In Italy, fewer and fewer people die of covid. On May 25, civil protection reported 92 deaths, 34 of which in Lombardy. The day before there were fifty, and zero in Lombardy. But if the deaths are fewer and fewer, can we hope that even in the presence of a recovery in infections, mortality remains low? Could it not be the case that, as happened from the beginning in Germany, the growth of the infected corresponds to a line only slightly rising of the dead, therefore a different scenario and in many ways calming? Or are we deluding ourselves?
Italy is currently third (after Belgium and France) in the ratio between deaths and confirmed cases of covid-19, known as Case fatality rate (Cfr) : 14.1 percent. The world average is 6.6 percent, that of Germany 4.6 percent, of Iceland 0.5 percent. The Cfr obviously grows with age, becoming maximum above 80-90 years.
In essence, the history of lethality from February to today seems to suggest that we are moving from an Italian to an Icelandic scenario.
Mistakes and surprise effect
How is it possible that the same virus in March killed almost half of the patients and ten times less in May? In recent days someone has claimed, like the virologist Massimo Clementi, that the virus has meanwhile changed, losing part of its aggressiveness. But waiting to receive definitive confirmations or denials of this hypothesis, we can stick to a more solid explanation: from a medicine of war we have finally returned to a normal medicine, which must face a normal, albeit insidious, disease. Basically, if the virus has not changed, there are still several cases that go to the hospital.
Why then so many deaths between March and April?
The first hypothesis indicates possible therapeutic errors committed in the face of a still poorly understood disease, and in conditions of extreme emergency. Luciano Gattinoni, founder of the Lombard school of intensive care and now stationed in Göttingen, questioned by me on the subject, gives an example:
In the first week of covid, critically ill patients were treated in intensive care with positive pressure ventilation around 15-16 centimeters of water. After one month the pressure was adjusted to 7-8. In short, in the emotion of the first moments, on the one hand too much has been done and, on the other, not many things have been done, such as an accurate analysis of the CTs. On the other hand, I understand very well that at that time, with the hospital full of deaths, it was unthinkable to deal with pathophysiology. No attention was paid to the fact that we were not faced with the characteristics of respiratory failure that we were used to seeing in previous decades. There was something different.
March is the cruelest month, but April is no joke
Do we remember the month of March in Lombardy? Exponential case ascent, skipped tracking, saturated wards and intensive care, seriously ill people shipped by plane to Germany, military trucks that moved hundreds of coffins from the martyred city of Bergamo to the crematoriums of Modena, followed by a few cars of astonished relatives. In hospitals, half of the sick die in the ward and in therapies.
On March 21, the doctors of Pope John XXIII of Bergamo write on Catalyst del New England Journal of Medicine:
Our hospital is highly contaminated and we are already beyond the point of collapse: 300 beds out of 900 are occupied by covid-19 patients. More than 70 percent of intensive care places are reserved for covid-19 seriously ill patients who have reasonable hope of survival. The situation is so serious that we are forced to operate well below our standards of care. The wait for an ICU post lasts hours. Older patients are not revived and die in solitude without even the comfort of appropriate palliative care. Families cannot have any contact with terminally ill patients and are informed of the death of their loved ones by telephone, by well-meaning but exhausted and emotionally destroyed doctors. In the surrounding areas the situation is even worse. Hospitals are overcrowded and close to collapse, and there are no medications, mechanical fans, oxygen and masks and protective suits for healthcare personnel. Patients lie on mattresses resting on the floor. (…) We are learning that hospitals can be the main transmission vehicles of covid-19, as they quickly fill up with infected patients who infect uninfected patients. The regional health system itself contributes to the spread of contagion, as ambulances and health workers quickly become carriers. Healthcare workers are asymptomatic carriers of the disease or sick without any surveillance.
The case of the Crema hospital
The cruelest month had come early, and the general manager of the Crema Germano Pellegata hospital remembers it well:
In mid-March we had 70-80 accesses of covid patients to the emergency room per day. Out of 400 beds in our hospital, 350 were occupied by these cases, 120 in ventilation, 18 in intensive care, 28 in the field hospital hurriedly mounted by the army and managed by the Cuban health brigade.
And Crema is not Codogno, the epicenter of the outbreak, nor Alzano, nor Bergamo, where the numbers reported in the chronicle of those days are mind-boggling. Remember Pellegata:
We thought we were ready. Like all Lombard hospitals, we had updated the pandemic plans at the end of 2019. In January, given what was happening in China, we had stocks: 20 thousand FP2 and three thousand FP3, suits, helmets, boots. Since the first case on February 20, we have converted the hospital by triplicating the beds in intensive care, closing operating blocks and coronary units, transforming the adjacent respiratory rehabilitation structure into a hospital and putting the three pneumologies into a system; we started training all staff, having to put ophthalmologists to deal with pneumonia.
But even in the structures that have rapidly managed to turn into covid hospitals, the response for a few weeks has not been optimal. The oxygen consumption, for example, during the epidemic peak increased by 15 times, forcing the Crema hospital to intervene quickly to reinforce the system with new tanks and with other precautions that could bring the right pressure in the ventilation departments.
Death with covid (and many other diseases)
A study conducted in the Cremasco hospital on the first 411 hospitalized with covid-19 symptoms, most of which confirmed with a tampon or with Tc (which is very reliable, while the tampon is wrong twice out of ten), gives reason to whom ( like INPS) claims that the cases and deaths from covid are more than those recorded by civil protection. In this first phase of the epidemic at Crema hospital, 17.5 percent will die (percentage destined to increase in the following weeks): two thirds are male, with an average age of 81 years; zero deaths under 60.
