|Year : 2022 | Volume
| Issue : 3 | Page : 253-260
Role of ferritin as “Core Marker” in the assessment of severity, response to therapy and predicting outcome in COVID-19 pneumonia: A large, two-center, prospective, observational study of 1000 cases in tertiary care setting in India
Shital Patil1, Gajanan Gondhali2, Abhijit Acharya3
1 Department of Pulmonary Medicine, MIMSR Medical College, Latur, India
2 Internal Medicine, MIMSR Medical College, Latur, India
3 Department of Pathology, MIMSR Medical College, Latur, India
|Date of Submission||04-Mar-2022|
|Date of Decision||22-May-2022|
|Date of Acceptance||23-May-2022|
|Date of Web Publication||28-Jul-2022|
Dr. Shital Patil
MIMSR Medical College, Latur, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: Coronavirus disease 2019 (COVID-19) pneumonia is heterogeneous disease with variable effect on lung parenchyma, airways, and vasculature, leading to long-term effects on lung functions. Robust data of ferritin in bacterial infection are available, and now its role as an inflammatory marker in COVID-19 pneumonia during initial assessment and planning of treatment is evolving. Materials and Methods: Prospective, two-center, observational study conducted from July 2020 to May 2021, in MIMSR Medical College and Venkatesh Hospital Latur, India, included 1000 COVID-19 cases confirmed with reverse transcription-polymerase chain reaction. All cases were assessed with lung involvement documented and categorized on high-resolution computed tomography (CT) of the thorax, oxygen saturation, inflammatory marker, Ferritin at the entry point, and follow-up during hospitalization. Age, gender, comorbidity, and use BIPAP (bi-level positive airway pressure)/NIV (noninvasive ventilation) (BIPAP/NIV) and outcome with or without lung fibrosis as per CT severity were key observations. CT severity scoring was done as per universally accepted standard scoring tool as score <7 as mild, 7–14 as moderate, and score >15 as severe affection of lung. Statistical analysis is performed using Chi-square test. Results: Age (<50 and >50 years) and gender (male versus female) have significant association with ferritin in predicting severity of COVID 19 pneumonia (P < 0.00001) and (P < 0.010), respectively. CT severity score at the entry point with ferritin level has a significant association (P < 0.00001). Ferritin level has a significant association with the duration of illness (P < 0.00001). Comorbidities have a significant association with normal and abnormal ferritin levels, respectively (P < 0.00001). Ferritin level has a significant association with oxygen saturation (P < 0.00001). BIPAP/NIV requirement during treatment in critical care settings has a significant association with ferritin level (P < 0.00001). Timing of BIPAP/NIV requirement during the course of COVID-19 pneumonia in critical care settings has a significant association with ferritin level (P < 0.00001). Follow-up ferritin titer during hospitalization as compared to entry point normal and abnormal ferritin has a significant association in post-COVID lung fibrosis, respectively (P < 0.00001). Conclusions: Ferritin is easily available, sensitive, reliable, cost-effective, and universally acceptable inflammatory marker in COVID-19 pneumonia. Ferritin has a very crucial role in COVID-19 pneumonia in predicting the severity of illness and assessing response to treatment during hospitalization. Follow-up ferritin titer during hospitalization and at discharge can be used as early predictor of post-COVID lung fibrosis.
