Variation of COVID-19 Specific Immunoglobulin's and Some Inflammatory Factors in COVID-19 Patients in the Sabratha Isolation Center, Western Libya

Research Article | DOI: https://doi.org/10.31579/2766-2314/053

Variation of COVID-19 Specific Immunoglobulin's and Some Inflammatory Factors in COVID-19 Patients in the Sabratha Isolation Center, Western Libya

  • Azab Elsayed Azab 1*
  • J.M. Jbireal 1
  • S. Alzahani 2
  • Rabia A. M. Yahya 3
  • 1* Department of Physiology, Faculty of Medicine, Sabratha University, Libya.
  • 2 Department of Physiology, Sabratha Higher Institute of Medical Technology, Libya.
  • 3 Department of Pharmacology, Faculty of Medicine, Sabratha University, Libya.

*Corresponding Author: Azab Elsayed Azab, Department of Physiology, Faculty of Medicine, Sabratha, University, Libya.

Citation: Azab Elsayed Azab, J.M. Jbireal1, S. Alzahani and Rabia A. M. Yahya. (2021) Variation of COVID-19 Specific Immunoglobulin's and Some Inflammatory Factors in COVID-19 Patients in the Sabratha Isolation Center, Western Libya. J, Biotech. and Bioprocessing 2(7); DOI: 10.31579/2766-2314/053

Copyright: © 2021, Azab Elsayed Azab, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 04 August 2021 | Accepted: 24 August 2021 | Published: 03 September 2021

Keywords: SARS-CoV-2, COVID-19, coronavirus, IgG, IgM, CRP, ferritin, D-dimer, sabratha isolation center, western libya

Abstract

Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic causing significant mortality and morbidity and implementation of strict isolation measures. Serological testing can diagnose illness by detecting antibodies (IgM and IgG). Testing antibodies against SARS-CoV-2 is rapid and sensitive for the auxiliary diagnosis of COVID-19. The serum levels of CRP, D-dimers, and ferritin, which may be used in risk stratification to predict severe and fatal COVID-19 in hospitalized patients. 

Objectives The present study aimed to investigate the variations in COVID-19 Specific Immunoglobulin's and Some Inflammatory factors in COVID-19 Patients in Sabratha isolation center, Western Libya.  

Subjects and Methods: Sixty Confirmed COVID-19 patients hospitalized in the Isolation Centre located in Sabratha city, Libya from the 2nd October 2020 to the 2nd June 2021, were enrolled in this prospective study. Covid-19 patients were defined as positive cases after the detection of SARS-CoV-2 RNA in oro-nasopharyngeal swab samples. Data collected included demographic, clinical, and biological factors. Also, 30 healthy individuals without any chronic disease or respiratory symptoms were recruited for the control group. Blood samples were collected by vein puncture 5 ml of venous blood was withdrawn from each participant in the study by using disposable syringes under the aseptic technique; they were then transferred to a sterile tube for estimating biochemical parameters. Biochemical parameters were determined using automated COBAS E411 and INTEGRA 400 machines in the Sabratha Isolation Centre laboratory. The statistical significance of differences between groups was evaluated with the Kruskal-Wallis H test

Results: The results showed that patients with COVID-19 had a significant (P<0.0001) increase in IgM levels  at 0 day, 14 days, and 21 days, respectively compared with the healthy individuals. Also, IgG levels were showed a gradual significantly (P<0.0001) increase during COVID-19 Virus Infection among COVID-19  patients at 0 day, 14 days, and 21 days  compared with the controls. In addition, coronavirus infection caused a significant (P<0.0001) increase in D-dimer, CRP, and Ferritin levels compared with the healthy control individuals. 

Conclusion: It can be concluded that coronavirus infection caused a significant increase in IgM, IgG, D-dimer, CRP, and Ferritin levels at different periods compared to the controls. Further studies are needed to confirm these results. COVID-19 Specific Immunoglobulin's and Some Inflammatory factors in COVID-19 Patients These changes in IgM, IgG, D-dimer, CRP, and Ferritin levels during COVID-19 Virus Infection among COVID-19 patients may help the clinicians to better understand the COVID-19 and provide more clinical treatment options.

