Prognostic Significance of Hematological Parameters in Hospitalized Elderly with COVID-19

Background/Aim: COVID-19 is a global pandemic; it caused more than 256 million cases, early detection of patients at high risk of mortality is of great importance in saving lives of COVID-19 patients. “In our study” we aimed to utilize the hematological parameters in predicting prognosis and mortality among elderly patients diagnosed with COVID19 infection admitted at Geriatric isolation hospital, Ain Shams University during the period from 26/12/2020 to 20/6/2021. Methods : This is a retrospective cohort study involving elderly patients admitted at Geriatric isolation hospital, Ain Shams University during the period from 26/12/2020 to 20/6/2021.Retrospective evaluation of medical records was used to collect data. The study included patients older than 60 years with proof of SAR-CoV2 by nasopharyngeal swab. Serial complete blood count parameters were reported during admission: hemoglobin (Hb), Total leukocytic count (TLC), Neutrophils (N), lymphocytes (L), platelets (PLT), Red Cell Distribution Width (RDW), Neutrophil/lymphocyte(NLR), platelet/lymphocyte(PLR) ratios were calculated, other hematological parameters as C-reactive protein (CRP) and ferritin were reported. Results : Among 50 hospitalized COVID 19 patients with mean age of 68.5 years, 54% were males. Mortality of those patients has statistically significant association with presence of high NLR, CRP, Ferritin and lymphopenia on admission and the likelihood of patients’ mortality will rise with presence of NLR>12.4, CRP>120mg/L, FERRITIN>493.6mcg/L and Lymphocytes≤0.88 *10 9/ L on admission, however, presence of CRP>120mg/L is an independent factor for mortality in hospitalized elderly with COVID 19. Conclusion : Hematological parameters as (NLR, CRP, Ferritin and lymphopenia) are predictor markers for mortality in hospitalized elderly with COVID-19.


INTRODUCTION
By the end of 2019, many cases of pneumonia with unknown etiology emerged in Wuhan, Hubei Province, China.The pneumonia spread rapidly.
Then, more patients had similar symptoms.On 7 January 2020, the ovel corona virus was detected in the throat swab sample of one patient by the Chinese Center for Disease Control and Prevention (CDC).As the situation became worse, WHO announced the pandemic disease as corona virus disease 2019 (COVID- 19). (1)the most reported symptoms of COVID-19 are fever, dry cough, dyspnea and fatigue.There are various reported non-respiratory symptoms (e.g.diarrhea, nausea, vomiting, headache, and muscle pain). (2)It has been reported that COVID-19 may progress to acute respiratory distress syndrome, followed by septic shock, refractory metabolic acidosis, coagulation dysfunction, multiple organ failure and death.
(3) These adverse events represent 50% to 75% of deaths.They are more common in elderly patients and in those with previous comorbidities, especially diabetes, cardio and cerebrovascular diseases, obesity; cancer, digestive, endocrine, nervous, and respiratory systems pathologies. (4)severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) like many other known viruses can cause hematological changes that can predict the severity of infection.The occurrence of hematological manifestations was able in discriminating the severe and non-severe patients with COVID-19.A blood workup as well as continuous tracking of hematological changes could reveal risks of disease progression. (5)The most common hematological changes related to COVID-19 were lymphocytopenia, neutrophilia, mild thrombocytopenia, eosinopenia, and less common, thrombocytosis.Occasionally, reactive lymphocytes have been reported.However, leukocytic count may remain normal, become reduced or increased in response to SARS-COV2 infection.Many reports suggested that leukocytosis, lymphopenia and thrombocytopenia were related to disease severity and even fatality in COVID-19 cases. (6)Moreover, multiple observational studies have suggested that the neutrophil to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) considered as inflammatory markers of immunemediated, metabolic, and neoplastic diseases.They were commonly investigated as useful predictors for the prognosis in multiple diseases.Recent research of COVID-19 indicated patients with severe infection tended to have higher NLR. (7)Earlier reports have also indicated that Creactive protein (CRP) levels at admission and before discharge or death are markers of bad prognosis in patients with COVID-19.Higher (CRP) values during the early stages of the disease were associated with extensive lung involvement; Higher (CRP) values have been correlated with increased mortality in COVID-19 patients. (8)Also, High serum ferritin prior to the terminal event (which is, survival or death) were more significantly associated with death as the final outcome and high serum ferritin values at time of admission have been independently associated with a severe disease course. (9)

OBJECTIVE:
In our study, we aimed to utilize the hematological parameters in predicting the prognosis and mortality among elderly patients diagnosed with COVID19 infection admitted at Geriatric isolation hospital, Ain Shams University during the period from 26/12/2020 to 20/6/2021.