Keywords: Coronavirus disease 2019 pneumonia, ferritin, inflammatory marker, lung fibrosis, oxygen saturation
|How to cite this article:|
Patil S, Gondhali G, Acharya A. Role of ferritin as “Core Marker” in the assessment of severity, response to therapy and predicting outcome in COVID-19 pneumonia: A large, two-center, prospective, observational study of 1000 cases in tertiary care setting in India. Indian J Respir Care 2022;11:253-60
|How to cite this URL:|
Patil S, Gondhali G, Acharya A. Role of ferritin as “Core Marker” in the assessment of severity, response to therapy and predicting outcome in COVID-19 pneumonia: A large, two-center, prospective, observational study of 1000 cases in tertiary care setting in India. Indian J Respir Care [serial online] 2022 [cited 2022 Aug 11];11:253-60. Available from: http://www.ijrc.in/text.asp?2022/11/3/253/352646
| Introduction|| |
The current pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, originally emerged from China, but has since then confirmed cases 274,628,461 and deaths 5,358,978 worldwide, 34,752,164 confirmed cases 478,007 total deaths in India alone. The International Federation of Clinical Chemistry and Laboratory Medicine Task Force on COVID-19 has been established to synthesize up-to-date information on the epidemiology, pathogenesis, and laboratory diagnosis and monitoring of COVID-19, as well as to develop practical recommendations on the use of molecular, serological, and biochemical tests in disease diagnosis and management.,
COVID-19 pneumonia is heterogeneous disease with variable effects on lung parenchyma, airways, and vasculature, leading to long-term effects on lung functions. Although lung is the primary target organ involvement COVID-19, many patients have documented pulmonary and extrapulmonary manifestations due to various pathophysiological mechanisms as immune activation, inflammatory, thrombogenic, and direct viral affection to the lungs and extrapulmonary tissues.,
Ferritin is a highly ubiquitous iron-binding protein first isolated in 1937 from horse spleen, since then its isolation methodology and role as acute-phase reactant and role as marker of inflammation has been evolved over decades. Various inflammatory markers such as ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP), interleukin (IL)-6, and D-dimer have been evaluated in this pandemic and now robust data are available regarding its usefulness in analyzing severity, decision-making in critical cases, assessing response to interventions, and predicting outcome. Cytokine syndrome is defined as “A group of conditions sharing the same pathological mechanisms with different etiologies, causing massive release of pro-inflammatory cytokines resulting into aberrant activation of immune and coagulation systems.” Cytokine storms have direct association with raised ferritin levels and indirectly, it will help in predicting ongoing inflammatory surge, resulting in cytokine storm. Cytokine storm is the most dreadful event in the pathophysiology of COVID-19 pneumonia and ultimately, it will lead to either direct cytokine-induced lung injury manifesting as ALI/ARDS or extrapulmonary systemic secondary hemophagocytic lymphohistiocytosis. Studies have documented significantly raised ferritin with other inflammatory markers in COVID-19 pneumonia, and now, COVID-19 has been included in conditions causing hyperferritinemia.
Ferritin analysis was found to be very crucial in this COVID-19 pneumonia, apart from routine inflammatory marker, its usefulness as marker of underlying immunosuppression. In addition, it is useful in predicting the severity of illness in patients suffering from comorbidity as diabetes mellitus and in geriatric cases and marker of increased morbidity in these cases.,,
In the present study, we have utilized Ferritin as a basic marker in laboratory panel workup in all COVID patients and analyzed as core marker during follow-up in all admitted patients to assess response to therapy and predictor of post-COVID fibrosis as the dismal outcome of this pandemic of pneumonia in the tertiary care setting.
| Materials and Methods|| |
This study was approved by the Institutional Review Board/Ethics Committee at Venkatesh Hospital and Critical Care Center Latur India and MIMSR Medical college Latur India, (Approval # VCC/14-2020-2021; Approval date 19/07/2020).
Prospective, two-center, observational study, conducted from July 2020 to May 2021, in MIMSR Medical College and Venkatesh Hospital Latur, India, included 1000 COVID-19 cases confirmed with reverse transcription polymerase chain reaction (RT PCR), to find out the role of Ferritin in predicting severity of illness, assessing response to therapy and outcome as post-COVID fibrosis in diagnosed COVID-19 pneumonia cases admitted in the critical care unit. A total of 1000 cases were enrolled in the study after written and informed consent was obtained from all individual participants admitted in indoor units after assessing overall status to give consent and whenever required taken from attendants of critically ill admitted cases.
- Inclusion criteria: COVID-19 patients, confirmed with RT-PCR, above the age of 18 years, hospitalized in the study centers, including those with comorbidities and irrespective of severity and oxygen saturation were included in the study
- Exclusion criteria: Those not willing to give consent, not able to perform ferritin and not willing to remain in follow-up were excluded.
