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The Early Phase of the COVID-19 Outbreak in Lombardy, Italy

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The Early Phase of the COVID-19 Outbreak in Lombardy, Italy The early phase of the COVID-19 outbreak in Lombardy, Italy Cereda D1*, Tirani M1,2*°, Rovida F3*, Demicheli V4, Ajelli M5, Poletti P5, Trentini F5, Guzzetta G5, Marziano V5, Barone A6, Magoni M7, Deandrea S2, Diurno G1, Lombardo M8, Faccini M4, Pan A9, Bruno R10,11, Pariani E12, Grasselli G13,14, Piatti A1, Gramegna M1, Baldanti F3,11#, Melegaro A15,16#, Merler S5# * These authors contributed equally to this work # These authors are joint senior authors 1 Directorate General for Health, Lombardy Region, Milano, Italy 2 Department of Hygiene and Preventive Medicine, Health Protection Agency of Pavia, Pavia, Italy 3 Molecular Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 4 Health Protection Agency of the Metropolitan Area of Milan, Milano, Italy 5 Center for Information and Communication Technology, Bruno Kessler Foundation, Trento, Italy 6 Regional Agency for Innovation and Procurement, Milano, Italy 7 Epidemiology Unit, Health Protection Agency of Brescia, Brescia, Italy 8 ASST Lodi, Lodi, Italy 9 Infectious Diseases Unit, ASST di Cremona, Cremona, Italy 10 Infectious Diseases Unit, Fondazione IRCCS Policlinico San Matteo, Italy 11 Department of Clinical, Surgical, Diagnostics and Pediatric Sciences, University of Pavia, Pavia, Italy 12 Department of Biomedical Sciences for Health, University of Milan, Milano, Italy 13 Department of Pathophysiology and Transplantation, University of Milan, Milano, Italy 14 Department of Anesthesia, Intensive Care and Emergency, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy 1 15 Department of Social and Political Sciences, Bocconi University, Milano, Italy 16 Carlo F. Dondena Centre for Research on Social Dynamics and Public Policy, Bocconi University, Milano, Italy °Corrisponding author: Marcello Tirani Directorate General for Health, Lombardy Region, Piazza Città di Lombardia 1, 20124, Milano +39 333.3553594 [email protected] Key words: COVID-19, SARS-CoV-2, epidemiology, transmission dynamics, reproduction number, Coronavirus, Lombardy outbreak 2 Abstract Background In the night of February 20, 2020, the first case of novel coronavirus disease (COVID-19) was confirmed in the Lombardy Region, Italy. In the week that followed, Lombardy experienced a very rapid increase in the number of cases. We analyzed the first 5,830 laboratory-confirmed cases to provide the first epidemiological characterization of a COVID-19 outbreak in a Western Country. Methods Epidemiological data were collected through standardized interviews of confirmed cases and their close contacts. We collected demographic backgrounds, dates of symptom onset, clinical features, respiratory tract specimen results, hospitalization, contact tracing. We provide estimates of the reproduction number and serial interval. Results The epidemic in Italy started much earlier than February 20, 2020. At the time of detection of the first COVID-19 case, the epidemic had already spread in most municipalities of Southern- Lombardy. The median age for of cases is 69 years (range, 1 month to 101 years). 47% of positive subjects were hospitalized. Among these, 18% required intensive care. The mean serial interval is estimated to be 6.6 days (95% CI, 0.7 to 19). We estimate the basic reproduction number at 3.1 (95% CI, 2.9 to 3.2). We estimated a decreasing trend in the net reproduction number starting around February 20, 2020. We did not observe significantly different viral loads in nasal swabs between symptomatic and asymptomatic. Conclusions The transmission potential of COVID-19 is very high and the number of critical cases may become largely unsustainable for the healthcare system in a very short-time horizon. We observed a slight decrease of the reproduction number, possibly connected with an increased population awareness and early effect of interventions. Aggressive containment strategies are required to control COVID- 19 spread and catastrophic outcomes for the healthcare system. 