key: cord-0803113-5gvq968i
authors: Olivieri, Fabiola; Sabbatinelli, Jacopo; Bonfigli, Anna Rita; Sarzani, Riccardo; Giordano, Piero; Cherubini, Antonio; Antonicelli, Roberto; Rosati, Yuri; Del Prete, Simona; Di Rosa, Mirko; Corsonello, Andrea; Galeazzi, Roberta; Domenico Procopio, Antonio; Lattanzio, Fabrizia
title: Routine laboratory parameters, including complete blood count, predict COVID-19 in-hospital mortality in geriatric patients
date: 2022-04-11
journal: Mech Ageing Dev
DOI: 10.1016/j.mad.2022.111674
sha: 22df2ffb40cd08d3c8c5450f73e797999ec5f807
doc_id: 803113
cord_uid: 5gvq968i

To reduce the mortality of COVID-19 older patients, clear criteria to predict in-hospital mortality are urgently needed. Here, we aimed to evaluate the performance of selected routine laboratory biomarkers in improving the prediction of in-hospital mortality in 641 consecutive COVID-19 geriatric patients (mean age 86.6±6.8) who were hospitalized at the INRCA hospital (Ancona, Italy). Thirty-four percent of the enrolled patients were deceased during the in-hospital stay. The percentage of severely frail patients, assessed with the Clinical Frailty Scale, was significantly increased in deceased patients compared to the survived ones. The age-adjusted Charlson comorbidity index (CCI) score was not significantly associated with increased risk of death. Among the routine parameters, neutrophilia, eosinopenia, lymphopenia, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, procalcitonin, IL-6, and NT-proBNP showed the highest predictive values. The fully adjusted Cox regressions models confirmed that high neutrophil %, NLR, derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), and low lymphocyte count, eosinophil %, and lymphocyte-to-monocyte ratio (LMR) were the best predictors of in-hospital mortality, independently from age, gender, and other potential confounders. Overall, our results strongly support the use of routine parameters, including complete blood count, in geriatric patients to predict COVID-19 in-hospital mortality, independent from baseline comorbidities and frailty.

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been recognized as the causative agent for human coronavirus disease . COVID-19 patients are characterized J o u r n a l P r e -p r o o f Since age is the main risk factor for COVID-19 severe outcomes, geriatric patients should be extensively investigated. A recent study demonstrated that, besides age, immune and laboratory features at hospital admission can affect mortality prediction substantially more than the presence of concomitant clinical comorbidities (Lombardi et al., 2021) . In addition, when daily values and trends over time of relevant laboratory parameters were evaluated during the intensive care unit (ICU) stay in association with the severe outcomes in COVID-19 critically ill patients, both daily values or trends over time of parameters associated with acute organ dysfunction, acid-base derangement, coagulation impairment, or systemic inflammation were associated with patient survival (Zanella et al., 2021) . However, even if recently consistent evidence of a positive association between a number of routine laboratory biomarkers and COVID-19 severity was provided, further research is needed to clarify whether these results would be consistent across different countries and populations.

Our objective was to examine the association between the most commonly investigated laboratory biomarkers, especially routine blood count parameters, at hospital admission for COVID-19 and inhospital mortality, in an Italian sample of COVID-19 geriatric patients.

The present study used data from the Report-Age COVID project, an observational study conducted at the Italian National Center on Aging (IRCCS INRCA). It aims to deepen our understanding of COVID-19 in older patients hospitalized and diagnosed with COVID-19. All patients aged 65 years and above with confirmed COVID-19 who were admitted to the INRCA hospital from 1 st March 2020 to 24 th June 2021 were included in the study. The only exclusion criterion was lack of informed consent. The confirmed case was defined as a patient who had been confirmed to be infected with SARS-CoV-2 by real-time reverse transcriptase-polymerase chain reaction assay regardless of the clinical symptoms.

J o u r n a l P r e -p r o o f Estimated Glomerular Filtration Rate (eGFR) was estimated according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Levey et al., 2009 ).