Researchers Giuseppe Pinter Lauria of the Besta Institute in Milan and Guido Caldarelli of the Imt of Lucca have analyzed, in particular, the diseases that have complicated the picture and played a role in the death of the most fragile. Thanks to a network analysis developed by Caldarelli, it can in fact be understood that death does not depend on age itself, but occurs especially in those suffering from heart diseases, kidney failure, cancer, hypertension, diabetes and respiratory diseases which they are arranged in characteristic clusters.
Another study on the epidemic in Lombardy, Veneto and Reggio Emilia from 21 February to 21 April resulted in a lethality of 27.6 percent, and observed that comorbidity plays a crucial role in covid death up to 80 years after of which age-related fragility seems to prevail.
Today, the general manager of the Crema hospital is able to give us the complete picture of the lethality that draws a comforting trend:
Deaths in the entire period from 23 February to 19 May amounted to 19 per cent of covid patients: 2.8 per cent in the first week, 7.9 per cent in the second, 26 per cent in the third, 24 per cent in the fourth, 38 percent the fifth week (March 22-29), 24 percent the sixth, 23 percent the seventh, 19 percent the eighth, 16 percent the ninth, 7.7 percent the tenth and 7.3 percent one hundred eleventh.
Does the virus give up? The data of San Raffaele
The hematologist Fabio Ciceri is the deputy scientific director of the San Raffaele hospital in Milan, heavily involved in the covid-19 emergency. As we have seen, even here lethality drops from week to week from 29 percent of the onset to 2 percent of the last few weeks. “For a couple of weeks, we have hardly seen covid patients anymore, and the few who come have no serious forms,” says Ciceri. The main Milanese public hospitals that have performed a function of hub in the epidemic, like the Sacco and the Niguarda, they still have new symptomatic cases, but in fewer numbers as the days go by.
The disease seems to have lost strength everywhere: and if it is not the mutated virus, what can it depend on? Fabio Ciceri offers three explanations:
Hospital and home care is more appropriate than in the early days and administered earlier. It has been pointed out that, beyond the pneumonia, the disease presented an inflammatory and thrombosis picture, to be treated with anticoagulants and immunomodulatory therapies. In addition, by emerging from the emergency and with more beds available, hospitals respond better. Another important point is the seasonality: in February-March in the serological tests of the patients we found flu viruses and other viruses that suggest concomitant infections and, therefore, aggravating the picture. Air pollution, irritating the respiratory tract, also overexpresses the Ace2 receptors and worsens the prognosis.
Asked if he expects a recovery of the epidemic, Ciceri is optimistic:
We do not expect a recovery of serious cases. During the emergency in Lombardy it was not possible to trace the infected and their contacts, but by now the system has been run in to catch the sick in time to isolate them and, if necessary, treat them early. We experienced a fracture between hospital and territory that is now being recomposed.
To the hospital only when needed
Luciano Gattinoni also insists on the relationship between territory and hospital when I ask him to explain the success of Germany.
Why are there fewer deaths in Germany? In my opinion, the first and biggest difference with Italy is that they kept the sick more at home. In Germany, when he arrives at the hospital, the patient finds himself in front of a billboard with written on Nicht betreten, do not enter! Those who have symptoms, even if only suspicious of covid, be it a cold or conjunctivitis, do not set foot in the hospital, they must ring a bell and someone will come to take care of him. In the vast majority of cases, these people are sent home and taken over by general practitioners. And be careful: 50 percent of the staff who receive these patients are GPs who take turns in hospital. In Germany, general medicine is combined with hospital care, not separate from us, where family doctors have an “agreement” with the NHS. This rift in Germany does not exist: there is integration. This kept people who didn’t need it away from hospitals, saving many lives.
But it is the epidemiologist of the Ats Milano Antonio Russo, author of the most recent Evaluation of excess mortality in the first five months of 2020 in relation to the previous five years, who frames the decline in covid deaths in the most convincing way:
In the last months of 2019 and in the first two of 2020 there was a lower mortality in Milan as elsewhere in Italy, which led to the accumulation in the population of a reservoir of fragile people affected by a heavy immediate mortality. The persistence of the epidemic mainly affected the elderly population with many comorbidities, who became infected and died (over five thousand of the six thousand more deaths in the Milanese conurbation). This reservoir of ‘early’ mortality has run out, and now they have remained more resistant to the effects of the virus, in addition to the fact that now the elderly have understood that they must protect themselves from infection more than young people, thanks also to a targeted action by the doctors of family. This could be one of the reasons why emergency rooms have seen less severe patients for some time.
In other words, the “spared” from the normal excess of winter mortality due to flu and other causes fell first, followed by the most fragile population by age and by the other diseases that accompany the last years of life of a large part of the elderly population. Epidemiology calls it harvest effect, the last and fatal harvest.
Viral load and super diffusion
Moving from epidemiology to biology, the repeated sequencing on the viral genome found in swabs made in Lombardy would tend for the moment to exclude a more aggressive Lombard variant than the others, which would now have weakened. However, it could be assumed that not the virulence has changed, but the average infectious load of the cases. Like any poison, viruses are indeed more lethal in large doses. It could therefore be that the average infectious load, which grew with the spatiotemporal concentration of the contagions in the Lombardy clusters due to super diffusion, also facilitated by hospital infections, has now returned to very low levels. And that this can remain, with careful monitoring and avoiding super-diffusion events.
Note 1. The Case fatality rate (Cfr), the ratio between deaths and recorded cases, should not be confused with the Infection fatality rate (Ifr), the ratio between the dead and all infected (even those not yet identified) that for covid it varies from 1 per thousand to 1 per cent.