COVID-19 in Patients with Cancer: Insights from a
Tertiary Care Intensive Care Unit
Nissar Shaikh
Hamad Medical Corporation
Mohammad Al Wraidat
Hamad Medical Corporation
Anood A. Al-Assaf
Hamad Medical Corporation
Salma K. Al-Kaabi
Ministry of Public Health
Ahmad A. Abujaber
Hazm Mebaireek General Hospital, Hamad Medical Corporation
Samar Jasim
Hamad Medical Corporation
Salha Bujassoum
Hamad Medical Corporation
Muna A. Almaslamani
Hamad Medical Corporation
Mohamad Y. Khatib
Hamad Medical Corporation
Mohamed A. Yassin
Hamad Medical Corporation
Abdulqadir J. Nashwan ( anashwan@hamad.qa )
Hazm Mebaireek General Hospital, Hamad Medical Corporation
Research Article
Keywords: Acute kidney injury, cancer, COVID-19, invasive and noninvasive ventilation, ICU, secondary
infections, shock
Posted Date: April 17th, 2023
DOI: https://doi.org/10.21203/rs.3.rs-2779474/v1
License: This work is licensed under a Creative Commons Attribution 4.0 International License.
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Page 1/16
Additional Declarations: No competing interests reported.
Page 2/16
Abstract
Background & Aim: Since The emergence of the COVID-19, patients with cancer have been among the
most vulnerable patients, as this infection can be severe and mostly requires intensive care therapy.
Literature discussing the risk factors and the outcome of these patients in intensive care units (ICU) is
accumulating. Our study aims to search for the incidence of COVID-19 infection in cancer patients and
analyses their associated comorbidities, possible risk factor for infections, and their outcomes.
Methods: Patients with active cancer under treatment and those recently diagnosed with cancer and had
confirmed COVID-19 infection requiring ICU admission were included in our study over 8 months, from
March to October 2022. Patient demographic data, comorbidities, ICU stay, duration of hospital stay,
oxygenation/ventilatory requirements, treatment, secondary bacterial infection, and outcome were
collected from the COVID-19 patients' registry in the ICU. Data were entered into the SPSS program
version 23, and results were considered statistically significant at p ≤ 0.05.
Results: A total of 24 patients with cancer and COVID-19 infection required intensive care therapy. The
most common type of malignancy in those patients was solid organ tumor (13 vs. 11 patients), and most
of the study sample were males (20/ 83.3%). Seventy-five percent (18 patients) required intubation and
invasive ventilation. Twenty-nine percent (7 patients) had secondary bacterial pneumonia and
bacteremia. In addition, 70% had septic shock and required vasopressors. Acute kidney injury (AKI) due to
rhabdomyolysis (P<0.001), secondary bacterial infection (P<0.006), bacteremia and pneumonia (P<0.02),
invasive ventilation (P<0.02) and requiring muscle relaxant (P<0.02), the requirement for High flow nasal
cannula and prone position (P<0.03 and 0.01) respectively, shock (P<0.004) were significantly associated
with increased mortality. Patients with cancer and COVID-19 had higher severity scores (P<0.003), longer
ventilation duration (P<0.002), and ICU stay (P<0.002). Overall mortality was 45%.8, there was no
significant difference in mortality rate between patients with solid organ tumors and hematological
malignancy with COVID-19 infection requiring intensive care therapy (P<0.68).
Conclusion: Cancer patients requiring ICU were more prone to develop AKI, rhabdomyolysis, secondary
infection, requiring ventilation and prone position, and septic shock. These patients had a significantly
high mortality rate and were severely ill, requiring prolonged ventilation and ICU stays.
Background
COVID-19 has emerged as a serious worldwide infection with a high fatality rate. It originated in China
and quickly spread to the world, leading to more than 5 million deaths by 2021. Cancer patients are more
susceptible to COVID-19 infection and its complication than the general population due to their
immunosuppressed status and associated comorbid conditions. Up to date there are few original studies
and metanalyses about cancer patients with COVID-19 infections from the western part of the world.