Continuous variables were reported as either mean and standard deviation or median and interquartile range based on their distribution (assessed using the Shapiro-Wilk test). Comparison of variables between groups was performed by unpaired Student's t-test or Mann-Whitney U test as appropriate. Tertiles of laboratory parameters were calculated and, as other categorical variables, were expressed as absolute number and percentage and analyzed by Chi-square test.

The association between tertiles of % Neutrophils, % Lymphocytes, neutrophil-to-lymphocyte ratio (NLR), derived NLR ratio (dNLR, calculated as neutrophil count divided by the result of WBC count minus neutrophil count), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), and in-hospital death was initially investigated by Kaplan Meier curves. Therefore, we built Cox proportional hazards analysis to derive unadjusted (Model 1), age-and gender-adjusted (Model 2) and age-gender-and Clinical Frailty Scale (CFS)-adjusted (Model 3) hazard ratios (HR) and 95% confidence intervals (95% CI) of the association between all independent variables and study outcome. The length of hospital stay was used as the time to failure variable for the model. Schoenfeld's test was used to test proportional hazards assumptions.

Finally, six multivariable models were estimated adjusting for confounders that resulted statically significant in the previous step. Independent variables for these models were tertiles of % 

A total of 641 consecutive geriatric patients (mean age 86.6 ± 6.8) who were hospitalized at the INRCA hospital (Ancona, Italy) due to COVID-19 were included in the analysis. 34% (220/641) of the enrolled patients were deceased during the in-hospital stay. The mean number of days from hospital admission to discharge for the recovered patients was 17.3±11.1, and that for the deceased patients was 12.8±9.2. The minimum number of days for which patients in the recovered group remained hospitalized was 1 day, while the maximum number was 92 days for survived patients and 56 days for deceased patients.

With respect to medication use, most of the patients received corticosteroids during their hospital stays (n 462, 72.1%); with no significant difference (p=0.652) between deceased (n. 161, 73.2%) and survived (n. 301, 71.5%).

The clinical and laboratory characteristics of the study cohort (total patients= 641; survived patients = 421 and deceased patients = 221) upon admission are reported in Table 1 . Deceased patients were significantly older than survivors, and male sex was significantly more common among deceased patients.

The most frequent comorbidities among the cohort of patients were hypertension, dementia, and diabetes (Table 1) . Surprisingly, the proportions of subjects in each tertile of CCI score were not significantly different between survived and deceased patients, as well as single comorbidities. As expected, the proportions of patients with severe frailty, classified as CFS 7-9, were significantly increased in deceased patients (54.1 % in deceased vs 37.8 % in the survived patients). Among J o u r n a l P r e -p r o o f patients with a CFS score of 7, which indicates severe frailty but no imminent risk of death, the observed mortality was 35.3 %. On the other hand, mortality for patients with CFS scores of 8 and 9 was 44.2 % and 52.4 %, respectively. All the routine laboratory variables analyzed in this cohort were significantly different between deceased and survived patients, except for hemoglobin, basophil count, and serum potassium (Table 1) .

All the continuous variables reported in Table 1 were then categorized into tertiles, as reported in Table 2 . Regarding the WBC differential counts and the derived indexesneutrophil-tolymphocyte ratio (NLR), derived NLR ratio (dNLR), calculated as neutrophil count divided by the result of WBC count minus neutrophil count, platelet-to-lymphocyte ratio (PLR), and lymphocyteto-monocyte ratio (LMR)deceased and survived patients were characterized by significantly different distributions among tertiles. The proportion of patients with the highest neutrophil counts, both absolute and relative, was significantly higher among the deceased patients, whereas an opposite trend was observed for lymphocytes. Notably, also eosinopenia was significantly more frequent in deceased than surviving patients (Table 2) .

Receiver Operating Characteristic (AuROC) curves were computed to assess the ability of neutrophil and lymphocyte percentage counts, as well as NLR, to predict in-hospital mortality Regarding the other biochemical variables, a significantly higher proportion of deceased patients was characterized by increased levels of D-dimer, glucose, sodium, potassium, NT-proBNP, CRP, procalcitonin, IL-6, ferritin, and by reduced eGFR.

