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C O L L E G E O F C A R D I O L O G Y F O U N DA T I O N . T H I S I S A N O P E N A C C E S S A R T I C L E U N D E R

T H E C C B Y - N C - N D L I C E N S E ( h t t p : / / c r e a t i v e c o mm o n s . o r g / l i c e n s e s / b y - n c - n d / 4 . 0 / ) .

VIEWPOINT

VOICES OF CARDIOLOGY

The Outbreak of COVID-19 in ItalyFighting the Pandemic

Ciro Indolfi, MD, Carmen Spaccarotella, MD

I n Italy, the unexpected pandemic of COVID-19has caused a never-seen-before disaster in termsof hospitalizations and deaths.

On January 9, 2020, the Chinese Center for DiseaseControl and Prevention reported that a new coronavi-rus, severe acute respiratory syndrome coronavirus-2(SARS-Cov-2), had been identified as the causativeagent of coronavirus disease-2019 (COVID-19), and thegenomic sequence was made public.

Italy was the first European nation to be affectedby COVID-19 with 143,626 confirmed total cases and18,279 deaths to date (1). The pandemic has mainlybeen located in northern Italy (Figure 1), partiallysparing, for the moment, the southern part of thecountry. Italy was not prepared for COVID-19,currently a planetary health emergency with1,436,198 cases and 85,522 deaths worldwide (2). TheItalian crisis provoked by COVID-19 is the mostserious event in Italian history after World War II; it isa national human, health, and economic tragedy.COVID-19 mortality in Italy has been 9%, higherthan that in China. The reasons for this highmortality are unclear. However, the infected fatalityrate may actually be lower because the tests havenot been widespread compared to other countriessuch as South Korea. Furthermore, the oldest popu-lation in Italy may have increased mortality. Infact, the median age in Italy of those who have died isw80 years (Figure 2). No patient <20 years of age

ISSN 2666-0849

From the University Magna Graecia of Catanzaro, Catanzaro, Italy. Dr.

Indolfi is Governor of the Italian Chapter of the American College of

Cardiology. Both authors have reported that they have no relationships

relevant to the contents of this paper to disclose.

The authors attest they are in compliance with human studies commit-

tees and animal welfare regulations of the authors’ institutions and Food

and Drug Administration guidelines, or patient consent where appro-

priate. For more information, visit the JACC: Case Reports author

instructions page.

has been hospitalized or has died. Only 1% of thedeaths have been detected in patients <50 years ofage.

THE START OF COVID-19 IN ITALY

On February 21, 2020, the first Italian patientwith COVID-19 was diagnosed, a 38-year-old manhospitalized at Codogno Hospital, Lodi, in northernItaly. Also, in northern Italy, on February 21, 2020,another outbreak of viruses was discovered inVò Euganeo (Padua) and, in the Veneto region, thefirst death was reported, a 78-year-old man in a hos-pital in Padua. He was the first of a long series ofdeaths. The mortality rate in the Lombardy regionalone, with a total of 10,022 deaths, is greater than thenumber of deaths in China (3,342 total deaths).

WHAT HAS HAPPENED IN ITALY?

Social containment, early and rapid throughout anation, is the most effective measure for controllingthe spread of COVID-19; this social containmentperhaps was delayed in Italy (Figure 3). Italy was thefirst nation in Europe affected by COVID-19 and wastherefore caught unprepared. The rapid spread ofCOVID-19 and the dangerousness of the disease, verydifferent from the normal seasonal influenza, wereperhaps initially underestimated. Today, the entirenation is on lockdown, and cities and towns havebecome isolated, as seen in Figure 3, showing adeserted Rome today.

In Italy, the tests for COVID-19 have been per-formed mainly on symptomatic subjects. Tests werenot performed initially in health care professionals(who could, therefore, have contributed to the spreadof the disease) as well as in symptomatic patients athome. Finally, Italy, like the majority of nations, wasnot prepared for the rapid spread of the pandemic,and many protection systems such as masks,

https://doi.org/10.1016/j.jaccas.2020.03.012

FIGURE 1 Number of COVID-19 Cases Reported by Each Region in Italy

The graphic shows the number of coronavirus disease-2019 (COVID-19) cases in the

Italian regions. It is evident that the vast majority of cases were condensed in northern

Italy (data from the Istituto Superiore di Sanità).

FIGURE 2 Age of Patients Who Died Due to COVID-19

The median age of patients who have died and patients with a definite coronavirus dis-

ease-2019 (COVID-19) diagnosis.

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produced almost exclusively abroad, were not suffi-cient even for health personnel. In addition, there aresimply not enough ventilators for all patients whoneed them, raising important ethical issues.