These studies were inconsistent in their conclusions. More extensive studies have concluded that cancer
patients have a higher risk of COVID-19 infection with worse outcomes [1]. Subsequent studies disagreed
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with the former and mentioned that cancer diagnosis and treatment were not associated with any worse
results [2]. More recent studies stated that the outcome of COVID-19 infection in cancer patients is
determined by the patients’ pre-existing condition, not the specific type of malignancy [3]. Moreover, these
studies have investigated patients with mild and moderate cases admitted to hospital medical wards, not
high acuity patients in intensive care units. Up to date, Medical literature from the Middle East region
regarding cancer patients with COVID-19 infection is lacking, especially data about patients in critical
care units and their outcomes.
Patients And Methods
All the patients in this study were admitted to the intensive care unit of Hazm Mebaireek Hospital (The
main COVID-19 designated facility in Qatar), Hamad Medical Corporation in Qatar with severe COVID-19
infection. Data was collected from the ICU patients’ registry. This is a secondary analysis of a previously
approved study (MRC:01-20-607) by the medical research center at Hamad Medical Corporation (Doha,
Qatar) [15].
A total of 1660 patients with severe COVID-19 infection were admitted to ICU (Intensive care unit)
between March and October 2020. Of these 1660 patients, 24 had a history of cancer (on treatment or
newly diagnosed). The records for these 24 patients with a background of cancer and COVID-19 infection
admitted to the ICU were reviewed. Data about the demographic parameters, type of cancer, stage of
cancer, associated diseases and underlying comorbidities, type of cancer treatment, the severity of
COVID-19 disease, SOFA (Sequential organ failure assessment) score, length of intensive care unit
stay(ICU stay), hospital length of stay, and patients’ outcome were collected from the hospital ICU COVID19 patients’ registry. Data was entered and analyzed using SPSS version 23. Categorical variables were
reported using numbers (n) and percentages (%). Continuous variables are reported as mean ± SD, and
categorical variables are represented as frequency and percentage. Due to the small sample size, we
opted to conduct a univariate non-parametric analysis to measure the correlation between the variables
and the patients' mortality, namely Chi2 and Man Whitney (U) test. Differences were considered
statistically significant at p ≤ 0.05.
Results
During the study, 24 cancer patients were admitted to the intensive care unit with COVID-19 infection and
related complications. Most patients had solid organ tumors (13/ 54.16%,) with lung cancer being the
most common cancer in this group. The remainder of the patients had hematological malignancies (11/
45.84%), and chronic lymphocytic leukemia was the most common type among these patients. Most of
these cancer patients received treatment with chemotherapy (Table 1).
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Table 1
Type and treatment of carcinoma and out come
Type of Carcinoma (Ca)
Ca treatment
Outcome
Type of tumor {n
(%)}
Ca Colon
Surgery and Chemotherapy Therapy
Survived
Solid organ tumors
Ca Colon
Surgery, Radiotherapy, and
Chemotherapy Therapy
Survived
13(54.16)
Renal cell Ca
None
Survived
Brain Tumor
Surgery
Survived
Hepatocellular Ca
Chemotherapy
Survived
Hepatocellular Ca
Palliative care
Died
Lung Ca
Surgery + Chemotherapy
Died
Lung Ca
Chemotherapy + radiotherapy and
Immunotherapy
Died
Lung Ca
Chemotherapy
Survived
Ca Breast
Surgery, Radiotherapy, and
Chemotherapy Therapy
Survived
Ca esophagus
Chemotherapy
Died
Ca Stomach
None
Survived
Ca Prostate
Chemotherapy
Died
Multiple myeloma
Chemotherapy
Died
Acute promyelocytic
leukemia
None
Died
Acute promyelocytic
leukemia
None
Survived
Chronic myelocytic
leukemia
Chemotherapy
Survived
Chronic myelocytic
leukemia
Chemotherapy
Died
Chronic myelocytic
leukemia
Chemotherapy
Survived
Chronic Lymphocytic
Leukemia
Chemotherapy
Died
Chronic Lymphocytic
Leukemia
Chemotherapy
Survived
Chronic Lymphocytic
None
Survived
Page 5/16
Hematological
Malignancies
11(45.84)
Leukemia
Chronic Lymphocytic
Leukemia
Chemotherapy
Died
T-cell lymphoma
Chemo and Hormonal therapy
Died
Overall, most patients were male (20) (83.3%) and expatriate people (22/91.7%. The mean age was 53.92
years, and the most common comorbidity was hypertension (12/ 56%) (Table 2).
