“Serial ferritin titer” monitoring in COVID-19 pneumonia: valuable inflammatory marker in assessment of severity and predicting early lung fibrosis — prospective, multicentric, observational, and interventional study in tertiary care setting in India

Abstract
Introduction
The COVID-19 pneumonia is a heterogeneous disease with variable effect on lung parenchyma, airways, and vasculature leading to long-term effects on lung functions.

Materials and methods
Multicentric, prospective, observational, and interventional study conducted during July 2020 to May 2021, in the MIMSR Medical College and Venkatesh Hospital Latur India, included 1000 COVID-19 cases confirmed with RT-PCR. All cases were assessed with lung involvement documented and categorized on HRCT thorax, oxygen saturation, inflammatory marker, ferritin at entry point, and follow-up during hospitalization. Age, gender, comorbidity, and use of BIPAP/NIV and outcome as with or without lung fibrosis as per CT severity were key observations. CT severity scoring is done as per universally accepted standard scoring tool as score < 7 as mild, 7–14 as moderate, and score > 15 as severe affection of the lung. Statistical analysis is done by using chi-square test.

Observations and analysis
In study of 1000 COVID-19 pneumonia cases, 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 entry point with ferritin level has significant correlation in severity scores < 8, 8–15, and > 15 documented in normal and abnormal ferritin level as in 190/110, 90/210, and 40/360, respectively (p < 0.00001). Ferritin level has significant association with duration of illness, i.e., 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). Comorbidity as diabetes mellitus, hypertension, COPD, IHD, and obesity has significant association in COVID-19 cases with normal and abnormal ferritin level respectively (p < 0.00001). Ferritin level has significant association with oxygen saturation in COVID-19 pneumonia cases; cases with oxygen saturation > 90%, 75–90%, and < 75% are observed as normal and abnormal ferritin level in 110/100, 150/340, and 60/240 cases, respectively (p < 0.00001). BIPAP/NIV requirement during the course of COVID-19 pneumonia in critical care setting has significant association with ferritin level; cases received BIPAP/NIV during hospitalization were documented normal and abnormal ferritin level in 155/445 and 165/235 cases, respectively (p < 0.00001). Timing of BIPAP/NIV requirement during course of COVID-19 pneumonia in critical care setting has significant association with ferritin level; cases received BIPAP/NIV at entry point < 1 day, 3–7 days, and after 7 days of hospitalization were documented significance in fourfold raised ferritin level in 110/70, 150/160, and 30/80 cases, respectively (p < 0.00001). Follow-up of ferritin titer during hospitalization as compared to entry point abnormal ferritin has significant association in post-COVID lung fibrosis (p < 0.00001). Follow-up of ferritin titer during hospitalization as compared to entry point normal ferritin has significant association in post-COVID lung fibrosis (p < 0.00001).

Conclusion
Ferritin is easily available, sensitive and reliable, cost-effective, and universally acceptable inflammatory marker in COVID-19 pandemic. Ferritin has very crucial role in COVID-19 pneumonia in predicting severity of illness and assessing response to treatment during hospitalization. Follow-up of ferritin titer during hospitalization and at discharge can be used as early predictor of post-COVID lung fibrosis.