A total of 1190 COVID-19 RT-PCR cases admitted to Venkatesh Hospital (390 cases) and MIMSR Medical college (800 cases) were enrolled. A total of 190 cases excluded (168 cases excluded due to not willing to follow-up till 12 weeks of study and the death of 22 cases). Triaging of 1000 cases done with clinical assessment as oxygenations status, laboratory evaluation with the inflammatory marker as ferritin and radiological marker as computed tomography (CT) severity on high-resolution computer tomography (HRCT) thorax and hospitalized in indoor units accordingly. Initial and follow-up Ferritin titers were analyzed and evaluated for its association with severity assessment, oxygen saturation, ventilator support requirement, and timings of ventilator support application is recorded. Ferritin follow-up titers were analyzed again. Clinical outcome, clinical parameters, and improvement or deterioration in association with Ferritin follow-up titers were monitored. Ferritin follow-up titers were analyzed and the final radiological outcome as post-COVID-lung fibrosis was evaluated with follow-up HRCT thorax in association with ferritin titer [Figure 1].
All study cases were undergone following assessment before enrolling in the study
COVID-19 RT-PCR test was performed on nasopharyngeal samples collected with all standard institutional infection control policies, if the first test results were negative and radiological features clearly documenting pneumonia, we have repeated the RT-PCR test and enrolled all cases with positive COVID-19 RT-PCR test. HRCT of the thorax to assess the severity of lung involvement, and categorized as mild if score <7, moderated if score 8–15, and severe if score >15 or 15–25. Clinical assessment and routine biochemistry and hematological workup with viral inflammatory markers as CRP, ferritin, LDH, and IL-6 titers. Entry point Ferritin titer was utilized as assessment tool of severity of illness with clinical parameters. If Ferritin analysis was normal at entry point, then ferritin titer was repeated on day of discharge from hospital or done during hospitalization if clinical course deteriorates. If Ferritin analysis was abnormal at entry point, we repeated on every 72 h as follow-up to assess severity, progression of illness and also titer level utilized to assess response to medical treatment. Follow-up HRCT thorax was done after 12 weeks or 3 months of discharge from hospital for analysis of post-COVID lung fibrosis in selected cases with abnormal D-Dimer level at discharge and required BIPAP/NIV during hospitalization and cases required oxygen supplementation at home.
Methodology of ferritin titer assessment
- Principle: Sandwich immunoluminometric assay
- Interpretation of results with reference values: (1) Male: 14-250 ng/ml. (2) Female: Age <45 years old 6–160 ng/ml and age ≥45 years old 5–200 ng/ml. (3) Results may differ between laboratories due to variations in population and test method. Each laboratory should establish its own reference range
- Interpretation of results: (1) Negative: Values with in normal limit as per gender. (2) Positive: Value above reference range as per gender. (3) Significant: Two-fold raised value as per gender. (4) Highly significant: Four-fold raised as per gender. (5) Follow-up significance: Values raised or decreased in two-to-four-fold change as per gender.
The statistical analysis was performed using Chi-square test in R is available as a Free Software under the terms of the (Free Software Foundation's GNU General Public License in source code form, Vienna, Austria). Significant values of χ2 were seen from probability table for different degrees of freedom required. P value was considered statistically significant if it was below 0.05 and highly significant in case if it was <0.001.
Observations and analysis
In the present study, 1000 COVID-19 pneumonia cases confirmed by COVID-19 RT PCR, males were 650/1000 and females were 350/1000, age >50 were 600 cases and age <50 were 400 cases.
Significant association in Ferritin and COVID-19 pneumonia has been documented with variables such as age, gender, diabetes mellitus (DM), ischemic heart disease (IHD), hypertension (HTN), chronic obstructive pulmonary disease (COPD), and obesity (P < 0.00001) [Table 1].
|Table 1: Other variables and ferritin level in COVID-19 Pneumonia cases (n=1000)|
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CT severity score at entry point with Ferritin level has significant correlation in COVID-19 pneumonia cases (P < 0.00001) [Table 2].
|Table 2: Correlation of CT severity (at entry point) and ferritin in COVID-19 cases (n=1000)|
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Ferritin level has significant association with duration of illness (Doi) in COVID-19 pneumonia cases (P < 0.00001) [Table 3].
|Table 3: Duration of illness at entry point during hospitalization and Ferritin level in COVID-19 pneumonia cases (n=1000)|
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Ferritin level has significant association with oxygen saturation in COVID-19 pneumonia cases (P < 0.00001) [Table 4].
|Table 4: Association of oxygen saturation at entry point and ferritin level in COVID-19 pneumonia (n=1000)|
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BIPAP/NIV requirement during course of COVID-19 pneumonia in critical care setting has significant association with Ferritin level (P < 0.00001) [Table 5].
