Researchers in Italy have found that the proportion of people dying from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be on the decline in Italy.
Their retrospective study of almost 2,000 infected individuals across two Italian provinces, found that the SARS-CoV-2 case-fatality rate fell significantly between March and April, both overall and when participants were assessed by subgroups of age and comorbidity.
Lamberto Manzoli (Department of Medical Sciences, University of Ferrara) and colleagues say their findings are the first to demonstrate a significant decline in SARS-CoV-2-related deaths in the country over time.
They report that between March and April 2020, the death rate fell by more than half across all age groups, with the most significant decrease observed for those at the highest risk due to other health conditions.
A pre-print version of the paper is available in medRxiv, while the article undergoes peer review.
Novel Coronavirus SARS-CoV-2 This scanning electron microscope image shows SARS-CoV-2 (round blue objects) emerging from the surface of cells cultured in the lab. SARS-CoV-2, also known as 2019-nCoV, is the virus that causes COVID-19. The virus shown was isolated from a patient in the U.S. Image captured and colorized at NIAID's Rocky Mountain Laboratories (RML) in Hamilton, Montana. Credit: NIAID
Italy has seen one of the highest death tolls
As of May 26th, 2020, the number of reported SARS-CoV-2 infections worldwide was more than 5,495,000, and the number of lives claimed was more than 346,000, with case-fatality rates significantly varying between countries.
Since the outbreak began in Wuhan, China, in December 2019, Italy has seen one of the highest death tolls, with the number of recorded deaths reaching more than 32,000 and the estimated case-fatality rate reaching an estimated 14%.
Experts working closely with patients report a fall in fatalities
Manzoli and the team say that over recent weeks, some clinical experts actively involved in caring for infected individuals have reported a significant decrease in SARS-CoV-2-related deaths, which they think may be attributable to more targeted treatment approaches. However, currently, the evidence for this is either anecdotal or based on case studies, and no robust evidence is available.
Now, Manzoli and the team have conducted a retrospective study of 1,946 patients (aged a mean of 58.8 years) infected with SARS-CoV-2 across two Italian provinces to investigate whether there has been any change in case-fatality rate over time.
What did the study involve?
Information was collected on all people in the provinces of Ferrara and Pescara, who were diagnosed between March 3rd (when first cases of onset were recorded) and April 25th, using local registries and clinical health records. Participants were followed until May 5th.
The case-fatality rate was compared between the first 29 days following index day (3rd to March 31st) and the following 25 day period from 1st to April 25th.
What did the study find?
One-hundred-and-seventy-seven people died after an average of 11.7 days of follow-up; 135 of 1244 people in the March group died, and 42 of 702 people in the April group died.
The average age of those who died in March was 78 years, and the average age of those who died in April was 87 years.
After adjustment for potential confounding factors including age and various comorbidities, the overall case-fatality rate fell by more than 50% in April, compared to March.
Among the elderly, the rate fell from 30% to 13% and among participants with hypertension, it fell from 23.% to 12%; diabetes 30% to 8.0%; cardiovascular disease 31% to 12%; chronic obstructive pulmonary disease 30% to 11% and renal disease 32% to 12%.
With the exception of patients who had cancer, the risk of death was significantly lower in April, compared to March across all subgroups, ranging from a 20% lower risk among those with renal disease to a 51% lower risk among those aged 80 years or older.
Potential explanations for the observed fall in fatalities
Manzoli and team say it is difficult to discern which factors are most likely accountable for the observed findings.
“The first, most obvious explanation, is that the healthcare system might have been overcrowded during the epidemic peak in March, with a loss of efficacy,” says the team.
However, in the present cohort, infection rates were comparatively low and did not exceed the capacity of the critical care services in these particular provinces.
Other potential factors include infection with a mutated, less fatal strain of the virus, which some experts have suggested could emerge during the pandemic. However, this theory has been widely contested and is not currently supported by data.
Another potential explanation is improvements in healthcare and organization, including a greater number of hospital beds and better treatment and clinical management of infected individuals over time.
“Concerning the therapy, a growing number of clinicians suggest that the current therapeutic approach, based upon the early administration of more tailored medications, is considerably improving the clinical course of COVID-19,” writes Manzoli and team.
Randomized trials are needed to confirm findings
The authors say this study provides the first evidence of a significant decrease in SARS-CoV-2 case-fatality rates in Italy over time.
However, “the findings are inevitably preliminary and require confirmation from further datasets and ongoing randomized trials,” concludes the team.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.