Characteristics, comorbidities and laboratory measures associated with disease severity and poor prognosis in young and elderly patients with COVID-19 admitted to medical wards in Emilia-Romagna region, Italy: a multicentre retrospective study

Published: 21 June 2023
Abstract Views: 872
PDF: 230
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.


Background and Objectives. A relatively small number of studies have investigated the characteristics, comorbidities and laboratory measures associated with prognosis in patients with COVID-19, admitted to Internal Medicine Units (IMU) in Italy. Therefore, we performed a retrospective multicentre study to identify baseline features, predisposing to severe disease and poor outcomes, in adult individuals with SARS-CoV-2 infection, hospitalized in 5 IMUs in the Emilia-Romagna region (Italy). Materials and Methods. We included 129 consecutive patients (male 75, median age 68 years) from 1st March 2020 to 31st October 2021. Patients’ baseline characteristics, comorbidities, laboratory measures, and outcomes were collected. Results. At admission, the factors significantly associated with a higher risk of in-hospital mortality included: age (median 68 vs. 83 years in survived vs. dead patients, P=0.000), diabetes [Odds Ratio (OR) 4.00, P=0.016], chronic obstructive pulmonary disease (OR 4.60, P=0.022), cancer (OR 5.81, P=0.021), acute- (OR 9.88, P=0.000) and chronic-renal failure (OR 6.76, P=0.004). During the study period, 16 individuals died (12.4%), all over 70 years old. In deceased vs. non-deceased patients were detected: i) more elevated white blood cells and neutrophils-counts and lower lymphocytes count; ii) higher levels of total/direct bilirubin, creatinine, C-reactive-protein, lactate-dehydrogenase, ferritin, but only a slight Interleukin-6 increase; iii) a trend of lower vitamin D values. Conclusions. We proposed a new I index, a modified form of the Age-Adjusted Charlson Comorbidity Index, by considering pO2/FiO2 ratio, to better characterize the severity of COVID-19. Furthermore, we critically discuss our results with the current assumption which considers COVID-19 as a pathological condition associated with cytokine storm.



PlumX Metrics


Download data is not yet available.