|Table 5: Correlation of BIPAP use with Ferritin level in COVID-19 pneumonia cases (n=1000)|
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Timing of BIPAP/NIV requirement during course of COVID-19 pneumonia in critical care setting has significant association with Ferritin level (P < 0.00001) [Table 6].
|Table 6: BIPAP/noninvasive ventilation initiation time at entry point and Ferritin level COVID-19 pneumonia cases (n=600)|
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Follow-up Ferritin titer during hospitalization as compared to entry point abnormal Ferritin has significant association in post-COVID lung fibrosis (P < 0.00001) [Table 7].
|Table 7: Abnormal Ferritin level at entry point (n=680) and follow-up and its correlation with post-COVID lung fibrosis|
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Follow-up Ferritin titer during hospitalization as compared to entry point normal Ferritin has significant association in post-COVID lung fibrosis (P < 0.00001) [Table 8].
|Table 8: Normal ferritin level (n=320) at entry point and follow-up and its correlation with post-COVID lung fibrosis|
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| Discussion|| |
Correlation of computed tomography severity (at entry point) and ferritin in coronavirus disease 2019 cases
In the present study, CT severity score at entry point with ferritin level has significant correlation i.e., score <8, 8–15 and >15 documented normal and abnormal ferritin level as in 190/110, 90/210 and 40/360, respectively, of total 1000 study cases (P < 0.00001). We have documented CT severity as the best visual marker of severity of COVID-19 pneumonia which can be correlated with inflammatory markers like ferritin, CRP, IL-6 LDH, D-Dimer and Lymphopenia, lymphocyte platelet ratio, and it will help in triaging cases in casualty and help in targeting interventions in indoor units accordingly to have successful treatment outcome. Authors Zhou et al. Kömürcüoğlu et al. documented similar observation in their study, mentioned that radiological severity as per HRCT thorax has correlation with inflammatory markers such as Ferritin, CRP, D-Dimer, and lymphopenia and observed prognostic role of these markers in COVID-19 pneumonia. Author Quirit et al., Zhou et al., Alroomi et al., Del Valle et al., and Huang et al., Montecino-Rodriguez et al., Dhont et al., and Wu et al. observed similar observation as positive association with CT severity and as CT severity increases which is the marker of more lung parenchymal inflammation and resulted in increased inflammatory burden documenting increased ferritin. Fox et al. documented in autopsy series in New Orleans regarding high ferritin level in cases with advanced pneumonia showing necrosis and hyaline membrane formation on histopathology of lung specimens.
Duration of illness at entry point during hospitalization and ferritin level in coronavirus disease 2019 pneumonia cases (n = 1000)
In the present study, ferritin level has significant association with Doi, i.e., cases Doi <7 days, 8–15 days and >15 days of onset of symptoms documented normal and abnormal ferritin levels in 30/310, 160/300, and 130/70 cases, respectively (P < 0.00001). Although ferritin is raised in COVID-19 pneumonia, we have documented that proportionate number of cases with Doi <1 week or 7 days and many cases with Doi >2 weeks or 15 days had normal ferritin level, while pneumonia cases between 7 and 14 days of illness had abnormal or raised ferritin level. Authors Zhou et al., Alroomi et al., Dhont et al., and Wu et al. observed that as Doi increases which ultimately resulting into progression of pneumonia and having high ferritin level in these cases. Raised Ferritin after 2nd week of illness may indicate worsening of COVID-19 pneumonia or secondary bacterial infection; which can be confirmed with procalcitonin assessment and it will help clinician to formulate antibiotics policy and important role in management. Reason for secondary bacterial infections in these cases may be immunosuppression due to hyperferritinemia or concurrent use of systemic corticosteroids in these cases. Authors, Abbaspour et al., Alroomi et al., and Meloni et al. documented usefulness of procalcitonin with other inflammatory markers and help in guiding treatment approach to curtail underlying bacterial infection and prevent mortality in intensive care units.
