European Journal of Cardiovascular Medicine

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major healthcare problem around the world, with significantly higher morbidity and mortality in patients with coexisting conditions such as diabetes mellitus and hypertension (1).  The clinical presentation can be heterogeneous, ranging from asymptomatic to severe disease, which can be associated with a cytokine storm. The pathogenesis of COVID-19 is not fully understood, but is probably multifactorial, resulting in a systemic hyperinflammatory response and associated thromboembolic complications in severe cases (2).

The importance of the trace element zinc for the development and function of the immune system across all kinds of species has been proven in numerous studies (3-5). As zinc deficiency results in altered numbers and dysfunction of all immune cells, subjects with suboptimal zinc state have an increased risk for infectious diseases, autoimmune disorders, and cancer (5-8).  As mild zinc deficiency is largely sub-clinical, it is unnoticed in most people. However, the World Health Organization (WHO) assumes that at least one third of the world population is affected by zinc deficiency (9,10). The fact that zinc deficiency is responsible for 16% of all deep respiratory infections world-wide (11) provides a first strong hint on a link of zinc deficiency with the risk of infection and severe progression of COVID-19 and suggests potential benefits of zinc supplementation.

 C-reactive protein is a homopentameric acute-phase inflammatory protein, a highly conserved plasma protein that was initially discovered in 1930 by Tillet and Francis while investigating the sera of patients suffering from the acute stage of Pneumococcus infection and was named for its reaction with the capsular (C)-polysaccharide of Pneumococcus (12,13). In the presence of calcium, CRP binds to polysaccharides such as phosphocholine (PCh) on microorganisms and triggers the classical complement pathway of innate immunity by activating C1q (14). CRP is a member of the pentraxin family, which includes other structurally related molecules such as serum amyloid A (15,16). Transcriptional induction of the CRP gene mainly occurs in hepatocytes in the liver in response to increased levels of inflammatory cytokines, especially interleukin-6 (IL-6) (17).C-reactive protein levels are known to increase dramatically in response to injury, infection, and inflammation. CRP is mainly classified as an acute marker of inflammation, but research is starting to indicate important roles that CRP plays in inflammation.

Aim of the study: As COVID-19 is a novel infection and   zinc supplements were a part of COVID-19 treatment. The present study is focused on the serum zinc levels and its correlation with inflammatory markers like CRP.

Objectives of the study:

1. To estimate the serum levels of zinc and CRP in COVID-19 positive patients.
2. To correlate serum zinc levels with CRP in COVID-19 positive patients.

After obtaining institutional ethical committee approval, Analytical cross-sectional study was done in patients with COVID-19 positive by RTPCR (reverse transcription polymerase chain reaction) admitted in Ramnarayan Ruia Govt General hospital (RUIA), Tirupati, one of the COVID-19 Teritary care Hospital in Andhra Pradesh.

Inclusion criteria: COVID-19 positive patients (by RTPCR), Who have given informed and written consent.

Exclusion criteria: COVID 19 negative and COVID- 19 positive who have not given the consent.

Sample collection: Under aseptic precautions ,5 ml of venous blood is collected in to a plain tube, allowed it to clot and centrifugation done to obtain serum. Thus, obtained serum was utilized for the estimation of zinc and CRP values.

Study methods: serum zinc and CRP levels were estimated by Beckmen coulter AU 480 fully automated analyzer according to the kit provided by the manufacturer. Normal value of serum zinc is 80-120 mcg/dl. Normal value of CRP is 0.3-1.0 mg/dl

Statistical analysis:

Totally 86 subjects were included in the study by random sampling, of which 51% are males and 49% are female. Unpaired t test is used to compare mean values of zinc and CRP in males and females and to compare the mean values of serum zinc and CRP based on age. P value < 0.05 is significant.

Table-1: The mean values of serum zinc and CRP in males and females

The mean value of serum zinc (97.53 mcg/dl ) in male patients is more when compared to the mean value   (87.11 mcg/dl ) in female patients and the difference is not statistically significant (p =0.26).

The mean value of CRP in male patients (2.14 mg/dl )   is lower than the mean value in female patients(3.15mg/dl) and the difference is not statistically significant (p=0.168).