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Table 2
Demographic and clinical variables
Variable
Gender
Nationality
Diabetes Mellitus
Hypertension
Coronary artery disease
Chronic Kidney disease
Chronic obstructive pulmonary disease
Chronic liver disease
Acute kidney injury
Rhabdomyolysis
Secondary infections
Source of secondary infections
*MDRO infection
Number(n)
Percentage (%)
Male
20
83.3
Female
4
16.7
Qataris
2
8.3
Non-Qataris
22
91.7
No
13
54.2
Yes
11
45.8
No
12
50
Yes
12
50
No
20
83.3
Yes
4
16.7
No
23
95.8
Yes
1
4.2
No
23
95.8
Yes
1
4.2
No
22
91.7
Yes
2
8.9
No
14
58.3
Yes
10
41.7
No
17
70.8
Yes
7
29.2
No
9
37.5
Yes
15
62.5
No
9
37.5
Blood
7
29.2
Lung
7
29.2
Urine
1
4.2
No
16
66.7
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Variable
Intubation
Muscle relaxant
Non-invasive ventilation
High-flow nasal cannula
Proning
*ECMO
Methylprednisolone
Tocilizumab
Vasopressor
Convalescent plasma
ICU Mortality
Number(n)
Percentage (%)
Yes
8
33.3
No
6
25
Yes
18
75
No
8
33.3
Yes
16
66.7
No
17
70.8
Yes
7
29.2
No
20
83.3
Yes
4
16.7
No
11
45.8
Yes
13
54.2
No
23
95.8
Yes
1
4.2
No
7
29.2
Yes
17
70.8
No
15
62.5
Yes
19
37.5
No
7
29.2
Yes
17
70.8
No
18
75
Yes
6
25
No
13
54.2
Yes
11
45.8
Following COVID-19 infection, acute kidney injury occurred in 10 patients (41%) and rhabdomyolysis in 7
patients (29.2%). Secondary infections complicated the course of 15 patients (62.5%), and the most
frequent sources of secondary infection were lung and blood (29.2%) each (Table 2). Seventeen patients
(70.8%) developed sepsis and required vasopressors to support their hemodynamic status. Six patients
(25%) required convalescent plasma therapy for primary COVID-19 virus infection.
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Respiratory-wise, seven patients (29.2%) required non-invasive ventilatory support, four patients (16.7%)
were managed with high flow nasal cannula (HFNC), eighteen patients (75%) required intubation and
invasive ventilation, and 16 patients (66.7%) required muscle relaxants to facilitate their ventilation.
Thirteen patients (54.2%) required prone ventilation to improve their oxygenation (Table 2), and one
patient (4.2%) required ECMO support (Extra-corporal membrane oxygenation).
Laboratory results revealed elevated D-dimer, fibrinogen, and CPR for all patients [6.59, 5.21, 171,
respectively]. The initial SOFA score was around 4 (3.92), and the worst SORA score was 11.83. The
average number of days on mechanical ventilation was 15.83 +- 16.34, the mean ICU stay was 18.88
+-16.12 days, and the mean hospital stay was 31.33 +- 16.51 days (Table 3).