Introduction

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a worldwide pandemic since it emerged in December 2019 [1]. In only a few months after initial discovery in Wuhan, China, SARS-CoV-2 and the associated coronavirus disease 2019 have become a global pandemic causing significant mortality and morbidity and implementation of strict isolation measures [2]. Adverse outcomes of COVID-19 were associated with comorbidities, including cardiovascular disease, lung disease, and hypertension. These conditions are more prevalent in men and linked to smoking and drinking alcohol [3, 4]. Epidemiological studies showed that elder patients were more susceptible to severe diseases [4, 5], while children tend to have milder symptoms [4, 6, 7].

COVID-19 is from the same group of ribonucleic acid (RNA) viruses that caused severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) [8-11]. Corona viruses are enveloped, non segmented, single  stranded, positive-sense RNA viruses named after their corona- or crown like surface projections observed on electron microscopy that correspond to large surface spike proteins. Corona viruses are classified in the Nidovirales order [11-13]. 

Presently the tested against COVID-19, not exclusively to the analyzed infection however to anticipate the movement towards serious and deadly structures, these indicators will empower hazard delineation, guide interventional studies to target patients at the upgraded hazard of creating extreme sickness and improve the portion of restricted human and specialized assets in the continuous pandemic. Additionally, ID of lab boundaries equipped for segregating among serious and non-extreme cases, or those at high or generally safe of mortality, will consider advanced clinical situational mindfulness [14]. 

The fast and precise determination of COVID-19 adds to infection and flare-up administration by empowering speedy and exact general wellbeing observation, avoidance and control measures. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) has been the primary means for diagnosing SARS-CoV-2 [15, 16]. However, molecular detection carries the risk of false-negatives because of low viral loads in specimens [16, 17]. Serological testing, another common laboratory diagnostic, can diagnose illness by detecting antibodies [16]. Knowing the pervasiveness of antibodies to the infection in the populace is significant as far as understanding its spread, and carrying out measures to control it. Seroprevalence surveys are necessary to inform and assist global policymakers in planning measures that could alleviate the economic burden of the disease, and prevent the collapse of the healthcare system [18].

Antibodies protect the host by binding to specific antigens (proteins) on the virus to neutralize its fusion and entry into the host cell and facilitate recognition and killing by phagocytic immune cells [2, 19]. In the SARS epidemic, the detection of IgM and IgG allowed for serological diagnosis [20, 21]. 

Antibodies secure the host by restricting to explicit antigens (proteins) on the infection to kill its combination and section into the host cell and work with acknowledgment and killing by phagocytic invulnerable cells [2, 19]. In the SARS plague, the recognition of IgM and IgG took into consideration serological determination [20, 21].Testing antibodies against SARS-CoV-2 is rapid and sensitive for the auxiliary diagnosis of COVID-19 [21, 22]. In humans, three kinds of antibodies or immunoglobulins have been the objective of COVID-19 serological tests: IgM, IgG, and IgA. Albeit the elements of the insusceptible reaction in COVID-19 are not completely seen, normally IgM antibodies are delivered by having invulnerable cells during the beginning phases of a viral disease. IgG is often the most abundant antibody in the blood and plays a more prominent role in the later stages of infection and in establishing long-term immune memory [2, 23]. While IgM and IgG antibodies have been the main applicants in COVID-19 serological test improvement, ongoing investigations show that IgA, predominately present in the mucosal tissue, may likewise play a critical role in the immune response and disease progression [2, 24]. Seroprevalence of Immunoglobulin Gamma antibodies against severe acute respiratory syndrome coronavirus 2 is important as a tool to estimate the extent of infection in a population [25]. Previous studies showed that the detectable antibodies concentrations persisted for more than two years in Middle East respiratory syndrome and severe acute respiratory syndrome coronavirus ‐infected patients [1, 26, 27].

