Philippine College of Physicians Research Paper

Adapted from the

Philippine Council for Health Research and Development

Department of Science and Technology
CAPSULE RESEARCH PAPER

Program / Project Title: CALL Score Validation in Predicting Risk Progression in

Patients with COVID-19 Pneumonia in a Tertiary Government

Differences in Clinical
Manifestation, Laboratory
Parameters
and Risk of Severe Disease in
Adult
Differences in Clinical
Manifestation, Laboratory
Parameters
and Risk of Severe Disease in
Adult
1. Program/Project Participants:
Program Leader: JOSE EMMANUEL I FRANCIA MD

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Co-authors/ Co-investigators:

MA. MELISSA MONICA TURAO-AGONCILLO MD

Department, Institution: Department of Internal Medicine, Victoriano Luna Medical Center,

Armed Forces of the Philippines Health Service Command

Corresponding Author’s e-mail address: jef_099999@yahoo.com

2. Research Site:
 In Victoriano Luna Medical Center, AFP Health Service Command, Brgy. Pinyahan, Quezon
City
 No external sites
3. Research Theme:  Disaster response/risk reduction
 Drug discovery or Efficacy/Safety Diagnostics accuracy
determination  Info/Communication/Technology for
 Response to drugs or procedures with Health
therapeutic equipment/biomedical devices  Ecology/Health and climate change
 Genetics/ Biomolecular adaptation
Hospital procedure/KAP survey/quality of care  Others: Disease Severity Assessment
4. Introduction/Background/Literature Search

During the last quarter of 2019, cluster of patients in Wuhan, China was found to have flu-
like diseases not attributable to any of the currently known viruses. It was observed that majority
of the affected population belong to 60- to 65-year-old group especially those who have
underlying chronic medical conditions (Centers for Disease Control and Prevention, 2020a). Due
to the then insufficient knowledge about the properties, pathogenicity, and virulence of the novel
coronavirus, clinicians that manage COVID-19 patients are faced with a great challenge with
regard to the standard of care among the infected individuals. More so, there was still no
sufficient data gathered as to the protocol regarding the aggressiveness of the treatment needed
to prevent the progression of the disease or even death.
Based on the extensive review of available local and international literature, as well as
published and unpublished studies, there were only a number of scoring systems developed to
help predict disease progression in patients with COVID-19 pneumonia. One of these is the
comorbidity, age, lymphocyte, and LDH (CALL) score which aids in predicting the risk of disease
progression based on the cumulative score from the abovementioned parameters (Ji et al., 2020).
Unfortunately, to date, there is limited validation studies that were done locally and internationally
outside the original setting where the score system was first developed.
5. Rationale/Relevance of the Study

This study hopes to add to the current number of literatures that will assess the
applicability of CALL score. With its confirmed usefulness, early prediction in disease progression
will aid in a more effective resource allocation as well as prevention of death. This study aims to
validate the CALL Score in predicting risk progression in patients with COVID-19 pneumonia at
Victoriano Luna Medical Center.
6. Conceptual Framework

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 Figure 1. Conceptual Framework of the Study

The study population will be dichotomized according to the disease progression: stable
and progressive. Outcome variables of the study includes the total CALL score, risk stratification,
and clinical outcome. Vaccination status was treated as a possible confounder in this study.

7. Objectives:
A. General Objective
This study aims to validate the CALL Score in predicting the risk progression of patients
with COVID-19 pneumonia at Victoriano Luna Medical Center.

B. Specific Objectives
1. To characterize the study population in terms of the following demographic and
clinical variables:
i. Age
ii. Sex
iii. BMI
iv. Comorbidities
v. LDH level
vi. Lymphocyte count
vii. Disease severity upon admission; and
viii. Clinical outcome
2. To determine there is a significant association between the demographic and clinical
variables and the disease progression.
3. To determine the correlation of CALL score and the disease progression.
8. Methodology
A. Research Design:
 Meta-analysis  Retrospective Prospective

Observational  Cohort  Case-control Cross-sectional  Experimental

B. Participants: COVID-19 positive patients at Victoriano Luna Medical Center

Inclusion Criteria:
COVID-19 positive patients at Victoriano Luna Medical Center confirmed by real-time reverse
transcriptase polymerase chain reaction (RT-PCR) assay by the local and the national testing
hubs from March 2020 to March 2021

Exclusion Criteria:
Patients who are aged less than 18 years and those who present with severe COVID-19
symptoms.

C. Sample Size estimate and procedure:

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Sample size calculations is made based on the following formula:
( 1− p )
n=Z 2 p
e2
Where by n = the required minimum sample size
e = margin of error
p = estimated proportion of stroke
z = standard normal deviate corresponding to 95% confidence level=1.96

The sample size was estimated based on the assumption that 63.9% of the patients would
not progress to severe COVID-19 pneumonia (Ji et al., 2020). Using the population proportion,
reliability of 95% and a maximum allowable error of 10%, a sample size of 89 was obtained which
was adjusted to 107 accounting for attrition and/or data losses.