Table 3
Descriptive Statistics: Age, inflammatory markers, the
severity of the illness, and length of stay
Variables
Mean
Std. Deviation
Age(years)
53.92
18.717
D-Dimer (mcg/mL)
6.59
23.560
Fibrinogen (Grams/L)
5.21
2.132
CRP (mg/L)
171.15
108.040
Mechanical Ventilation days
15.83
16.343
Ventilator free days
7.14
4.979
Worst SOFA During ICU STAY
11.83
5.585
SOFA SCORE Admission
3.92
2.948
TOTAL HOSPITAL DAYS
31.33
16.518
TOTAL ICU DAYS
18.88
16.128
The Table 4 shows the variables' impact on the patients' mortality rate (outcome). The AKI (acute kidney
injury) was significantly associated with higher mortality in COVID-19 cancer patients (P < 0.001). Other
variables that have detrimentally affected the mortality rate in these patients were rhabdomyolysis (P <
0.04), the presence of secondary infections (P < 0.006), and sepsis (P < 0.02) (Table 4). Patients requiring
intubation, invasive ventilation, and muscle relaxants had a significantly higher death rate (P < 0.02).
Moreover, the mortality rates were higher in patients with shock requiring vasopressor (P < 0.004), prone
position (P < 0.01), and high-flow nasal cannula (P < 0.03) (Table 4).
Page 9/16
Table 4
Clinical and demographic variables and outcome
Variable
Gender
Nationality
Diabetes Mellitus
Hypertension
Coronary artery disease
Chronic Kidney disease
Chronic obstructive pulmonary disease
Chronic liver disease
Acute kidney injury
Rhabdomyolysis
Secondary infections
Source of secondary infections
Mortality
P Value
No {n (%)}
Yes {n (%)}
Male
11(84.6%)
9(81.8)
Female
2(15.4)
2(18.2)
Qataris
1(7.7)
1(9.1)
Non-Qataris
12(92.3)
10(90.9)
No
8(61.5)
5(45.5)
Yes
5(38.5)
6(54.5)
No
8(61.5)
4(36.4)
Yes
5(38.5)
7(63.6)
No
12(92.3)
8(72.7)
Yes
1(7.7)
3(27.3)
No
12(92.3)
11(100)
Yes
1(7.7)
0(0)
No
12(92.3)
11(100)
Yes
1(7.7)
0(0)
No
12(92.3)
10(90.9)
Yes
1(7.7)
1(9.1)
No
12(92.3)
2(18.2)
Yes
1(7.7)
9(81.8)
No
12(92.3)
5(45.5)
Yes
1(7.7)
6(54.5)
No
8(61.5)
1(9.1)
Yes
5(38.5)
10(90.9)
No
8(61.5)
1(9.1)
Blood
2(15.4)
5(45.5)
Lung
3(23.1)
4(36.4)
Urine
0(0)
1(9.1)
Page 10/16
0.63
0.71
0.35
0.20
0.23
0.54
0.36
0.71
< 0.001
0.01
0.006
0.02
*MDRO infection
No
10(76.9)
6(54.5)
Yes
3(23.1)
5(45.5)
No
6(46.2)
0(0)
Yes
7(53.8)
11(100)
No
7(53.8)
1(9.1)
Yes
6(46.2)
10(90.9)
No
5(38.5)
2(18.2)
Yes
8(61.5)
9(91.8)
No
13(100)
7(63.6)
Yes
0(0)
4(36.4)
No
9(69.2)
2(18.2)
Yes
4(30.8)
9(81.3)
No
7(53.8)
0(0)
Yes
6(46.2)
119100)
No
11(84.6)
7(63.6)
Yes
2(15.4)
4(36.4)
No
8(61.5)
7(63.6)
Yes
5(38.5)
4(36.4)
Hematological malignancies
No
5(38.5)
6(54.5)
Solid organ malignancies
Yes
8(61.5)
5(45.5)
Intubation
Paralysis
Methylprednisolone
High-flow nasal cannula
Prone position
Vasopressor
Convalescent plasma
Tocilizumab
0.26
0.018
0.02
0.26
0.03
0.01
0.004
0.23
0.62
0.68
The overall number of fatalities in our group of patients was 11 (45.84%). Five of these patients (20.84%)
had a solid organ tumor, whereas 6 patients (25%) had a hematological malignancy (Tables 1 and 2).