Bergamo, a city in Lombardy of 122,000 in-habitants, had a very high number of infections(10,043), perhaps because the importance of socialcontainment to favor economic activities was under-estimated. A particularly crowded Atlanta-Valenciafootball match, with >50,000 Bergamo spectators, isanother hypothesis to explain the high number ofinfections. Noninvasive ventilation is the first formof therapy for many patients hospitalized withsevere interstitial cases of pneumonia, who, however,suddenly may require intubation for rapid lungdeterioration. Medical therapy in these patients isempirical, although chloroquine, azithromycin, high-dose steroids, tocilizumab, lopinavir/ritonavir, hepa-rin, and other drugs have been empirically tested. Ithas been recently suggested that other health caresystems should prepare for a massive increase inICU demand during an uncontained outbreak ofCOVID-19 (3).

CLINICIANS AND NURSES PAID A

VERY HIGH PRICE IN ITALY

Health care workers in Italy paid a very high pricewith more than 11,000 confirmed cases, 100 clinicianskilled by COVID-19 and many with burnoutsyndrome.

The epidemic in Italy has also found territorialmedicine to be unprepared, which has not been ableto handle the problems of individual people and ofpeople positive for tests. Thus, during the days ofnational quarantine, it is extremely difficult for thepopulation to interact with territorial institutions forall disease-related problems.

Based on the Italian experience, it has becomeevident that western health care systems havebeen built around the concept of patient-centeredcare, but an epidemic requires a change of perspec-tive toward a concept of community-centered care(4). It has been postulated that >2,500 hospitalbeds for patients in intensive care units will beneeded in only 1 week to treat acute respiratorydistress syndrome caused by SARS-CoV-2-pneumoniain Italy (5).

PANDEMIC SOLUTIONS ARE REQUIRED

FOR THE ENTIRE POPULATION,

NOT ONLY FOR HOSPITALS

We are learning that hospitals might be the mainCOVID-19 carriers, as they are rapidly populated by

infected patients, facilitating transmission to unin-fected patients. Patients are transported by ourregional system, which also contributes to spreadingthe disease as the ambulances and personnel rapidlybecome vectors. Finally, Italy does not produce

FIGURE 3 Rome Deserted During the Rule of Social Distancing

This photograph shows an unusual, deserted Rome after the lockdown for coronavirus

disease-2019.

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containment systems; for example, the masksand ventilation systems are not produced in Italy, andthis has caused a supply vulnerability when othernations have substantially reduced internationalrelations.

THE UNIVERSAL ITALIAN HEALTH SYSTEM

It has been previously reported that the quality of theuniversal Italian health system and healthy behaviorshave contributed in the past to the country’s favor-able overall health (6). In a race against time in anunprecedented health national health emergency,with an organizational effort never seen before inItaly, hundreds of doctors and nurses (many thenSARS-CoV-2 positive) are fighting this horrible dis-ease. The advantage of the Italian health system isthat all citizens may have access to medical therapies.However, in recent years, health policy has pro-foundly changed in Italy. The number of beds hasbeen reduced, and regional autonomy has

accentuated inequalities in the quality of services onthe national territory.

THE CARDIOLOGIST’S PERSPECTIVE IN THE

COVID-19 ERA

Cardiologists in Italy are overwhelmed in this un-precedented battle against COVID-19 for reasonsrelated to the disease per se, to the rapid conversionof many hospitals to COVID-19 treatment centers, andto the changes in health management caused by thepandemic (3).

It is now evident that patients with COVID-19have cardiac involvement, in some cases indepen-dent of the lung disease. An increase in troponinlevels has been documented in a percentage ofCOVID-19 patients linked to “noncoronary” myocar-dial damage frequent in many respiratory diseases.Furthermore, type I or type II myocardial infarctiontriggered by the inflammatory response of thevirus were also reported in COVID-19. Important forall of us on the front lines, as clinicians, we areadvised according to the American College of Cardi-ology statement (7) to measure troponin only ifthe diagnosis of acute myocardial infarction isbeing considered on clinical grounds, although thelevels of troponin are very important becausethey correlated to the subsequent prognosis inCOVID-19. It is very difficult when we see so manypatients each day, to determine the care and neces-sary tests while balancing the benefit and clinicalneeds.

The other reason why cardiologists are deeplyconcerned is directly related to resources; that is, therapid reorganization of hospitals in Italy and the busyemergency system together with the patients expe-riencing cardiovascular diseases. In many hospitals,especially in northern Italy, which has a high per-centage of patients with COVID-19, cardiac care unitswere the first to be transformed into COVID-19 units(Figure 4). Appropriate personal protective equip-ment (PPE) was available late in the pandemic in theItalian cath labs (Figure 5). Hub centers have createddedicated pathways for COVID-19 patients with acutecoronary syndromes, and cardiology staff have nowbeen trained to perform procedures on infected pa-tients. Furthermore, telemedicine has been imple-mented to allow the cardiologists, when possible, toconduct virtual COVID-19 visits and electrocardiog-raphy readings. It is difficult when you do not havethe patient in front of you but unfortunately a

FIGURE 4 COVID-19 Intensive Care Unit in Italy

COVID-19 requires the activation of specific intensive therapy centers with particular

attention to the prevention of health personnel. Photo is courtesy of Federico Longhini,

MD, Professor of anesthesiology at Magna Graecia University.

