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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 19  |  Issue : 2  |  Page : 99-102

Association between C-Reactive protein at time of presentation and severity of COVID-19 pneumonitis and can C-Reactive protein improve referral system from periphery?


Department of Medicine, Government Medical College, Surat, Gujarat, India

Date of Submission03-Nov-2021
Date of Decision25-Jan-2022
Date of Acceptance10-Feb-2022
Date of Web Publication29-Apr-2022

Correspondence Address:
Vitan Kautukkumar Patel
Department of Medicine, Government Medical College, Surat - 395 001, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/am.am_126_21

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  Abstract 


Introduction: The world has been under one vicious COVID-19 wave after the other for nearly 2 years, and the battle is still on. We know that the majority of serious infections have significant high-resolution computed tomography (HRCT) changes; a predictor for them would be a vital tool in this battle! Aims and Objectives: The study aimed to assess the correlation between C-reactive protein (CRP) at the time of presentation and HRCT score in patients with severe COVID-19 infection. Methods: In this prospective, single-center study of 121 patients with severe COVID-19 infection in a tertiary COVID-19 care center. Patients were assessed for the relationship between CRP levels and chest radiography in COVID-19 patients. Results: In patients who survived in severe COVID-19 infection, CRP on admission had a significant correlation with HRCT score with P = 0.019, and in patients who did not survive, CRP on admission had a significant correlation with HRCT score with P = 0.005. CRP at day 5 was also significantly correlated to HRCT score with P = 0.035 in survivors and P = 0.001 in patients who did not survive. Conclusion: In centers where HRCT chest is not available or financial resources are a major concern, we suggest early CRP, repeated after 3–5 days, could be a very useful prognostic factor for significant lung involvement during the course of illness. This, in turn, could be a very useful tool in determining a need for admission, referral to higher centers, or more intensive therapy early on.

Keywords: COVID-19, C-reactive protein, high-resolution computed tomography, predictor


How to cite this article:
Solu MG, Patel VK, Ramawat SS, Yadav CR, Kendole NC, Thakkar MK, Shah RN, Bhanvadia PD. Association between C-Reactive protein at time of presentation and severity of COVID-19 pneumonitis and can C-Reactive protein improve referral system from periphery?. Apollo Med 2022;19:99-102

How to cite this URL:
Solu MG, Patel VK, Ramawat SS, Yadav CR, Kendole NC, Thakkar MK, Shah RN, Bhanvadia PD. Association between C-Reactive protein at time of presentation and severity of COVID-19 pneumonitis and can C-Reactive protein improve referral system from periphery?. Apollo Med [serial online] 2022 [cited 2022 Jul 1];19:99-102. Available from: https://www.apollomedicine.org/text.asp?2022/19/2/99/344426


  Introduction Top


COVID-19 infection first appeared in Wuhan in late 2019 and was declared a pandemic on the date of March 11, 2020.[1] Since then, most of the world has suffered two or three massive and devastating waves of COVID-19 to date, with more than 246 million cases and 4.99 million confirmed deaths by November 1, 2021.[2]

High-resolution computed tomography (HRCT) chest has been a vital test for identifying severe cases of COVID-19 and prognosis.[3],[4],[5] However, it is not available everywhere, especially in rural regions. High cost is another hindrance in India and other developing nations. Plus, by the time significant changes develop on HRCT, patients may be out of viremic phase, and antivirals or steroids might have limited value.

Studies so far have already shown us that C-reactive protein (CRP) rises when COVID-19 cases worsen.[6] CRP is also easily available, even in rural and cheap. If CRP at the time of presentation could correlate with later HRCT changes, the development of severe disease that could be a very valuable tool in detecting potential severe COVID-19 infection early on.

Objective

Our objective is to assess the correlation between C-reactive protein (CRP) at the time of presentation and HRCT score in patients with severe COVID-19 infection.


  Methods Top


Study design

Our study is an observational cross-sectional study aimed at assessing the correlation between CRP levels at presentation in COVID-19 patients and the development of HRCT chest changes.