Table 5 shows the variables and their association with patients’ outcomes (mortality rate). Age was more
advanced in patients who died; however, it was not statistically significant (P0.08). The SOFA score on
admission (sequential organ failure assessment), CRP, d-dimer, and fibrinogen levels were not statistically
significant in association with higher patients’ mortality rates (Table 5). The main correlations were found
to be associated to the total ICU days, mechanical ventilation days, and SOFA scores during ICU stay as
they were significantly higher in patients who died (P 0.002, 0.002, 0.003, respectively) (Table 5).
Page 11/16
Table 5
Age, inflammatory markers, disease severity, hospital stay, and patients' outcomes
Variable
Mortality
Number
Mean Rank
Sum of Ranks
P value
Age (years)
No
13
10.15
132.00
0.08
Yes
11
15.27
168.00
No
13
12.27
159.50
Yes
11
12.77
140.50
No
13
8.62
112.00
Yes
11
17.09
188.00
No
13
11.65
151.50
Yes
11
13.50
148.50
No
13
11.00
143.00
Yes
11
14.27
157.00
No
13
11.65
151.50
Yes
11
13.50
148.50
No
13
12.54
163.00
Yes
11
12.45
137.00
No
7
4.64
32.50
Yes
11
12.59
138.50
No
13
12.42
161.50
Yes
9
10.17
91.50
No
13
8.50
110.50
Yes
11
17.23
189.50
Total hospital stays (days)
Total ICU stay (days)
SOFA Score admission
D-Dimer
Fibrinogen(g/L)
CRP(Mg/L)
Mechanical ventilation (days)
Ventilator free days
Worst SOFA
0.86
0.002
0.53
0.27
0.53
0.90
0 .002
0.42
0.003
Discussion
Oncology patients are more susceptible to COVID-19 infection and its adverse sequelae than non-cancer
patients. In those patients, COVID-19 caused by coronavirus 2 (SARS-COV2) leads to acute respiratory
failure, a fatal complication that disproportionately affects vulnerable patients with underlying medical or
surgical comorbidities [4]. In addition, cancer patients with COVID-19 infection can rapidly deteriorate and
develop serious organ dysfunction requiring intensive care admission (ICU).
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In this pandemic, ICU utilization may need triage and prioritization of patient's admission based on
patient’s outcomes. There is scarce data about COVID-19 complications and the requirement for intensive
care therapy in cancer patients, which will help in the appropriate triaging of intensive care therapy
requirements. Cancer patients requiring intensive care therapy mortality was 45%, much lower than the
mortality described by Nadkarni et al. in their metanalysis, which was 60%. Whereas another study
dictates a mortality of 56% in their population [5]. Solid organ malignancies were common in our
population. Joerger et al. also had most solid organ cancer patients requiring intensive care therapy [7]. In
other studies, solid organ malignancies are common in the patient population [4].
In comparison to solid organ malignancies, it’s reported in the literature that hematological malignancies
require more ICU admission and significantly higher mortality [8]. In our study, the hematological
malignancy patients were slightly higher in number, but there was no statistical significance. Joerger M et
al. also did not find a significant difference in the outcome of patients with both malignancies. However,
their solid organ malignancies were more than those of hematological malignancies [7].
