An assessment of case-fatality and infection-fatality rates of first and second COVID-19 waves in Italy COVID-19 fatality rate in Italy

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Tommaso Filippini
Federico Zagnoli
Matteo Bosi
Maria Edvige Giannone
Cristina Marchesi
Marco Vinceti


SARS-CoV-2, outbreak, case-fatality rate, infection-fatality rate, epidemiology, wave, seroprevalence, public health, COVID-19


Background and aim: The exact COVID-19 severity is still not well defined and it is hotly debated due to the a few methodological issues such as the uncertainties about the spread of the SARS-CoV-2 infection.

Methods: We investigated COVID-19 case-fatality rate and infection-fatality rate in 2020 in Italy, a country severely affected by the pandemic, basing our assessment on publicly available data, and calculating such measures during the first and second waves.

Results: We found that province-specific crude case-fatality rate in the first wave (February-July 2020) had a median value of 12.0%. Data about infection-fatality rate was more difficult to compute, due to large underestimation of SARS-CoV-2 infection during the first wave when asymptomatic individuals were very rarely tested. However, when using as a reference population-based seroprevalence data for anti-SARS-CoV-2 antibodies collected in May-July 2020, we computed an infection-fatality rate of 2.2%. During the second wave (Sep-Dec 2020), when SARS-CoV-2 testing was greatly increased and extended to many asymptomatic individuals, we could only compute a ‘hybrid’ case/infection-fatality rate with a value of 2.2%, similar to the infection-fatality rate of the first wave.

Conclusions: Overall, this study allowed to assess the COVID-19 case- and infection-fatality rates in Italy before of variant spread and vaccine availability, confirming their high values compared with other airborne infections like influenza. Our findings for Italy were similar to those characterizing other Western European countries.