Setting

Our study was performed in a tertiary care hospital, which has served as a government COVID-19 management center for the entire district, with a large number of patients being treated for severe infections in intensive care unit (ICU). It is also important to note that though our hospital is generally a referral center, during the first wave and early part of the second wave, we were the primary center, and patients came directly once they developed symptoms as it was the center with most resources in the city and other options were very limited and usually were full or very costly.

Participants

For our study, a total of 121 patients were included in the study from June 2020 to January 2021, of which 77 were male and 44 were female. Patients were selected by random purposive sampling in the ICUs. Patients were followed till discharge or death. Of 121, 54 patients survived, while 67 patients passed away.

Inclusion criteria

All patients admitted in our COVID-19 ICUs or semi-critical units, with

  1. A positive COVID-19 reverse transcription–polymerase chain reaction (RT-PCR) test and
  2. Required NRBM/noninvasive or invasive ventilation and
  3. Gave written informed consent
  4. Patient having done HRCT chest.


Exclusion criteria

  1. Pregnant women
  2. Patients having lung malignancies or metastasis.


Variables

CRP, sometimes also called pentraxin 1, is a nonglycosylated protein in the pentraxin family. It is an acute-phase reactant formed by the liver and released into the blood within a few hours after tissue injury, an infection, or other cause of inflammation. A high level of CRP in the blood generally means that there may be an inflammatory process ongoing in the patient.[7]

The other important variable is HRCT chest findings. With severe infection, patients tend to develop significant changes in lung parenchyma in HRCT. Most of the patients with severe infections have lung parenchymal ground-glass opacities or crazy-paving pattern or consolidation, which is usually bilateral and peripheral, more likely than not in middle or lower parts of lungs.[8]

Our study was aimed at analyzing the correlation between CRP levels at the time of presentation and HRCT changes that developed in patients with severe disease. All the patients were treated with standard guidelines with steroids and antiviral agents, as well as anticoagulants and antibiotics whenever indicated.

Data sources/management

At the time of admission, CRP was done and repeated at day 5 (RT-PCR done at the tie of admission as well. Our team of clinicians collected data regarding exposure history, clinical symptoms, complications, computed tomography (CT) chest findings, and outcomes. CT scans were done on day 5 usually or later. We compared the CRP at the time of presentation with HRCT changes that would develop to evaluate the value of CRP in predicting changes that would develop later. We also did a similar analysis with CRP done on day 5 to see if CRP levels then corresponded with HRCT changes and whether changes in CRP levels corresponded with final outcomes in some way.

Bias

As patients were selected in purposive sampling from ICU setup with a severe infection, there is a possibility of selection bias in the study.

Study size

For our study, we tried to get the maximum number of patients possible from June 2020 to January 2021, which met our inclusion criteria and gave consent to join the study and had HRCT chest scans. We aimed at least 100 patients and in the end, recruited 121 patients.

Quantitative variables

In this study, we correlated CRP levels at the time of presentation with HRCT changes developed in our patients. We also checked the correlation with CRP levels at day 5 with HRCT changes. We divided our patients into two groups: one that survived COVID-19 and one that did not because that itself is the grade of severity of the disease, and we wanted to gather additional data if CRP level at the beginning or at day 5 could give us an inkling at risk of mortality.

Statistical methods

Reports were evaluated using HRCT total severity score,[9] each score is scored as 0 (0%), 1 (1%–25%), 2 (26%–50%), 3 (51%–75%), and 4 (76%–100%). Scores of all five lobes were averaged out. During the study, both of the CRP reports were correlated with HRCT chest findings that patients developed using HRCT total severity score with Kruskal–Wallis test[10] (one-way ANOVA on ranks) and Spearman correlation[11] to see the association of CRP at the time of presentation as well as at day 5 with HRCT chest findings.