Subsequently, three different univariate Cox regression models that were unadjusted (model 1), ageand gender-adjusted (model 2), and age-, gender-, and CFS-adjusted (model 3), were computed for each variable (Table 3 ). The risk of mortality of patients in the highest tertile of neutrophil % at hospital admission was five to six-fold higher compared to the lowest tertile. Similar results were J o u r n a l P r e -p r o o f obtained for eosinopenia, and lymphopenia (%). Overall, neutrophilia, eosinopenia and lymphopenia (%) had the best ability in predicting in-hospital death.

NLR score showed a good predictive performance, whereas the other derived indices, i.e., dNLR, PLR, and LMR showed reduced predictive values. The Kaplan-Meier survival estimates and logrank tests for comparison for the abovementioned parameters are reported in Figure 2 .

Among the routine biochemical parameters, CRP, procalcitonin, IL-6, and NT-proBNP showed the highest predictive values (Table 3 and Supplementary Table 2 ).

Finally, fully adjusted Cox regressions models evaluating the predictive value of (a) neutrophil, lymphocyte and eosinophils percentage counts as well as (b) absolute counts, (c) NLR, (d) dNLR, (e) PLR, and (f) LMR, were fitted adjusting for age, gender, and tertiles of the variables significant at the univariate level. The results, reported in Table 4 and Supplementary 

The coronavirus disease 2019 (COVID-19) is characterized by a high rate of hospitalization, respiratory failure, and death, especially in the oldest patients. Intensive efforts were undertaken to early predict the most severe COVID-19 outcomes, ideally at the point of hospital admission.

Early prediction of COVID-19 in-hospital mortality relies usually on age and patients' preexisting comorbidities (Kim et al., 2021) . We enrolled a cohort of more than 600 COVID-19 patients with a mean age of 86 years, aimed to evaluate the role of routinely measured biomarkers of immunity and inflammation, in predicting in-hospital mortality. Growing evidence supports the relevant role played by inflammation in the progression of various viral pneumonia infectious, including J o u r n a l P r e -p r o o f COVID-19, since severe inflammatory responses contribute to weak adaptive immune response. In this framework, circulating biomarkers that can represent immune status and inflammation could predict COVID-19 prognosis.

Our results demonstrate that in geriatric patients admitted to hospital for COVID-19 the blood count parameters and some circulating biomarkers of inflammation have the best performance in predicting short-term mortality. We confirmed that COVID-19 outcomes were predicted by baseline frailty, i.e. before the onset of COVID 19 disease, estimated with the use of CFS. A number of recent studies demonstrated that the presence of severe frailty can stratify patients with COVID-19 at increased risk of in-hospital death, thus suggesting that the evaluation of frailty can support decision making about medical care in adult patients admitted to hospital with COVID-19 (Covino et al., 2021; Marengoni et al., 2021; Rebora et al., 2021; Saragih et al., 2021; Yang et al., 2021; Zhang et al., 2021) .

Surprisingly, preexisting comorbidities, evaluated through the age-adjusted CCI score, were not significantly associated with an increased risk of death in our cohort of older patients. Our results are in line with those reported recently in older patients affected by COVID-19 (Lombardi et al., 2021) . Additionally, about half of the enrolled patients had CCI equal or greater to 1 and about 25% had CCI equal or greater to 2 in our study, thus suggesting that overall comorbidity burden may have reduced discriminatory capacity in such a complex population of older frail patients. The percentage of patients with severe frailty was higher in deceased than in survived COVID-19 patients, confirming that frailty more than comorbidities is associated with in-hospital mortality. In this real-world population, prognostic factors different from those highlighted in other younger cohorts are likely to emerge.

Overall, these data suggest that the oldest patients admitted to hospital for COVID-19 with severe frailty and imbalanced blood cell counts and increased inflammatory circulating biomarkers are characterized by a significantly increased risk of death, independently from preexisting comorbidities.

