Journal Article

Hypothesis to explain the severe form of COVID-19 in Northern Italy

Pichierri, Giuseppe, Mastrangelo, Giuseppe, Cegolon, Luca, Cinquetti, Sandro, Bellizzi, Saverio, Sotgiu, Giovanni, Pichierri, Jennifer

2020

Overview

Of patients with COVID-19, 14%–15% develop severe pneumonia and 5%–6% a critical condition requiring admission to intensive care unit (ICU).2–4 Death may eventually occur after an average of 17.8 days since the onset of symptoms.5 Among all countries, Italy (which was the first European COVID-19 cluster) presents a critical disease pattern as of 8 May 2020, having the third highest number of COVID-19 cases in the world after the USA and Spain, the fourth highest prevalence of the disease after Spain, Belgium and the USA, the third highest total number of deaths attributed to COVID-19 after the USA and the UK, and the third highest prevalence of COVID-19 mortality after Belgium and Spain, despite a current 1% rate of severe/critical disease among active cases, which has been progressively decreasing over time.1 The cross-country discrepancies in the burden of COVID-19 observed so far across the globe cannot be explained only by differences in population age structures.6–8 In fact, Japan has a population double that of Italy, with the proportion of subjects older than 65 being 28.8% in Japan vs 21.7% in Italy.9 10 Nonetheless, as of 8 May 2020, the difference in COVID-19 prevalence between Japan (122 per million) and Italy (3570 per million) is massive.1 Likewise, in Germany the percentage of individuals >65 is reportedly 22.1% (hence slightly higher than Italy), but the prevalence of COVID-19 is currently 2022 per million.1 11 In Iran the proportion of people >65 is 5.5% (hence much younger than the Italian, German and Japanese populations), but the prevalence of COVID-19 is 1246 per million, as of 8 May 2020.1 12 The mortality rate for COVID-19 is reportedly enhanced by 5.6%–10.5% in the presence of any comorbidities (hypertension, diabetes, cardiovascular diseases, cancer and/or chronic respiratory conditions) and becomes significantly and progressively higher after 50 years of age,4 6 although the severe form of the disease increases linearly at any age stage.5 Cold dry weather is a recognised risk factor for respiratory infections, rendering viruses as influenza more stable and individuals more susceptible.13 14 This applies also to SARS-CoV-2, the viability and transmissibility of which reportedly reduce with hot and humid weather conditions.14 Moreover, unfavourable disease progression and clinical outcomes of COVID-19 were found to be associated with cigarette smoking in a systematic review.15 A number of factors may have contributed to enhancing the risk of infection with SARS-CoV-2 in Northern Italy. The universal use of face masks was initially discouraged in Italy in order to preserve the limited supplies of personal protective equipment for professional use in healthcare settings; another argument initially was that face masks are ineffective in protecting against coronavirus infections.17 Further major findings of the relevant literature have been summarised in figure 1. The affected areas in Northern Italy (regions of Lombardy, Emilia-Romagna, Piedmont and Veneto) are characterised by high population density18 and recognised air pollution,19 20 especially from fine particulate matter (PM2.5), which was found to increase the risk of death from COVID-19 in the USA.21 Northern Italy includes several cities which, similarly to Philadelphia (USA) during the Spanish flu pandemic in 1918,22 are historically important and densely populated, where social gatherings as well as business activities are certainly fundamental—the latter being vital to the economy of the entire country. [...]the intense case finding in Italy was preceded by an initial overall underestimation of the COVID-19 threat by the Italian government and subsequently by the general population, who perceived the disease as just some sort of influenza, despite worrying news from the first affected country (China).23 Thereafter SARS-CoV-2 was also going to spread to other European countries, which have also now been heavily affected by the disease.1 Figure 1.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Air pollution / Antibody-Dependent Enhancement / Betacoronavirus / Cardiovascular diseases / Coinfection / Commentary / Comorbidity / Coronavirus Infections - diagnosis / Coronavirus Infections - epidemiology / Coronavirus Infections - physiopathology / Coronavirus Infections - prevention & control / Coronaviruses / COVID-19 / COVID-19 Vaccines / dengue / Diabetes / Epidemiology / Global health / Health risks / Humans / Hypertension / Influenza / Italy - epidemiology / Mass Screening / Middle East respiratory syndrome / Mortality / Pandemics / Pandemics - prevention & control / Particulate matter / Pneumonia, Viral - diagnosis / Pneumonia, Viral - epidemiology / Pneumonia, Viral - physiopathology / Pneumonia, Viral - prevention & control / Population density / prevention strategies / Protective equipment / Public health / Risk Factors / SARS / SARS-CoV-2 / Viral Vaccines / Viruses