Inflammatory biomarkers including C‑reactive protein (CRP), and IL-6 are significantly elevated in the early stages of the disease. In this regard, inflammation-associated biomarkers and coagulation test screening, including the assessment of IL-6, C‑reactive protein, and  D-dimer [28]. C‑reactive protein is a plasma protein induced by various inflammatory mediators such as IL-6 and produced by the liver [28, 29]. In this process, the increased level of CRP is associated with disease severity [28, 30]. Biomarkers, such as high serum ferritin have also emerged as poor prognostic factors [31]. Recent clinical data have indicated CRP [32, 33] and other factors may be related to the severity of COVID-19 [5, 33]. Tan et al. [34] found that C‑reactive protein is a good accurate diagnostic tool in early predicting severe Coronavirus disease 2019. Overall, literature evidence suggests that in the early stage of COVID-19, CRP levels could reflect disease severity [34].

D-dimer and other Fibrin degradation products (FDPs) are the products of fibrin degradation that appear after blood clot destruction due to fibrinolysis in the blood. Blood d-dimer concentrations can help the diagnosis of thrombosis [28, 35]. There were numerous differences in laboratory findings between patients admitted to the ICU and those not, including, higher levels of D-dimer in ICU patients [36, 37].

 Ferritin is an acute phase protein that can be released from damaged hepatocytes [33, 38]. It is known that ferritin levels may increase during inflammatory, infectious and malignant diseases among others [39]. Also, hyperferritinemia has been previously recognized in abnormal liver function conditions or metabolic syndrome [33, 40-42]. The role of ferritin seems to be ignored even though clinical observation has discovered abnormal ferritin levels in severe COVID-19 patients [5, 33]. Ferritin variations were also consistent with CT manifestation, presenting the ability to act as a sensitive and accurate indicator. Then, the diagnostic value of ferritin for the incidence of severe illness was compared to that of age, sex, CRP, and LYM%, which had been recognized as the risk factors of COVID-19 [33, 34, 43, 44]. 

Clinicians should consider the serum levels of CRP, D-dimers, and ferritin, which may be used in risk stratification to predict severe and fatal COVID-19 in hospitalized patients [45].

Objective

The present study aimed to investigate the variations in COVID-19 specific immunoglobulin's and some inflammatory factors in COVID-19 Patients in Sabratha isolation center, Western Libya.

Subjects and Methods

Sixty Confirmed COVID-19 patients hospitalized in the Isolation Centre located in Sabratha city, Libya from the 2nd October 2020 to the 2nd June 2021, were enrolled in this prospective study. Covid-19 patients were defined as positive cases after the detection of SARS-CoV-2 RNA in oro-nasopharyngeal swab samples. This study was approved by the Research and Ethical Committee of the Faculty of Medicine, Sabratha University. Demographic data were extracted from electronic medical records and patient files. Data collected included demographic, clinical, and biological factors, as well as complications at admission and during the hospital stay. Any missing or uncertain data were collected and clarified through direct communication with the relevant health care providers and family members of patients. Also, 30 healthy individuals without any chronic disease or respiratory symptoms were recruited for the control group. Blood samples were collected by vein puncture 5 ml of venous blood was withdrawn from each participant in the study by using disposable syringes under the aseptic technique. Biochemical parameters were determined using automatic immunoassay analyzer- Snibe Maglumi 2000 Plus, COBAS E411, and INTEGRA 400 machines in the Sabratha Isolation Centre laboratory.

Statistical analysis

Continuous variables were presented as medians (interquartile range [IQR]). The data were analyzed using Graph Pad Prism software version 7. The Kolmogorov-Smirnov test was used to assess the normality of the distribution of continuous variables. The statistical significance of differences between groups was evaluated with the Kruskal-Wallis H test.  A  P-value of <0>was used to establish statistical significance.

Results

The mean age of the patients was 62.7 years (20–90 years); sixty patients, 39 males (39%) and 21 females (35%) were included in the current study (Figure. 1).

Figure. 1: Distribution of patients according to gender.

