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MONITORING THE "CYTOKINE STORM ": C-reactive protein (CRP) and dysregulation of immune response in COVID-19

  • timer  9.5 Minutes to read
  • 18 May 2021
  • Written by Horiba Medical
  • General Practice

Background

A novel strain of the coronavirus (COVID-19) – a pneumonia-like respira­tory illness – has begun to spread rapidly across the globe ever since it firstly appeared in the Chinese city of Wuhan in late December 2019. On 30th January 2020, the World Health Organization declared COVID-19 as a "public health emergency of international concern". On 9th March 2020, the WHO announced that "the threat of a pandemic has become very real".

The global mortality rate for COVID-19 currently stands at 3.4%, much higher than that of the seasonal flu which kills only about 0.1 percent of those infected. The death toll from the potentially deadly virus had reached more than 4,280 on the last count, with more than 65,700 people getting recoveries. Deaths have been reported from China, Iran, South Korea, Italy, France, the US, the UK, Japan, Australia, Spain, Thailand, the Philippines and Switzerland.

CORONA INFECTION: India Scenario

ICMR: A total of 271 individuals have been confirmed positive among suspected cases and contacts of known positive cases till date.

 

Laboratory investigations for COVID-19

Molecular assays to diagnose 2019-nCoV (RT-PCR)
Several assays that detect the 2019-nCoV have been and are currently under development, both in-house and commercially. Some assays may detect only the novel virus and some may also detect other strains (e.g. SARS-CoV) that are genetically similar.

Confirmation of infection is by doing RT-PCR for SARS-CoV-2
Laboratory abnormalities in patients with COVID-2019 infection:

Source: Giuseppe Lippi* and Mario Plebani

 

CRP, blood counts and COVID-19

Although CRP does not normally elevate significantly in mild viral respiratory infections, levels have shown to increase in severe cases, such as in avian influenza H1N1 and H7N9, and during SARS epidemics in 2003. A similar significant increase of CRP has also been reported in COVID-19 patients.
COVID-19 (coronavirus disease-19) involves humans as well as animals and may cause serious damage to the raspiratory tract including the lung. This pathogenic virus has been identified in swabs performed on the throat and nose of patients who suffer from or are suspected of the disease. When COVID-19 infect the upper and lower respiratory tract it can cause mild or highly acute respiratory syndrome with consequent release of pro-inflammatory cytokines, including interleukin (IL)-1b and IL-6. In response to infection or inflammation, the macrophages secrete IL-6 and IL-1B, this stimulates the hepatocytes to produce CRP in higher amount.
A retrospective study on the clinical characteristics of 128 COVID-19 cases with laboratory confirmed from Xiangyang No. 1 Hospital from January 2020 to 16th February 2020. The study pointed out white blood cell counts in the normal range of overall patients, but severe group patients were increased significantly (P < 0.01). Lymphocytes of overall patients were decreased. C-reactive protein (CRP) level of all patients were increased markedly, but it in the severe group was significantly higher than that in the non-severe group (P < 0.01).

Another study on clinical characteristics of 140 patients infected with SARS-CoV-2 was shown that an 91.9% patients has increased CRP level, and this results up to 96.4% when comes to severe patients.

 

Dysregulation of immune response in patients with COVID-19

Dysregulation of immune response, especially T lymphocytes, might be highly involved in the pathological process of COVID-19. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of COVID-19.
The current study demonstrated several novel information about dysregulated immune response in COVID-19 patients that SARS-CoV-2 might be mainly acting on lymphocytes, especially T lymphocytes, inducing a "cytokine storm" in the body, and gen­erating a series of immune responses to damage the corresponding organs. Thus, surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of COVID-19.