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1. Neagu M, Calina D, Docea AO, et al. Back to basics in COVID-19: Antigens and antibodies-Completing the puzzle. J Cell Mol Med 2021; 25 (10): 4523-33.
2. Docea AO, Tsatsakis A, Albulescu D, et al. A new threat from an old enemy: Reemergence of coronavirus (Review). Int J Mol Med 2020; 45 (6): 1631-43.
3. Salamanna F, Veronesi F, Martini L, et al. Post-COVID-19 syndrome: The persistent symptoms at the post-viral stage of the disease. A systematic review of the current data. Front Med (Lausanne) 2021; 8: 653516.
4. Di Castelnuovo A, Costanzo S, Antinori A, et al. Lopinavir/ritonavir and darunavir/cobicistat in hospitalized COVID-19 patients: Findings from the multicenter Italian CORIST study. Front Med (Lausanne) 2021; 8: 639970.
5. Tsatsakis A, Calina D, Falzone L, et al. SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19. Food Chem Toxicol 2020; 146: 111769.
6. Vinceti M, Filippini T, Rothman KJ, et al. Lockdown timing and efficacy in controlling COVID-19 using mobile phone tracking. EClinicalMedicine 2020; 25: 100457.
7. Cheng Y, Ma N, Witt C, et al. Face masks effectively limit the probability of SARS-CoV-2 transmission. Science 2021: eabg6296.
8. Ortega-Garcia JA, Ruiz-Marin M, Carceles-Alvarez A, et al. Social distancing at health care centers early in the pandemic helps to protect population from COVID-19. Environ Res 2020; 189: 109957.
9. Saez M, Tobias A, Varga D, et al. Effectiveness of the measures to flatten the epidemic curve of COVID-19. The case of Spain. Sci Total Environ 2020; 727: 138761.
10. Signorelli C, Scognamiglio T, Odone A. COVID-19 in Italy: impact of containment measures and prevalence estimates of infection in the general population. Acta Biomed 2020; 91 (3-S): 175-9.
11. Abu-Raddad LJ, Chemaitelly H, Coyle P, et al. SARS-CoV-2 antibody-positivity protects against reinfection for at least seven months with 95% efficacy. EClinicalMedicine 2021; 35: 100861.
12. Callaway E. Could new COVID variants undermine vaccines? Labs scramble to find out. Nature 2021; 589 (7841): 177-8.
13. Calina D, Hernández AF, Hartung T, et al. Challenges and scientific prospects of the newest generation of mRNA-based vaccines against SARS-CoV-2. Life 2021; 11 (9): 907.
14. Vinceti M, Filippini T, Rothman KJ, et al. SARS-CoV-2 infection incidence during the first and second COVID-19 waves in Italy. Environ Res 2021; 197: 111097.
15. 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 (11): 1899-913.
16. Ciceri F, Castagna A, Rovere-Querini P, et al. Early predictors of clinical outcomes of COVID-19 outbreak in Milan, Italy. Clin Immunol 2020; 217: 108509.
17. Perone G. The determinants of COVID-19 case fatality rate (CFR) in the Italian regions and provinces: An analysis of environmental, demographic, and healthcare factors. Sci Total Environ 2021; 755 (Pt 1): 142523.
18. Copat C, Cristaldi A, Fiore M, et al. The role of air pollution (PM and NO2) in COVID-19 spread and lethality: A systematic review. Environ Res 2020; 191: 110129.
19. Marques M, Domingo JL. Positive association between outdoor air pollution and the incidence and severity of COVID-19. A review of the recent scientific evidences. Environ Res 2021: 111930.
20. Levi A, Barnett-Itzhaki Z. Effects of chronic exposure to ambient air pollutants, demographic, and socioeconomic factors on COVID-19 morbidity: The Israeli case study. Environ Res 2021; 202: 111673.
21. European Parliament. Air pollution and COVID-19. 2021. [Accessed September 8, 2021].
22. Filippini T, Rothman KJ, Cocchio S, et al. Associations between mortality from COVID-19 in two Italian regions and outdoor air pollution as assessed through tropospheric nitrogen dioxide. Sci Total Environ 2021; 760: 143355.
23. Filippini T, Rothman KJ, Goffi A, et al. Satellite-detected tropospheric nitrogen dioxide and spread of SARS-CoV-2 infection in Northern Italy. Sci Total Environ 2020; 739: 140278.
24. Carugno M, Fedrizzi L, Borroni E, et al. Air pollution exposure increases the probability of SARS-CoV-2 infection and influences the immune response of healthcare workers affected by COVID-19. Environ Health Perspect 2021; 2021 (1): P-272.
25. [Decreto del Presidente del Consiglio dei Ministri. Ulteriori disposizioni attuative del decreto-legge 25 marzo 2020, n. 19, convertito, con modificazioni, dalla legge 25 maggio 2020, n. 35, recante «Misure urgenti per fronteggiare l'emergenza epidemiologica da COVID-19», e del decreto-legge 16 maggio 2020, n. 33, convertito, con modificazioni, dalla legge 14 luglio 2020, n. 74, recante «Ulteriori misure urgenti per fronteggiare l'emergenza epidemiologica da COVID-19»]. [Accessed August 30, 2021]. GU Serie Generale n.275 2020; 275 04 Nov 2020 - Suppl. Ordinario n. 41.