Effect of Coronavirus infection on IgM, and IgG levels in COVID-19 Patients

The results in table.1 and figure. 2 show that patients with COVID-19 had a significant (P<0>) increase in IgM levels [median (IQR), AU/mL], 2.50 (1.23-12.85), 12.10 (1.70-78.30), and 8.30 (5.90-48.00) at 0 day, 14 days, and 21 days, respectively compared with the healthy individuals [1.40 (0.98-2.03)]. Also, IgG levels [median (IQR), AU/mL], were showed a gradual significantly (P<0>) increase in during COVID-19 Virus Infection among COVID-19 patients at 0 day, 14 days, and 21 days  [8.80 (1.700-121.3), 154.0 (75.30-416.3), and 291.8 (243-510) compared with the controls 1.50 (1.00-2.40) (Table. 1& Figure. 3).

IQR:  Interquartile range,(***) significant difference compared with the controls at (P<0>
Table (1): Median (IQR) of IgM, and IgG in control and during COVID-19 Virus Infection among COVID-19 Patients
Figure.2: Median (IQR) of IgM in controls and during COVID-19 Virus Infection among COVID-19 Patients.
Figure.3: Median (IQR) of IgG  in controls and during COVID-19 Virus Infection among COVID-19 Patients.

Effect of Coronavirus infection on serum D-dimer, CRP, and Ferritin levels in COVID-19 Patients

Coronavirus infection caused a significant (P<0>) increase in D-dimer levels (µg/ml) [median (IQR)], 0.61 (0.40-1.40), 0.65 (0.37-2.28), and  0.67 (0.42-3.12), in CRP levels (mg/L) 495.4 (228-1010), 664 (232.5-1285), and 261 (119.2-605.0), and in Ferritin levels (µg/L) 62.75 (23.08-183.7), 51 (9.7-93), and 26.55 (4.73-67.25) compared with the healthy control individuals 0.28 (0.20-0.32), 68.15 (45.10-99.28), and 2.35 (1.38-3.18), respectively (Table. 2& Figures. 4-6).

IQR:  Interquartile range, (***) significant difference compared with the controls at (P<0>
Table (2): Median (IQR) of serum D-dimer, C- reactive protein (CRP), and Ferritin levels in control and during COVID-19 Virus Infection among COVID-19 Patients.
Figure.4: Median (IQR) of D-dimer in controls and during COVID-19 Virus Infection among COVID-19 Patients
Figure.5: Median (IQR) of C-reactive protein in controls and during COVID-19 Virus Infection among COVID-19 Patients
Figure.6: Median (IQR) of Ferritin in controls and during COVID-19 Virus Infection among COVID-19 Patients.

Discussion

Serum immunoglobulin's against severe acute respiratory syndrome coronavirus‐2 were detectable within the first weeks after the onset of symptoms [1, 46-49]. They were detectable as early as 4 days and reached a peak in the second week after onset [1, 5, 46-48, 50]. Almost all the infected cases had seropositive antibodies in the first 3 weeks post‐illness onset [1, 46]. So, positive detection of IgM and IgG antibodies specific to SARS-CoV-2 has also been recognized as deterministic evidence for confirmed SARS-CoV-2 infection [51-53]. Serological tests may be important tool to estimate the prevalence of virus infection, virus lethality, and provide information about risk factors and immunity such as the patient’s location, and age [18, 54]. Previous studies have suggested that the upsurge of IgG antibody to SARSCoV correlates with the clinical worsening of pneumonia [55-58]. Studies on severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) showed that virus-specific antibodies were detectable in 80–100% of patients at 2 weeks after symptom onset [46, 57, 60-63]. 

