Falling death rates bring hope that coronavirus may be in retreat

Another example of hypotheses emerging from those observing and analysing data, as opposed to the predominant modelling approach. Which is closer to the scientific approach? – Owl

Tom Whipple, Science Editor www.thetimes.co.uk 

At one point intensive care doctors were having to choose who lived or died. Then weeks later Matteo Bassetti, the head of infectious diseases at San Martino hospital in Genoa, said that something had shifted.

“The strength the virus had two months ago is not the same strength it has today,” he said late last month. He was not alone in this view.

In America, where New York’s health system so nearly collapsed, one virologist agreed cautiously. Maybe the coronavirus was burning itself out. After rampaging through the east coast it was no longer causing the same damage.

“It’s in the nature of these viruses to get tired after a while,” Lee Riley, a professor of infectious diseases at the University of California, Berkeley, said.

Scattered groups of doctors around the world are beginning to whisper about a change. What might have changed is the virus itself, they say.

Or it might be that in the array of treatments thrown at it, almost all as yet unproven, we have got better at coping with it. If so, perhaps a second wave might not be as terrible as the first.

These rare shafts through the doomy clouds of coronavirus have radiated around the world. But so too have the rebuttals of other scientists, desperate that the world does not lower its guard.

They say that the genetics of the disease show that nothing has changed. The evidence from ongoing outbreaks suggests that we are still helpless against its ferocity. They point out that these clinicians were providing anecdotes when the world needed hard statistics.

In two Italian regions, however, scientists have gone through the statistics and found some unexpected validation to turn anecdote into data.

An analysis of death rates from Ferrara, in Emilia-Romagna, and Pescara, in Abruzzo, has produced striking results. “From March to April, the death rate decreased by more than 50 per cent in all age-classes,” the paper found. The fall was largest among the elderly, from 30 to 13 per cent. The gap remained when factoring other explanations, such as pre-existing conditions.

The results could be explained in other provinces as due to hospitals learning to cope, but these facilities never had the crowding experienced elsewhere in Italy.

Lamberto Manzoli, from Ferrara University, did the analysis after reports from doctors. “Physicians who were quite expert in the disease were going on television and saying the same thing,” he said. “That the mortality and morbidity was decreasing. So I said, ‘OK, let’s check.’” And when he did: “Honestly, I was surprised.”

Professor Riley told the science publication Elemental that he had reached a similar view. After studying reports from New York there were hints of an improvement in recoveries from the disease, he said.

“I don’t know of other experts who think the way I do,” he said. “And I could be totally off the mark. But I look at real-world data instead of predictive models to come up with my ideas.” He said the virus had mutated to become weaker, an opinion dismissed by many.

Dr Manzoli said that the most likely explanation was not that the virus had changed but that we have.

When the first cases arrived in Italian hospitals, doctors followed what was known as the Chinese protocol. They waited until the condition worsened and patients were given ventilation if there was a respiratory failure.

But doctors noticed that the disease did not affect only breathing, it also seemed to cause blood clots and maladaptive immune responses. A cocktail of drugs was administered to treat this along with other medications that — they hoped — attacked the virus.

“They started early,” Dr Manzoli said. “They didn’t wait until the symptoms were severe.” Maybe among the variety of treatments they hit on something that worked. “People are still dying,” he said. “But the rate is decreasing.”

The pre-print website medRxiv released the findings with its own, very big, caveats. The study has not yet been through peer review. None of the drugs given by the hospitals has yet been shown to work. One, hydroxychloroquine, has been found not to work.

As the world tackles the pandemic, this lone study offers the possibility of hope. A second wave could come. But perhaps it will not strike with the same ferocity. “We have reasons to believe this new approach is working,” Dr Manzoli said. “This has to be confirmed elsewhere but this is something positive.”

The problem is, however, that by the standard of evidence on which medicine relies, we still know nothing.

Peter Horby, an epidemiologist at Oxford University, ran the recent trial that showed hydroxychloroquine — an antimalarial hailed by President Trump — was ineffective against coronavirus. He and his colleagues said at the time that the ad hoc use of drugs in emergencies was hindering the search for treatment.

Professor Horby said that we should remember this when looking to explain the Italian findings. “The use of unproven therapeutics outside of clinical trials makes it almost impossible to attribute changes in fatality rates to any specific drug or intervention,” he said. “There will have been multiple simultaneous changes and what you observe is an average effect.”

He is running a larger trial, known as Recovery, that is looking at a range of drugs of the kind used in Italy and elsewhere. Maybe some will have small effects, maybe cumulatively they will have large effects. He cannot say.

“We don’t know which, if any, of the listed treatments are effective or if other unmeasured effects . . . are the reason for the improvements.” In other words, we still know nothing.

For Dr Manzoli, whose region suffered some of the worst effects of the virus, that argument is both self- evidently true and was, at the height of the pandemic, impossible to assess.

“Fatality was so high in the first phases, people were dying unbelievably frequently,” he said. “The disease was so lethal, I totally understand that physicians tried everything. If I see so many people dying and there is no treatment . . . as a physician I am obliged to try something.”

Perhaps from that pit of despair, from back-to-back shifts by exhausted nurses, from doctors deciding who should get oxygen and who should be left to die, from hospitals whose wards spilt into waiting rooms, we have hit upon the rudiments of a treatment.

Or perhaps like hydroxychloroquine, Mr Trump’s “game-changer” that never was, it will be yet another false dawn in the long night of coronavirus.