COVID-19 Scan for Oct 22, 2020

News brief

CDC prison study helps redefine SARS-CoV-2 close contact

A paper published yesterday in the Morbidity and Mortality Weekly Report highlights a case study the Centers for Disease Control and Prevention (CDC) has used to update how it defines close contacts of people infected with SARS-CoV-2, the virus that causes COVID-19.

The study, conducted by the CDC, Vermont Department of Health (VDH), and the Vermont Department of Public Corrections, involved a Vermont corrections facility employee who had multiple brief encounters with six incarcerated or detained persons (IDPs) on Jul 28, while their SARS-CoV-2 test results were pending. On Jul 29, all six inmates received positive test results, and on Aug 5, the corrections officer tested positive as well.

Initially, the corrections officer was not considered a candidate for contact tracing because he did not fit the VDH definition, based in the CDC guidance, of a close contact (a person who's been within 6 feet of an infected individual for 15 consecutive minutes). But VDH review of surveillance video and standard correctional officer shift duty responsibilities indicated that while the officer had never spent 15 consecutive minutes within 6 feet of any of the infected inmates, he had numerous brief encounters that cumulatively totaled more than 15 minutes over a period of 24 hours (17 minutes total).

Although the officer wore a mask, gown, eye protection, and gloves during each encounter, the inmates wore masks during only some of the encounters. Because COVID-19 incidence was low both in the county where the officer lives and where the prison is located, the authors of the study concluded that he likely contracted the virus during one of these encounters.

"In correctional settings, frequent encounters of ≤6 feet between IDPs and facility staff members are necessary; public health officials should consider transmission-risk implications of cumulative exposure time within such settings," the authors wrote.

At a press conference yesterday, CDC Director Robert Redfield, MD, cited the data from the study as one of the reasons the agency updated its definition of a close contact, which is now defined as someone who's been within 6 feet of an infected person for a cumulative total of 15 minutes or more over a 24-hour period.
Oct 21 MMWR case report

Tocilizumab study shows no benefit in moderately ill COVID-19 patients

The immunosuppressive drug tocilizumab (Actemra) didn't prevent clinical worsening or death in hospitalized adult patients with moderate COVID-19 illness, a randomized, controlled trial published yesterday in the New England Journal of Medicine (NEJM) shows, confirming findings from other studies published earlier this week.

The double-blind study, led by researchers at Massachusetts General Hospital, involved 243 patients at seven Boston hospitals from Apr 20 to Jun 15 with moderate coronavirus, hyperinflammation, and at least two of the following symptoms: pneumonia, fever, and low blood oxygen concentrations.

Two-thirds of the patients received a single dose of intravenous tocilizumab, and the remainder were given a placebo and usual care. Most patients required extra oxygen via nasal cannula.

The tocilizumab and placebo groups were equally likely to need intubation or die (hazard ratio [HR] in the tocilizumab group, 0.83) and to deteriorate clinically (HR for tocilizumab group, 1.11).

At day 14, 18.0% of patients in the tocilizumab group and 14.9% of those receiving a placebo clinically worsened. Median time to discontinuation of extra oxygen was 5.0 days in tocilizumab-treated patients and 4.9 days in the placebo group. At 14 days, 24.6% of tocilizumab-treated patients and 21.2% of patients receiving placebo still required extra oxygen.

Twenty-two patients receiving tocilizumab developed neutropenia (low levels of infection-fighting neutrophil blood cells), versus one in the placebo group, but the tocilizumab group had fewer severe infections.

At 28 days, 17 of 161 patients (10.6%) in the tocilizumab group and 10 of 81 patients (12.5%) in the placebo group had been intubated or died (11 were intubated and six died before intubation in the tocilizumab group, while eight were intubated and two died before intubation in the placebo group).

While tocilizumab might benefit patients with severe COVID-19, and some benefit or harm in moderately ill patients can't be ruled out, the authors said, routine use of the drug isn't warranted in moderately ill patients. They noted that their results mirror those of other studies that found no advantage with tocilizumab.

"Findings from this randomized, double-blind, placebo-controlled trial indicated that this intervention had no significant effect on the risk of intubation or death, on disease worsening, on time to discontinuation of supplemental oxygen, or on any of the efficacy outcomes we examined," the researchers wrote.
Oct 21 NEJM study

PTSD symptoms noted in 29% of Norwegian health workers

A survey of healthcare and public service providers in Norway shows high rates of mental health problems, especially among those with direct COVID-19 patient care, highlighting the need for mental health monitoring and support.