  Results Top


Participants

We followed our 127 patients till their final outcome [Table 1], i.e., discharge or death, and analyzed the association between CRP and severity of lung involvement in chest HRCT scans.
Table 1: Kruskal-Wallis test analysis for survivors

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Descriptive data

At the time of admission, in our subgroups who survived, in the end, had a mean age of 52.33 with standard deviation (SD) of 14.14. At presentation, mean pulse was 79.11 with SD of 11.92, mean systolic blood pressure of 126.81 with maximum of 140 and minimum of 102, and mean SpO2 was 97.22 with maximum of 99 and minimum of 92 at the time of presentation. Our subgroups who did not survive in the end had a mean age of 58.49 with SD of 13.24. At presentation, mean pulse was 84.44 with SD of 14.66, mean systolic blood pressure of 116.88 with maximum of 140 and minimum of 70, and mean SpO2 was 96.22 with maximum of 99 and minimum of 88 at the time of presentation.

Outcome data

Of 54 survivors, 21 were females, while 33 were males. Of 77 patients who did not survive, 23 were females, while 44 were male. We analyzed their data to see the correlation of their CRP at the time of admission with changes that patients developed in HRCT chest and repeated the same with CRP done on day 5.

Main results

Among the survivors, the correlation of CRP levels at the time of admission with changes in HRCT chest was significant, with P = 0.019, while correlation CRP levels at day 5 of admission with changes in HRCT chest was still significant, with P = 0.035 [Table 1]. Among the patients who did not survive, the correlation of CRP levels at the time of admission with changes in HRCT chest was highly significant, with P = 0.003. While correlation CRP levels at day 5 of admission with changes in HRCT chest was still highly significant, with P = 0.001 [Table 2].
Table 2: Kruskal-Wallis test analysis for nonsurvivors

Click here to view


We also calculated Spearman's rank correlation coefficient for both survivors and nonsurvivors on day 1 and day 5, which all showed a significant correlation between CRP and HRCT chest changes [Table 3] and [Table 4].
Table 3: Spearman's rank correlation coefficient for survivors

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Table 4: Spearman's rank correlation coefficient for nonsurvivors

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  Discussion Top


Previous studies have shown that HRCT scores can be a very useful prognostic factor for mortality in COVID-19 infections.[12],[13] HRCT involvement in lungs in COVID-19 has become a standard fare in management in higher centers. Previous studies by Wang have shown a strong correlation between early high CRP levels and severe COVID-19 infections.[12],[13] A study by Herold et al. has shown that CRP can be a strong predictor for need for mechanical ventilation as well.[14] It would be interesting to analyze the correlation between CRP at the time of admission and HRCT chest findings.

Our study has shown a strong correlation between CRP levels at the time of presentation and total severity score in HRCT in all our subcategories. However, in looking a bit deeper, the results are even more interesting. During Kruskal–Wallis test analysis in our study, the P value in survivors on the day of presentation was 0.019, but it became 0.035 on day 5. Hence, while high CRP value on either day was strongly correlated with higher involvement of lungs in HRCT chest, the mean values as well as mean ranks dropped slightly on day 5. On the other side, in patients who did not survive, the correlation between CRP on day of admission and HRCT severity was 0.003, and it was even more significant at day 5, with P = 0.001. Mean values and mean rank values remained at similar levels too on day 5 compared to on the day of admission, despite optimal treatment. Notably, this group did not have any patients with a score 1 on HRCT findings.

We had similar findings when used Spearman's rank correlation coefficient for analysis. P value for correlation between CRP on day of admission and HRCT score was 0.001, while for day 5 CRP, it was 0.040 in patients who eventually survived. Interestingly, P value in this analysis for patients who did not survive was 0.0001 both on the day of admission and day 5, despite optimal therapy.

In view of these findings, it appears that CRP done at any point during the early phase of COVID-19 has a significant correlation with HRCT scores and lung involvement in COVID-19 infections. Even more, interestingly, the correlation is stronger in patients who did not survive even at the beginning. Plus, patients who showed response to therapy had a fall in CRP levels at day 5, while patients who eventually succumbed had the same or higher level of CRP in general at day 5 compared to the day of admission.

