COVID-19 Scan for Jun 29, 2021

News brief

Analysis of 10 studies shows ivermectin not effective in treating COVID-19

A new meta-analysis of 10 studies shows ivermectin (IVM), an anti-parasite drug, is not an effective treatment for COVID-19 and is not a viable treatment option for patients. The study was published yesterday in Clinical Infectious Diseases.

The authors analyzed results from 10 randomized control trials (RCTs) that included 1,173 patients total, and looked for IVM's effect on all-cause mortality, length of hospital stay, adverse events, and viral clearance compared to standard of care.

COVID-19 patients had mild disease in 8 of the trials, moderate in 1 trail, and mild to moderate in 1 trial.

IVM did not reduce all-cause mortality when compared to controls (relative risk, 0.37; 95% confidence interval [CI], 0.12 to 1.13) or length of stay versus controls (0.72 days, 95% CI, −0.86 to 2.29). Adverse events, severe adverse events, and viral clearance were similar between IVM and controls, the authors found.

"The quality of evidence was low or very low for all outcomes. Subgroup analyses by severity of COVID-19 disease or risk of bias were mostly consistent with main analyses, except a significant effect on all-cause mortality in three RCTs at high risk of bias,” the authors wrote.

IVM gained interest as a COVID-19 treatment after Australian researchers showed IVM to be active against SARS-CoV-2 in cell cultures by drastically reducing viral RNA at 48 hours. This led to the use of IVM as a COVID-19 treatment in some low- and middle-income countries throughout 2020.
Jun 28 Clin Infect Dis study

Chinese COVID vaccine produces good immune response in children

China-based Sinovac's CoronaVac COVID-19 vaccine appears to be safe and produces a good immune response in Chinese children as young as 3, according to phase 1 and 2 results published in The Lancet Infectious Diseases yesterday.

The researchers gave two low (1.5 micrograms), two high (3.0 micrograms), or two placebo doses to 72 children in phase one and 480 children in phase two. All were from Hebei province, ranged in age from 3 to 17 years, were healthy, and had no history of SARS-CoV-2 infection. The mean ages were 8.3 years and 9.2 years for phase 1 and phase 2, respectively, and participants were enrolled from Oct 31 to Dec 30, 2020.

More than 93% who received two doses of the vaccine developed SARS-CoV-2 antibodies 28 days after the second dose, and the authors recommend two 3.0-microgram doses for all children and adolescents.

In phase 1, 100% of all vaccine recipients made antibodies regardless of dosage, although more neutralizing antibodies were detected among those who received 3 micrograms (117.4 vs 55.0 geometric mean titers). In phase 2, 97% of those in the low-dose group and 100% of those in the high-dose group produced detectable SARS-CoV-2 antibodies.

No serious adverse reactions occurred except for one case of unrelated pneumonia in a placebo recipient. Adverse reactions occurred across both studies in 26% of low-dose participants, 29% of high-dose recipients, and 24% receiving placebos. Injection-site pain was the most common symptom, with 16% in the low-dose group, 16% in the high-dose group, and 2% in the placebo group.

"Given the distinct immunogenicity profile and development stage of children, post-marketing surveillance of the vaccine safety should be done and maintained for a longer period than that in adults," write Xiaohui Zou and Bin Cao, of the China-Japan Friendship Hospital in Beijing, in a commentary. Still, they conclude, "This promising result should inspire the ongoing trial of other COVID-19 vaccines in children younger than 12 years."
Jun 28 Lancet Infect Dis study and commentary
Jun 28 Lancet press release

Face mask prototype used to diagnose COVID-19

Tiny, disposable sensors to diagnose SARS-CoV-2 infection can be fitted into face masks and integrated into clothing like lab coats, according to a study yesterday in Nature Biotechnology. Researchers from the Massachusetts Institute of Technology (MIT) and Harvard University built off previous research that created paper-based diagnostics for viruses like Ebola and Zika based on freeze-dried cellular machinery.

Upon activation with water, the first freeze-dried biological reaction cuts open the virus membrane to expose RNA, the second amplifies the spike-coding gene, and the third detects, cuts, and reports any spike gene fragments via technology based on clustered regularly interspaced short palindromic repeats (CRISPR), according to a Harvard news release.

The study goes through different test iterations, some using color changes to the visible eye as diagnostic results and others using fluorescence that can be picked up by a spectrometer as well as different settings, such as a face mask or a jacket. For the face mask, the researchers note that the sensor has four modular components: a hydration reservoir that would be broken for one-time use diagnostics, a large pad for sample collection, a wax-patterned microfluidic paper-based analytical device, and a lateral flow assay strip.

The researchers say that the detection limit meets the same standard as reverse transcription-polymerase chain reaction assay tests, all within 90 minutes and at room temperature, and that the test does not cross-react with RNA from other common coronavirus strains.

"We've demonstrated that we can freeze-dry a broad range of synthetic biology sensors to detect viral or bacterial nucleic acids, as well as toxic chemicals, including nerve toxins," said senior author James Collins, PhD, original developer of the sensor technology, in an MIT press release. "We envision that this platform could enable next-generation wearable biosensors for first responders, health care personnel, and military personnel."
Jun 28 Nat Biotechnol study
Jun 28 Harvard press release
Jun 28 MIT press release

Metabolic activator treatment reduces COVID-19 recovery time

A combination of metabolic activators (CMAs) reduced COVID-19 recovery time in mild to moderate cases, according to phase 2/3 results published in Advanced Science yesterday.

Both study phases involved randomized treatment and placebo groups in a 3:1 ratio, with the treatment group receiving a combination of nicotinamide riboside, L-serine, N-acetyl-L-cysteine, and L-carnitine tartrate, which are all involved with mitochondrial function. All participants were outpatients, receiving treatment or placebo daily for 14 days, starting on the day of diagnosis.

