COVID-19 Scan for Nov 30, 2020

News brief

SARS-CoV-2 may enter the brain through the nose

A small German autopsy study of COVID-19 victims in Nature Neuroscience today demonstrates the presence of SARS-CoV-2—the virus that causes COVID-19—in nasal structures and the brain, suggesting that the virus crosses into the central nervous system (CNS) via nasal surfaces that contain nerve endings for smell.

COVID-19 CNS effects—loss of smell and taste, headache, fatigue, nausea, vomiting, acute cerebrovascular disease, and impaired consciousness—are widely reported and suggest viral penetration of the CNS, but the mechanism of entry remains unclear.

The researchers assessed nasal olfactory surfaces, associated nerve structures, and several CNS regions for evidence of viral RNA and proteins using in-situ hybridization and immunohistochemical staining in 33 patients who died of COVID-19 between March and August. COVID-19–associated neurologic symptoms in the study patients had included impaired consciousness, bleeding in the brain, headache, behavioral changes, and strokes.

Of the 33 autopsy patients, 60.6% (20 of 33) showed evidence of SARS-CoV-2 RNA in olfactory mucosa—the lining of the nasal cavity containing sensory nerve endings for smell. The presence of viral particles in the olfactory tract and the proximity of nerve tissues suggests that SARS-CoV-2 may invade the CNS through olfactory nerves that control the sense of smell, the authors wrote.

In a news release emailed to journalists, the authors highlighted the detection of SARS-CoV-2 spike protein in cells expressing markers of neurons. "Olfactory sensory neurons may be infected, as well as in the brain areas that receive smell and taste signals," they noted.

"The findings are not surprising," Gitte Moos Knudsen, MD, DMSc, of Copenhagen University, said in a Science Media Centre statement today. "Central nervous system entry through the nasal epithelium is a recognized mode of viral uptake and would not be unique to SARS-CoV-2," she added.

Dysfunction of the cardiovascular, pulmonary, and renal systems is considered a major cause of severe or lethal COVID-19 cases. Notably, 18.1% (6 of 33) of autopsies revealed the presence of the virus in the medulla oblongata, or brain stem—a structure that controls breathing and cardiac function—suggesting that SARS-CoV-2 invasion of brain structures may play a role in COVID-19 complications.

"It is possible that SARS-CoV-2 infection, at least in some instances, might aggravate respiratory or cardiac insufficiency—or even cause failure—in a CNS-mediated manner," the authors wrote.
Nov 30 Nat Neurosci study
Nov 30 Science Media Centre statement

Estradiol hormone therapy may protect against COVID-19 death

A study late last week in BMC Medicine found that pre-menopausal women with higher natural levels of the sex hormone estradiol are 15% more likely to be infected with SARS-CoV-2 than men but less likely to become seriously ill or die, pointing to a potential protective role of sex hormones in COVID-19 outcomes. The study also found that estradiol hormone therapy for peri- and post-menopausal women significantly improves survival rates for infected women.

Estradiol is known to influence the expression of the human angiotensin-converting enzyme 2 (ACE2) protein, which facilitates SARS-CoV-2 cellular entry. It also appears to play a role in blocking cytokine production pathways, which may be implicated in the "cytokine storm"—an immune system overreaction seen in some patients with severe COVID-19.

Researchers collected retrospective data from 68,466 COVID-19 patient electronic health records in the 17-country TriNetX Real-World database, classifying patients into 5-year age-groups, and two female subgroups—women ages 15 to 49 and those 50 years and older. The 37,086 SARS-CoV-2–infected women were further classified into groups receiving supplementary estradiol in the form of either oral contraceptives or estradiol hormone therapy for peri- and post-menopausal conditions ("users") and women not taking supplemental hormones ("non-users").

The COVID-19 fatality risk for peri- and post-menopausal users was 50% less than in non-users (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.18 to 0.62; hazard ratio [HR], 0.29; 95% CI; 0.11 to 0.76). Only 2.3% of older women users died from COVID-19, versus 6.6% of non-users.

Younger, pre-menopausal women have 15% higher frequencies of COVID-19 than age-matched men, but men have 50% higher fatality rates than women, suggesting a possible association with higher estrogen levels, the study authors wrote.

Smaller effects were observed for younger women taking estradiol hormones than in non-users, with similar fatality risk for both groups. "This may be the case because endogenous estradiol levels are typically already higher in younger women than for post-menopausal women, thus drowning out any differences between user/not-user groups," the authors noted.

The authors urge further study of the protective role of estradiol in light of its strong effect on COVID-19 fatality in older women.

"A brief, 7-day course of estradiol, delivered via a transdermal patch, could be a safe approach to reduce symptom severity in adult men and in older women, when administered prior to intubation," the authors concluded.
Nov 25 BMC Med study

CDC: Symptoms not enough to tell COVID-19 from similar infections

A Centers for Disease Control and Prevention (CDC) study published in Open Forum Infectious Diseases late last week found wide overlap between symptoms of COVID-19 and those of other respiratory illnesses, demonstrating that clinical symptoms alone are insufficient to distinguish between them.

The researchers compared symptoms of non-hospitalized patients of all ages—with and without laboratory-confirmed SARS-CoV-2 infection—who sought medical care for an acute respiratory illness at US Flu Vaccine Effectiveness (VE) network study sites in Michigan, Pennsylvania, Texas, Washington, and Wisconsin from Mar 26 to Aug 15.