 In the present study the mean value of serum zinc is more and CRP value is less in male patients when compared to female patients. Where as in female patients the serum zinc value is less and CRP value is more when   compared to the male patients.

Of total 86 subjects 53% were of age <50 years and 47% were of the age >50 years.

Table-2: The mean values of serum zinc and CRP based on age.

The mean value of serum in zinc in patients with age >50 years (100.22 mcg/dl) is more when compared to the mean value of patients with age group <50 years (85.68 mcg/dl)  and the difference is  not statistically significant (p=0.121).The mean value of CRP in patients with age >50 years (2.91 mg/dl) is slightly more when compared to the mean value of patients with age <50 years (2.39 mg/dl) and the difference is statistically not significant (p=0.480)

There were 34 patients whose serum zinc value is <70. Mean value of serum zinc in these  patients is  49.34 mcg/dl and the mean value of CRP is 3.22 mg/dl. When the values of serum zinc and CRP are plotted on a scattered diagram, there is no correlation seen between zinc and CRP values.

Graph-1: Correlation of serum zinc & CRP (serum zinc is<70 mcg/dl)

There were 31 patients whose serum zinc value is 80-120mcg/dl

Mean value of serum zinc in these patients is  99.9 mcg/dl and the mean value of CRP is 2.27 mg/dl.When the values of serum zinc and CRP are plotted on a scattered diagram, there is no correlation seen between zinc and CRP value

Graph-2: Correlation of serum zinc & CRP (serum zinc is 80-120mcg/dl)

There were 21 patients whose serum zinc value is >120, mean value of serum zinc in these  patients is  152.59 mcg/dl and the mean value of CRP is 2.0 mg/dl. When the values of serum zinc and CRP are plotted on a scattered diagram, there is negative correlation seen between zinc and CRP values.

Graph-3: Correlation of serum zinc & CRP (serum zinc is>120 mcg/dl)

A study conducted by Jothimani D et al, in 2020, showed that a significant number of COVID-19 patients were zinc deficient. (18).

A study conducted by Lukasz Szarpak et al, in 2021, showed that Zinc supplementation did not have any beneficial impact on the course of COVID-19. (19)

A study conducted by Soodeh Rajeghi Jahromi et al, in 2021, suggested that increasing levels of Se (selenium) and Zn (Zinc) were accompanied by a decrease in serum CRP level. (20)

In our present study   mean value of serum zinc is high and the value of CRP is low in male covid patients when compared to the female COVID-19 patients. The mean value of serum zinc and CRP in COVID-19 patients with age>50 yrs is high when compared to the covid patients with age <50 years. The higher values of zinc may be due to supplementation of multi vitamins along with zinc before the occurrence of covid infection.  

In covid patients with serum zinc <70 mcg/dl. Mean value of serum zinc in these patients is  49.34 mcg/dl and the mean value of CRP is 3.22 mg/dl. When the values of serum zinc and CRP are plotted on a scattered diagram, there is no correlation seen between zinc and CRP values.

In covid patients with serum zinc in normal limits 80-120 mcg/dl, mean value of serum zinc in these patients is  99.9 mcg/dl and the mean value of CRP is 2.27 mg/dl. When the values of serum zinc and CRP are plotted on a scattered diagram, there is no correlation seen between zinc and CRP values.

In covid patients with serum zinc >120 mcg/dl, mean value of serum zinc in these patients is  152.59 mcg/dl and the mean value of CRP is 2.0 mg/dl. When the values of serum zinc and CRP are plotted on a scattered diagram, there is negative correlation seen between zinc and CRP values.  

Limitation: The size of the sample is small in the present study, further research on serum micronutrients levels and inflammatory markers is required considering a large sample size.

The present study showed that the mean value of serum zinc is high and CRP is low in male patients compared to the female patients, the mean value of zinc is high in patients with age >50 years than in patients with age <50 years. Further research is required considering a large sample size and other comorbidities.

Conflict of interest: None

Financial support: MRU, SV medical college, Tirupati.

Acknowledgements:

The funding for the present research was provided by Multi-Disciplinary Research unit (MRU), DHR, S.V. Medical college Tirupati. The authors are thankful to MRU staff for the support

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