METHODS:
A retrospective cohort study was done using the medical records from Ain Shams Geriatrics University hospital from 26/12/2020 to 20/6/2021.A sample of 50 elderly patients older than 60 years both males and females with proof of SAR-CoV2 by nasopharyngeal swab were included.Sample size was suggested as 50 cases with expected 17 severe and 12 deaths achieves a power of 80% to detect an AUC of the ROC curve of at least 0.80 against the null value of 0.50 with level of significance of 0.05.While cases below 60 years old, those with preexisting hematological disorders, and those with end organ disease affecting CBC parameters e.g.chronic liver disease (CLD), chronic renal failure (CRF) were excluded.Demographic and clinical characteristics, co morbidities, laboratory findings, and outcome data of each patient were obtained from medical records.Serial complete blood count parameters were reported during their admission: hemoglobin (Hb), Total leukocytic count (TLC), Neutrophils (N), lymphocytes (L), platelets (PLT), Red Cell Distribution Width (RDW), Neutrophil/lymphocyte, platelet/lymphocyte ratios were calculated and other hematological parameters as Creactive protein (CRP) and ferritin were also reported.Qualitative variables were presented in the form of frequency tables (number and percent).A comparison between quantitative variables was carried out using student T test for parametric data and Mann Whitney test for nonparametric data.A comparison between qualitative variables was carried out using Pearson's χ2 test.Correlation between two quantitative variables was carried out using the Spearman correlation coefficient.The statistical differences were accepted when P < 0.05 and P< 0.001 were considered highly significant, logistic regression and ROC curve was also used to detect predictors of mortality and their cut off value.

RESULTS:
A sample of 50 elderly patients diagnosed with COVID-19 admitted at Geriatric isolation hospital from 26/12/2020 to 20/6/2021 was taken.Among those patients, the mean age was 68.5 years, 54% were males ( The likelihood of patients' mortality will rise with presence high NLR>12.4,CRP>120 mg/L, FERRITIN>493.6mcg/L and Lymphocytes≤0.88 *10 9/ L on admission so they can be used as predictors for mortality when present on admission, however, presence of CRP>120mg/L is an independent factor for mortality in hospitalized elderly with COVID 19.(Table 5).Through follow up of hematological parameters across length of hospital stay(day0,7-10 days after admission, at mortality), there is statistically significant difference in CRP between on admission and at mortality While there is statistically significant difference in Ferritin across the time and between on admission and at mortality (table 6).Furthermore, the induction of acute kidney damage and the extent of the cardiac injury has been directly linked with the CRP concentrations. (20)hrough follow up of hematological parameters across length of hospital stay patients at mortality, there is statistically significant difference in CRP between on admission and at mortality While there is statistically significant difference in Ferritin across the time and between on admission and at mortality that was supported by a retrospective study done by Chen et al.,2020 at which 548 patients with COVID-19 with different outcome (discharged or deceased) serial hematological parameters across 3 times period were recorded and showed that in non-survivor group there is upward trend or maintained higher levels of CRP and ferritin during hospitalization. (21)lso in retrospective study done by Mueller et al.,2020 at which 100 patients were included for evaluation and showed that rising CRP predicts subsequent respiratory deterioration and progressive respiratory failure later during their hospital course and subsequent mortality. (22)hat was in partial contrast with Chen et al., 2021 study at which serial laboratory parameters were collected retrospectively and patients were divided into two groups survived and non-survived and showed that CRP showed gradually increasing differences on prior to death.Unexpectedly, ferritin remained relatively elevated in both two groups throughout hospitalization as in Chen et al., 2021 study patients with malignancies and immunosuppression weren't excluded and that may affect inflammatory markers not only COVID19 infection effect. (23)

CONCLUSION
Hematological parameters as (NLR, CRP, Ferritin and lymphopenia) are predictor markers for mortality in hospitalized elderly with COVID-19.