Signa Vitae. 2021; 17(3): 174-180. doi: 10.22514/sv.2021.068
Original Research
The role of IL-6 receptor inhibitor treatment in critical patient monitoring with COVID-19
Fulya Çiyiltepe1,*,, Ayten Saraçoğlu2, Yeliz Bilir1, Elif Akova Deniz1, Elif Bombacı1, Kemal Tolga Saraçoğlu1

1Department of Anesthesiology and Reanimation, University of Health Sciences, İstanbul Kartal Dr. Lütfi Kırdar City Hospital, 34865 Istanbul, Turkey

2Department of Anesthesiology and Reanimation, University of Marmara, 34722 Istanbul, Turkey

*Corresponding Author(s):drfulyadanaci@hotmail.com (Fulya Çiyiltepe)

History Submitted: 17 February 2021 | Accepted: 15 March 2021 | Published: 08 May 2021
Copyright:  ©2021  The Author(s). Published by MRE Press.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

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Abstract

Objectives: The COVID-19 disease can manifest itself with acute respiratory distress syndrome, renal failure, and septic shock in critically ill patients. There are opinions that there is a correlation between high IL-6 levels and disease severity. In our intensive care unit, we evaluated the changes in the laboratory data and radiological involvement severity of our patients who underwent tocilizumab treatment and examined the appropriate laboratory parameter in the treatment follow-up and its effect on survival.

Methods: In the critical patient follow-up of COVID-19, 17 of the 23 patients treated with tocilizumab had a mortal course (Group 1) and the remaining 6 (Group 2) were. The C-reactive protein, lactate dehydrogenase, IL-6, D-dimer, procalcitonin, albumin, and ferritin values, which were routinely screened in our clinic on the day of tocilizumab treatment and the 5th day after, were recorded. Both the change between the two groups and the change between days 1 and 5 were analyzed.

Results: A total of 23 patients (55.35 ± 13.31 years) were included in the study. The computed tomography severity score assessed at the intensive care unit admission was statistically significantly higher in Group 2. The procalcitonin and lactate dehydrogenase values measured on day 5 after tocilizumab were significantly lower in Group 2. On the 5th day after treatment, the levels of C-reactive protein, ferritin, chest X-rays, IL-6 and D-dimer statistically significantly changed compared to the first day of the treatment. In correlation with the decrease in PCT as of the 5th day after tocilizumab administration, an increasing tendency was observed in 28-day survival.

Conclusion: This study demonstrated that tocilizumab treatment may positively contribute to the treatment by decreasing cytokine levels. PCT and LDH follow-up before and after treatment in critically ill patients who are receiving tocilizumab treatment can give an idea about survival.

Keywords:Coronavirus;IL-6 receptor inhibitor;Intensive care units;Tocilizumab;LDH;PCT;CRP
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Cite this article

Fulya Çiyiltepe, Ayten Saraçoğlu, Yeliz Bilir, Elif Akova Deniz, Elif Bombacı, Kemal Tolga Saraçoğlu. The role of IL-6 receptor inhibitor treatment in critical patient monitoring with COVID-19. Signa Vitae. 2021; 17(3): 174-180. doi: 10.22514/sv.2021.068

1. Introduction

COVID-19 disease, which develops due to coronaviruses, was first identified as causing respiratory diseases in Wuhan, Hubei Province, China in December 2019; Acute respiratory distress syndrome (ARDS), acute renal failure, and multiple organ failure have been identified as possible clinical signs associated with coronaviruses [1]. The presence of an unregulated immune response and hyperinflation that may exacerbate this condition has been advocated [2]. Preliminary reports showed that severely ill COVID-19 patients with poor prognosis had elevated levels of interleukin-6 (IL-6) [3]. In Chinese reports, low lymphocyte count and high levels of ferritin, lactate dehydrogenase (LDH), transaminase, and D-dimer have been associated with poor prognosis and cytokine storm in COVID-19 [4]. IL-6 is one of the main cytokines involved in the cytokine storm caused by COVID-19 infection [5]. It has been stated that tocilizumab (TCZ) can resist inflammatory cytokine release syndrome in patients with severe COVID-19 disease and the importance of early diagnosis and treatment [3, 6].

The data of 2 international, multicenter, randomized controlled studies conducted with TCZ are as follows; In the COVACTA [7] study, although the time to discharge from the hospital was shortened, no significant difference could be shown between the placebo group on the 28th day in terms of clinical status or mortality. In the EMPACTA [8] study, it was shown that patients who received TCZ had lower intubation need or mortality on the 28th day compared to the placebo group.