Lu R, Zhao X, Li J, et al. Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020;395:565-74. DOI:
WHO. WHO Coronavirus (COVID-19) Dashboard. 2023. Available from:
Benenson S, Oster Y, Cohen MJ, Nir-Paz R. BNT162b2 mRNA COVID-19 Vaccine Effectiveness among Health Care Workers. N Engl J Med 2021;384:1775-7. DOI:
Thompson MG, Burgess JL, Naleway AL, et al. Interim estimates of vaccine effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines in preventing SARSCoV-2 infection among health care personnel, first responders, and other essential and frontline workers – Eight U.S. Locations, December 2020-March. MMWR Morb Mortal Wkly Rep 2021;70:495-500. DOI:
Fiorino S, Zippi M, Gallo C, et al. The rationale for a multi-step therapeutic approach based on antivirals, drugs and nutrients with immunomodulatory activity in patients with coronavirus-SARS2-induced disease of different severities. Br J Nutr 2021;125:275-93. DOI:
Boban M. Novel coronavirus disease (COVID-19) update on epidemiology, pathogenicity, clinical course and treatments. Int J Clin Pract 2021;75. DOI:
Ghaebi M, Tahmasebi S, Jozghorbani M, et al. Risk factors for adverse outcomes of COVID-19 patients: Possible basis for diverse responses to the novel coronavirus SARS-CoV-2. Life Sci 2021;277. DOI:
Lamers MM, Haagmans BL. SARS-CoV-2 pathogenesis. Nat Rev Microbiol 2022;20:270-84. DOI:
Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, et al. SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev 2020;54:62-75. DOI:
Zeng F, Huang Y, Guo Y, et al. Association of inflammatory markers with the severity of COVID-19: A metaanalysis. Int J Infect Dis 2020;96:467-74. DOI:
Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033-4. DOI:
Cao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol 2020;20:269-70. DOI:
Dhar SK, Vishnupriyan K, Damodar S, et al. IL-6 and IL-10 as predictors of disease severity in COVID-19 patients: results from meta-analysis and regression. Heliyon 2021;7. DOI:
Aziz M, Fatima R, Assaly R. Elevated interleukin-6 and severe COVID-19: A meta-analysis. J Med Virol 2020;92:2283-5. DOI:
Blot M, Bourredjem A, Binquet C, Piroth L. Is IL-6 the right target in COVID-19 severe pneumonia? Am J Respir Crit Care Med 2021;203:139-40. DOI:
Leisman DE, Ronner L, Pinotti R, et al. Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes. Lancet Respir Med 2020;8:1233-44. DOI:
Cheng L, Li H, Li L, et al. Ferritin in the coronavirus disease 2019 (COVID-19): A systematic review and metaanalysis. J Clin Lab Anal 2020;34. DOI:
Khinda J, Janjua NZ, Cheng S, et al. Association between markers of immune response at hospital admission and COVID-19 disease severity and mortality: A meta-analysis and meta-regression. J Med Virol 2021;93:1078-98. DOI:
Aziz M, Haghbin H, Lee-Smith W, et al. Gastrointestinal predictors of severe COVID-19: Systematic review and meta-analysis. Ann Gastroenterol 2020;33:615-30. DOI:
Qin R, He L, Yang Z, et al. Identification of parameters representative of immune dysfunction in patients with severe and fatal COVID-19 infection: a systematic review and meta-analysis. Clin Rev Allergy Immunol 2023;64:33-65. DOI:
D’Ecclesiis O, Gavioli C, Martinoli C, et al. Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis. PLoS One 2022;17. DOI:
Belsky JA, Tullius BP, Lamb MG, et al. COVID-19 in immunocompromised patients: A systematic review of cancer, hematopoietic cell and solid organ transplant patients. J Infect 2021;82:329-38. DOI:
Avci GU, Kanat BB, Suzan V, et al. Clinical outcomes of geriatric patients with COVID-19: review of one-year data. AGING Clin Exp Res 2022;34:465-74. DOI:
Kim HJ, Hwang H, Hong H, et al. A systematic review and meta-analysis of regional risk factors for critical outcomes of COVID-19 during early phase of the pandemic. Sci Rep 2021;11. DOI:
Tateo F, Fiorino S, Peruzzo L, et al. Effects of environmental parameters and their interactions on the spreading of SARS-CoV-2 in North Italy under different social restrictions. A new approach based on multivariate analysis. Environ Res 2022;210:112921. DOI:
Bigdelou B, Sepand MR, Najafikhoshnoo S, et al. COVID-19 and Preexisting Comorbidities: Risks, Synergies, and Clinical Outcomes. Front Immunol 2022;13. DOI:
Du P, Li D, Wang A, et al. A Systematic Review and Meta-Analysis of Risk Factors Associated with Severity and Death in COVID-19 Patients. Can J Infect Dis Med Microbiol 2021;2021:6660930. DOI:
El-Sharkawy AM, Sahota O, Maughan RJ, Lobo DN. The pathophysiology of fluid and electrolyte balance in the older adult surgical patient. Clin Nutr 2014;33:6-13. DOI:
Pourfridoni M, Abbasnia SM, Shafaei F, et al. Fluid and electrolyte disturbances in COVID-19 and their complications. Biomed Res Int 2021;2021. DOI:
De Carvalho H, Richard MC, Chouihed T, et al. Electrolyte imbalance in COVID-19 patients admitted to the Emergency Department: a case-control study. Intern Emerg Med 2021;16:1945-50. DOI:
