Diagnostic Value of Blood Oxygen Saturation and

C-Reactive Protein (CRP) in Predicting Lung Sequels

in COVID-19 Infected Patients Admitted to Hospital: A

12-week Cohort Study

Samaneh Abiri 1, Mina Mohammadizadeh 2, Lohrasb Taheri 1, Seyed Reza Mousavi 3, Masihallah Shakeri 1, Elahe

Rahmanian 1, Naser Hatami 2, Erfan Ghanbarzadeh 4, Zhila Rahmanian 1, Navid Kalani 1

1 Research Center for Non-communicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran

2 Student Research Committee, Jahrom University of Medical Sciences, Jahrom, Iran

3 Assistant Professor of Spine Surgery, Department of Neurosurgery, School of Medicine, Chamran Hospital, Namazi Teaching

Hospital, Shiraz University of Medical Sciences, Iran

4 Student Research Committee, Guilan University of Medical Sciences, Rasht, Guilan, Iran

 Correspondence to:

Zhila Rahmanian, Assistant Professor of Internal Medi-

cine, Research Center for Non-communicable Diseases,

Jahrom University of Medical Sciences, Jahrom, Iran.

Telephone Number: 0098+9177916175

Email Address: dr.j.rahmanian@gmail.com

Received 2022-09-15

Revised 2022-11-18

Accepted 2022-11-29

Abstract

Background: Evidence of COVID-19 respiratory sequels is restricted and predisposing factors

are not well studied more than two years passing pandemic. This study followed COVID-19

patients 12 weeks after discharge from hospital for respiratory sequels. Materials and Meth-

ods: This was a prospective study on discharged COVID-19 patients in 2021, in Jahrom, Iran.

Exposure was COVID-19 clinical features at hospitalization, including symptoms and physi-

cal examination and laboratory ndings, and primary endpoint was 12-week lung sequel, be-

ing evaluated by a chest CT scan. Demographics and previous medical history were consid-

ered covariates. SPO2 and CRP 6-week changes were followed as an early tool for prediction

of 12-week lung sequel. Results: Totally, 383 participants (17 had sequels) with mean age

of 57.43±18.03 years old (50.13% male) completed 12-week study follow-ups. Ninety-one

(23.8%) subjects had an ICU admission history. SPO2% in 6th week was statistically signi-

cantly associated with a higher rate of 12-week sequelae (p<0.001). Also, patients having CT

scan scores between 40% to 50% (p=0.012) and higher than 50% (p=0.040) had higher chance

of experiencing lung sequelae than patients with CT scan score of below 40%, as well as having

ICU admission history and lower SPO2% at 6th week of discharge. There was a statistically

signicant increasing trend of SPO2% (P<0.001) and a statistically signicant decreasing trend

of CRP levels (P<0.001), overall. SPO2% increase after 6 weeks was lower in participants with

lung sequels than fully improved ones (P=0.002) and as well as total 12-week change in SPO2%

(P=0.001). CRP changes in none of evaluated periods were dierent among study groups

(P>0.05). Conclusion: Our results were in favor of closely following SPO2 levels after patient

discharge, while CRP assessment seems not helpful based on our results [GMJ.2023;12:e2695]

DOI:10.31661/gmj.v12i.2695

Keywords: Lung; Respiratory; COVID-19; Oxygen

GMJ.2023;12:e2695

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This is an open-access article distributed

under the terms of the Creative Commons

Attribution 4.0 International License

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Abiri S, et al. Oxygen Saturation and CRP and COVID-19 Lung Sequels

2GMJ.2023;12:e2695

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Introduction

Survivors of the previous coronaviruses of

SARS-CoV and MERS-CoV are reported

to experience persistent physiological defects

and abnormal radiology ndings associated

with pulmonary brosis[1, 2]. Long radiolog-

ical sequalaes of COVID-19 are also investi-

gated in research [3].

Months after passing the disease course in

hospitals, survivors might experience unre-

stored radiological ndings as well as mosaic

hypoattenuation [3], ground-glass opacities,

Interlobular septal thickening, and reticula-

tion [4].

Longitudinal studies of COVID-19 sequalaes

have focused on dierent physical and func-

tional consequences; while these studies are

restricted to not having the baseline data of

more advanced tests in follow-ups like pul-

monary function tests and functional exercise

capacity [5] and small number of participants.

Based on a meta-analysis performed by Hunt-

ley et al. suggested abnormal chest CT scan

ndings in both severe and mild cases [6].

Risk factors of pulmonary decreased function

and lung radiological pathology in the largest

cohort of COVID-19 survivors were stratied

based on the need for oxygen supplementa-

tion during the hospitalization, reecting the

severity of the disease [5].