The safety of TCZ for use in rheumatoid arthritis has been demonstrated in five phases III double-blind controlled studies [9]. However, it was approved for the treatment of cytokine release syndrome during the pandemic and close follow-up was recommended in terms of risks such as severe infections, thrombocytopenia, neutropenia, liver damage, and development of secondary infection [5]. In the multicenter international study [10] in a large group of patients in the intensive care unit (ICU), nine serious adverse events, including one secondary bacterial infection, five bleeding events, two cardiac events, and one visual impairment, were reported in the TCZ treatment group. Eleven serious adverse events were reported in the control group, including four bleeding events and seven thromboses. In the COVECTA study, the side effect profile was similar to that of the placebo group.

In the present study, we aimed to retrospectively present the clinical outcomes and the effect of treatment on the radiological changes and laboratory parameters associated with cytokine storm in our patients who were diagnosed with COVID-19 and treated with the IL-6 receptor inhibitor TCZ in the ICU. Thus, we aimed to recommend more appropriate follow-up parameters in patients receiving TCZ treatment.

2. Materials and methods

Following the approval of the Ethics Committee (Protocol No: 2020/514/179/15 Date: 11-JUN-2020), the data of the patients who were followed up with the diagnosis of COVID-19 in the intensive care units designated to patients with coronavirus in our hospital between March 23 and June 15, 2020, were retrospectively analyzed. Patients’ data including age, gender, date of ICU admission, and severity of involvement according to chest X-rays (CXR) obtained before and after treatment, whether they received immune plasma therapy or not, TCZ doses received and 28-day ICU mortality was accessed in the hospital information system and recorded.

Inclusion criteria:

(1) Patients older than 18 years old, whose SARS-CoV-2 infection was confirmed with a real-time Polymerase Chain Reaction (PCR) using nasopharyngeal swabs.

(2) Patients who underwent computed tomography (CT) before ICU admission.

(3) Patients who were administered TCZ due to COVID-19 infection during ICU stay.

Exclusion criteria:

(1) Patients whose data could not be accessed.

(2) Patients who were not diagnosed with COVID-19 by PCR test but were given TCZ due to potential COVID-19 diagnosis according to radiological and clinical findings.

In this study, C-reactive protein (CRP), LDH, IL-6, D-dimer, procalcitonin (PCT), and ferritin were considered as positive acute phase reactants that could indicate cytokine storm, and albumin was considered as a negative acute-phase reactant. The CRP, LDH, IL-6, D-dimer, PCT, albumin, and ferritin values, which were routinely screened in our clinic on the day of tocilizumab treatment and the 5th day after, were recorded.

TCZ was administered at a dosage of 8 mg/kg (maximum 800 mg) by two consecutive intravenous infusions 12 hours apart. All patients receiving intravenous TCZ were treated according to a standard pharmacological protocol, including antiviral drugs (favipiravir in a regimen of 1600 mg loading dose followed by 2 × 600 mg maintenance dose, for 5 days in total), antibiotic prophylaxis (azithromycin, ceftriaxone, or piperacillin/tazobactam), and 400 mg hydroxychloroquine. Additionally, patients who received convalescent immune plasma therapy were also noted.

Analyzes of the data obtained were interpreted by making the comparison between 17 patients with no survival at day 28 (Group 1) and 6 patients with survival (Group 2) in the light of the laboratory data of these 23 patients receiving treatment recorded on the day of tocilizumab treatment and 5 days after the treatment. Patients’ respiratory support type (invasive mechanical ventilation (IMV)), and the used oxygen delivery system (face mask (FM) or high-flow nasal cannula (HFNC)) were recorded before the treatment.

TCZ treatment was applied to patients without active infection, acquired immunosuppressive disease, and active tuberculosis.

2.1 Scoring of chest radiography and thorax tomography involvement

All CT examinations for the screening of SARS-CoV-2 pneumonia were performed with three scanners (128 section Philips ingenuity and 16-section Toshiba Alexion) without the use of contrast material. The main scanning protocol was as follows: tube voltage, 120 kVp; tube current modulation,120 mA-380 mA; detector configuration, 64 × 0.625 mm or 16 × 0.625 mm; rotation time, 0.5–0.7 s; slice thickness, 5 mm; and pitch, 0.984. The reconstruction kernel was lung with a thickness and an interval of 0.625 mm. All images were viewed in both lungs (width, 1200 HU; level, –700 HU) and mediastinal (width, 350 HU; level, 40 HU) settings. One radiologist (O.A.) with 20 years of experience, was blinded to the other clinical information and reviewed the chest CT scans independently in random order.