Strong evidence has been accumulated since the beginning of the COVID-19 pandemic that neutrophils play an important role in the pathogenesis of severe disease course and that neutrophilia represents a feasible and inexpensive biomarker of COVID-19 severity . In COVID-19 patients, neutrophilia associated with lymphopenia was observed in patients with increased disease severity and with poor prognosis (Picchi et al., 2021; Yang et al., 2020; Zhu et al., 2021) . A number of studies showed a correlation between markers derived from standard blood count tests, such as neutrophil-to-lymphocyte ratio (NLR), derived NLR ratio (dNLR, neutrophil count divided by the result of WBC count minus neutrophil count), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) and systematic inflammatory response in a number of age-related diseases, including cancer (Xu et al., 2021; Ying et al., 2014) , type 2 diabetes mellitus (T2DM) (Tong et al., 2004) , cardiovascular diseases (CVD) (Bhat et al., 2013; Ji et al., 2021) , and stroke (Cai et al., 2021a) .

A recent meta-analysis including 7,482 COVID-19 patients found significantly higher NLR in advanced stages compared to earlier stages of COVID-19 with good accuracy to diagnose and predict the disease outcome, especially mortality prediction (Alkhatip et al., 2021) .

These results could be explained, almost in part, taking into account the physio-pathological roles played by neutrophils. Neutrophils may not only damage host tissue, but they can also suppress the adaptive immune response, a role described for the so-called granulocytic myeloid-derived suppressor cells (MDSC), originally identified in cancer (Bronte et al., 2016) . MDSC cells have been described to inhibit lymphocyte proliferation via depletion of arginine by Arginase-1 (Rodriguez et al., 2009) 

Recent reports suggested that steroid therapies can impair the use of NLR as a marker of outcome and disease severity in COVID-19 patients, and its use should be limited to naïve patients before starting potential interfering therapies (Gelzo et al., 2021) . No significant impact on mortality was observed in our cohort based on steroid therapies after admission, while no data were available on steroid therapies before hospital admission. In October 2020, the Italian Medicines Agency (AIFA) recommended the use of glucocorticoids, especially dexamethasone, in COVID-19 patients who required supplemental oxygen therapy and ventilation, after the positive findings of the RECOVERY trial (The RECOVERY Collaborative Group et al., 2021) . Before this recommendation, the use of glucocorticoids was dependent upon clinical judgment, and in some cases even contraindicated due to negative interactions with the innate immune response in the context of a viral infection (Sarzani et al., 2021) . We enrolled COVID-19 positive patients admitted at INRCA hospital from 1st March 2020 to 24th June 2021. For this reason, about 28% of COVID-19 patients did not receive glucocorticoids, with no significant difference between deceased and survived. Of note, the proportion of patients treated with glucocorticoids is in line with previous reports describing an increasing trend in the use of dexamethasone and other corticosteroids between March and September 2020 (Ioannou et al., 2022) .

Interestingly, our results showed a significant association between low eosinophil counts and COVID-19 severe outcomes. It was suggested that eosinophils could play beneficial functions in COVID-19 patients, probably contributing by controlling the exacerbated inflammation induced by neutrophils (Cortes-Vieyra et al., 2021) . Even if the role of eosinophils in inflammation remains controversial, recent evidence suggested that different eosinophils subpopulations in the same tissue could differentially modulate inflammatory responses (Kanda et al., 2021) . The anti-inflammatory role of eosinophils was observed in murine models, demonstrating that eosinophils can locally produce anti-inflammatory and pro-resolving lipid mediators, such as protectin D1 and resolvin E3, through a 12/15-lipooxygenase-mediated biosynthetic route, thus promoting resolution by counterregulating the neutrophil influx and stimulating the ingestion of apoptotic neutrophils by J o u r n a l P r e -p r o o f macrophages, as well as increasing phagocyte clearance into draining lymph nodes (Yamada et al., 2011) . Our results are in line with the historical role of the eosinophil count as a non-specific biomarker of acute infection (Abidi et al., 2008) . Indeed, in our cohort normal eosinophil counts have been associated with more favorable outcomes, and this observation may reflect a markedly reduced infection severity and stress response, as well as a reduced incidence of bacterial superinfections in survivor patients.