Phase 2 data were similar to phase 3 results, which found that COVID-19 recovery time among 304 Turkish patients was 5.7 days in the treatment group and 9.2 days in the placebo group (adjusted hazard ratio, 5.77; 95% confidence interval, 4.17 to 7.96). Overall, phase 3 patients were young (mean, 36.3 years), male (57.6%), and healthy (mean body mass index, 26.7; 9.2% with high blood pressure; 6.2% with type 2 diabetes).

By day 14, serum alanine aminotransferase, lactate dehydrogenase, and creatinine levels were also significantly improved in the CMA group compared with the placebo group. (In both groups, aspartate aminotransferase and C-reactive protein were lower and platelets, white blood cells, neutrophils, lymphocytes, hemoglobin, cholesterol, and triglyceride were higher, which the researchers attribute to patient recovery.) Two of the 229 patients in the intervention group (0.6%) had rashes and skin redness, but no serious adverse events occurred.

"Dysfunctional mitochondria have been implicated in worsened progression for Covid-19, and we are pleased to find that the combination of these metabolic activators helps to remedy the stress put on the body of an infected patient," said lead author, Adil Mardinoglu, PhD, in a KTH, Royal Institute of Technology press release.

"In conclusion," the researchers write, "we evaluated the efficacy and safety of CMA in combination with HQ [hydroxychloroquine] or FP [favipiravir] therapy in patients with mild-to-moderate COVID-19 and observed that combination therapy is safe and beneﬁcial in patients with mild-to-moderate COVID-19."
Jun 28 Adv Sci study
Jun 28 KTH press release

News Scan for Jun 29, 2021

News brief

AHRQ publishes antibiotic stewardship toolkit for long-term care

The Agency for Healthcare Research and Quality (AHRQ) yesterday released a toolkit to improve antibiotic use in long-term care facilities.

The toolkit consists of presentations, slides, posters, and other documents that provide guidance on how to create a culture of safety around antibiotic prescribing, develop and improve antibiotic stewardship programs, and learn and disseminate best practices for common infectious disease syndromes in long-term care settings. It also includes an explanation of the "Four Moments of Antibiotic Decision Making," a step-by-step approach that clinicians can use to achieve optimal antibiotic prescribing.

This is the third antibiotic stewardship toolkit published by AHRQ, which has also developed them for acute care hospitals and ambulatory care settings.

The toolkit is based on the experiences of more than 400 US hospitals that took part in AHRQ's Safety Program for Improving Antibiotic Use, a 5-year project to improve stewardship and antibiotic prescribing in acute care, ambulatory care, and long-term care facilities across the country.
Jun 28 AHRQ toolkit

Thai hospital study finds alarming levels of critical antibiotic resistance

A large-scale surveillance study of hospitals in Thailand found high levels of critical antibiotic resistance in clinically important gram-negative bacteria, researchers reported yesterday in Antimicrobial Agents and Chemotherapy.

The analysis of 187,619 isolates of four gram-negative bacterial species (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii complex [ABC], and Pseudomonas aeruginosa) submitted by 47 hospitals found that 50% were critically drug-resistant. E coli was the most commonly isolated bacteria. The prevalence of extended-spectrum cephalosporin resistance was higher in E coli than in K pneumoniae, but carbapenem resistance was 4.5-fold higher in K pneumoniae (17.2%) than in E coli (3.8%). Critical drug resistance in ABC ranged from 66.4% to 78.7% across all specimens, with 41.9% of isolates found to be extensively drug-resistant (XDR) and 35.7% multidrug-resistant (MDR).

Molecular analysis of 12,915 isolates found that the blaCTX-M, blaNDM, and blaOXA-48-like resistance genes were prevalent among extended-spectrum cephalosporin-resistant and carbapenem-resistant E coli and K pneumoniae, while blaOXA-23-like was the most common carbapenemase gene in XDR/MDR A baumannii, and blaIMP was the most common in XDR/MDR P aeruginosa.

The study authors note that carbapenem resistance in E coli and K pneumoniae has more than tripled in Thailand in less than a decade and is now significantly higher than in other Southeast Asian countries. They link the increase to inappropriate prescribing of carbapenems in the country's hospitals, and suggest that widespread over-the-counter antibiotic use is playing a role in rising resistance to other antibiotics.

"The threat of bacterial resistance should be critically addressed in Thailand and in the region for the necessity of appropriate antimicrobial prescription in clinical practice," they wrote. "In addition, the public policy regarding the self-consumption of antibacterial agents should be emphasized to reduce the risk of acquiring drug-resistant infections."
Jun 28 Antimicrob Agents Chemother abstract

H5 avian flu outbreaks strike more wild birds in China and Russia

In the latest avian flu outbreak developments, China reported a highly pathogenic H5N8 outbreak in wild birds in a region where it hadn't been detected before, and Russia reported two more outbreaks in wild birds that involved an H5 strain.

China's H5N8 began on Jun 10, striking waterfowl in Ningxia autonomous region in the north-central part of the country, according to a recent notification from the World Organization for Animal Health (OIE). The virus killed 38 black-necked grebes, a type of waterfowl.

Earlier this month, China reported a similar H5N8 outbreak in wild birds in Shaanxi province in the northwest.

Russia reported two H5 outbreaks in wild birds in Tuva Republic in southern Siberia, both found during active surveillance. The events began on May 29, and taken together, the virus infected 14 clinically health aquatic birds, such as ducks, grebes, cormorants, and gulls. The last H5 detection in that part of Russia occurred in 2010.
Jun 25 OIE report on H5N8 in China
Jun 23 OIE report on H5 in Russia