The images were interpreted using the lung window setting. A standardized protocol was followed for assessing the CT images [11]. The subsegmental, segmental, and lobar anatomic distributions were recorded. The extent of the lesions was evaluated as focal, multifocal, and diffuse. The zonal predominance was evaluated as upper, middle, lower lung; central, middle, or peripheral location [12]. A mixed pattern was described as the presence of crazy paving and air bronchogram [13]. Each of the five lung lobes was assessed for the degree of involvement.

Scoring the percentages of each of the five lobes was performed using the Severity Score [14]:

(1) <5% involvement

(2) 5%–25% involvement

(3) 26%–49% involvement

(4) 50%–75% involvement

(5) >75% involvement

The total CT score is the sum of the individual lobar scores and can range from 0 (no involvement) to 25 (maximum involvement) when all the five lobes show more than 75% involvement.

The CXR scoring system includes two steps. First, the lungs were divided into six zones on frontal chest projection (two upper zones, two middle, and two lower). Second, each zone was scored based on the following:

0: No lung abnormalities

1: Interstitial infiltrates

2: Interstitial predominance with interstitial and alveolar infiltrates

3: Alveolar predominance with interstitatial and alveolar infiltrates

The researchers added the scores of the six lung zones for an overall score between 0 and 18. A thoracic radiologist (O.A.) independently assessed each chest X-ray, evaluating the original score.

2.2 Statistics

Findings were analyzed using IBM SPSS Statistics 25. In the paired comparison of numerical data groups, the Independent Samples T test was used for those who fit the normal distribution, the Mann Whitney-U test for those who did not, and the Chi-square test for the examination of discrete variables. The results were evaluated at a 95% confidence interval, and the value of P < 0.05 was considered statistically significant [15].

3. Results

None of the patients enrolled in the study needed to be excluded from the study. A total of 23 patients aged from 22 to 81 years of age (55.35 ± 13.31 years) were included in the study. While immune plasma was administered to eight patients, 15 patients did not receive immune plasma. Seventeen patients (Group 1) who did not survive till day 28 and 6 patients who survived (Group 2) were evaluated.

Our patients who were divided into two groups according to their 28-day survival results in the ICU did not significantly differ in demographic characteristics, the duration of treatment in the ICU, the day of ICU follow-up when TCZ treatment was applied, and whether they received immune plasma therapy or not. The CT severity score assessed at the ICU admission was statistically significantly higher in Group 1 compared to Group 2 (P < 0.05, Table 1 and Fig. 1).

Table 1.Demographic characteristics of the groups.
Group 1 (n = 17)Group 2 (n = 6)P
Age58.35 ± 11.9246.83 ± 14.390.067s
ICU stay (day)12.35 ± 7.36 (11)18.50 ± 11.96 (19)0.505m
CT score10.75 ± 4.2816.50 ± 2.260.006*s
TCZ receivingday5.94 ± 4.55 (5)4.17 ± 3.06 (2.5)0.396m
Gender
Female1 (5.9%)0 (0.0%)0.544k
Male16 (94.1%)6 (100.0%)
Immuneplasma
No11 (64.7%)4 (66.7%)0.931k
Yes6 (35.3%)2 (33.3%)
CT, Computed Tomography; ICU, Intensive Care Unit; TCZ, Tocilizumab.ˢ İndependent Samples T test: values are given as mean ± Standard deviation.ᵐ Mann Whitney U test: values are given as mean ± Standard deviation (median).ᵏ Chi-square test: values are given as frequency (percentage). *P < 0.05: statistically significant difference.
Demographic characteristics of theg roups. CT, Computed Tomography; ICU, Intensive Care Unit; TCZ, Tocilizumab.

Fig. 1.Demographic characteristics of theg roups. CT, Computed Tomography; ICU, Intensive Care Unit; TCZ, Tocilizumab.

It was found that the PCT and LDH values of our patients measured on day 5 after TCZ were significantly lower in Group 2 than in Group 1 (P < 0.05, Table 2 and Fig. 2).

