coronary artery bypass grafting, PE/DVT; pulmonary
embolism/deep vein thrombosis, AF; atrial fibrillation, CHF; congestive heart failure,
HIV; human immunodeficiency virus

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 Table 2: Baseline laboratory, ECG and chest X-ray findings; ICU group versus no ICU

group

ICU group No ICU group P value

Accepted Article
N=57 N=167
Complete blood count
White blood cell, K/μL 7.8 [5.5, 10.2] 6.6 [5.0, 8.7] 0.040
Neutrophil, K/μL 5.4 [4.1, 8.0] 4.9 [3.2, 6.7] 0.012
Lymphocyte, K/μL 1.0 [0.63, 1.28] 1.0 [0.7, 1.40] 0.45
Hemoglobin, g/dL 13.4 [12.1, 15.5] 13.7 [12.7, 15.0] 0.63
Platelet, K/μL 155 [124, 208] 169 [131, 216] 0.38
Biochemistry panel
Glucose, mg/dL 132 [103, 190] 111 [97, 136] 0.006
BUN, mg/dL 24 [13, 38.5] 15 [11, 23] <0.001
Creatinine, mg/dL 1.13 [0.83, 1.50] 0.91 [0.69, 1.23] 0.003
AST, U/L 52 [36.5, 68] 38 [27.5, 54.5] 0.004
ALT, U/L 32.5 [20, 51.3] 30 [20, 48] 0.54
Total bilirubin, mg/dL 0.5 [0.4, 0.8] 0.5 [0.38, 0.8] 0.35
Albumin, g/dL 3.2 [2.9, 3.7] 3.4 [3.1, 3.7] 0.12
LDH, U/L 486 [356, 648] 334 [256, 447] <0.001
CPK, U/L 174 [72.5, 518] 93 [66, 355] 0.36
Coagulation
PT-INR 1.1 [1.0, 1.2] 1.05 [1.0, 1.1] 0.19
APTT (s) 33.3 [29.7, 36.8] 31.4 [27.9, 36.6] 0.15
D-Dimer (at admission), 1.52 [0.90, 3.22] 0.84 [0.58,1.45] <0.001
μg/mL
D-Dimer (peak), μg/mL 3.83 [2.11, 19.0] 1.05 [0.65, 2.21] <0.001
Fibrinogen. mg/dL 556 [347, 694] 571 [465, 710] 0.43
Inflammation marker
CRP or hsCRP, mg/L 100 [48.8, 195] 60.2 [34.3, 119] 0.001
Procalcitonin, ng/mL 0.24 [0.11, 0.69] 0.10 [0.05, 0.26] <0.001
Ferritin, ng/mL 1071 [376, 2204] 500 [292, 1041] 0.003
IL-6 (at admission), pg/L 127 [58.9, 301] 36.7 [18.6, 70.8] <0.001
IL-6 (peak), pg/L 217 [99.8, 1408] 37.8 [19.0, 71.8] <0.001
Others
pH (venous blood gas) 7.39 [7.34, 7.42] 7.41 [7.38, 7.44] 0.002
Lactate, mmol/L 1.50 [1.20, 2.40] 1.35 [1.06, 1.80] 0.008
BNP, pg/mL 63.6 [11.2. 337] 25.2 [10.0, 137] 0.037
Troponin T, ng/mL 0.17 [0.01, 0.10] 0.01 [0.01, 0.03] 0.010

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 ECG
AF 7.3% (4/55) 3.3% (5/150) 0.23
PAC 1.8% (1/55) 3.3% (5/150) 0.57
PVC 5.5% (3/55) 2.7% (4/150) 0.33
CRBBB 5.5% (3/55) 6.7% (10/150) 0.75
Accepted Article
CLBBB 1.8% (1/55) 1.3% (2/150) 0.80
T wave inversion 7.3% (4/55) 9.3% (14/150) 0.64
ST depression 0.0% (0/55) 1.3% (2/150) 0.39
ST elevation 5.3% (3/57) 0.0% (0/167) 0.003
Chest X ray 98.3% (56/57) 97.0% (162/167) 0.62
Multifocal pneumonia 73.2% (41/56) 51.9% (84/162) 0.005
Lobular consolidation 1.8% (1/56) 0.6% (1/161) 0.43
Pleural effusion 12.5% (7/56) 5.6% (9/162) 0.086