Most of the literature about cancer patients with comorbidities and COVID-19 infection mentioned
hypertension as the most frequent comorbidity [9]. In our patient’s population also, hypertension was the
most common comorbidity. In our patient population, hypertension was the most prevalent comorbidity in
COVID-19 patients [10]. Secondary bacterial infections occurred in 62.6% of our cancer patients, including
pneumonia and bacteremia. Maki et al. also reported that secondary bacterial infection in COVID-19
cancer patients increased with the severity of COVID-19, and with severe infection, 81% of patients had
secondary bacterial infections [11]. De Costa et al. reported that 57.9% of these ICU COVID-19 patients
had secondary bacterial ventilatory-associated pneumonia, and 49.5% had MDRO bacterial infections
(multi-drug resistant organism. More cancer patients required oxygen supplementation, non-invasive and
invasive ventilation, and proning, as they had severe COVID-19 infection. Comparing the age of the cancer
patients with COVID-19 infection requiring intensive care admission, outpatients were younger, with an
average of 53 years, the mean was higher, and the severity of the disease increased from admission to
ICU. Moreover, the patient population's AKI (Acute Kidney Injury) is most probably due to rhabdomyolysis,
secondary bacterial infection, bacteremia, pneumonia, a requirement of non-invasive and invasive
ventilation, and requirement of vasopressor due to shock were significantly associated with mortality.
It's well described in the literature the requirement of oxygen supplementation and ventilation, either noninvasive or invasive ventilation, increased the risk of death in COVID-19 cancer patients [13]. However, AKI
and rhabdomyolysis are not described in the literature to increase mortality in COVID-19 cancer patients.
Secondary bacterial infection and multi-drug resistant pneumonia in general COVID-19 patients were
reported to increase mortality [12]. Still, our study confirms that COVID-19 cancer patients with secondary
bacterial infection, bacteremia, pneumonia, and vasopressor requirement due to septic shock significantly
increase the risk of death. Fortunately, MDRO (multi-drug resistance organism) infections in our cancer
patients did not show any significant increase in mortality.
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The age of our COVID-19 patients did not have a significant impact on the outcome, sepsis markers (CRP,
D-dimer, fibrinogen) were also not significantly differ for mortality with cancer, but those cancer patients
who died had significant progress of the disease (higher SOFA score), mechanical ventilation days and
more prolonged ICU stay.
Pathania et al. also described that the cancer patients requiring intensive care had more extended ICU
stays, more ventilator days, and worst outcomes [13]. Biovana et al., in their study, concluded that CRP
and D-dimer levels are useful for the severity of COVID-19 in general. Still, nothing was mentioned about
its comparison impact on patient outcomes [14].
Conclusion
In our patients, solid organ malignancies overnumbered hematological malignancies; mortality was lower
than mentioned in the literature. Secondary infection, pneumonia, bacteremia, AKI, rhabdomyolysis,
invasive, non-invasive ventilation, and shock were significant risk faction for mortality in COVID-19 cancer
patients. The patient's age and sepsis markers were raised but not significantly associated with COVID-19
cancer patients' mortality. COVID-19 cancer patients with mortality were sicker and had longer ICU stay
and ventilator days than the surviving patients.
Declarations
Statement of Ethics: This study has been approved by the IRB at the Medical Research Center in Hamad
Medical Corporation (Doha, Qatar) (MRC:01-20-607). The study has been conducted in accordance with
the ethical standards noted in the 1964 Declaration of Helsinki and its later amendments or comparable
ethical standards. IRB of Hamad Medical Corporation waived the need for informed consent due to
retrospective nature of the study.
Consent for publication
Not applicable.
Availability of data and material
All generated data is included in this published article.
Competing interests
The authors declare that they have no competing interests.
Funding Sources:
None.
Page 14/16
Author Contributions: All authors made substantial contributions to conception and design, acquisition of
data, or analysis and interpretation of data; took part in drafting the article or revising it critically for
important intellectual content; agreed to submit to the current journal; gave final approval of the version
to be published; and agree to be accountable for all aspects of the work.
Acknowledgment: Open Access funding provided by the Qatar National Library.
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