Table 2.Comparison of laboratory data between groups on the first and on the fifth day of TCZ treatment.
Group 1 (n = 17)Group 2 (n = 6)P
CRP 1st183.84 ± 95.85150.27 ± 120.090.603s
CRP 5th70.21 ± 72.4817.92 ± 15.370.143s
IL-6 1st1059.4 ± 2737.8 (291.4)588.8 ± 816.9 (294.7)0.726m
IL-6 5th1411.2 ± 1578.2 (922.9)1576.2 ± 1891.4 (810.25)0.877m
LDH 1st691.18 ± 226.72556.83 ± 142.090.192s
LDH 5th1107.5 ± 924.0 (887.5)510.75 ± 92.8 (527.5)0.029*m
D dimer 1st6534.7 ± 7861.3 (2370)2006.0 ± 1302.95 (1580)0.108m
D dimer 5th13805.0 ± 12096.6 (7900)10015.0 ± 13441.4 (4470)0.26m
PCT 1st4.80 ± 7.66 (1.13)0.57 ± 0.42 (0.49)0.090m
PCT 5th1.51 ± 1.15 (1.375)0.19 ± 0.13 (0.136)0.011*m
Albumin 1st26.24 ± 4.02 (25)27.50 ± 3.45 (27.5)0.418m
Albumin 5th26.55 ± 5.5030.0 ± 7.300.310s
CXR score 1st10.76 ± 4.0912.67 ± 2.940.309s
CXR score 5th14.59 ± 2.8913.50 ± 3.510.461s
Ferritin 1st1107.9 ± 424.8 (1210)796.9 ± 490.6 (621)0.196m
Ferritin 5th676.4 ± 438.7 (436.5)339.0 ± 160.7 (316)0.126m
CRP, C Reactive Protein; CXR, Chest X-Ray; IL, Interleukin; LDH, Lactate Dehydrogenase; PCT, Procalcitonin; 1st, The first day of TCZ treatment; 5th, Fifth day of TCZ treatment. s Independent Samples T test: values are given as mean m Standard deviation. ᵐ Mann Whitney U test: values are given as mean ± Standard deviation (median). *P < 0.05: statistically significant difference.
Comparison of laboratory data between groups on the first and on the fifth day of TCZ treatment. CRP, C Reactive Protein; CXR, Chest X-Ray; IL, Interleukin; LDH, Lactate Dehydrogenase; PCT, Procalcitonin; 1st, The first day of TCZ treatment; 5th, Fifth day of TCZ treatment.

Fig. 2.Comparison of laboratory data between groups on the first and on the fifth day of TCZ treatment. CRP, C Reactive Protein; CXR, Chest X-Ray; IL, Interleukin; LDH, Lactate Dehydrogenase; PCT, Procalcitonin; 1st, The first day of TCZ treatment; 5th, Fifth day of TCZ treatment.

According to the data obtained on the 5th day after treatment, the levels of CRP, ferritin, IL-6, CXR, and D-dimer of 23 patients who were treated with TCZ statistically significantly changed compared to the first day of the treatment. While there was a significant decrease in CRP and ferritin values (P < 0.05), D-dimer, IL-6 and radiological involvement severity score significantly elevated (P < 0.05, Table 3).

Table 3.Changings on radiological involvement and laboratory data the first and 5th days of TCZ treatment.
The first day (n = 23)The fifth day (n = 23)P
CRP168.21 ± 102.88 (166.5)55.26 ± 64.06 (33.2)0.003*
IL-6936.64 ± 2376.5 (291.4)1461.95 ± 1600.3 (922.9)0.050*
LDH656.13 ± 213.56 (637)958.31 ± 836.13 (792.5)0.162
D-dimer5505.5 ± 7154.2 (2335)12857.5 ± 12096.1 (7075)0.009*
PCT3.65 ± 6.76 (0.685)1.07 ± 1.13 (0.415)0.160
Albumin26.57 ± 3.8527.63 ± 6.10.544s
CXR scoring11.26 ± 3.8514.64 ± 2.630.001*s
Ferritin1056.64 ± 455.28 (1174.5)587.08 ± 388.6 (420.0)0.005*m
CRP, C Reactive Protein; CXR, Chest X-Ray; IL, Interleukin; LDH, Lactate Dehydrogenase; PCT, Procalcitonin; TCZ, Tocilizumab. s IndependentSamples T test: valuesaregiven as mean ± Standard deviation. ᵐ Mann Whitney U test: values are given as mean ± Standard deviation (median). ᵏ Chi-square test: values are given as frequency (percentage). *P < 0.05: statistically significant difference.