26. Ministery of Health. Anti COVID-19 vaccine report 2021 [Accessed August 30, 2021].
27. Modenese A, Gobba F. Increased risk of COVID-19-related deaths among general practitioners in Italy. Healthcare (Basel) 2020; 8 (2): 155. [Accessed August 30, 2021].
28. Berselli N, Filippini T, Paduano S, et al. Seroprevalence of anti-SARS-CoV-2 antibodies in the Northern Italy population before the COVID-19 second wave. Int J Occup Med Environ Health 2021; 35 (1).
29. Della Valle P, Fabbri M, Madotto F, et al. Occupational exposure in the Lombardy Region (Italy) to SARS-CoV-2 infection: Results from the MUSTANG-OCCUPATION-COVID-19 study. Int J Environ Res Public Health 2021; 18 (5): 2567.
30. Battiston R. [COVID-19: Prima e seconda ondata a confronto]. Scienzainrete 2020.
31. NATO Rapid Deployable Corps - Italy. Two new COVID-19 drive-through testing centres in Milan and Solbiate Olona 2020. [Accessed Ausgust 30, 2021].
32. ISTAT - Italian National Institute of Statisics. SARS-CoV-2 seroprevalence survey: Data tables. 2021. [Accessed August 31, 2021].
33. Ahammed T, Anjum A, Rahman MM, et al. Estimation of novel coronavirus (COVID-19) reproduction number and case fatality rate: A systematic review and meta-analysis. Health Sci Rep 2021; 4 (2): e274.
34. WHO. Estimating mortality from COVID-19. 2020. [Accessed September 8, 2021].
35. Verity R, Okell LC, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: A model-based analysis. Lancet Infect Dis 2020; 20 (6): 669-77.
36. Odone A, Delmonte D, Gaetti G, et al. Doubled mortality rate during the COVID-19 pandemic in Italy: Quantifying what is not captured by surveillance. Public Health 2021; 190: 108-15.
37. Battegay M, Kuehl R, Tschudin-Sutter S, et al. 2019-novel Coronavirus (2019-nCoV): Estimating the case fatality rate - A word of caution. Swiss Med Wkly 2020; 150: w20203.
38. Chirico F, Nucera G, Magnavita N. Estimating case fatality ratio during COVID-19 epidemics: Pitfalls and alternatives. J Infect Dev Ctries 2020; 14 (5): 438-9.
39. Ioannidis JPA. Global perspective of COVID-19 epidemiology for a full-cycle pandemic. Eur J Clin Invest 2020; 50 (12): e13423.
40. Ioannidis JPA. Over- and under-estimation of COVID-19 deaths. Eur J Epidemiol 2021; 36 (6): 581-8.
41. Odone A, Delmonte D, Scognamiglio T, et al. COVID-19 deaths in Lombardy, Italy: Data in context. Lancet Public Health 2020; 5 (6): e310.
42. Ministry of Health. Anti-COVID vaccination campaign. [Accessed August 30, 2021].
43. ISS - Italian National Health Institute. Italian National Health Institute first report on SARS-CoV-2 variants. 2021. [Accessed August 30, 2021].
44. CPD - Italian Civil Protection Department. COVID-19 data. [Accessed August 30, 2021].
45. ISTAT - Italian National Institute of Statisics. COVID-19 deaths in Italy. Report March 5, 2021. [Accessed August 30, 2021].
46. Lash TL, VanderWeele TJ, Haneuse S, et al. Modern Epidemiology. 4th Edition ed: Wolters Kluwer; 2020
47. ECDC - The European Centre for Disease Prevention and Control. Data on 14-day notification rate of new COVID-19 cases and deaths. [Accessed August 30, 2021]
48. ISS - Italian National Health Institute. FluNews - Italy. Report of integrated seasons flu serveillance. [Accessed August 30, 2021].
49. ISTAT - Italian National Institute of Statisics. Deaths and causes 2021. [Accessed August 30, 2021].
50. Gianfredi V, Santangelo OE, Provenzano S. The effects of COVID-19 pandemic on the trend of measles and influenza in Europe. Acta Biomed 2021; 92 (4): e2021318.
51. ISTAT - Italian National Institute of Statisics. Populations and households 2020. [Accessed August 30, 2021].
52. Fabiani M, Onder G, Boros S, et al. Case fatality rate of SARS-CoV-2 infection at regional level and across different phases of the epidemic in Italy. Version of January 20, 2021. Roma: Istituto Superiore di Sanità; 2021
53. He W, Yi GY, Zhu Y. Estimation of the basic reproduction number, average incubation time, asymptomatic infection rate, and case fatality rate for COVID-19: Meta-analysis and sensitivity analysis. J Med Virol 2020; 92 (11): 2543-50.
54. Soliman AT, Alyafei F, Elalaily R. COVID-19 virus case fatality rate: How to avoid errors in calculation of data during the outbreak? Acta Biomed 2020; 91 (2): 222-3.
55. ECDC - The European Centre for Disease Prevention and Control. Technical Report: Novel coronavirus (SARS-CoV-2). Discharge criteria for confirmed COVID-19 cases: When is it safe to discharge COVID-19 cases from the hospital or end home isolation? [Accessed August 30, 2021].
56. Kault D. Superspreaders, asymptomatics and COVID-19 elimination. Med J Aust 2020; 213 (10): 447-8.e1.
57. Okell LC, Verity R, Watson OJ, et al. Have deaths from COVID-19 in Europe plateaued due to herd immunity? Lancet 2020; 395 (10241): e110-e1.