One of the interesting differences between the first and second waves of COVID-19 in India was how and where they spread, as well as how fast they spread. While the rural population was largely untouched in India during the first wave, the second wave touched the villages as well as the cities. Almost all states of India showed effective reproduction number (Rt) >1, including in rural regions.[15],[16],[17] During the second wave, due to the rapidly rising crisis, health-care services were severely affected, and resources were scarce. Third-wave, if and when it appears in India, might have similar epidemiology and issues. Identifying high-risk patients early with limited resources would be very valuable in such a case.

These results could show us a way to identify patients who might eventually end up needing ICU care early on and go for a more aggressive management from get go to improve our medical care. In suspected or confirmed cases for COVID-19, a high CRP at the time of the first presentation to a medical facility or a rising serial CRP could indicate future intensive care requirement even in the absence of severe symptoms. In rural settings, this could help us identify patients who need a referral to higher centers with ICU facilities before patients worsen clinically and transfer across long distances add to mortality and morbidity. In towns and cities, this could guide us to admission and more intensive therapy in relatively asymptomatic patients, overall impacting the mortality and morbidity of this dreaded pandemic.

Limitations and strength

Our study was limited to ICU patients admitted in our hospital since those were the patients who had more common HRCT chest involvement as well as received the most comprehensive treatment during a certain period. Which, along with stronger restrictions of the hospital itself, even for relatives entry during COVID-19 waves, with inclusion criteria requiring both positive RTPCR status and HRCT done limited the number of patients that could be enrolled. Due to unawareness of more details of the disease as well as fear regarding COVID-19 initially, relative reluctance is also an issue. A study with a higher number of participants and a more detailed view on the overall length of stay and long-term COVID-19 morbidity would be beneficial.


  Conclusion Top


In centers where the HRCT chest is not available or financial resources are a major concern, we suggest early CRP, repeated after 3–5 days, could be a very useful prognostic factor for significant lung involvement during the course of illness. This, in turn, could be a very useful tool in determining a need for admission, referral to higher centers, or more intensive therapy early on.

Ethical approval

During this study, procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration. Approval of the Institutional Ethics Committee was obtained.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Li J, Yan R, Zhai Y, Qi X, Lei J. Chest CT findings in patients with coronavirus disease 2019 (COVID-19): A comprehensive review. Diagn Interv Radiol 2021;27:621-32.  Back to cited text no. 4
    
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Zhang J, Meng G, Li W, Shi B, Dong H, Su Z, et al. Relationship of chest CT score with clinical characteristics of 108 patients hospitalized with COVID-19 in Wuhan, China. Respir Res 2020;21:180.  Back to cited text no. 8
    
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Li K, Fang Y, Li W, Pan C, Qin P, Zhong Y, et al. CT image visual quantitative evaluation and clinical classification of coronavirus disease (COVID-19). Eur Radiol 2020;30:4407-16.  Back to cited text no. 9
    
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Mukaka MM. Statistics corner: A guide to appropriate use of correlation coefficient in medical research. Malawi Med J 2012;24:69-71.  Back to cited text no. 11
    
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Wang L. C-reactive protein levels in the early stage of COVID-19. Med Mal Infect 2020;50:332-4.  Back to cited text no. 12
    
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Wang G, Wu C, Zhang Q, Wu F, Yu B, Lv J, et al. C-reactive protein level may predict the risk of COVID-19 aggravation. Open Forum Infect Dis 2020;7:ofaa153.  Back to cited text no. 13
    
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Herold T, Jurinovic V, Arnreich C, Lipworth BJ, Hellmuth JC, Bergwelt-Baildon MV, et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immun 2020;146:128-36.  Back to cited text no. 14
    
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Jain VK, Iyengar KP, Vaishya R. Differences between first wave and second wave of COVID-19 in India. Diabetes Metab Syndr 2021;15:1047-8.  Back to cited text no. 15
    
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Iftimie S. First and second waves of coronavirus disease-19: A comparative study in hospitalized patients in Reus, Spain. PLoS One 2021;16:e0248029.  Back to cited text no. 16
    
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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