No significant difference was detected between Group 1 and Group 2 regarding the respiratory support and O2 delivery system provided to the patients from day 1 to day 5 of the treatment (Table 4).

Table 4.Respiratory supports of the first and 5th days of TCZ treatment.
Group 1 (n = 17)Group 2 (n = 6)P
1st day respiratory supports
Face mask1 (5.9%)1 (16.7%)0.499k
HFNC6 (35.3%)3 (50.0%)
Intubated10 (58.8%)2 (33.3%)
5th day respiratory supports
HFNC2 (11.8%)3 (50.0%)0.146k
Intubated9 (52.9%)2 (33.3%)
Mortality6 (35.3%)1 (16.7%)
HFNC, High-Flow Nasal Cannula; TCZ, Tocilizumab. ᵏ Chi-square test: values are given as frequency (percentage).

A statistically significant association was indicated between the increase of the CT score assessed at ICU admission and the decrease of PCT level on the 5th day after treatment and survival on day 28 (P = 0.006 and 0.049, Table 5).

Table 5.Relationshipbetween CT scoreand PCT changeswith ICU survival.
CT score before TCZPCT on the 5th day after TCZ
Survival on the 28th day of hospitalizationPearson correlation0.5700.578
P value0.006**0.049*
N2312
Correlation is significant at the 0.01 level (2-tailed).**
Correlation is significant at the 0.05 level (2-tailed).*
CT, Computed Tomography; ICU, Intensive Care Unit; PCT, Procalcitonin; TCZ, Tocilizumab.

The treatment was not stopped due to the development of side effects in any of the patients who received TCZ.

4. Discussion

This study evaluated the effect of TCZ therapy on the outcome of patients with COVID-19. Our results support the effectiveness of TCZ in the prevention or treatment of cytokine storms caused by COVID-19. In many patients, acute phase reactant levels such as CRP, PCT and ferritin decreased, whereas LDH, IL-6 and D-dimer levels increased. In correlation with the decrease in PCT as of the 5th day after TCZ administration, an increasing tendency was observed in 28-day survival.

In a comprehensive review on TCZ, CRP and IL-6 were preferred primarily as follow-up markers [16]. In our study, emphasizing the importance of PCT follow-up may be remarkable in the follow-up of these patients. In a recent multi-center study [10] conducted on critically ill patients in the ICU, in which 353 patients were tocilizumab, 48 were sarilumab, and 402 were the control group, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab was reported to improve outcomes. In this study, subgroup analysis was made according to CRP. In our study, it has been shown that tocilizumab treatment can positively contribute to the treatment by lowering cytokine levels.

Regarding the mean age and gender distribution of the patients, our results correspond to similar studies [17]. It has been reported that IL-6 can be used to assess the severity of the infection and predict prognosis in COVID-19 patients [18]. Similarly, some studies have defined hyperferritinemia and IL-6 as predictors of poor outcome and based on this, shown a hyperinflammatory process as the main cause of death [3]. In a case series of 15 patients with COVID-19, PanLuo et al. [19] shared their experiences with TCZ and reported that after TCZ treatment, blood plasma levels of IL-6 initially increased but then decreased, and CRP levels decreased. IL-6 is eliminated mainly by IL-6R mediated clearance [20], and binding of TCZ to IL-6 inhibits receptor-mediated clearance of IL-6, leading to its accumulation in serum. This is interpreted as the main reason for elevated IL-6 levels in the first phase after TCZ treatment. When all our patients were considered regardless of survival, there was significant elevation in IL-6 and D-dimer levels from pre-treatment to post-treatment, while there was a significant fall in CRP levels. However, neither CRP nor D-dimer has been shown is to be effective in predicting survival.

In the study conducted by Toniative et al. [21], 10 days after TCZ administration, the levels of CRP, fibrinogen, and ferritin levels dropped off towards the normal range, while D-dimer and IL-6 levels were reported to increase in both improved and worsened cases. LDH and ferritin levels were determined as parameters that showed a significant decrease with treatment on day 5.

Analysis of the peripheral blood of 69 severely ill COVID-19 patients indicated elevated ferritin levels compared to patients with non-severe disease, and serum ferritin levels were concluded to be closely related to the severity of COVID-19 [22]. Consistent with this, another study reported that ferritin levels in patients who died of COVID-19 were elevated at admission to the hospital and during hospitalization. After the 16th day of hospitalization, the median values of serum ferritin levels exceeded the upper limit in these patients, and it was thought that ferritin levels increased steadily [4]. Although there was no significant difference between the patient groups in terms of serum ferritin levels in ourstudy, considering the association between elevated ferritin levels and poor prognosis, it was thought that a significant fall in ferritin levels after TCZ treatment support the effectiveness of the treatment.

