Lessons from Italy

For a variety of reasons, Italy failed to contain the initial surge of the pandemic. Its advanced health care network is its only solace; the focus is now on management rather than prevention.

A patient in a biocontainment unit is carried on a stretcher from an ambulance which arrived at the Columbus Covid 2 Hospital in Rome, on March 17.

“Europe is now the epicentre”: World Health Organisation (WHO) Director General Dr Tedros Adhanom Ghebreyesus declared in Geneva on March 13, as confirmed cases of novel coronavirus (COVID-19) infection rose in Italy and the virus spread to all European Union (E.U.) countries.

On March 20, Italy reported 5,900-odd fresh cases and 627 deaths, the highest daily tally of mortality reported from anywhere in the world. The total number of cases in Italy had crossed 40,000 and deaths 4,000, overtaking the death toll in China. The authorities were caught unawares. Ironically, just as the Olympic torch was being lit in Athens, there was a blaze of COVID-19 in Italy.

As the centre of gravity of the unprecedented pandemic shifts decisively westward, it is pertinent to ask: Why Italy?

Europe, after the tumult of two World Wars, had embarked on the road to recovery through mutual cooperation, exemplified by the Maastricht Treaty in 1993, which established it as a union of constituent nations, a borderless region to facilitate trade and the free movement of people. The union, reinforced by the post-War emphasis on welfare, led to the western side of the continent establishing some of the most advanced health care systems, which resulted in the high life expectancy rates seen now. Indeed, death rates exceeded birth rates, putting the population in a state of decline where the net replacement rate was less than one. Thus, Europe aged, even as it became relatively wealthy.

Italy’s famed Colosseum and other attractions drew millions of tourists each year, making the country the fifth most popular tourist destination. An open border meant that the incoming tourist could travel anywhere in Europe. Perhaps these factors, that is, an ageing population, a high rate of internal migration, and a constant flow of tourists proved to be its undoing when the pandemic came knocking at its door.

In the movie Contagion (2011), a health care thriller rediscovered after the COVID-19 spread, an epidemiological surveillance officer explains the term R0, “the reproduction number”, which in public health jargon shows how fast a disease spreads in the community. In epidemiology, the R0 of an infection can be thought of as the expected number of cases directly generated by one case in a population where all individuals are susceptible to infection. The R0 for Covid-19 has been estimated to range from 1.5 to 3.5 and to effectively stop the pandemic, we need to reduce this to less than 1. This is what is meant by “flattening the curve”, a term that has gone viral in social media, which possibly explains why the benefits of quarantine and social distancing have gained social acceptance so quickly. What makes Covid-19 different from flu is the fact that humans lack antibodies to fight it, which is why it is termed “novel”. By implication, this means the lack of effective treatment and hence a higher mortality rate. As the case count increased from a few hundreds to several thousands, China’s apparently draconian lockdown worked to ebb the spread of the disease. The measures, which appear to have struck a wrong chord with Europeans, have had fatal consequences.

Such is the field of public health that when things are good, people hardly notice. Clean water, good hygiene, good health care, are all taken for granted until the system collapses. On February 20, the first case emerged in Italy. This was a healthy young male who was initially not a coronavirus suspect. His only significant history was that he was at a dinner with a few Chinese tourists two weeks earlier. The health care system was oblivious to coronavirus; it only came to light because a few diligent doctors notified COVID-19. An outbreak, which was initially thought of as an isolated event, was already spreading in every European nation. Particularly alarming was the development of several clusters throughout the continent. Significantly, it is the relatively rich northern Italian region of Lombardy which bore the brunt of the disease. Dr Giacomo Gracelli, head of intensive care medicine, in Milan, described this as a “big surprise”.

Lombardy, the industrial capital of Italy and the fashion capital of Europe, has had close connections with China. Several thousand Chinese work in factories there. Significantly, direct flights connected Milan with Wuhan, the original source of the outbreak. All the factors had led to the failure of identification of the “index case” or the “case zero”, which would have been the first imported case in Europe. Importantly, contact tracing from Patient #1 did not work in Italy. The country, along with Spain (the second most affected country in Europe) is popular with retirement planners. Its beaches and villas have attracted several post-retirement settlements. Thus, a rapidly multiplying cluster of infections, which affected a predominantly older population, put a severe strain on one of the most developed health care systems in the world.