58. Papachristodoulou E, Kakoullis L, Parperis K, et al. Long-term and herd immunity against SARS-CoV-2: Implications from current and past knowledge. Pathog Dis 2020; 78 (3): ftaa025.
59. Fan G, Yang Z, Lin Q, et al. Decreased case fatality rate of COVID-19 in the second wave: A study in 53 countries or regions. Transbound Emerg Dis 2021; 68 (2): 213-5.
60. Hauser A, Counotte MJ, Margossian CC, et al. Estimation of SARS-CoV-2 mortality during the early stages of an epidemic: A modeling study in Hubei, China, and six regions in Europe. PLoS Med 2020; 17 (7): e1003189.
61. Porcheddu R, Serra C, Kelvin D, et al. Similarity in case fatality rates (CFR) of COVID-19/SARS-CoV-2 in Italy and China. J Infect Dev Ctries 2020; 14 (2): 125-8.
62. Hoseinpour Dehkordi A, Alizadeh M, Derakhshan P, et al. Understanding epidemic data and statistics: A case study of COVID-19. J Med Virol 2020; 92 (7): 868-82.
63. Gupta S, Kumar Patel K, Sivaraman S, et al. Global epidemiology of first 90 days into COVID-19 pandemic: Disease incidence, prevalence, case fatality rate and their association with population density, urbanisation and elderly population. J Health Manag 2020; 22 (2): 117-28.
64. Balasco N, D'Alessandro V, Ferrara P, et al. Analysis of the time evolution of COVID-19 lethality during the first epidemic wave in Italy. Acta Biomed 2021; 92 (2): e2021171.
65. Friston KJ, Parr T, Zeidman P, et al. Dynamic causal modelling of COVID-19. Wellcome Open Res 2020; 5: 89.
66. Gandolfi D, Pagnoni G, Filippini T, et al. Dynamic causal modeling of the COVID-19 pandemic in Northern Italy predicts possible scenarios for the second wave. medRxiv 2020: 2020.08.20.20178798.
67. Lippi G, Henry BM, Sanchis-Gomar F, et al. Updates on laboratory investigations in coronavirus disease 2019 (COVID-19). Acta Biomed 2020; 91 (3): e2020030.
68. Di Castelnuovo A, Costanzo S, Antinori A, et al. Heparin in COVID-19 patients is associated with reduced in-hospital mortality: The multicenter Italian CORIST study. Thromb Haemost 2021; 121 (8): 1054-65.
69. Guaraldi G, Meschiari M, Cozzi-Lepri A, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol 2020; 2 (8): e474-e84.
70. Veronese N, Demurtas J, Yang L, et al. Use of corticosteroids in coronavirus disease 2019 pneumonia: A systematic review of the literature. Front Med (Lausanne) 2020; 7: 170.
71. Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA 2020; 323 (18): 1775-6.
72. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020; 323 (13): 1239-42.
73. Gianfrancesco M, Hyrich KL, Al-Adely S, et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: Data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis 2020; 79 (7): 859-66.
74. Romagnolo A, Balestrino R, Imbalzano G, et al. Neurological comorbidity and severity of COVID-19. J Neurol 2021; 268 (3): 762-9.
75. ISTAT-ISS. National Institute of Statistics and National Institute of Health. Impact of COVID-19 epidemic on total mortality in the resident population 2021. [Accessed August 30, 2021].
76. Signorelli C, Odone A, Gianfredi V, et al. COVID-19 mortality rate in nine high-income metropolitan regions. Acta Biomed 2020; 91 (9-S): 7-18.
77. Beatty K, Hamilton V, Kavanagh PM. Just a bad flu? Tackling the "infodemic" in Ireland through a comparative analysis of hospitalised cases of COVID-19 and influenza. Public Health 2021; 194: 19-24.
78. Stojanovic J, Boucher VG, Boyle J, et al. COVID-19 is not the flu: Four graphs from four countries. Front Public Health 2021; 9: 628479.
79. Calina D, Docea AO, Petrakis D, et al. Towards effective COVID19 vaccines: Updates, perspectives and challenges (Review). Int J Mol Med 2020; 46 (1): 3-16.
80. Odone A, Vitale M, Signorelli C. The identity of public health in COVID-19 times. Acta Biomed 2020; 91 (9-S): 5-6.
81. Odone A, Lugo A, Amerio A, et al. COVID-19 lockdown impact on lifestyle habits of Italian adults. Acta Biomed 2020; 91 (9-S): 87-9.
82. Stirparo G, Oradini-Alacreu A, Migliori M, et al. Public health impact of the COVID-19 pandemic on the emergency healthcare system. J Public Health (Oxf) 2021: fdab212.
83. Green MS, Peer V, Schwartz N, et al. The confounded crude case-fatality rates (CFR) for COVID-19 hide more than they reveal-a comparison of age-specific and age-adjusted CFRs between seven countries. PLoS One 2020; 15 (10): e0241031.
84. Davies NG, Abbott S, Barnard RC, et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science 2021.
85. Rubino S, Kelvin N, Bermejo-Martin JF, et al. As COVID-19 cases, deaths and fatality rates surge in Italy, underlying causes require investigation. J Infect Dev Ctries 2020; 14 (3): 265-7.
86. CPD - Italian Civil Protection Department. Anti COVID-19 Vaccine Report [Accessed August 30, 2021].

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