The current study showed that corona virus infection caused a significant (P<0>) increase in serum IgM  and IgG levels  at 0 day, 14 days, and 21 days, compared with the healthy individuals. Similar results were recorded by previous studies [1, 16, 21, 46, 58, 64]. During viral infection with SARS-CoV-2, the production of specific antibodies against the virus is consistent in most patients, except for immunodeficient patients. IgM can be detected as early as 3 days after infection and provides the first line of humoural immunity defense, after which high-affinity IgG responses are initiated and play a key role in long-term immune memory [21, 64]. It seems to be conclusive that IgM titer increases rapidly within the first 2 weeks, persists in the following 1 to 2 weeks as the virus is being cleared, and declines by the 4th week after illness onset as the virus nucleic acid turns negative [1, 65]. Therefore, the decline of IgM may be an indicator of virus clearance, which may help determine the true nucleic acid conversion negative in conjunction with RT‐PCR testing. It could serve as a criterion for discharge and in ending quarantine, especially for mildly symptomatic or asymptomatic cases [1]. The IgM level showed heterogeneity within the group of deceased cases, and some patients had very high IgM levels which might be in the active status of the disease or very low IgM levels due to the long disease course. The increased IgM level in the deceased case group might be related to the higher disease severity in these patients and indicate a poor prognosis. Alternately, cytokine storm, severe immune dysfunction, and other comorbidities might be the important risk factors in these cases [21, 65-68].

Hsueh et al.,  [57] reported that seroconversion for IgG (mean 10 days) occurred simultaneously, or 1 day earlier, than that for IgM and IgA (mean 11 days for both). IgG could be detected as early as 4 days after the onset of illness. The earliest time at which these three antibodies reached peak levels were similar (mean 15 days). A high IgG level (1:800) could persist for > 3 months.

Long et al., [46] reported that Seroconversion for IgG and IgM occurred simultaneously or sequentially. After seroconversion, IgM and IgG titers were plateaued within 6 days. After 17-19 days of the onset of COVID-19 symptoms, a positive virus-specific IgG  was reached 100%,  while after 20-22 days of the  onset of COVID-19 symptoms, a positive virus-specific IgM reached a peak of 94.1%.  Three weeks after the onset of the sympatoms of COVID-19, the virus-specific IgM and IgG antibody titers were increased in patients [46].

Jin et al., [16] reported that the sensitivities of serum IgM and IgG antibodies to diagnose COVID-19 were 48.1% and 88.9%, and the specificities were 100% and 90.9%, respectively. In the COVID-19 group, the IgM-positive rate increased slightly at first and then decreased over time; in contrast, the IgG-positive rate increased to 100% and was higher than IgM at all times. However, the median IgG titer after conversion to virus-negative was double that before, and the difference was significant. The authors concluded that viral serological testing is an effective means of diagnosis for SARS-CsoV-2 infection. 

Hou et al., [21] reported that IgM levels increased during the first week after SARS-CoV-2 infection, peaked for 2 weeks and then reduced to near-background levels in most patients. The immunoglobulin M antibody levels were slightly higher in deceased patients than recovered patients, but, in these groups, the immunoglobulin G antibody levels did not significantly differ. The authors concluded that quantitative detection of IgM and IgG antibodies against SARS-CoV-2 quantitatively has potential significance for evaluating the severity and prognosis of COVID-19.

Zhang et al., [52] found that the IgM and IgG positive rates were 50% and 81% on day 0 (the day of first sampling) and increased to 81% and 100%, respectively, on day 5. The IgG-positive rate was consistently higher than the IgM-positive rate, and this phenomenon was also observed in the study by Jin et al., [16] and Zhang et al., [52].

Liu et al., [53] observed that the IgM antibody response to SARS-CoV-2 occurred earlier and peaked earlier than the IgG antibody response; the IgM antibody response began to decline at week 3 of the illness, while the IgG antibody response persisted and was maintained in patients with COVID-19; and severe cases of COVID-19 tended to have a more vigorous response in both IgG and IgM antibodies to COVID-19 illness. Importantly, the timing of IgM and IgG antibody occurrence in patients varies greatly, and this variation in timing may be associated with age as well as comorbidity [53, 69]. More care needs to be taken when using levels of anti-SARS-CoV-2 antibodies to make a clinical diagnosis of COVID-19 or determine discharge criteria [53].