Eighty per cent of COVID-19 patients were asymptomatic, thereby reducing the total positive tests in comparison to the prevalence of the disease. However, 40 per cent of those diagnosed positive also required hospitalisation, 12 per cent required intensive care, a few among them the most critical equipment. Perhaps no other disease that we know in modern medicine has required such a high level of ventilator utilisation. What started as a small number escalated rapidly to several thousands.

On March 8, the Lombardy provincial government ordered a lockdown as the number of cases rose to 8,000. The order did not go down well with the people and at least 10,000 people escaped to the south. This led to the spread of the disease to other regions of the country, which forced the government to order a total lockdown on March 9. Hospitals were scrambling to make beds for patients. The ICU utilisation of COVID-19 patients was particularly high and health care was a scarce resource. Had not some office bearers of medical organisations organised regional hospitals, the situation would have been far worse. The ICUs were split to treat exclusive coronavirus patients and for other medical conditions. Soon many hospitals had to convert every ICU into a COVID-19 ICU, which severely impaired the response to other medical and surgical conditions. Elective surgical operations were stopped; trauma cases were attended to with a lower standard of care; heart disease patients were left with no beds in ICUs; and the problems compounded. Maurizio Cecconi, president-elect of intensivists (those specialised in work in ICUs) forum, warned other countries: “Do not underestimate. It is not flu. Do not lose time.”

A significant feature of the outbreak in its early days was the high infection rate among health care personnel, which had a significant impact on the system’s ability to treat the surge of cases. In the first week of March, about 10 per cent of the samples that tested positive turned out to be from health care professionals. This was attributed to the incorrect usage of personal protective equipment, particularly because of the shortage of such equipment. The workers who tested positive had to go into quarantine, creating a further shortage of manpower. Retired doctors and university students were drafted, possibly resulting in lowering the standard of care. The number of nurses trained to operate ventilators was also low. This was a critical bottleneck in Italy.

The administration drew up a plan: given up on containment and focus on management and treatment. In order to reduce infections among health care workers, six-hour shifts were allocated when the workers could not eat, drink water or use the restroom and had to wear head-to-toe protective equipment. Lombardy had 700 ICU beds when the epidemic broke out. A massive scaling up became necessary to increase the capacity to 1,200 beds. But almost all the beds have been occupied by coronavirus patients.

Perhaps the most significant aspect of this epidemic in Italy was the response from the people. They were not used to restrictions. They could not follow the stringent discipline enforced in China. Nearly 44,000 people have been booked across the country for defying prohibition orders.

Epidemiologists warn that the epidemic has not yet attained its peak in Italy. Since the incubation period of the virus is up to 14 days, it is expected that cases would continue to pile up until at least March 23. The logic of this assessment is based on the 14-day interval from the lockdown initiated on March 9. Experts have argued that even if the lockdown was only partially effective, it would have helped in bringing about a quicker flattening of the peak. The high rate of mortality has also been attributed to the drug Ibuprofen, an over-the-counter pain reliever as well as an antipyretic whose availability has been duly curtailed since then. Ibuprofen lowered the subjects’ immune response, which hampered their recovery.

An unprecedented positive feature of the crisis is how Italian doctors have managed to contribute a wealth of information, disseminating scientific knowledge through clinical papers, even as they have been handling the biggest medical crisis of their lives. Doctors have reported that supportive care and mechanical ventilation have benefited patients. Younger patients reportedly responded better to CPAP (continuous positive airway pressure), a method of non-invasive ventilation.