Laboratory results of 140 COVID-19 patients

 

 

Disease severity

 

 

Laboratory parameters

All patients (n = 138)

Non-severe patients (n = 82)

Severe patients (n = 56)

value

Leukocytes (x109/L; normal range 3,5-9,5)

Increased – No./total No. (%)

Decreased – No./total No. (%)

4,7 (3,7-6,7)

17/138 (12,3)

27/138 (19,6)

4,5 (3,5-5,9)

4/82 (4,9)

18/82 (22,0)

5,3 (4,0-9,0)

13/56 (23,2)

9/56 (16,1)

0,014

0,003

0,513

Lymphocytes (x109/l; normal range 1,1-3,2)

Decreased – No./total No. (%)

0,8 (0,6-1,1)

104/138 (75,4)

0,8 (0,6-1,2)

58/82 (70,7)

0,7 (0,5-1,0)

46/56 (82,1)

0,048

0,160

Lymphocytes percentage (%, normal range 20-50)

16,9 (9,2-26,0)

20,0 (12,5-28,4)

12,7 (7,7-22,0)

<0,001

Eosinophils (x109/l; normal range 0,02-0,52)

Decreased – No./total No. (%)

0,01 (0,0-0,05)

73/138 (52,9)

0,02 (0,008-0,05)

39/82 (47,6)

0,01 (0,0-0,06)

34/56 (60,7)

0,451

0,165

Eosinophils percentage (%, normal range 0,4-8)

0,3 (0,0-1,0)

0,5 (0,08-1,0)

0,2 (0,0-0,8)

0,166

D-Dimer (μg/mL; normal range 0-0,243)

Increased – No./total No. (%)

0,2 (0,1-0,5)

35/81 (43,2)

0,2 (0,1-0,3)

12/43 (27,9)

0,4 (0,2-2,4)

23/38 (60,5)

<0,001

0,004

C-reactive protein (CRP) (mg/L; normal range 0-3)

Increased – No./total No. (%)

34,2 (12,5-67,4)

125/136 (91,9)

28,7 (9,5-52,1)

72/81 (88,9)

47,6 (20,6-87,1)

53/55 (96,4)

<0,001

0,199

Procalcitonin (PCT) (ng/mL; normal range 0-0,1)

Increased – No./total No. (%)

0,07 (0,04-0,1)

41/118 (34,7)

0,05 (0,03-0,1)

16/68 (23,5)

0,1 (0,06-0,3)

25/50 (50,0)

<0,001

0,004

Serum amyloid A (SAA) (mg/L; normal range 0-10)

Increased – No./total No. (%)

92,53 (44,6-161,3)

46/51 (90,2)

91,5 (24,9-163,2)

29/34 (85,3)

108,4 (54,1-161,6)

17/17 (100,0)

0,600

0,156

Serum Creatine Kinase (U/L; normal range 40-200)

Increased – No./total No. (%)

72,5 (52,2-115)

4/60 (6,7)

83,0 (56,0-112,0)

1/35 (2,8)

66,0 (38,5-144,0)

3/25 (12,0)

0,192

0,298

Note: Data are shown as median (IQR); COVID-19, coronavirus disease 2019; IQR, Interquartile range; P values denoted the comparison between non-severe and severe subgroups.

 

This study also pointed out CRP, an inflammatory marker, being an easily available & established assay, can be used as monitoring tool during therapy process.

 

  • Increase in CRP levels seems to track with disease severity and prognosis. In a patient with severe respiratory failure and a normal CRP, one can consider non-COVID etiologies (such as heart failure).
  • Young found low CRP levels in patients not requiring oxygen (mean 11 mg/L, interquartile range 1-20 mg/L) compared to patients who became hypoxemic (mean 66 mg/L, interquartile range 48-98 mg/L).
  • Ruan found CRP levels to track with mortality risk (surviving patients had a median CRP of ~40 mg/L with an interquartile range of ~10-60 mg/L, whereas patients who died had a median of 125 mg/L with an interquartile range of ~60-160 mg/L).

 

Summary

  • Blood count + CRP testing is a recommendable mark for the initial evaluation of coronavirus patients.
  • Blood count + CRP testing is a monitor tool as an inflammatory marker during therapy process for coronavirus patients.

 

 

Read here the original article («Medical Newsletter COVID-19») from Horiba Medical.

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