Abbreviation: ECG; electrocardiogram, ICU; intensive care unit, BUN; blood urea
nitrogen, AST; aspartate aminotransferase, ALT; alanine aminotransferase, LDH; lactate
dehydrogenase, CPK; creatine kinase, PT-INR; prothrombin time-international
normalized ratio, APTT; activated partial thromboplastin time, CRP; C-reactive protein,
hsCRP; high sensitivity C-reactive protein, IL-6; interleukin-6, AF; atrial fibrillation,
CRBBB; complete right bundle branch block, CLBBB; complete left bundle branch
block, PAC; premature atrial contraction, PVC; premature ventricular contraction
Table 3: In-hospital treatment and outcomes; ICU group versus no ICU group

ICU group No ICU group P value

N=57 N=167
Initial admission to ICU 57.9% (33/57) 0.0% (0/167) <0.001
Activation of RRT 15.8% (9/57) 2.4% (4/167) <0.001
Nosocomial infection 5.3% (3/57) 3.0% (5/167) 0.43
Treatment
Hydroxychloroquine 89.5% (51/57) 82.6% (138/167) 0.22
Completion of 88.2% (45/51) 96.4% (133/138) 0.034
hydroxychloroquine treatment
Azithromycin 75.4% (43/57) 57.5% (96/167) 0.016
Corticosteroid 64.9% (37/57) 11.4% (19/167) <0.001
Corticosteroid pulse 2.7% (1/37) 0.0% (0/19) 0.47
Tocilizumab 28.1% (16/57) 4.2% (7/167) <0.001
Vasopressor 40.4% (23/57) 0.6% (1/167) <0.001
Phenylephrine 10.5% (6/57) 0.6% (1/166) <0.001
Norepinephrine 40.4% (23/57) 0.6% (1/166) <0.001
Vasopressin 12.3% (7/57) 0.6% (1/166) <0.001
Epinephrine 1.8% (1/57) 0.6% (1/166) 0.43
Dobutamine 5.3% (3/57) 0.6% (1/166) 0.022
Oxygen 94.7% (54/57) 57.2% (95/166) <0.001
NPPV 12.3% (7/57) 0.6% (1/166) <0.001

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 IMV 59.6% (34/57) 0.0% (0/166) <0.001
Tracheostomy 8.8% (5/57) 0.0% (0/166) <0.001
Bacterial Infection 29.8% (17/57) 9.9% (15/152) <0.001
Fungal Infection 10.5% (6/57) 0.0% (0/167) <0.001
Dialysis 10.9% (6/55) 0.6% (1/165) <0.001
Accepted Article
Liver failure 3.5% (2/57) 0.0% (0/166) 0.015
VT 0.0% (0/57) 0.0% (0/166) -
NSTEMI type 1 8.8% (5/57) 0.0% (0/166) <0.001
NSTEMI type 2 22.8% (13/57) 9.0% (15/166) 0.022
STEMI 5.3% (3/57) 0.0% (0/166) 0.003
Catheterization 1.8% (1/57) 0.0% (0/166) 0.087
VF/Pulseless VT 1.8% (1/57) 0.0% (0/166) 0.087
CPR 17.5% (10/57) 1.2% (2/166) <0.001
Length of stay 15 [7, 20] 6 [4, 9] <0.001
Length of ICU stay 7 [3, 15] - -
Length of IMV 11.5 [3.8, 18.3] - -
Death 55.4% (31/56) 5.5% (9/164) <0.001
Remains in hospital 1.8% (1/57) 1.8% (3/164) 0.98
Remains in ICU 0.0% (0/57) - -

Abbreviation: ICU; intensive care unit, RRT; rapid response team, NPPV; noninvasive
positive pressure ventilator, IMV; invasive mechanical ventilator, VT; ventricular
tachycardia, NSTEMI; non-ST elevation myocardial infarction, STEMI; ST elevation
myocardial infarction, VF; ventricular fibrillation, VT; ventricular tachycardia, CPR;
cardiopulmonary resuscitation

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