Pineda, Immah Marie R.

Batch 2024
APPRAISING AN ARTICLE ON PROGNOSIS CLINICAL SCENARIO

I. APPRAISING DIRECTNESS

Does the study provide a direct enough answer to your clinical question in terms of the
type of patients (P), exposure/ intervention (E), and outcome O)?

Yes, the patients in the study are confirmed COVID-19 patients with characteristics
comparable to the patient in the case. Almost half of the participants were males. The
mean age of the participants is 47 years old which is close to the patient’s age (57
years old) and the presence of comorbidities is similar to more than 30% of the
participants. The study used a scoring model called AACC which predicts the risk of
progression to severe COVID-189 disease based on age, presence of comorbidities,
and levels of albumin and CRP. These factors were the ones provided in the case to
answer the problem regarding the patient’s progression.

Clinical Scenario Research Article

P 57 year old, male; with comorbidities
(hypertension), smoking; with confirmed
COVID-19 and has symptoms
419 patients with confirmed COVID-19;
mean age was 47.1 years (21% were
older than 60); almost half were males;
More than 30% had at least one
underlying comorbidity

E Has laboratory values of: LDH = 242 AACC scoring model in which the
u/L, CRP = 18 mg/L, albumin = 65 g/L scoring is based on the age, albumin,
CRP, and presence of comorbidities

O Risk of deteriorating from COVID-19 Risk of progression to severe COVID-

19 disease

II. APPRAISING VALIDITY

1. Were all important prognostic factors considered?

Yes, the study divided the subjects between stable and severe groups in which
different relevant clinical characteristics were compared and were found to be
significantly different between the two groups such as age, comorbidity, lymphocyte
count, albumin (ALB), D-dimer, C reactive protein (CRP), and lactate dehydrogenase
(LDH) levels. These factors underwent Cox regression analysis which demonstrated
that among the following above, comorbidity, ALB level, CRP level, and age 60 years
showed independent risk factors for severe COVID-19 in these patients.

2. Were unbiased criteria used to detect the outcome in all patients?

Yes, the criteria used to detect the outcome were unbiased since the data were
collected retrospectively from patients’ medical records and attending doctors which
include clinical baseline data, laboratory parameters, length of stay, and laboratory
results from the tests the patients underwent upon admission.
 Pineda, Immah Marie R.
Batch 2024

3. Was the follow-up rate adequate?

The data collection occurred upon admission which took place from January 22 to
March 30, 2020, and clinical outcomes were followed up until April 30, 2020. However,
it was not stated in the article whether or not there are dropouts and what is the
dropout and follow-up rate. But it can be presumed in the discussion part of the article
that there were no dropout rates during the study since the initial 419 participants were
given a score using the AACC model at the conclusion of the study, with 254 (60.6%)
scored 0–1 point and were considered low risk, and 134 (32.0%) scored 2–3 points
and were considered intermediate risk, and 31 (7.4%) scored 4–5 points and were
considered high risk.

4. If clinical prediction rules are being tested, was a separate validation study done?

No, according to the discussion part of the study, it was stated that one of the
limitations and recommendations of the study was “a validation group should be
included to further validate the scoring model” (Discussion, Page 8). Only a derivation
cohort was done in which OPLS-DA was used to evaluate the influence of parameters
on the severity of COVID-19 which determined the top five parameters that influenced
the severity which are CRP, ALB, age 60 years, comorbidity, and LDH. Afterwhich,
they developed a predictive nomogram that determined the predictive accuracy for the
progression of COVID-19. The C-index was 0.86, which indicated good accuracy.

III. APPRAISING RESULTS

1. How likely are the outcomes over time?

The individual hazard ratios were already provided in the article upon performing cox
regression analysis. For the presence of comorbidities, the hazard ratio was 3.17 (95%
CI 1.96–5.11), which indicates that this is associated with an increased risk of having
severe COVID-19. This is also illustrated in the Kaplan Meier curve found in Figure 2B
which shows that, at Day 7, the blue line is at 55% progression-free rate, while the
yellow line is at 88% progression-free rate, which indicates that over time, there is a
better progression-free rate for those without comorbidity.

For the ALB level equal to or greater than 40 g/dL, the hazard ratio was 3.67 (95% CI
 Pineda, Immah Marie R.
Batch 2024

1.91–7.02) and is actually the parameter with the highest HR, indicating that this factor
is associated with increased risk of having severe COVID-19. This is also illustrated in
the Kaplan Meier curve found in Figure 2F which shows that, at Day 7, the blue line is
at 59% progression-free rate, while the yellow line is at 94% progression-free rate,
which indicates that over time, there is a better progression-free rate for those with
ALB levels below 40 g/dL.