Previous studies have identified higher rates of post-traumatic stress disorder (PTSD) among healthcare workers during pandemics due to fear of infection, higher patient deaths, responsibility for difficult decisions, and disruption of social support. The risk of pandemic-associated mental health problems has also been shown to be higher for women, younger workers, people previously diagnosed as having a mental disorder, and those lacking social support.

The authors of the PLOS One study published yesterday assessed PTSD, anxiety, and depression symptoms in 1,773 workers—doctors, nurses, clinical psychologists, social workers, politicians, and other professions—from Mar 31 to Apr 7 using standard assessment tools from the Diagnostic and Statistical Manual of Mental Disorders-5.

Overall, 28.9% of the workers showed clinical or subclinical symptoms of PTSD, 21.2% had moderate to severe symptoms of depression, and 20.5% had moderate to severe symptoms of anxiety, all markedly higher than pre-pandemic population estimates. Similar levels of anxiety were found among those working directly and indirectly with COVID-19 patients, but workers with direct patient contact showed significantly higher rates of PTSD (36.5% vs 27.3%) and depression symptoms (26.2% vs 20.1%).

The highest levels of PTSD were found in politicians, social workers, and nurses. Anxiety and depression were highest in nurses, social workers, and other health workers. The analysis also confirmed an association between pre-existing psychiatric diagnoses of anxiety and depression and higher PTSD symptoms.

The authors caution that working directly or indirectly with COVID-19 patients is a PTSD risk factor that should warrant additional monitoring and support for pandemic workers, and they add, "These disorders are associated with reduced cognitive capacities, which may lead to unfavorable consequences in pandemics where the pressure to make decision[s] is already high given the intensity of pandemic incidents," the study authors note.
Oct 21 PLOS One study

Wide variations found in country-level case-fatality rates

Crude COVID-19 case-fatality rates (CFRs)—the proportion of deaths among diagnosed cases—show wide disparities and are a misleading indicator of country-level differences, a separate PLOS One study yesterday found. When fatality rates are broken down by age distribution much lower disparities exist, allowing for more accurate country-level comparisons the authors say.

Early pandemic estimates of CFR were around 2.3%, but more recent country-level data show a wider range, leading to erroneous conclusions about the success or failure of healthcare approaches in different countries, the authors maintain. The researchers evaluated the age distribution of CFRs in seven countries with widely varying overall CFR values and population age structures.

They examined published data from Israel, South Korea, China, Spain, Sweden, Italy, and Canada on crude and age-specific CFRs in 10-year age-groups (0 to 9, 10 to 19, etc) from February through August.

Crude CFRs showed a remarkably wide range—from 0.82% for Israel to 14.20% for Italy— while age-adjusted CFRs varied far less—4.20% for China to 10.80% for Italy. Mean CFRs across all countries were too low to report for age-groups below 20 years, strikingly low (0.07%) for the 20-to-29 age-group, and rising to 26.92% for the 80+ age-group. Notably, trends in age-adjusted CFRs were remarkably consistent across all seven countries, with CFRs increasing steeply in those over age 70.

"After adjusting for age, the marked differences in the crude CFRs were substantially reduced. These findings demonstrate the importance of accounting for age when comparing rates in general and CFRs in particular," the authors wrote.

The results also confirm the unhelpful nature of crude CFR for country-level comparisons. "The assumption that differences between countries in testing policies or standard of treatment accounted for the wide discrepancies in CFRs, is not well-founded," the authors said. "The substantial reduction in the differences in the age-adjusted CFRs suggest[s] that differences in the standard of healthcare between these countries may not play as important a role in affecting the death rates, as some have hypothesized," the authors added.
Oct 21 PLOS One study

News Scan for Oct 22, 2020

News brief

Report shows significant drop in European veterinary antibiotic sales

Sales of veterinary antibiotics in European countries fell by more than one-third from 2011 through 2018, according to a report yesterday from the European Medicines Agency (EMA).