Circulating ferritin, CRP, and D-dimers were reported to be expressed to a similar extent or more robustly expressed in COVID-19 compared with other acute states [70]. The results current study showed that patients with COVID-19 had a significant increase in serum CRP during COVID-19 Virus Infection among COVID-19 patients at 0 day, 14 days, and 21 days compared with the controls. These results run parallel to the results of the previous studies [28, 53, 65, 71, 72]. The CRP was elevated in 65% of COVID-19 patients on admission and elevated in 93.9% of severe COVID-19 patients [28, 53]. CRP levels are strong biological indicators to represent the severity of the COVID-19 infection. CRP seems to be one of the first biomarkers to show physiological complications in COVID-19 patients. In a study, CRP was elevated in 60.7% of patients [71]. A cut-off of >10 mg/L for CRP is a predictor of poor outcome [44]. A retrospective study showed that a CRP level of 26 mg/L could serve as a cut-off to predict progression to severe disease [65]. Twenty-six studies in the second analysis showed significantly higher CRP in severe COVID-19 compared to non-severe COVID-19 [44, 73, 74]. C-reactive protein (CRP) levels are increased in COVID-19 patients and it has been shown that survivors had median CRP values of approximately 40 mg/L, while non-survivors had median values of 125 mg/L, indicating a strong correlation with disease severity and prognosis [45, 75]. CRP levels in COVID-19 patients who died were much higher than in patients who survived [28, 66]. The increase in CRP is strongly associated with COVID-19 severity and critical condition [28, 72].

Elevated D-dimer levels are very frequently seen in patients with COVID-19. Several meta-analyses have shown that D-dimer levels have prognostic value and correlate with disease severity and in-hospital mortality [73]. D-dimer can be an early marker to guide the management of Covid-19 patients [74]. Correlations of abnormal coagulation parameters with poor prognosis have been observed. Non-survivors have shown significantly higher levels of plasma D-dimers compared to survivors [45, 76]. Coagulopathy and overt disseminated intravascular coagulation appear to be associated with high mortality rates. Among the coagulation parameters, D-dimer elevation > 1 ug/L was the strongest independent predictor of mortality [5, 45].

The present study showed that coronavirus infection caused a significant (P<0>) increase in the serum D-dimer levels compared with the healthy control individuals. This result is similar to the study of Guan et al., [71] who reported that the d-dimer level was significantly elevated among non-survivors compared to survivors. Also, Huang et al. [44] reported that COVID-19 patients with 0.5 μg/mL or higher levels of d-dimer on admission need critical care support. Previous studies showed that d-dimer levels were higher in non-survive COVID-19 patients compared to survive ones [28, 76]. D-dimer on admission upper than 2.0 μg/mL can predict mortality in hospitals among COVID-19 patients. The d-dimer level can be a basic and helpful biomarker to identify the patients with poor prognosis in the early stages and help to the management of COVID- 19 patients [28, 77]. 

Viral clearance is the golden standard for defining the recovery of COVID-19 infections and predicting hospital length is extremely vital in the COVID-19 pandemic due to the lack of medical resources. Thus, authors suppose ferritin could act as both an effective discriminator for severity of illness and a predictor for prognosis [33, 66]. Ferritin is an intracellular protein that contains iron and is the major form of iron stored in the cells. Although this protein is found in most tissue and organs, small amounts are secreted into the blood and are the carrier of iron. Ferritin is used as an indirect marker of the total amount of iron stored in the body [28, 78]. Ferritin concentration increases significantly during infection or cancerous conditions. Also, ferritin is an acute phase reactant that rises in the course of the disease [28, 79]. 