For the CRP level equal to or greater than 10 mg/L, the hazard ratio was 3.16 (95% CI
1.68–5.96) which indicates that this factor is also associated with an increased risk of
having severe COVID-19. This is also illustrated in the Kaplan Meier curve found in
Figure 2G which shows that, at Day 7, the blue line is at 56% progression-free rate,
while the yellow line is at 95% progression-free rate, which indicates that over time,
there is a better progression-free rate for those with CRP levels below 10 mg/L.

Lastly, for ages equal to or greater than 60 years old, the hazard ratio was 2.31
(95%CI 1.43–3.73) which indicates that this factor is associated with an increased risk
of having severe COVID-19. This is also illustrated in the Kaplan Meier curve found in
Figure 2C which shows that, at Day 7, the blue line is at 42% progression-free rate,
while the yellow line is at 86% progression-free rate, which indicates that over time,
there is a better progression-free rate for those with age below 60 years old.
 Pineda, Immah Marie R.
Batch 2024

2. How precise are the estimates of likelihood?

The given hazard ratios (HR) in the article were at 95% CI with HR of Age 60 and
above is within 1.43 to 3.73, having the difference of 2.3 indicating a narrow and
significant CI since it does not cross the null value (HR = 1). It also has the narrowest
CI in the study, making it the parameter with the greatest precision, as seen also in the
Figure 1 below. The HR of presence of comorbidities is within 1.96 to 5.11, having a
difference of 3.5 indicating a narrow and significant CI since it does not cross the null
value. However, it is relatively wider than the narrowest CI (Age 60 and above),
therefore less precise. The HR of CRP levels equal to or above 10 mg/L is within 1.68
to 5.96, with a difference of 4.28, which is also wider than the narrowest CI (Age of 60
and beyond), but still significant since it does not cross the null value. Lastly, the HR of
ALB levels equal to or above 40 g/dL is within 1.91 to 7.02, having the highest
difference of 5.11, indicating the widest CI and with the least precision compared to
the parameter with the narrowest CI (Age of 60 and beyond), but still significant since
it does not cross the null value.

Figure 1. Hazard ratios and confidence intervals

IV. ASSESSING APPLICABILITY

1. Are there biological issues that may affect applicability? (Consider the influence of sex,
co-morbidity, race, age, and pathology)

The gender of the participants was equally distributed in the study, however, the age of
the patient is relatively younger than the ones that the study predicted to have severe
 Pineda, Immah Marie R.
Batch 2024

covid which is 60 years old and above. At the same time, the patient in the case is a
Filipino which may not be represented by the study’s population since all of the
participants are Chinese. It was also written in the limitations of the study found in the
discussion part of the article that the “results have a limited sample size and it does not
necessarily represent the overall results of patients in China or even in the world.”
(Discussion, Page 8). Lastly, the patient’s comorbidity, which is hypertension, may
affect his outcome. As written in the discussion, “It is notable that patients with
comorbidities, especially diabetes and cardiovascular diseases, were prone to severe
COVID-19” (Discussion, Page 7).

2. Are there socio-economic issues affecting applicability?

Access to hospitals that can cater to COVID cases is limited nowadays since the
hospitals are in full capacity. There is also a limited availability of medications used to
manage symptoms of patients with COVID which can be detrimental to the patient’s
prognosis. However, since the patient was already taken to the hospital, he will have a
lesser risk to deteriorate since he can be monitored already and appropriate
management to his symptoms will be given (assuming there is adequate supply of
medications and ventilatory aids), compared to those who were not admitted to the
hospitals.

V. INDIVIDUALIZING THE RESULTS

What is the estimate of prognosis in your patient?

Based on the scoring model developed in this study called the COVID-19-American
Association for Clinical Chemistry (AACC) (age 60 years, ALB, comorbidity, and CRP),
with a score ranging from 0 to 5 points, the patient belonged to Class C of confirmed
COVID-19 patients since he is <60 years old (0 point), has an albumin level of 65 g/L (2
points), with comorbidities (1 point) and a CRP level of 18 mg/L (1 point) having a total
score/points of 4/5 indicating ‘High risk of severe COVID’ with a risk of more than
50%. However, I would still encourage the family of the patient to keep their hopes up
since the patient is already admitted in the hospital which means that appropriate
monitoring and management will be done to him and the probability of regaining health
from COVID relatively increases compared to those who are not.