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necessity. The emergency system (118) in some re-gions is overwhelmed by COVID-19–positive patients.Local doctors are also exhausted from this unprece-dented COVID-19 commitment. The Italian catheteri-zation laboratories have greatly reduced electiveroutine nonurgent activities, which have beencompletely stopped in those regions with a highnumber of infected patients.

Importantly, a novel finding was documentedby a recent ongoing survey by the Italian Societyof Cardiology. The survey found a 50% reduction inhospitalizations for acute coronary syndromes inthis week of the pandemic, compared with thesame period of last year, even in regions notheavily affected by COVID-19 (data on file of theItalian Society of Cardiology). Of note, the surveyalso showed that some patients with ST-segmentelevation myocardial infarction were admitted tothe catheterization laboratory with a great delay(much longer than 120 min), even in low infectiondensity regions where cardiac care unit beds areavailable. The reduction is very strong forpatients with non–ST-segment elevation myocardialinfarction but a reduction of 30% has also beenobserved for patients with ST-segment elevationmyocardial infarction. The reasons for this substan-tial reduction are still unclear, perhaps related topatients’ fear of becoming infected during the hos-pital stay, the lack of availability of local clinicians, orto the fact that the 118 emergency system is extremelybusy dealing with COVID-19 patients (in someregions).

There has been recent concern in the cardiologycommunity about the possible negative effect ofangiotensin-converting enzyme inhibitors andangiotensin AT1 receptor inhibitors in patientswith COVID-19. The Italian Cardiology Society, aswell as the European Cardiology Society, released adocument in which they recommended continuingthese drugs in patients with COVID-19, especiallyin the presence of left ventricular dysfunction.Further studies, however, are needed to showthe effect of renin-angiotensin system inhibitorsin the general population at risk or affected byCOVID-19.

If we were to write a take-home message, it isthat we need to be optimistic. We hope that thiscatastrophe will be very helpful for Italy andother countries in terms of rethinking the health or-ganization of the future and rebuilding an even moreefficient health system. The lesson that Italy has

learned from this pandemic is that we must be pre-pared, and we must always plan for the worstand hope for the best scenario. Italian politiciansshould rethink the linear cuts made in recent years topublic health, as well as to the reduction in thenumber of doctors, residents, beds, and resources tomaintain the quality of medical services in allItalian regions. Once again, the importance ofresearch, now little considered in Italy, should bereassessed in the face of catastrophes such as thatcaused by SARS-CoV-2, to achieve rapid therapeuticstrategies.

FIGURE 5 Catheterization Laboratory in the COVID Era

Percutaneous coronary intervention performed with appropriate personal protective equipment in the pandemic.

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Italy, as it has done in the past, will improve itshealth and economic systems after this tragedy.Probably nothing will be like before, and this catas-trophe will be a great opportunity to further improvean efficient and effective national universal healthsystem.

ADDRESS FOR CORRESPONDENCE: Dr. Ciro Indolfi,Division of Cardiology, CCU and Interventional Car-diology, Director, Research Center for CardiovascularDiseases University Magna Graecia, Viale Europa S/N,8800 Catanzaro, Italy. E-mail: indolfi@unicz.it.

RE F E RENCE S

1. Dipartimento della Protezione Civile. COVID-19Italia - Monitoraggio della situazione. Availableat: http://opendatadpc.maps.arcgis.com/apps/opsdashboard/index.html#/b0c68bce2cce478eaac82fe38d4138b1. Accessed April 2020.

2. World Health Organization. Coronavirus (COVID-19). Available at: https://who.sprinklr.com.Accessed April 2020.

3. Grasselli G, Pesenti A, Cecconi M. Critical careutilization for the COVID-19 outbreak in Lombardy,Italy. JAMA 2020 Mar 13 [E-pub ahead of print].

4. Nacoti M, Ciocca A, Giupponi A, et al. Atthe epicenter of the Covid-19 pandemic andhumanitarian crises in Italy: changing per-spectives on preparation and mitigation.NEJM Catalyst 2020 Mar 21 [E-pub ahead ofprint].

5. Remuzzi A, Remuzzi G. COVID-19 and Italy: whatnext? Lancet 2020;395:1225–8.

6. GBD 2017 Italy Collaborators. Italy’s HealthPerformance, 1990-2017: Findings From the

Global Burden of Disease Study 2017. LancetPublic Health 2019;4:e645–57.

7. American College of Cardiology. Available at:https://www.acc.org/latest-in-cardiology/articles/2020/03/18/15/25/troponin-and-bnp-use-in-covid19.Accessed April 2020.

KEY WORDS COVID-19, Italy, pandemic, SARS-CoV-2