A few cases of anecdotal evidence of success have been attributed to chloroquine and azithromycin combinations. China had been using a Lopinavir/Ritonavir combination, a protease inhibitor used in human immuno virus infection with varying levels of success. The most significant finding released recently was the usage of Favipravir, an antiviral approved in Japan for flu, being successful with significant remissions. However, all the drugs have not been put through rigorous trial and their use has been observed only anecdotally. It might take several months before a permanent cure is approved. Other therapies such as serum from recovered patients have also shown good results but they proved to be costly and associated with many side-effects. Italian experts have called other European countries to use the advantage of time—a luxury Italy did not have—apart from epidemiological surveillance, contact tracing, isolation, physical distancing, quarantine, and, if possible, lockdown. The critical part is training the personnel to ensure that they do not contract the infection.

Italy, being one of the countries with the oldest populations in the world with a high rate of diabetes (5.3 per cent of the population) and hypertension (35-45 per cent), coincidentally contributed to more deaths. Older people are not expected to survive mechanical ventilation owing to these comorbidities. The average utilisation of a ventilator was at least a week in Italy, and a conscious decision was made to use life-saving machines on those whose chances of survival were better, generally between the old and the young.

The mortality rate among the older population has been high. Italy has reported only two deaths below the age of 40. This broadly compares with the data released from China. Malnutrition and immuno compromised states do increase coronavirus mortality. The youngest person to die was a 21-year-old man who was suffering from leukaemia.

One glimmer of hope in this crisis is the relative sparing of children so much so that the United Kingdom tried to “#KeeptheSchoolsOpen” to generate herd immunity, which eventually proved futile because this only helped the faster spread of the infection to the elderly. However, the lower instance of hospitalisation in children needs to be taken lightly as the disease is still evolving and its response in conditions of malnutrition in developing countries is unknown.

So far, there has been no evidence of reinfection. Patients are being discharged once two swabs return negative. Italy has been testing only symptomatic people since March 10 as the testing had overwhelmed the capacity at laboratories.

The WHO has recommended the idea of “Test, test, test”. South Korea is the best example of flattening the curve approach to COVID-19 with tests as high as 5,200 per 10 lakh population, eventually reducing transmission and nearing containment. Italy has done 2,100, the United States 74 and India 5 per 10 lakh population. The tests have been done using a method called RT-PCR, which is costly to implement in a country with a large population like India. The low test rate has been a cause of concern with India reportedly having only 150,000 test kits for a population of 140 crore. Scarce resources need to be directed at target populations, striking a fine balance between testing and over-testing. It is also imperative to increase capacity significantly as the general population is anxious and a sense of unrest could soon take hold.

Several vaccine candidates have been under development and the first clinical trials in the U.S. have begun. However, they are at least 18 months away from mass administration. Candidates with established clinical safety could get faster approvals depending on the prevailing pandemic proportions.

The European response has been quite different from China’s, characterised by varied, sometimes even bizarre, response strategies. The governments were not prepared and failed to contain the initial surge. which resulted in a chain reaction. Europe’s advanced health care network is its only solace as is the fact that the focus is on management rather than prevention.

Italy is not a backward nation. It is not a poor country. It also has a long history of welfare capitalism. If a health care crisis can affect such a nation, it shows a general lack of preparedness to fight epidemics. It is ironical to see how a country figuring among the highest ICU beds per capita could run out of the resource. It is imperative that governments around the world realise that public health departments are important and the governments dole out enough recapitalisation measures. It is also ironical how 10 years of progress in financial markets could be wiped out in four weeks just because we did not plan for an outbreak.

The era of public health began with John Snow mapping the points of contaminated water supply in London 150 years ago. Population health, health care modelling, outbreak modelling and epidemiological intelligence services need to be ramped up and such resources need to be made available in rich and poor countries.

With a predominantly young population, India may appear deceptively to be at an advantage. However, India cannot afford to be complacent. Vigilant screening and isolation of suspected cases needs to be done. The country is still in stage II (local transmission), during which training to health care professionals, vigorous contact tracing and improved testing capacity should be the immediate priority. Ramping up ICU beds and arranging for ventilators for urgent use requires to be a key priority. The best way India can manage this epidemic is by stopping its spread in a densely populated country with high levels of air pollution and a high prevalence of respiratory diseases. Recall that tuberculosis kills 60,000 Indians every year.

Dr Saiprasath J. is a Chennai-based medical practitioner.