Other potential risk factors of having remained

or progressive lung damage is less evaluated

and there is no available hallmark or biomark-

er predicting lung sequalaes .

Salem et al.’s three month cohort for fol-

low up of some biomarkers as well as ESR,

platlet count, and D-dimer, was unable to

nd any assosiation with lung sequales [7].

In this study, we aimed to evaluate the base-

line clinical factors of COVID-19 hospital-

ization course with 12 week lung squeal.

Materials and Methods

This was a prospective cohort study per-

formed on COVID-19 patients who were hos-

pitalized in wards of the Peymanieh Hospital

in Jahrom, South of Iran, in 2021. The proto-

col of this work was authorized with code of

“IR.JUMS.REC.1400.036”, by the ethics in

research committee of the Jahrom University

of Medical Sciences. All participants signed

the informed consent form.

Study population

Sampling was conducted based on the sim-

ple-available method from patients being ad-

mitted to oor wards. Based on a study with

3.13% radiological lung sequel [8], with an

alpha of 0.05 and power of 80%, anticipating

6% lung sequel in our samples, 357 partici-

pants were needed as sample size, based on

the formula for the prospective study [9].

Inclusion criteria were being hospitalized

for COVID-19 and getting discharged after

recovery. Also satisfaction for attendance in

recalls at 6 and 12 weeks after discharge in

the recruitment center was required for re-

cruitment. COVID-19 was conrmed by nasal

swap using polymerase chain reaction (PCR)

test.

As we have used High-resolution comput-

ed tomography (HRCT) scan at 12 weeks of

follow-up, only patients with baseline CT

scan records were recruited. Exclusion crite-

ria were death and not attending follow-ups.

Patients who had a new respiratory disease,

infectious disease, or acute chest syndrome

during the 12 weeks of study were also ex-

cluded.

To exclude long COVID-19 or reinfection,

patients were followed by a nasal swab PCR

test performed at 6th and 12th week of dis-

charge, and positive cases were excluded.

We recruited 458 patients. Finally, 383 sub-

jects completed both 6 and 12-week fol-

low-ups with 16.37% loss to follow-up rate.

Study outcomes

Exposure was COVID-19 clinical features

at hospitalization. These features includ-

ed symptomatology, physical examinations

(PHEs), laboratory data, past medical history

(PMHx), and demographic data.

Symptoms were recorded based on the pa-

tient reported signs. PHEs were performed

by a general practitioner and blood oxygen

saturation (SPO2%) was measured at admis-

sion time. It was measured by the same Pulse

Oximeter device for all patients (BPL Medi-

cal Technologies, India). Heart echocardiog-

raphy was conducted if indicated by a cardi-

ologist and cardiac ejection fraction rate was

Oxygen Saturation and CRP and COVID-19 Lung Sequels Abiri S, et al.

GMJ.2023;12:e2695

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recorded. Laboratory data on CRP levels were

recorded in rst blood samples taken at ad-

mission. A baseline HRCT was conducted if

indicated by the general practitioner’s request.

A semi-quantitative CT severity scoring [10]

was applied based on the radiologist’s report.

SPO2 measurement

Patients were recommended to give rest their

bodies for at least 10 minutes before measur-

ing their blood oxygen level. Then, they had

to sit up straight, relax, and keep their hands

close to the level of heart. the Pulse Oximeter

was placed on the tip of index nger, direct-

ly on the skin on the index nger of the right

hand above the nails and patient had to not

move at all while measuring. 3 such measure-

ments were performed and highest one was

recorded.

Outcome

12-week lung sequalae was the primary out-

come of this study. A chest CT scan was con-

ducted 12 weeks after discharge and reported

by the radiologist for any lung abnormality.

CRP levels were evaluated at 6 week fol-

low-up and at 12th week of discharge along

with the SPO2% measurement.

Statistical analysis

Description of study variables was expressed

by frequency (relative frequency%) for di-

chotomous variables and mean±SD for con-

tinuous ones. We stratied data based on the

quartiles of the CT scan score [Q1: 25th quan-

tile. Q3: 75th quantile] and having or not hav-

ing lung sequalae in 12th week.

Univariable statistical analyses were per-

formed comparing study variables within the

quartiles of the CT scan score or presence of

lung sequalae at 12 weeks by independent

T-test and Mann-Whitney, ANOVA and Kru-

skal–Wallis for continuous variables and Chi-

square or sher exact test for binary data.

Repeated measures analysis was conducted

to compare data of time-varying variables in

3-time endpoints of T0, or initial referral to

hospital, T6 at 6 weeks after discharge from

the hospital, and T12 at 12 weeks after dis-

charge.

Multivariate analyses were conducted by

assuming lung sequelae at 12th week as the

primary outcome using the Cox regression.