In addition to cell counts, we also observed that increased levels of PCT, IL-6, CRP, and NT-proBNP were associated with in-hospital mortality for COVID-19. Traditionally, PCT has been used in clinical practice as a diagnostic marker of bacterial infection, aiding clinical decisions surrounding the use of antibiotics. A recent meta-analysis including a total of 7716 patients demonstrated that patients with elevated procalcitonin on admission were at a higher risk of severe and critical COVID-19, although the underlying pathophysiological mechanisms were not clarified (Shen et al., 2021) . It was postulated that this positive association could reflect bacterial coinfection, although currently, there is insufficient evidence to validate this hypothesis (Heer et al., 2021; .

In a recent study on patients admitted for COVID-19, PCT elevation was associated with several clinical, radiological, and laboratory characteristics of disease severity. However, PCT elevation was strongly associated with hospital mortality only in subjects older than 75 years (Ticinesi et al., 2021) .

Regarding IL-6 levels and COVID-19 mortality, a recent prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, including 10,930 patients with a median age of 61 years, the administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality (WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) WorkingGroup et al., 2021) . Notably, IL-6 was recognized as the best circulating biomarker of inflammaging, and increased IL-6 levels were observed in several age-related diseases (reviewed in Olivieri et al., 2021) .

NT-proBNP has been used in clinical practice as a diagnostic marker of heart failure, a condition commonly observed in older patients. However, increased NT-proBNP circulating levels can be observed in association with conditions characterized by an exacerbation of inflammation. Recent evidence suggested that NT-proBNP is frequently elevated in COVID-19 and it is strongly and independently associated with mortality (Caro-Codon et al., 2021) . Recent evidence suggested that, besides age, the evaluation of NT-proBNP, IL-6, and lactate dehydrogenase (LDH) can predict inhospital mortality of COVID-19 patients regardless of other comorbidities (Ruscica et al., 2021) .

Our study has some limitations that need to be addressed, most notably its retrospective nature and single-center design. Moreover, interpretations of our findings could be limited by the sample size.

However, clinical and laboratory data were collected and analyzed for all the admitted patients, in adherence with the original Report-Age COVID-19 protocol. Nonetheless, by including all the patients admitted at the INRCA-IRCCS facilities between March 2020 to June 2021 we believe that data from our study population could represent a fair estimate of the outcomes of COVID-19 in geriatric patients. An additional limitation may be represented by the difficulty of discriminating deaths due to COVID-19 from deaths associated with COVID-19. We believe that, especially in older patients, estimation of mortality should take into account also preexisting comorbidities that are exacerbated by the systemic inflammatory status induced by the disease, and also by the less known direct effects of SARS-CoV-2 on organs other than the lung (Gupta et al., 2020) .

Furthermore, the documented large excess of deaths during the COVID-19 pandemic period (Wang et al., 2022) clearly indicates that even without severe lung involvement and hypoxia, the inflammatory context of the viral infection and other overlapped infections can precipitate cardiovascular events, including atherothrombotic manifestations and venous thromboembolism.

Therefore, in designing our analyses we decided to consider the all-cause mortality as the primary endpoint.

Overall, baseline laboratory abnormalities reflect both the extent of baseline vulnerability at the time of admission and the degree of disease severity. The interaction between these two factors, which act synergistically in determining the likelihood of in-hospital mortality, can be highlighted by the prompt assessment of routine laboratory parameters. Our results strongly support the use of these laboratory tests, including complete blood cell count, available within minutes to hours after hospital admission, in addition to clinical evaluation, to assess the degree of disease severity and to predict in-hospital mortality in the setting of geriatric patients with COVID-19, independently from preexisting comorbidities.

Università Politecnica delle Marche (RSA grant to FO).

The authors declare that they have no conflict of interest. Yang, Y., Luo, K., Jiang, Y., Yu, Q., Huang, X., Wang, J., Liu, N., Huang, P., 2021 . The Impact of Frailty on COVID-19 Outcomes: A Systematic Review and Meta-analysis of 16 Cohort Studies. J Nutr Health Aging 25, 702-709.