In the series of 77 patients who received TCZ treatment, Moreno-Pérez et al. [23] stated that LDH was a marker of mortality and that according to all TCZ responses evaluated, no difference was found regarding the effect on the length of stay in the ICU. In our study, similar basal LDH levels were observed between the mortal group and the well-survived group, but the LDH level measured on the 5th day after treatment was found to be significantly higher in the mortal group.

Even though the TCZ response was shown with pre-treatment and post-treatment laboratory parameters in our study, no significant difference was found between the groups in the days of ICU stay. However, a statistically significant association was detected between the elevation of the thoracic CT score assessed at admission to the intensive care unit and survival at ICU on day 28.

In the autopsy results of the patients who died of COVID-19, macroscopic features that have been reported include pleurisy, pericarditis, pulmonary consolidation, pulmonary edema, and microscopic findings include inflammatory infiltrates mainly composed of monocytes and macrophages, and diffuse alveolar damage, minimal lymphocyte infiltration, and large atypical pneumocytes and multinucleated giant cells [24, 25]. Autopsy results are similar to macrophage activation syndrome (MAS) characterized by cytokine storm, yet in severe COVID-19 cases, there have been several abnormal laboratory parameters observed similar to those in MAS. The absence of other features such as classical organomegaly led to the assumption that hyperactivation of the immune system is mainly limited to the lung parenchyma [26].

The uncontrolled proliferation of immune cells, the production of proinflammatory mediators, and the development of cytokine storm syndrome are thought to be the main cause of lung involvement [27]. When we analyzed our results, we concluded that the patients that experienced the cytokine storm most intensively were the patients who benefited most from anti-cytokine treatment.

In a prospective series of 100 consecutive patients admitted to the hospital with ARDS on the 10th day of TCZ in Italy, 77 patients experienced a significant decrease in CXR and improvement in respiratory conditions, while 23 patients reported worsening breathing and 20 died [21]. In contrast with these results, our study consisting of 23 patients demonstrated a significant decrease in the CXR involvement score rated at the evaluation of the treatment on day 5, and there was no significant difference between the groups in terms of the type of respiratory support and the need for O2.

Another prominent treatment option in the management of critically ill COVID-19 patients has been the application of convalescent immune plasma. However, despite less comprehensive studies [28] recommending the procedure; there are studies with a higher number of patients that argue the procedure to be non-efficient [29]. In this study, 8 patients were administered immune plasma therapy and the rate of plasma therapy was similar between the groups. Therefore, we think that immune plasma treatment did not affect the results of TCZ treatment in this study group.

It is recommended to monitor the acute phase reactants such as CRP, PCT, ferritin, D-dimer for following the effectiveness of TCZ, which is applied as an alternative treatment method in COVID-19 patients [23]. In the data we evaluated retrospectively, the most effective change was detected in PCT values, and thus, it was thought to have an important value in reflecting survival. We found an increase in survival associated with a decrease in PCT, especially on day 5. We attribute this to the role of PCT as a secondary infection marker. The absence of secondary infection can be directly related to survival. These results made us think that PCT and LDH follow-up is more effective in predicting prognosis than radiological improvement in patientswith TCZ treatment.

The limitation of this study is retrospective design and low sample size.

5. Conclusions

All kinds of clinical data are valuable in COVID-19 infection, for which there is no definitive treatment yet and many therapies are presented in the guidelines as non-precise recommendations. This study demonstrated that TCZ treatment may positively contribute to the treatment by decreasing cytokine levels. PCT and LDH follow-up before and after treatment in ICU patients who are receiving TCZ treatment can give an idea about survival.

Author contributions

FÇ: Conceptualization, Methodology, Software. AS: Data curation, Writing—Original draft preparation. YB: Visualization, Investigation. EAD: Supervision. EB: Software, Validation. KTS: Writing—Reviewing and Editing.

Ethics approval and consent to participate

The ethical committee of Kartal Dr. Lütfi Kırdar City Hospital declared ethical approval for the current study (Protocol No: 2020/514/179/15 Date: 11-JUN-2020).

Acknowledgment

I would like to express my gratitude to all those who helped me during the writing of this manuscript.

Funding

This research received no external funding.

Conflict of interest

The authors declare no conflict of interest.

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