News Scan for Mar 08, 2021

COVID-19 hospital deaths
;
Viral load, duration with B117 variant
;
Resistance genes in diphtheria

US COVID-19 hospital death rate declined markedly last year

US in-hospital mortality for COVID-19 was almost 14% overall but decreased 15 percentage points from March to August 2020, with higher rates in older patients, according to a research letter published in JAMA Network Open late last week.

The researchers used data from 555 US medical centers via the Vizient clinical database on 192,550 adults hospitalized with COVID-19 across the 6 months. In-hospital mortality was 13.6%, which rose to 16.6% when the researchers included those discharged to hospice. In-hospital mortality (not including hospice), however, declined dramatically over the study period, from 22.1% in March to 6.5% in August. The biggest 1-month drop was from April to May, going from 18.1% to 12.0%.

The data also confirmed higher death rates with advancing age, with every 10-year age-group increasing in mortality rate, going from 1.4% in those 18 to 29 to 26.6% of those 80 years or older. (For reference, 6.6% of hospitalized adults in the study were in this youngest subgroup, compared with 16.2% of the oldest age-group.)

Almost 30% (28.9%) of the study cohort was admitted to the intensive care unit (ICU), which was associated with a median stay of 15 days (vs 6 days for those not in the ICU), as well as a median cost of $39,825 (vs $10,520).

Overall, 52.2% of Americans hospitalized with COVID-19 were men, 43.3% were White, and 65.2% were covered by Medicare or Medicaid. The most common comorbidities were high blood pressure (61.5%), diabetes (38.4%), and obesity (27.4%).
Mar 5 JAMA Netw Open research letter

 

Higher viral RNA load, duration noted with COVID-19 B117 variant

The COVID-19 variant B117 first identified in the United Kingdom produces higher RNA loads than other strains of the SARS-CoV-2 virus, and its RNA persists for longer, according to a study published last week by the International Journal of Infectious Diseases.

The researchers collected nasopharyngeal swabs from December 2020, when B117 was first announced, through February 2021 in Italy's Abruzzo region. Across 313 B117-infected individuals and 2,344 people infected with other COVID-19 strains, viral load was estimated by using threshold cycle (Ct) values that detected the N protein encoding gene and the S gene. Only those with Ct values of 20 or less were considered for the study (the lower the Ct value, the more easily the test was able to detect viral RNA in the sample).

Those with B117 had a median Ct value of 15.8, compared with the 16.9 of those infected by other COVID-19 variants. An additional Mann-Whitney Test on a subgroup of people (136 with B117 and 965 with other COVID-19 variants) indicated that those with B117 had RNA positivity for a median 16 days, versus 14 days for those with non-B117 SARS-CoV-2.

Because of insignificant differences in mortality rate and clinical signs of COVID, the researchers add that B117 has a similar effect on populations as other COVID-19 variants.

"Our analysis, performed in a given time period, suggests that [B117] persists longer in the respiratory tract of infected individuals reaching higher RNA loads with respect to those of other SARS-CoV-2 variants," the researchers write. "Although not a good predictor for viral load at [an] individual level, Ct values may give an indirect indication of the viral load in the population, as already seen in other studies."
Mar 5 Int J Infect Dis
study

 

Genomic analysis shows growth of resistance genes in diphtheria

Genomic analysis of Corynebacterium diphtheriae—the bacterium that causes the respiratory disease diphtheria—showed an increase in the average number of antimicrobial resistance (AMR) genes per genome per decade, UK and Indian scientists reported today in Nature Communications.

In the study, a team led by researchers from the University of Cambridge analyzed a collection of 502 C diphtheriae genomes that included 61 novel isolates from India, which has reported the highest number of diphtheria cases in the last few years, and 441 publicly available genomes. The isolates in the study covered 16 countries and territories and were collected over 122 years.

The analysis revealed that C diphtheriae is a genetically diverse species, with multiple distinct clonal populations circulating in the same geographic location, and that the more recently isolated genomes had a disproportionately high number of AMR genes, with a significant positive correlation between the average number of AMR genes per genome and the decade of isolation. Isolates collected from 2010 through 2019 had almost four times as many AMR genes as those collected in the 1990s.

The sulphonamide resistance gene sull was the common AMR gene detected and was found mainly in Indian isolates, along with aminoglycoside, chloramphenicol and trimethoprim resistance genes. Only one macrolide resistance gene was found, and no beta-lactam resistance genes were detected. This is noteworthy because erythromycin and penicillin are the traditionally recommended antibiotics of choice for early-stage diphtheria.

The study authors suggest the bacterium may be acquiring resistance genes in response to antibiotics exposure in the environment or during treatment for other bacterial infections.

In addition, the analysis found 18 different variants of the diphtheria toxin gene, which is the main virulence factor associated with the disease and is the target of the vaccine. Although diphtheria vaccines have been around for decades and remain effective, the number of cases reported globally has increased in recent years, and the authors say it's important to understand how the disease is evolving and spreading.

"We mustn't take our eye off the ball with diphtheria, otherwise we risk it becoming a major global threat again, potentially in a modified, better adapted, form," lead author Ankur Mutreja, PhD, of the Cambridge Institute of Therapeutic Immunology & Infectious Disease, said in a university press release.
Mar 8 Nat Comm study
Mar 8 University of Cambridge press release

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