COVID-19 infection: the China and Italy perspectives

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Since its first report in December 2019, despite great efforts made in almost every country worldwide, this disease continues to spread globally, especially in most parts of Europe, Iran, and the United States. Here, we update the recent understanding in clinical characteristics, diagnosis strategies, as well as clinical management of COVID-19 in China as compared to Italy, with the purpose to integrate the China experience with the global efforts to outline references for prevention, basic research, treatment as well as final control of the disease. Being the first two countries we feel appropriate to evaluate the evolution of the disease as well as the early result of the treatment, in order to offer a different baseline to other countries. It is also interesting to compare two countries, with a very significant difference in population, where the morbidity and mortality has been so different, and unrelated to the size of the country.

Fig. 1. Spread and dynamics of the COVID-19 pandemic.

Spread and dynamics of the COVID-19 pandemic on a worldwide scale (a), source Worldmeter (www.worldmeters.info), and on Italy (b), modified with permission from PNAS USA, 2020. 10.1073/pnas.2004978117.

Fig. 2. COVID-19 pandemic in different countries.

Cumulative numbers of cases (a) and deaths (b) in China, European, and the United States. Distributions of the cases (c). The inset in panel a reports the new cases in Italy as to 10 May, showing a drastic reduction on morbidity. Source Worldmeter (www.worldmeters.info) and Protezione Civile (http://www.protezionecivile.gov.it/attivita-rischi/rischio-sanitario/emergenze/coronavirus). Distribution of laboratory confirmed cases of COVID-19 in the Italy, China, and the USA, as of 10 May 2020.

Fig. 3. SARS-Cov spike glycoprotein.

The coronavirus SARS-Cov-2 spike (S) glycoprotein is responsible for viral entry into the cell and it is the major target of antibody recognition. SARS-Cov-2 S is an ectodomain trimer. All three coronaviruses causing severe acuter respiratory syndrome coronavirus (SARS-Cov), Middle-East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 are closely related and contain a transmembrane spike, S, glycoprotein with two functional subunits able to bind the cells (S1 subunit) and responsible for fusion of the viral and cellular membrane (S2 subunit). SARS-Cov-2 spike S shows a closed and an open conformation (depicted), where only the closed conformation binds the human ACE2 receptor-binding domain. The structure shown was obtained by Cryo-EM (closed: PBD = 6VXX at 2.8 Å resolution; open: PBD = 6VYB at 3.2 Å resolution) was released on 11 March 2020 from Walls et al..

Fig. 4. ACE2 receptor binding the SARS-Cov-2 virus.

The initial step of SARS-Cov-2 viral entry during the infection is the binding of the viral trimeric spike protein (cleaved into S1 and S2 subunits, the former of which contains the receptor-binding domain, RBD) to the dimeric human receptor angiotensin-converting enzyme 2 (ACE2) which is here represented in the complex with the membrane protein that it chaperones, BoAT1. ACE2 is formed by an N-terminal peptidase domain (PD) and the C-terminal collectrin-like domain (CLD). ACE2 shows a closed and an open (depicted) conformation at the PD level of contact; however, only the closed conformation binds the RBD of SARS-Cov-2. The structure shown was obtained by Cryo-EM at 2.9 Å resolution (PBD = 6M17) was released on 11 March 2020 from Yan et al..

Fig. 5. Computer tomography image of COVID-19.

Early (a) and late stage of COVID-19 (b) computer tomography of the lung showing a diffuse interstitial pneumonia.

Fig. 6. Daily incidence of new infections and future scenarios.

The Leopoldina Statement reported the daily incidence of new covid-19 infections in Germany (a blue dots and line) followed by a statistical modeling of new infections, with full implementation of all proposed measure of containment (hygiene recommendations, physical distancing, nose and mouth protection, testing, digital data tracking, selected targeted quarantine) with a very gradual relaxation of restrictive measures imposed to public life (a, green line 1). Conversely, the scenario proposes a fast reactivation of the infections (a, reddish line 2) if the proposed measures fail to be implemented. The read frequency of cases in South Korea (b), despite full implementation, shows that sporatic new infections cannot be fully avoided despite serious prevention, resulting in a low grade of endemic cases.