The current study showed that coronavirus infection caused a significant (P<0>) increase in the serum Ferritin levels compared with the healthy control individuals. This result is similar to the result of the study of Dahan et al., [80]  who reported that a significant increase in ferritin levels was demonstrated in patients with moderate and severe disease, compared to patients with mild disease (P = 0.006 and 0.005, respectively). Severe patients had significantly higher levels of ferritin (2817.6 ng/ml) than non-severe patients (708.6 ng/ml) P = 0.02. Caoet al., [33] reported that patients with elevated ferritin levels (>200 ng/mL) had a higher incidence of severe illness when compared with those with normal ferritin levels (≤ 200 ng/mL) (50.0% vs 2.9%). In addition, the severity of illness manifested a significantly higher level of ferritin as compared with non-severe ones (median 921.3 vs 130.7 ng/mL, p < 0>

Also, Zhou et al., [5] found that ferritin levels were elevated in cases of COVID-19 with fatal outcomes compared with survivors. Li et al., [81] found that significantly elevated ferritin levels in patients with severe COVID-19. A decrease in ferritin levels was not seen along with patient improvement. Therefore, it was suggested that it is a sensitive marker of severe COVID-19, but it cannot be used for disease assessment.  Al-Samkari et al., [82] recorded that elevated ferritin, and CRP were higher in patients with thrombotic complications. This knowledge thus suggests that elevated ferritin level is a marker of severe COVID-19 and is associated with thrombotic complications [39]. In addition, Lin et al., [83] reported that Chinese patients with severe Sars-CoV2 disease showed higher levels of serum ferritin than patients with a not severe one, confirming data from other authors on Chinese [84, 85]  and Caucasian populations [86, 87].  Studies on ferritin levels in COVID-19 patients have yielded equivocal results. It is not clear whether it is a bystander or a true characteristic of the disease [88]. Two retrospective studies have reported the minimal role of ferritin in predicting ICU admission and the need for ventilation and failure in predicting mortality [83, 89]. But another study and a meta-analysis showed findings to the contrary; ferritin levels could predict severe disease and mortality ([44, 83]. Elevation of ferritin levels may be due to secondary haemophagocytic lympho-histiocytosis (sHLH) and cytokine storm syndrome that has been reported in severe COVID-19 patients. Based on body temperature, organomegaly, blood cell cytopenia, and ferritin levels, a predictive H-score has been proposed to estimate the risk of developing secondary haemophagocytic lymphohistiocytosis [45, 90]. Serum levels of ferritin progressively increased with the severity of the disease and correlate with poor prognosis in COVID-19 patients. Increased ferritin levels could be indicative of a strong inflammatory reaction in COVID-19 and recent studies suggest that increased levels of circulating ferritin levels play a critical role by contributing to the development of a cytokine storm [91, 92], resembling macrophage activating syndrome [93]. Ferritin is a key mediator of immune dysregulation, especially under extreme hyperferritinemia, via direct immune-suppressive and pro-inflammatory effects, contributing to the cytokine storm [94, 95]. Laboratory findings in patients with severe COVID-19 showed data consistent with cytokine storm involving elevated inflammatory markers, including ferritin, which has been associated with critical and life-threatening illness [90].

Conclusion

It can be concluded that coronavirus infection caused a significant increase in IgM, IgG, D-dimer, CRP, and Ferritin levels at different periods compared to the controls. Further studies are needed to confirm these results. COVID-19 Specific Immunoglobulin's and Some Inflammatory factors in COVID-19 Patients These changes in IgM, IgG, D-dimer, CRP, and Ferritin levels during COVID-19 Virus Infection among COVID-19 patients may help the clinicians to better understand the COVID-19 and provide more clinical treatment options.

References

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Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

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Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

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Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

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Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

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Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

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Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

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Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

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Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

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Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

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Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

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Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

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Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

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S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

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Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

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George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

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Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

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Khurram Arshad

Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

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Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

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Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

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Maria Dolores Gomez Barriga

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.

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Dr Maria Dolores Gomez Barriga

Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.

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Dr Maria Regina Penchyna Nieto

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.

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Dr Marcelo Flavio Gomes Jardim Filho

Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”

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Zsuzsanna Bene

Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner

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Dr Susan Weiner

My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.

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Lin-Show Chin

My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.

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Sonila Qirko

My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.

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Luiz Sellmann

I would like to offer my testimony in the support. I have received through the peer review process and support the editorial office where they are to support young authors like me, encourage them to publish their work in your esteemed journals, and globalize and share knowledge globally. I really appreciate your journal, peer review, and editorial office.

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Zhao Jia