Correlation of BIPAP use with ferritin level in coronavirus disease 2019 pneumonia cases (n = 1000)
In the present study, BIPAP/NIV requirement during course of COVID-19 pneumonia in critical care setting has significant association with Ferritin level, i.e., cases received BIPAP/NIV with normal and abnormal ferritin level in 155/445, 165/235 cases, respectively [P < 0.00001] We have observed that ferritin level has very well correlation with requirement of BIPAP/NIV, high flow nasal canula oxygen supplementation and invasive mechanical ventilation in ICU setting. In the present study of 1000 cases, those required invasive ventilation were not included and excluded before enrollment of final 1000 cases due to death or poor outcome and unable to document follow-up for 12 weeks post discharge. Authors, Quirit et al. Zhou et al. Alroomi et al. observed in their study, high ferritin level is predictor of requirement of mechanical ventilation and poor predictor of outcome, especially when ferritin level is >1000 ng/ml. Authors Zhou et al. and Rasyid et al. observed that addition of neutrophil-to-lymphocyte ratio with ferritin is best predictor of ICU requirement and indirect useful marker of ventilatory support requirement in these cases. Del Valle et al. Montecino-Rodriguez et al., and Wu et al. documented correlation of ferritin level with mechanical ventilation requirement in intensive care unit. Rational for this observation is high ferritin and its strong association with extreme inflammatory burden in these patients having propensity to land in to hyperkinetic cytokine stimulation syndrome.
Correlation of oxygen saturation at entry point and ferritin level in coronavirus disease 2019 pneumonia cases (n = 1000)
In the present study, ferritin level has significant association with oxygen saturation, i.e., cases with oxygen saturation >90%, 75%–90%, and <75% observed as normal and abnormal ferritin level in 110/100, 150/340, and 60/240 cases, respectively (P < 0.00001). We have observed that, as oxygen saturation drops at entry point, ferritin level increases in significant number of COVID-19 cases. Rational for similar correlation may be hypoxia-inflammatory burden pathway go hand-in-hand and worsening of oxygenation is indicator of advanced pneumonia with inflammatory surge. Authors, Kömürcüoğlu et al., Alroomi et al., Rasyid et al. in Indonesia, and Sarfaraz et al. in Pakistan documented correlation of ferritin level with SPo2 level, and observed significant hypoxia in cases with high ferritin level above 1000 ng/ml. Authors Zhou et al., Del Valle et al., Montecino-Rodriguez et al., Dhont et al., and Wu et al. observed raised ferritin level will help in predicting severity of illness as many of these cases are having low oxygen saturation requiring interventions in intensive care units.
Correlation of BIPAP/NIV initiation time at entry point and Ferritin level coronavirus disease 2019 pneumonia cases (n = 600)
In the present study, timing of BIPAP/NIV requirement during hospitalization in critical care setting has significant association with ferritin level, i.e., cases received BIPAP/NIV at entry point <1 day, 3–7 days, and after 7 days of hospitalization were documented significance in four-fold raised ferritin level in 110/70, 150/160, and 30/80 cases, respectively (P < 0.00001).
We observed that early initiation of BIPAP/NIV in cases with oxygen saturation <89% at room air had beneficial effect in controlling systemic immune inflammatory syndrome which can be measured by ferritin level in follow-up; may be because of improvement in oxygenation and lung compliance after use of BIPAP/NIV; as hypoxia is important trigger for rise in inflammatory burden by means of hypoxia inducible transcription factor. Authors Zhou et al., Alroomi et al., Rasyid et al., Del Valle et al., Montecino-Rodriguez et al., and Wu et al. observed that ferritin level at entry point is very well, especially high level above 1000 ng/ml correlated with ventilatory support requirement in intensive care unit, many cases had cytokine storm like presentation with raised ferritin and other inflammatory markers like IL-6 and CRP.
Other important observation in this study
Correlation of abnormal ferritin level at entry point (n = 680) and follow up and its correlation with post-COVID lung fibrosis
In the present study, follow-up ferritin titer during hospitalization as compared to entry point abnormal ferritin titer has significant association in post-COVID lung fibrosis (P < 0.00001). The elevated levels of ferritin might be linked to the overproduction of inflammatory cytokines in severe COVID-19 pneumonia patients. Cytokines fight against the microbes but when the immune system becomes hyperactive, it can damage lung tissue. Thus, Ferritin production is induced by inflammatory cytokines and by tissue destruction both and final results of both the pathway is lung fibrosis. Authors, Alroomi et al., Dhont et al., and Ho et al. documented that Iron causes destructive effect due to inflammation which can be correlated with other inflammatory markers. Our findings are in accordance with documentations by Liu et al., Yasin et al., and Yu et al., and Wu et al., Ruan et al., Lin et al., Zhou et al., and Gandini et al., documented that raised titers during hospitalization and follow-up were having ongoing lung inflammation and can predict future lung fibrosis.