3 Introduction In the late night of February 20, 2020, the first case of novel coronavirus infectious disease (CoVID-19) was confirmed in the Lombardy Region, Italy, a district with 10 million inhabitants. The patient was a 38-year old healthy man (patient 1), admitted to the Hospital of Codogno, with a mild pneumonia resistant to therapy, no relevant travel history and no apparent exposure to diseased contacts. Starting with the morning of February 21, a strict proactive intervention for tracing and testing all patient’ contacts was set up. Although the patient zero could not be detected, an initial outbreak was identified around the city of Codogno. In the week that followed, Codogno area, as well as several neighboring towns in southern Lombardy, experienced a very rapid increase in the number of detected cases, which rose to over 530 positive samples by February 28 and 5,830 by March 8th. With the increase in the number of detected cases, also their spatial distribution expanded, reaching several other areas in northern Lombardy. Over this period, the Regional Health System, Local Health Authorities (ATS: Agenzia di Tutela della Salute), the Lombardy Reference Virology laboratories, and the National Health Institute (ISS: Istituto Superiore della Sanità) collaborated to introduce coordinated actions to limit the spread of the infection. Among these, isolation of cases, contact tracing, intensive testing, and the definition of a “red” quarantined area around the most affected towns. Here we provide an analysis of the first 5,830 laboratory-confirmed cases reported in Lombardy, with date of symptoms onset over the period from January 14 to March 8, 2020. Epidemiological analyses of the confirmed cases and their background demographic and exposure characteristics are presented here as well as the transmission dynamics of the infection within the Region. Also, the virological analysis on a subsample of the reported cases is included to provide preliminary assessment of the level of the viral load among symptomatic and asymptomatic cases. 4 Method The earliest case was detected through the Lombardy Notifiable Disease Surveillance System, which is routinely used to monitor about 80 infectious diseases including at the time of reporting COVID-19. Due to the relevance of this diagnosis for immediate intervention, the data was simultaneously confirmed by real time RT PCR by two independent Regional Reference Laboratories, and further confirmed by sequencing of the amplicons. As indicated by the ISS, the sample was then sent to the ISS Rome Laboratory for confirmatory testing. Nevertheless, immediate intervention measures were set up on the basis of the local laboratory data. Case definition The case definitions for suspected COVID-19 cases were based on the European Centre for Disease Prevention and Control (ECDC) case definitions. A suspected COVID-19 case was defined according to the following criteria: 1) a patient with acute respiratory tract infection (sudden onset of at least one of the following: cough, fever, shortness of breath) AND with no other aetiology that fully explains the clinical presentation AND at least one of these other conditions: a history of travel to or residence in China, OR patient is a health care worker who has been working in an environment where severe acute respiratory infections of unknown etiology are being cared for; OR 2) a patient with any acute respiratory illness AND at least one of these other conditions: having been in close contact with a confirmed or probable COVID-19 case in the last 14 days prior to onset of symptoms, OR having visited or worked in a live animal market in Wuhan, Hubei Province, China in the last 14 days prior to onset of symptoms, OR having worked or attended a health care facility in the last 14 days prior to onset of symptoms where patients with hospital- associated COVID-19 have been reported. 5 A probable case was defined as a suspected case for whom testing for virus causing COVID-19 is inconclusive (according to the test results reported by the laboratory) or for whom testing was positive with a specific real-time RT PCR assay detecting the SARS-CoV-2 virus responsible for the COVID-19. Confirmed case was a person with laboratory confirmation of virus causing of SARS-CoV-2 infection, irrespective of clinical signs and symptoms. Epidemiological data and statistical analysis Epidemiological data were collected through standardized interviews of confirmed cases and their close contacts performed by the ATS operators. The information gathered were used to fill the datasets and included: demographic backgrounds, dates of symptom onset, clinical features, respiratory tract specimen results, hospitalization, contact tracing. Investigators interviewed each positive subject and/or their relatives, where necessary, to determine the history of exposure during the 2 weeks before the symptom onset of the positive test result, including dates, times, relationships, hobbies, and other patterns of exposures. The definition of contact used in the epidemiological field investigation is provided in the Supplementary Material. Data from the local datasets were entered into a central database and analyzed. Cases with established epidemiological links were used to estimate the distribution of the serial interval (i.e., the time period between the time of onset of symptoms in a primary case and the time of onset in her/his secondary cases. Laboratory testing According to WHO suggestions, nasal swabs (UTM viral transport ®, Copan Italia S.p.a) from
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