Variables that had a P value of around 0.2

in univariable comparison of study groups

(based on the lung sequalae) were included in

multivariate analyses.

A Forest plot of Cox regression was used to

visualize the Hazzard ratio (HR) for each

comparison. Changes in SPO2 and CRP were

calculated and dened as new variables for

dierent periods and were compared by inde-

pendent T-test between the groups. All statis-

tical analyses were performed by IBM SPSS

Statistics for Windows, version 21 (IBM

Corp., Armonk, N.Y., USA). Data were visu-

alized using GraphPad Prism for Windows,

version 8.4 (GraphPad Inc., San Diego, Cal-

ifornia, USA).

Results

In this study, 383 participants were includ-

ed with mean age of 57.43±18.03 years old.

There were 192(50.13%) male subjects.

39.16% of participants had previous cardiac

diseases as the most prevalent PMHx; while

35.51% were known as previously healthy.

Dyspnea and cough were most common

symptoms (Table-1).Univariable analysis re-

vealed that all ICU admissions were counted

in patients with CT scan score in 4th quartile,

showing a statistically signicant dierence

(P<0.001).

Also, patients having 4th quartile CT scan

score had the least SPO2% at arrival, com-

pared to other quartiles (P<0.05); while hav-

ing the highest CRP levels compared to lower

quartiles of CT scan score (P<0.05).

There were 366 subjects with no remaining

problems in lung and 17 subjects were expe-

riencing lung sequels. None of the compared

variables were dierent in comparison of the

patients experiencing lung sequalae versus

completely improved ones, except the ICU

admission rate that was higher in patients

with 12-week sequalae compared to subjects

with no lung sequel (52.94% versus 22.4%;

P=0.0007), as shown in table 1.

There was a statistically signicant increasing

trend of SPO2% (P<0.001) overall and a sta-

tistically signicant decreasing trend of CRP

levels (P<0.001). The type of sequalaes was

Reticular in 4 subjects, Septal in 4, Cystic in

4GMJ.2023;12:e2695

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Abiri S, et al. Oxygen Saturation and CRP and COVID-19 Lung Sequels

6, and brosis in 3 subjects.

Multivariable analysis considering the 12-

week sequalae as the outcome was performed

based on the Cox regression. Figure-1 is

showing the HR of each variable for 12-week

sequalae. Lower SPO2% in 6th week was

statistically signicantly associated with a

higher rate of 12-week sequalae (HR=0.753

[CI95%, 0.684 to 0.828], P<0.001) versus

the baseline and 12th week SPO2% (P>0.05).

CRP levels in none of the evaluated timelines

were predictive of lung sequels (P>0.05).

Also, patients having CT scan scores in quar-

tile 2 (HR=0.110 [CI95%, 0.020 to 0.618],

P=0.012) and 4 (HR= 0.0.102 [CI95%, 0.11

to 0.902], P=0.040) had a higher chance of

experiencing lung sequalae than quartile 1, as

shown in Figure-1.

Having ICU admission history was associated

with an increased chance of experiencing lung

sequalae (HR=0.158 [CI95%, 0.429 to 0.058],

P<0.001).

Based on Figure-2, the amount of SPO2%

increase after 6 weeks was lower in partici-

pants with lung sequels than fully improved

ones (P=0.002) and as well as the total 12-

week change in the SPO2% (P=0.001); while

between the 6th and 12th week after disease,

SPO2% does not change dierently among

Figure 1. Forest plot of Cox regression for 12th week lung sequelae

NE: not estimated; Q: quartile; PMHx: past medical history; PHE: physical examination.

The plot was visualized by GraphPad Prism 8.

GMJ.2023;12:e2695

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Oxygen Saturation and CRP and COVID-19 Lung Sequels Abiri S, et al.

study groups (P=0.783). CRP changes in none

of evaluated periods were dierent among

study groups (P>0.05).

Discussion

Our study was a relatively large sampled-sized

cohort of COVID-19 survivors for a Medi-

um-term follow-up period. We found critical

COVID-19 patients to be at risk of higher

chance of remaining lung radiologic patholo-

gy than mild and moderate patients after about

3 months; while none of clinical factors relat-

ed to pre-existing medical conditions or man-

ifestations at arrival for hospitalization were

related. This nding is logically conrmed by

many research papers [7].

But the most important nding of this study

is the incidence of lung sequalaes in non-

ICU admitted patients or mild and moderate

COVID-19 patients among 17 patients with

lung sequalaes in our study, 8 had not expe-

rienced a complicated course of COVID-19.

Even patients having baseline lung involve-

ment of lower 40% were also at risk of expe-

riencing lung sequalaes .

This might bring a clinical challenge in pre-

dicting and preventing lung sequalaes in

COVID-19 patients.