Correlation of normal ferritin level (n = 320) at entry point and follow-up and its correlation with post-COVID lung fibrosis
In the present study, follow-up ferritin titer during hospitalization as compared to entry point normal Ferritin has significant association in post-COVID lung fibrosis (P < 0.00001). In this study, few nonsevere cases progressed and developed advanced pneumonia in the first 2 weeks of Doi. Therefore, health care institutions should also pay close attention to the mild patients, identify progressors early, and provide appropriate treatment to reduce mortality. Authors Zhou et al., Yu et al., and Yan et al. documented persistent abnormality in inflammatory markers indicates state of unstoppable inflammation, resulting in necrosis and resultant fibrosis, which is ultimate sequalae of ARDS either due to COVID-19 or MERS. Authors Ye et al., Xu et al., Song et al., Pan et al., and Shi et al. observed that increased fibromyxoid stroma and organized consolidations have propensity of residual lung fibrosis which has been very well correlated with increased inflammatory markers.
Correlation of other variables and ferritin level in coronavirus disease 2019 pneumonia cases
- In the present study, age of patient, i.e., <50 and > 50 years and gender have significant association in COVID-19 cases with normal and abnormal ferritin level (P < 0.00001) and (P < 0.010), respectively. Similarly, authors Zhou et al., Ma et al., Dahan et al., Quirit et al., Zhou et al., Alroomi et al., Rasyid et al., Del Valle et al., Sarfaraz et al., Montecino-Rodriguez et al., Ho et al., and Wu et al. observed role of ferritin in predicting severity in geriatric cases in their study
- In the present study, comorbidity as diabetes mellitus, COPD, hypertension, IHD, and obesity has significant association in COVID-19 cases with normal and abnormal Ferritin level (P < 0.00001). Authors, Zhou et al. Ma et al., Dahan et al., Quirit et al., Zhou et al., Alroomi et al., Rasyid et al., Del Valle et al., Sarfaraz et al., Huang et al., Montecino-Rodriguez et al., and Wu et al. observed role of ferritin in predicting severity in cases with comorbidities such as DM, HTN, IHD, CKD, and COPD.
Limitations of the study
Our study is having enough sample size and analyzed role of ferritin at entry point and follow-up during 12 weeks period and association with post-COVID-19 lung fibrosis is documented. Limitations of this study are multivariate analysis which will help in finer details associated with ferritin level and oxygenations status, severity of illness, ventilatory support requirement and post COVID lung fibrosis is not done. Second limitation is other confounding factors, leading to abnormal ferritin level and its effect on COVID-19 severity parameters were not possible. Third limitation is association of ferritin titer with other modes of intensive care treatments as high flow nasal canula and invasive mechanical ventilatory support is not assessed differently and cases predominantly on BIPAP/NIV were considered as ventilatory support, probably because majority of COVID-19 cases receiving high flow nasal canula were shifted to BIPAP/NIV and or mechanical ventilation in intensive care units.
| Conclusions|| |
Ferritin is easily available, sensitive, and universally acceptable inflammatory marker in COVID-19 pneumonia. Ferritin has very crucial role in COVID-19 pneumonia in predicting the severity of illness, especially follow-up titers have significant role in step-up or step-down interventions in critical care setting. Correlating Ferritin with variables such as Doi, oxygenation status, and timing of BIPAP/NIV has important role in predicting outcome.
Ferritin titer has significant associations in predicting progression of pneumonia, as proportionate number of pneumonia cases with mild variety on CT thorax with normal initial ferritin titer have progressed to critical course and we have documented follow-up titers has played crucial role in this setting which can be correlated with other inflammatory markers and guided to target interventions accordingly in intensive care units. Ferritin follow-up titer can help in predicting progression of COVID-19 pneumonia and need of aggressive interventions, and indicates more inflammatory lung parenchymal damage which is precursor of underlying lung fibrosis as long-term outcome.
Written and Informed consent was obtained from all individual participants admitted in indoor units after assessing overall status to give consent and whenever required taken from attendants of critically ill admitted cases.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]