The latest European Surveillance of Veterinary Antimicrobial Consumption (ESVAC), which includes data from 25 European Union (EU) and European Economic Area countries, shows that overall sales of veterinary antibiotics declined by 34.6%, with notable declines in sales of antibiotics considered critically important for human medicine. Sales of third- and fourth-generation cephalosporins fell by 24%, polymyxins by 70%, fluoroquinolones declined by 4%, and other quinolones decreased by 74%.

Eighteen of the 25 countries providing data saw sales declines of greater than 5%, while 5 countries saw increases of more than 5%.

"The steady decrease in sales of veterinary antibiotics over ten years shows that Europe is on the right track to fight antimicrobial resistance," Ivo Claassen, head of EMA's Veterinary Medicines Division, said in a press release. "EU guidance and national campaigns promoting prudent use of antibiotics in animals are having a positive effect."

Among the potential explanations for the sales declines are the implementation of responsible-use campaigns, restrictions on veterinary antibiotic use, increased awareness of the threat of antimicrobial resistance, and the implementation of targets for reductions in veterinary antibiotic sales.

The authors of the report note that differences in reported sales and sales patterns between countries are likely to be partly due to differences in the occurrence of bacterial disease, the composition of the animal population, and production systems, and that direct comparisons should not be made between countries without considering these differences. But the reduced sales of veterinary antibiotics in some countries indicate the potential for a reduction in other countries as well, they said.
Oct 21 ESVAC report
Oct 21 EMA press release

Drug makers share discontinued antibiotic research data

The Pew Charitable Trusts announced yesterday that Merck and Kyorin Pharmaceutical Co. of Japan have shared antibiotic research data from a discontinued joint research program with Pew's open-access Shared Platform for Antibiotic Research and Knowledge (SPARK).

The preclinical, previously unpublished data come from research the two companies conducted on a potentially novel way to attack gram-negative bacteria that involves targeting two types of enzymes—DNA gyrase and topoisomerase IV.

Pew launched SPARK in 2018 to spur basic research into new antibiotics for gram-negative bacteria. The database provides access to chemical and biological data from published and unpublished studies and discontinued research programs, with a focus on molecules that take new approaches to overcoming the defenses of gram-negative bacteria. SPARK is open to scientists from industry, academia, government, and nonprofit research groups, with the hope that they can learn from past research and gain insights that will advance antibiotic discovery efforts.

"As we face the COVID-19 pandemic—with millions of patients vulnerable to secondary infections due to weakened immune systems—the need for new antibiotics that can treat multidrug-resistant Gram-negative bacterial infections has never been greater," Kathy Talkington, MPaff, director of Pew's antibiotic resistance project, said in a press release. "Our hope is that the data from Merck’s research will help catalyze discovery of new antibiotics for Gram-negative pathogens."
Oct 21 Pew Charitable Trusts press release

WHO warns of ongoing risk of international polio transmission

The World Health Organization's (WHO's) International Health Regulations (IHR) Emergency Committee said today that the ongoing risk of international spread of poliovirus remains a public health emergency of international concern (PHEIC) and requires a coordinated response.

The IHR committee made the announcement following an Oct 14 meeting during which members reviewed 2020 data on wild poliovirus (WPV1) and circulating vaccine-derived polioviruses (cVDPVs). That data showed a 42% increase in global incidence of WPV1 cases in 2020 compared with 2019 (121 vs 85 from Jan 1 to Oct 5), with all cases detected in Pakistan and Afghanistan, and a 70% increase in the number of positive environmental samples (375 vs 221).

The data also showed that the number of cVDPV type 2 cases in 2020 is up, with 409 as of Oct 5, compared with 378 cases reported for all of 2019. Analysis of cVDPV2 isolates collected from April through June shows cross-border transmission between Pakistan and Afghanistan, and between several African countries (Ivory Coast, Mali, Guinea, Ghana, Central African Republic, Cameroon, Chad, Sudan, South Sudan, and Burkina Faso).

The committee also heard that routine immunization services and vaccine supplies have been routinely disrupted during the COVID-19 pandemic, and that surveillance indicators have dropped in many of the outbreak countries. The experts unanimously agreed that the risk of international spread of WPV1 and cVDPV2 is rising, and recommended the extension of temporary recommendations for another 3 months.

"The Committee recognizes the concerns regarding the lengthy duration of the polio PHEIC, but concludes that the current situation is extraordinary, with clear ongoing and increasing risk of international spread and ongoing need for coordinated international response," they said.
Oct 22 WHO IHR Emergency Committee statement