D. Data collection process:

Purposive sampling strategy will be used to review medical charts from Victoriano Luna
Medical Center. All eligible health charts will be assigned with a unique identification number in
order to maintain anonymity. A letter of permission will be secured and submitted to the Data
Privacy Officer prior to accessing the health records of patients (See Appendix 2 of the protocol).
Victoriano Luna Medical Center was chosen as the primary site of the study primarily based on
the proximity and the availability of data. Currently, this is where the principal investigator is doing
his residency training under the Department of Internal Medicine.
Demographic profile such as age, sex, and BMI as well as laboratory results such as
lymphocyte and LDH levels and health history of the patients will be obtained from the available
health records and will be recorded through a data collection form (See Appendix 1 of the
protocol). All patients will be stratified into different risk groups based on their cumulative CALL
score points. Parameters for severe COVID-19 as described in section 4.4.3.3 of the protocol will
be checked and recorded by the researcher through chart review made available at the
Outpatient Department. All patients will be grouped based on their clinical outcome: stable or
progressive which will include mortality. All accomplished assessment forms will be placed in a
secured file case and will be limited to the perusal of the researcher.

Data analysis:
All data will be encoded using Microsoft Excel and will be analyzed using Stata ver 13.0.
Categorical data such as sex, BMI, and comorbidities will be presented as percentages while
continuous variables such as age, lymphocyte count, and LDH will be presented as median and
interquartile range. Extended Chi-square or Fisher’s Exact Test will be used to determine
significant association of the four CALL score parameters between the stable and progressive
groups. Lastly, the utility of the scoring model will be assessed using receiver operating
characteristic (ROC) curves. The area under the ROC (AUROC) and optimal cutoff values will be
determined and assessed by the sensitivity, specificity, predictive values, and likelihood ratios. All
measures will be expressed with 95% confidence interval.
A. Ethical Consideration
Review of medical records will be done for data gathering. This method imposes minimal
risk related to privacy and confidentiality of participants’ identity. Furthermore, each subject will be
assigned an initial and a code number in order to protect the privacy and anonymity of the
participants. In the course of the study, the names of the participants will never be revealed.
These files will be limited to the researcher’s access will not be released for other purposes
except for this study only. This study will be done in accordance with ICH-GCP Guidelines and
principles and will begin upon approval by IRB. The results generated from the study will remain
confidential, but these can be used for academic purposes only.

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B. Estimated Budget by Source
Month or Year 1 (in pesos)

Maintenance
Source of Fund Personal and other Equipment
Total
services operating outlay
expenses

Hospital
0 0 0 0
Department

Counterpart 0 0 0 0

Other Sources 0 0 0 0

Total 0 0 0 0

C. Outcomes and Responsibilities of Research Personnel

The study utilized two personnel for its completion. The principal investigator
is CPT JOSE EMMANUEL I FRANCIA MC, currently a fourth year Internal Medicine resident of
the AFP Health Service Command, V. Luna Medical Center. The co-author is MA. MELISSA
MONICA TURAO-AGONCILLO MD who served as research adviser.

D. Dummy Tables:

Table 1. Patient characteristics based on demography, laboratory parameters, and

health history.
Stable Progressive p value
group n (%) group n (%)
Sex
Male
Female
Age, median (IQR)
≤ 60 years
> 60 years
BMI (kg/m2), median (IQR)
Co-morbidities
Hypertension
Diabetes
Cardiovascular disease
Chronic lung disease
HIV
Lymphocyte, median (IQR)
> 1.0 x 109/L
≤ 1.0 x 109/L
LDH, median (IQR)
≤ 250 U/L
250-500 U/L
> 500 U/L

Table 2. Proportion of enrolled patients who progressed to severe COVID-19 pneumonia

within each risk group.
Stable group Progressive p value
n (%) group n (%)
Class A

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 Class B
Class C
E. Endorsing Institution: Department of Internal Medicine, Victoriano Luna Medical Center,
Armed Forces of the Philippines Health Service Command
F. List of References:

1. Bartsch S., Ferguson M., McKinnell J., O’Shea K., Wedlock P., Siegmund S., & Lee B.
(2020). The Potential Health Care Costs And Resource Use Associated With COVID-19 In
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https://doi.org/10.1377/hlthaff.2020.00426.
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(2020). Resilience, COVID-19-related stress, anxiety and depression during the pandemic in
a large population enriched for healthcare providers. Translational Psychiatry 10:291.
https://doi.org/10.1038/s41398-020-00982-4.
3. Blbas H., Aziz K., Nejad S., & Barzinjy A. (2020). Phenomenon of depression and anxiety
related to precautions for prevention among population during the outbreak of COVID-19 in
Kurdistan Region of Iraq: based on questionnaire survey. Journal of Public Health.
https://doi.org/10.1007/s10389-020-01325-9.
4. Centers for Disease Control and Prevention (2020a, August). Coronavirus Disease 2019
(COVID-19) 2020 Interim Case Definition. Coronavirus Disease 2019 (COVID-19).
https://wwwn.cdc.gov/nndss/conditions/coronavirus-disease-2019-covid-19/case-definition/
2020/08/05/
5. Centers for Disease Control and Prevention (2020b, August). COVID-19 Associated
Hospitalization Related to Underlying Medical Conditions. Coronavirus Disease 2019
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discovery/hospitalization-underlying-medical-conditions.html.
6. Centers for Disease Control and Prevention (2020c, August). COVID-19 Hospitalization and
Death by Age. Coronavirus Disease 2019 (COVID-19).
https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/
hospitalization-death-by-age.html.
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S., Madhav M., Barrett C., & Marath A. (2020). Medical Costs of Keeping the US Economy
Open During COVID-19. Retrived from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388489/.
8. Covid19 (2021, July). Covid-19 Dashboard. Laging Handa. https://covid19.gov.ph/.
9. Gao J., Huang X., Gu H., Lou L., & Xu Z (2020). Predictive criteria of severe cases in
COVID-19 patients of early stage: A retrospective observational study. J Clin Lab Anal.
2020;00:e23562. https://doi.org/10.1002/jcla.23562.
10. Jain V. & Yuan J. (2020). Predictive symptoms and comorbidities for severe COVID-19and
intensive care unit admission: a systematic review and meta-analysis. International Journal
of Public Health. https://doi.org/10.1007/s00038-020-01390-7.
11. Ji D., Zhang D., Xu J., Chen Z., Yang T., Zhao P., Chen G., Cheng G., Wang Y., Bi J., Tan
L., Lau G., & Qin E (2020). Prediction for Progression Risk in Patients With COVID- 19
Pneumonia: The CALL Score. Infectious Diseases Society of America. DOI:
10.1093/cid/ciaa414.
12. Kamran S M, Mirza Z, Moeed H, et al. (November 07, 2020) CALL Score and RAS Score as
Predictive Models for Coronavirus Disease 2019. Cureus 12(11): e11368. DOI
10.7759/cureus.11368
13. Kirchhoffer (2020). Dignity, Autonomy, and Allocation of Scarce Medical Resources During
COVID-19. Journal of Bioethical Inquiry Pty. Ltd 2020. https://doi.org/10.1007/s11673-020-
09998-3.
14. Liu J., Zhang S., Wu Z., Shang Y., Dong X., Li G., Zhang L., Chen Y., Ye X., Du H., Liu Y.,
Wang T., Huang S., Chen L., Wen Z., Qu J., & Chen D. Clinical outcomes of COVID-19 in
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https://doi.org/10.1186/s13613-020-00706-3.

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 15. Magsambol B. (2020, April 17). Getting treated with coronavirus comes with a hefty price
tag. Rappler. https://rappler.com/newsbreak/iq/getting-treated-coronavirus-price-tag.
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COVID-19 severity and in- hospital death: A meta-analysis of observational studies.
Nutrition, Metabolism & Cardiovascular Diseases (2020) 30, 1236e1248.
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28). Predictive role of clinical features in patients with coronavirus disease 2019 for severe
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7347.2020.200384.
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with increased mortality and severity of disease in COVID-19 pneumonia: A systematic
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Characteristics of Patients with Severe Pneumonia Caused by the SARS-CoV-2 in Wuhan,
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1. Appendices (as applicable)

A. Letter of Approval/Authorization to conduct study from site

B. Informed Consent Form (English and Tagalog Versions)

- N/A
C. Data Collection Form
Demographic profile
ID number: Age:
Sex: Height
Weight: BMI:
Laboratory Profile
Lactate dehydrogenase
Lymphocyte count
Comorbidities
Hypertension ☐ Yes ☐ No
Diabetes ☐ Yes ☐ No
Cardiovascular disease ☐ Yes ☐ No

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 Chronic lung disease ☐ Yes ☐ No
HIV ☐ Yes ☐ No
Others (specify)
CALL Score
Comorbidity
Age
LDH
Lymphocyte
TOTAL Class
Clinical Profile
Initial disease severity classification
Outcome (progressed or death)

D. Curriculum Vitae of Project Leader

E. Good Clinical Practice Certificate of Project Leader

SIGNATURE:

NAME: JOSE EMMANUEL I FRANCIA MD

DESIGNATION: 4th Year Internal Medicine Resident

DATE: 17 December 2021

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 Appendix 1
Data Collection Form

Participant’s initial Code

Serotype Severity
Age
Sex
BMI
Height
Weight
Epidemic area
Low risk areas
High risk areas
Comorbidities
Diabetes mellitus
Hypertension
Hyperlipidemia
Heart disease
Duration of fever at
presentation
Temperature
Systolic BP
Diastolic BP
Heart rate

Laboratory Parameters

NS1 Antigen
Anti-Dengue Antibodies
IgM
IgG
Hemoglobin
Hematocrit
Platelet Count
Total Leukocyte Count
Ast
Alt
Serum Sodium
Serum Potassium
Serum Creatinine

Clinical Manifestations

Fever
Lethargy
Bleeding Gums
Anorexia

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Nausea
Vomiting
Diarrhea
Hemorrhagic Manifestations
Bleeding Gums
Petechiae
Ecchymoses
Purpura
Bruises
Hepatomegaly
Rashes
Abdominal Pain
Headache
Eye Pain
Myalgia
Arthralgia

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