Of a total of 4,961 patients, 916 tested positive for SARS-CoV-2 via reverse-transcription polymerase chain reaction, and 4,045 had respiratory symptoms but tested negative for the virus. Phone interviews and online questionnaires gathered information on demographics, health behaviors such as smoking status, and underlying medical conditions.

Cough was the most commonly reported symptom in both SARS-CoV-2–positive and –negative patients (86% and 83%, respectively; P < 0.01). Shortness of breath/difficulty breathing was reported less often by those with COVID-19 than without (40% vs 47%; P < 0.01), and 99% of patients reported fever and/or cough.

"Persons with COVID-19 reported a median of 7 (IQR, 5–8) of the assessed symptoms versus 6 (IQR, 4–7) for persons without COVID-19 (P < 0.01)," the authors said. "Among 4102 participants asked, 59% of persons with COVID-19 versus 19% of persons without COVID-19 reported diminished taste or smell (P < 0.01). Generalized symptoms (muscle aches or headache) and gastrointestinal symptoms (vomiting, diarrhea, or abdominal pain) were more common among persons with COVID-19 (91% and 57%, respectively) than among those without COVID-19 (83% and 50%, respectively; P < 0.01 for both)."

"Because of the wide overlap in COVID-19 symptoms with those of other respiratory illnesses, laboratory confirmation of SARS-CoV-2 infection will be critical, not only for limiting disease spread, contact tracing, and monitoring clinical course, but also for assessing the effectiveness of interventions during periods of co-circulation of SARS-CoV-2 and other respiratory viruses, including influenza," the authors noted.
Nov 26 Open Forum Infect Dis study

News Scan for Nov 30, 2020

News brief

Experts develop research agenda for pediatric infections, stewardship

A group of clinicians and researchers with expertise in pediatric healthcare-associated infections (HAIs) and antimicrobial stewardship has developed a list of high-priority research topics for improving health outcomes in children.

Published last week in Infection Control and Hospital Epidemiology, the list of recommendations was developed through a multistep, 7-month process that included literature review, interactive teleconferences, web-based surveys, and two in-person meetings. At the end of the process, experts from the Centers for Disease Control and Prevention and academic children's hospitals across the country came up with six HAI topics and six antimicrobial stewardship topics as high-priority targets for future research.

The authors of the paper say the research agenda is necessary because HAI rates in children are similar to those in adults, but pediatric HAIs differ significantly from those experienced by adults, and HAI prevention strategies developed and tested in adult settings cannot be easily implemented in pediatric settings. In addition, while general principles of antimicrobial stewardship are shared across patient populations and settings, there are important differences between adult and pediatric patients that need further investigation.

The six high-priority HAI topics included judicious testing for Clostridioides difficile infection, chlorhexidine bathing, measuring and preventing hospital bloodstream infection rates, surgical-site infection prevention, and surveillance and prevention of multidrug-resistant gram-negative rod infections.

The six antimicrobial stewardship topics included beta-lactam allergy de-labeling, judicious use of perioperative antibiotics, intravenous-to-oral conversion of antimicrobial therapy, developing a patient-level "harm index" for antibiotic exposure, and benchmarking and/or peer comparison of antibiotic use in common pediatric inpatient conditions.
Nov 26 Infect Control Hosp Epidemiol abstract

High-path avian flu outbreaks expand in Europe, other regions

More countries reported additional highly pathogenic H5N8 and H5N5 avian flu outbreaks in poultry, and numerous more—even outside of Europe—reported more detections of both strains in wild birds, according to the latest notifications from the World Organization for Animal Health (OIE).

Regarding poultry outbreaks, South Korea reported an event at a duck farm in North Jeolla province that began on Nov 26, the country's first such outbreak since March 2018. One sick bird was found, and officials culled 19,000 ducks at the facility, as well as 392,000 other ducks and chickens at other farms as a preventive step. An investigation into the source is still under way.

Elsewhere, Poland reported an H5N8 outbreak at a poultry farm in Wielkopolska province,

Meanwhile, H5N5 struck a Belgian broiler farm in West Flanders province, the first involving the strain since 2017. It started on Nov 18, killing 600 of 151,600 birds.

In wild bird developments, several countries reported more H5N8 detections, mainly in waterfowl. For example, Norway reported H5N8 in a wild goose found sick on Nov 22 in Rogaland province, the country's first such detection. And Iran reported H5N8 in wild geese found dead near Meyghan Lake in Markazi province, the country's first detection of the strain since 2018.

Other countries reporting wild bird outbreaks include Germany with both H5N5 and H5N8, Belgium with H5N8, Italy with H5, Sweden with H5N8, the Netherlands with H5N5, and Slovenia with H5N8.
Nov 30 OIE report on H5N8 in South Korea
Nov 26 OIE report on H5N8 in Poland
Nov 27 OIE report on H5N5 in Belgium
Nov 30 OIE report on H5N8 in Norwegian wild birds
Nov 23 OIE report on H5N8 in Iranian wild birds

In low-pathogenic avian flu developments, South Africa reported eight more H7 outbreaks at commercial ostrich farms. The events occurred from Sep 10 to Oct 7.
Nov 23 OIE report on low path H7 in South Africa