Ying, H.Q., Deng, Q.W., He, B.S., Pan, Y.Q., Wang, F., Sun, H.L., Chen, J., Liu, X., Wang, S.K., 2014. The prognostic value of preoperative NLR, d-NLR, PLR and LMR for predicting clinical outcome in surgical colorectal cancer patients. Med Oncol 31, 305. Zanella, A., Florio, G., Antonelli, M., Bellani, G., Berselli, A., Bove, T., Cabrini, L., Carlesso, E., Castelli, G.P., Cecconi, M., Citerio, G., Coloretti, I., Corti, D., Dalla Corte, F., De Robertis, E., Foti, G., Fumagalli, R., Girardis, M., Giudici, R., Guiotto, L., Langer, T., Mirabella, L., Pasero, D., Protti, A., Ranieri, M.V., Rona, R., Scudeller, L., Severgnini, P., Spadaro, S., Stocchetti, N., Vigano, M., Pesenti, A., Grasselli, G., Network, C.-I.I., 2021 . Time course of risk factors associated with mortality of 1260 critically ill patients with COVID-19 admitted to 24 Italian intensive care units. Intensive Care Med 47, 995-1008 . Zhai, N., Li, H., Song, H., Yang, Y., Cui, A., Li, T., Niu, J., Crispe, I.N., Su, L., Tu, Z., 2017 . Hepatitis C Virus Induces MDSCs-Like Monocytes through TLR2/PI3K/AKT/STAT3 Signaling. PLoS One 12, e0170516.

Zhang, X.M., Jiao, J., Cao, J., Huo, X.P., Zhu, C., Wu, X.J., Xie, X.H., 2021. Frailty as a predictor of mortality among patients with COVID-19: a systematic review and meta-analysis. BMC Geriatr 21, 186.

Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., Xiang, J., Wang, Y., Song, B., Gu, X., Guan, L., Wei, Y., Li, H., Wu, X., Xu, J., Tu, S., Zhang, Y., Chen, H., Cao, B., 2020. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395, 1054-1062.

Zhu, X., Yuan, W., Shao, J., Huang, K., Wang, Q., Yao, S., Lu, W., Liu, L., Fu, T., 2021. Risk factors for mortality in patients over 70 years old with COVID-19 in Wuhan at the early break: retrospective case series. BMC Infect Dis 21, 821. lymphocyte-to-monocyte ratio (LMR).

 Clear laboratory parameters to stratify older patients with COVID-19 at high risk of in-hospital death are urgently needed.

 Baseline degree of frailty, but not preexisting comorbidities, was significantly associated with inhospital COVID-19 mortality in geriatric patients.

 Among the routine parameters, neutrophilia, eosinopenia, lymphopenia, C-reactive protein, procalcitonin, IL-6, and NT-proBNP showed the highest predictive values for in-hospital mortality.

 High neutrophil percentage, low lymphocyte count, and high neutrophil-to-lymphocyte ratio are independent predictors of in-hospital mortality in geriatric patients.

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Potassium, median (IQR)

NLR, neutrophil-to-lymphocyte ratio; dNLR, derived NLR ratio (neutrophil count divided by the result of WBC count minus neutrophil count)

N-terminal probrain natriuretic peptide; PLR, platelet-to-lymphocyte ratio

LMR, lymphocyte-to-monocyte ratio

Note, #, absolute count; eGFR, estimated Glomerular Filtration Rate; CRP, C Reactive Protein; CT, procalcitonin

NLR, neutrophil-to-lymphocyte ratio; dNLR, derived NLR ratio (neutrophil count divided by the result of WBC count minus neutrophil count)

PLR, platelet-to-lymphocyte ratio

LMR, lymphocyte-to-monocyte ratio

NLR, neutrophil-to-lymphocyte ratio; dNLR, derived NLR ratio (neutrophil count divided by the result of WBC count minus neutrophil count)

PLR, platelet-to-lymphocyte ratio; LMR, lymphocyte-to

Hemoglobin, n (%) 0.198