Available tools being used for long-term re-

spiratory follow-up of COVID-19 patients

are pulmonary function tests, chest CT scans,

and biomarkers [11]; but none are evaluated

as monitoring tools. To this aim, after validat-

Baseline to 6th week 6th week to 12th week total

Changes in SPO2 %

Sequeled

Improved

✱

Baseline to 6th week 6th week to 12th week total

-150

-100

-50

Changes in CRP levels

Sequeled

Improved

Figure 2. changes in SPO2% and CRP levels in di󰀨erent timelines of (i) baseline to 6th week; (ii) 6th to 12th

week; (iii) total, baseline to 12th week; ns: not signicant; *: statistical di󰀨erence.

6GMJ.2023;12:e2695

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Abiri S, et al. Oxygen Saturation and CRP and COVID-19 Lung Sequels

As COVID-19 pandemic is getting less in-

tense with the help of broad vaccinations

worldwide, cases have tended to manifest

with less severity and less need for hospital-

ization [19, 20], management and follow-up

of outpatient COVID-19 have earned more

respect in 2022, and health systems are trying

to get changed to pre-COVID-19 era [21] for

utilization of the medical resources as well as

the application of the HRCTs for non-COVID

patients.

So having available, low-cost, and accurate

tools for monitoring COVID-19 outpatients

to prevent lung damage is important and we

propose following the O2 saturation before

conducting early CT scans.

Strengths and Limitations of study

This study, having a good sample size, was

restricted to some methodological and re-

source shortage issues. We were just able to

radiologically follow the respiratory function

of the participants and no pulmonary func-

tion tests were available. Our data might have

been aected by the eect of the independent

radiologists reviewing the HRCT results. Ra-

diologists were not blinded to the primary CT

scan record of the patients which might be a

source of bias.

Conclusion

The prevalence of lung sequalaes in patients

who were not admitted to the intensive care

unit is one of the study’s most signicant

ndings.

Even patients whose baseline lung

involvement is less than 40% are susceptible

to lung sequalaes.The clinical problem of

anticipating and preventing lung sequalaes

in COVID-19 patients may result from this.

We discovered that it is possible to anticipate

lung sequalaes using SPO2 uctuations that

are statistically distinct among participants

with varying degrees of lung involvement.

In almost all patients in our study, CRP levels

fell statistically signicantly throughout the

course of the 12 weeks; however, there was

no statistically signicant dierence in CRP

levels between individuals with long-term

respiratory sequalaes and the other patients.

ing adjusted time-varying potential predictors

of lung squeal, we evaluated the amount of

change in predictors to forecast the incidence

of parenchymal lung injury.

The clinical characteristics of patients evalu-

ated in this study are similar to previous re-

ports of COVID-19 patients in Jahrom city

[12] and our most evaluated patients were se-

lected within the infected population of city

during the 5th wave of disease in the city [13].

In this way, we found that SPO2 changes that

are statistically dierent among the subjects

with dierent severity of lung involvement

can be utilized to predict lung sequalaes.

SPO2 is also being used as a non-invasive

prognostic marker for critically ill patients of

COVID-19 [14].

In our study, it was revealed that the amount

of improvement of the SPO2 at 6 weeks after

discharge can be lower in participants with

lung sequels.

Other reports have also suggested that oxygen

saturation level can be utilized for follow-up

of both severe and mild/moderate COVID-19

cases along with a walk meter test [15]; while

as we had not any baseline physical evalu-

ation of the walk meter, we did not include

these factors.

We also found that age, need for ICU ad-

mission, and symptoms of dyspnea at arrival

could aect the SPO2 trend of change during

the time. But, the overall decrease of satu-

ration of oxygen after 6 weeks of discharge

compared with the baseline admission oxygen

saturation is an indication for further investi-

gations, based on our results.

Our study showed a statistically signicant

decrease in CRP levels during the 12 weeks

in almost all patients; while CRP levels were

not statistically dierent between the patients

with a long-term respiratory squeal and oth-

ers, research suggests that its raise is associ-

ated with the severity of COVID-19 during

the hospitalization [16] and in contrast to our

study, some report persistent high CRP levels

after 6 weeks of discharge [17].

Another study suggests that physicians should

not be awaiting early normalization of labora-

tory and clinical ndings of COVID-19 soon

after discharge [18], but no denitive change

range is proposed for none of the factors in

literature.

GMJ.2023;12:e2695

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Oxygen Saturation and CRP and COVID-19 Lung Sequels Abiri S, et al.

Acknowledgments

We would like to thank the Clinical Research

Development Unit of Peymaniyeh Educational

and Research and Therapeutic Center of

Jahrom University of Medical Sciences for

providing facilities for this work.

Conflict of Interest

The authors declare that there are no conflicts

of interest.

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