Zimmer MA, Zink AK, Weißer CW, et al. Hypernatremia-A manifestation of COVID-19: A case series. A A Pract 2020;14:e01295. DOI:
Fiorino S, Gallo C, Zippi M, et al. Cytokine storm in aged people with CoV-2 : possible role of vitamins as therapy or preventive strategy. Aging Clin Exp Res 2020; 32:2115-31. DOI:
Kim DH, Park HC, Cho A, et al. Age-adjusted Charlson comorbidity index score is the best predictor for severe clinical outcome in the hospitalized patients with COVID-19 infection. Med (Baltimore) 2021;100:E25900. DOI:
Elixhauser A, Steiner C, Harris DR, Coffey RM. Comorbidity Measures for Use with Administrative Data. Med Care 1998;36:8-27. DOI:
Soria A, Galimberti S, Lapadula G, et al. The high volume of patients admitted during the SARS-CoV-2 pandemic has an independent harmful impact on in-hospital mortality from COVID-19. PLoS One 2021;16:e0246170. DOI:
Bos LDJ, Sjoding M, Sinha P, et al. Longitudinal respiratory subphenotypes in patients with COVID-19-related acute respiratory distress syndrome: results from three observational cohorts. Lancet Respir Med 2021;9:1377-86. DOI:
Grasselli G, Tonetti T, Protti A, et al. Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study. Lancet Respir Med 2020;8:1201-8. DOI:
Fumagalli C, Rozzini R, Vannini M, et al. Clinical risk score to predict in-hospital mortality in COVID-19 patients: a retrospective cohort study. BMJ Open 2020;10:e040729. DOI:
Di Castelnuovo A, Bonaccio M, Costanzo S, et al. Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study. Nutr Metab Cardiovasc Dis 2020;30:1899-913. DOI:
Corradini E, Ventura P, Ageno W, et al. Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: results from the SIMI-COVID-19 study of the Italian Society of Internal Medicine (SIMI). Intern Emerg Med 2021;16:1005-15. DOI:
Mancusi C, Grassi G, Borghi C, et al. Determinants of healing among patients with COVID-19: the results of the SARS-RAS study of the Italian Society of Hypertension. J Hypertens 2021;39:376-80. DOI:
Santus P, Radovanovic D, Saderi L, et al. Severity of respiratory failure at admission and in-hospital mortality in patients with COVID-19: a prospective observational multicentre study. BMJ Open 2020;10:e043651. DOI:
Fumagalli C, Ungar A, Rozzini R, et al. Predicting Mortality Risk in Older Hospitalized Persons With COVID-19: A Comparison of the COVID-19 Mortality Risk Score with Frailty and Disability. J Am Med Dir Assoc 2021;22:1588-92.e1. DOI:
de Giorgi A, Fabbian F, Greco S, et al. Prediction of inhospital mortality of patients with SARS-CoV-2 infection by comorbidity indexes: An Italian internal medicine single center study. Eur Rev Med Pharmacol Sci 2020;24:10258-66.
Guglielmetti L, Kontsevaya I, Leoni MC, et al. Severe COVID-19 pneumonia in Piacenza, Italy - A cohort study of the first pandemic wave. J Infect Public Health 2021;14:263-70. DOI:
Lenti MV, Borrelli de Andreis F, et al. Impact of COVID-19 on liver function: results from an internal medicine unit in Northern Italy. Intern Emerg Med 2020;15:1399-407. DOI:
Russo V, Di Maio M, Mottola FF, et al. Clinical characteristics and prognosis of hospitalized COVID-19 patients with incident sustained tachyarrhythmias: A multicenter observational study. Eur J Clin Invest 2020;50. DOI:
Landolfo M, Maino A, Di Salvo E, et al. Renin–angiotensin system modulation and outcomes in patients hospitalized for interstitial SARS-CoV2 pneumonia: a cohort study. Intern Emerg Med 2022;17:1335-41. DOI:
Lombardi CM, Carubelli V, Iorio A, et al. Association of Troponin Levels with Mortality in Italian Patients Hospitalized with Coronavirus Disease 2019: Results of a Multicenter Study. JAMA Cardiol 2020;5:1274-80. DOI:
Hand DJ, Taylor CC. multivariate analysis of variance and repeated measures. multivariate analysis of variance and repeated measures. London and New York: Chapman and Hall, 1987. DOI:
Bauer DF. Constructing confidence sets using rank statistics. J Am Stat Assoc 1972;67:687-90. DOI:
Charlson Me, Pompei P, Ales Kl, Mackenzie Cr. A new method of classifying prognostic co-morbidity in longitudinal-studies - development and validation. J Chronic Dis 1987;40:373-83. DOI:
Kuswardhani RAT, Henrina J, Pranata R, et al. Charlson comorbidity index and a composite of poor outcomes in COVID-19 patients: A systematic review and meta-analysis. Diabetes Metab Syndr 2020;14:2103-9. DOI:
Mann A, Early GL. Acute respiratory distress syndrome. Mo Med 2012;109:371-5.
Biagi A, Rossi L, Malagoli A, et al. Clinical and epidemiological characteristics of 320 deceased patients with COVID-19 in an Italian Province: A retrospective observational study. J Med Virol 2020;92:2718-24. DOI:
Chen Y, Klein SL, Garibaldi BT, et al. Aging in COVID-19: Vulnerability, immunity and intervention. Ageing Res Rev 2021;65. DOI:
Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017;39:529-39. DOI:
Han H, Ma Q, Li C, et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect 2020;9:1123-30. DOI:
Fara A, Mitrev Z, Rosalia RA, Assas BM. Cytokine storm and COVID-19: a chronicle of pro-inflammatory cytokines. OPEN Biol 2020;10. DOI:
Del Valle DM, Kim-Schulze S, Huang HH, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med 2020;26:1636-43. DOI:
Yang Y, Shen C, Li J, et al. Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19. J Allergy Clin Immunol 2020;146:119-127.e4. DOI:
Gallo CG, Fiorino S, Posabella G, et al. COVID-19, what could sepsis, severe acute pancreatitis, gender differences, and aging teach us? Cytokine 2021;148. DOI:
Colafrancesco S, Alessandri C, Conti F, Priori R. COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome? Autoimmun Rev 2020;19. DOI:
Mahroum N, Alghory A, Kiyak Z, et al. Ferritin – from iron, through inflammation and autoimmunity, to COVID-19. J Autoimmun 2022;126. DOI:
Efthimiou P, Paik PK, Bielory L. Diagnosis and management of adult onset Still’s disease. Ann Rheum Dis 2006;65:564-72. DOI:
Zhang B, Tang G, He J, et al. Ferritin nanocage: A promising and designable multi-module platform for constructing dynamic nanoassembly-based drug nanocarrier. Adv Drug Deliv Rev 2021;176. DOI:
Perricone C, Bartoloni E, Bursi R, et al. COVID-19 as part of the hyperferritinemic syndromes: the role of iron depletion therapy. Immunol Res 2020;68:213-24. DOI:
Isaia G, Diémoz H, Maluta F, et al. Does solar ultraviolet radiation play a role in COVID-19 infection and deaths? An environmental ecological study in Italy. Sci Total Environ 2021;757. DOI:
Fiorino S, Carusi A, Hong W, et al. SARS-CoV-2 vaccines: What we know, what we can do to improve them and what we could learn from other well-known viruses. AIMS Microbiol 2022;8:422-53. DOI:
Ben-Eltriki M, Hopefl R, Wright JM, Deb S. Association between Vitamin D Status and Risk of Developing Severe COVID-19 Infection: A Meta-Analysis of Observational Studies. J Am Nutr Assoc 2022;41:679-89. DOI:
Chiodini I, Gatti D, Soranna D, et al. Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes. Front Public Heal 2021;9. DOI:
Oscanoa TJ, Amado J, Vidal X, et al. The relationship between the severity and mortality of SARS-COV-2 infection and 25-hydroxy vitamin D concentration - a meta-analysis. Adv Respir Med 2021;89:175-87. DOI:
Petrelli F, Luciani A, Perego G, et al. Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies. J Steroid Biochem Mol Biol 2021;211. DOI:
Kaya MO, Pamukcu E, Yakar B. The role of vitamin D deficiency on COVID-19: A systematic review and meta-Analysis of observational studies. Epidemiol Health 2021;43. DOI:
Argano C, Mallaci Bocchio R, Natoli G, et al. Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis. Pharmaceuticals 2023;16:130. DOI:
Bassatne A, Basbous M, Chakhtoura M, et al. The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis. Metabolism 2021;119. DOI:
Ghasemian R, Shamshirian A, Heydari K, et al. The role of vitamin D in the age of COVID-19: A systematic review and meta-analysis. Int J Clin Pract 2021;75. DOI:
Chen J, Mei K, Xie L, et al. Low vitamin D levels do not aggravate COVID-19 risk or death, and vitamin D supplementation does not improve outcomes in hospitalized patients with COVID-19: a meta-analysis and GRADE assessment of cohort studies and RCTs. Nutr J 2021;20. DOI:
Dissanayake HA, De Silva NL, Sumanatilleke M, et al. Prognostic and therapeutic role of vitamin D in COVID-19: systematic review and meta-analysis. J Clin Endocrinol Metab 2022;107:1484-502. DOI:
Fiorino S, Conti F, Gramenzi A, et al. Vitamins in the treatment of chronic viral hepatitis. Br J Nutr 2011;105:982-9. DOI:
Andreone P, Fiorino S, Cursaro C, et al. Vitamin E as treatment for chronic hepatitis B: Results of a randomized controlled pilot trial. Antiviral Res 2001;49:75-81. DOI:
Gil Á, Plaza-Diaz J, Mesa MD. Vitamin D: Classic and Novel Actions. Ann Nutr Metab 2018;72:87-95. DOI:
Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol 2014;144:138-45. DOI:
Freitas AT, Calhau C, Antunes G, et al. Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 disease severity. Sci Rep 2021;11. DOI:
Carlberg C, Haq A. The concept of the personal vitamin D response index. J Steroid Biochem Mol Biol 2018;175:12-7. DOI:

How to Cite

Fiorino, S., Carusi, A., Zappi, A., Tateo, F., Peruzzo, L., Zanardi, M., Savelli, F., Di Marzio, G., Cesaretti, S., Dazzani, F., Francesconi , R., Leandri , P., Tortorici , G., Vicari , S., Melucci, D., & Lari, F. (2023). Characteristics, comorbidities and laboratory measures associated with disease severity and poor prognosis in young and elderly patients with COVID-19 admitted to medical wards in Emilia-Romagna region, Italy: a multicentre retrospective study. Italian Journal of Medicine, 17(1).

Similar Articles

You may also start an advanced similarity search for this article.