COVID-19 Scan for Nov 17, 2020

News brief

Diaphragm dysfunction found in patients who died of COVID-19

A research letter published yesterday in JAMA Internal Medicine shows that patients who died of COVID-19 in the Netherlands were more than twice as likely to have scarring of their diaphragms than patients who died of other causes.

A research team led by Amsterdam University Medical Center compared diaphragm specimens from 26 patients who died of coronavirus with those of 8 patients who died of other causes at three academic medical centers in April and May. Weakness of the diaphragm, the main muscle responsible for breathing, can result in acute respiratory failure, prolong mechanical ventilation, and raise the risk of death.

The researchers found elevated expression of genes involved in fibrosis, or scarring, and evidence of fibrosis in the diaphragms of patients who died of COVID-19. The diaphragms of patients who died of other causes—even those who had undergone similar-length mechanical ventilation and intensive care unit stays—were half as likely to have such signs.

Angiotensin-converting enzyme 2 (ACE-2), which allows the coronavirus to enter diaphragm muscle fibers, was found in the diaphragms of both COVID-19 and control patients. Four of 26 coronavirus patients (15.4%) had evidence of viral RNA from SARS-CoV-2, the virus that causes COVID-19, in their diaphragm muscle fibers.

Compared with controls, patients with COVID-19 had a higher body mass index and were less likely to be given steroids. No patients in either group had neuromuscular disease on hospital admission. Median COVID-19 patient age was 71 years, 21 were men, and 24 received mechanical ventilation for a median of 12 days.

The authors said that it is unclear whether the abnormal diaphragm findings in COVID-19 patients are a direct result of infection or whether viral pneumonia (found in only 3 [37.5%] of patients without COVID-19) weakens the diaphragm muscles.

But they propose that severe coronavirus-related diaphragm muscle wasting may lead to diaphragm weakness and contribute to problems weaning patients from mechanical ventilation, chronic shortness of breath, and fatigue in survivors.
Nov 16 JAMA Intern Med research letter

Scientists find that SARS-CoV-2 does not replicate, cause disease in poultry

A US Department of Agriculture study yesterday in Emerging Infectious Diseases demonstrated a lack of SARS-CoV-2 susceptibility in poultry. Researchers exposed poultry species to both SARS-CoV-2, the virus that causes COVID-19, and to Middle East respiratory syndrome coronavirus (MERS-CoV), finding no disease, virus replication, or serum antibodies—and suggesting that poultry are unlikely to serve as vectors for the diseases.

SARS-CoV-2 and MERS-CoV are genetically similar to bat betacoronaviruses, and both appear to be zoonotic—passing from animals to people. Dromedary camels are thought to be the intermediary host for MERS-CoV, but the animal host for SARS-CoV-2 has yet to be definitively identified.

Poultry are widespread, have close contact with people, and are a significant contributor to worldwide food supply, leading to concerns of susceptibility to coronaviruses and a possible role in the transmission of SARS-CoV-2.

The researchers challenged 10 birds each of five poultry species—chickens, turkeys, Pekin ducks, Japanese quail, and white Chinese geese—with exposure to SARS-CoV-2 and MERS-CoV, testing for the viruses with reverse-transcription polymerase chain reaction (RT-PCR) at 2, 4, 7, and 14 days post-exposure. No clinical signs of the diseases were detected in any species, no viruses were detected via RT-PCR, and no antibodies to either virus were found in blood serum samples on day 14.

Chicken eggs with embryos were also tested for the ability to support viral replication, and no virus was recovered.
Nov 16 Emerg Infect Dis research letter

Study shows cross-neutralizing antibodies in recovering COVID patients

Patients recovering from severe COVID-19 infections show a strong neutralizing antibody response, with some people producing cross-neutralizing antibodies that are capable of neutralizing other types of coronaviruses, a study yesterday in Nature Microbiology reported.

Patients with severe disease had a higher frequency of circulating immune cells called T follicular helper (TFH) cells specific to SARS-CoV-2 spike proteins—surface molecules that allow the virus to bind to and penetrate host cells.

The researchers analyzed sera from 67 patients who were hospitalized for COVID-19 from Jan 23 to Mar 2 in Hunan, China—17 of whom were categorized as having severe disease. Blood serum collected on day 28 after discharge (44 to 52 days after symptom onset) was tested for immunoglobulin (Ig) G antibody binding against SARS-CoV-2, SARS-CoV—the virus that causes severe acute respiratory syndrome, or SARS—and MERS-CoV using enzyme-linked immunosorbent assay (ELISA).

All 67 patient sera samples contained neutralizing IgG antibodies for the S1 (median titer 4.61, interquartile range [IQR], 4.01 to 4.61) and S2 (median titer 4.91, IQR, 4.61 to 5.52) SARS-CoV-2 spike proteins. Patients with severe disease had higher levels of S1 and S2 antibodies, and neutralizing antibody titers were correlated with greater severity of disease (odds ratio [OR], 5.04; 95% confidence interval [CI], 1,003 to 25.30).

The severe group also showed a higher frequency of TFH cells compared with the non-severe group (P = 0.0006), suggesting a positive correlation with neutralizing antibody response in these patients. The authors conclude that TFH cells play a role in the initiation or maintenance of neutralizing antibody responses.

Antibodies from recovered COVID-19 patients efficiently neutralized SARS-CoV-2, but were less effective for the other viruses. For MERS-CoV, no binding was detected for the S1 spike protein, but 73.13% (49 of 67) of patient sera bound to S2 spike proteins, suggesting that COVID-19 survivors produce antibodies with cross-binding activity for both SARS-CoV-2 and MERS-CoV.

"The existence of cross-neutralizing antibodies in COVID-19-convalescent individuals provides the possibility to isolate broad neutralizing antibodies and to design pan-coronavirus vaccines," the authors noted.
Nov 16 Nat Microbiol study

News Scan for Nov 17, 2020

News brief

Study links COVID restrictions to increased UK dental antibiotic use

A study published late last week in the British Dental Journal suggests that restricted access to dental care in England during the early months of the COVID-19 pandemic resulted in a sharp rise in dental antibiotic prescribing.

In the study, researchers from the National Health Service (NHS) and the University of Manchester analyzed NHS data on dental antibiotic prescriptions dispensed by community pharmacists from January 2018 to July 2020. They aimed to describe trends in overall dental antibiotic use across England during that period and compare trends in the rate of use between the seven NHS England regions from April 2020, when COVID-19 restrictions were first put in place and dental practices were restricted to providing remote management of patients, to July 2020.

The results showed a downward trend in the number of antibiotic prescriptions dispensed to NHS dental patients up until March 2020, followed by a sharp upward trend that started in April 2020 and plateaued in July 2020 after dental practices were allowed to reopen. Compared to April to July 2019, dental antibiotic prescribing was 25% higher in April to July 2020. All areas of the country saw increases in prescribing in May and June, with the highest increase in London (60%) and lowest in the South West of England (10%). Overall, the highest rate of antibiotic dispensing to NHS dental patients occurred in the East of England in June (6.1 antibiotic prescriptions per 1,000 population).

The study was released on the same day as a white paper from FDI World Dental Federation that highlights how dental teams can help raise awareness, prevent and control infections, and optimize the use of antibiotics to help tackle the problem of antibiotic resistance.

"Patients waiting for access to care often receive more antibiotics than those patients who receive the right treatment immediately," study and white paper lead author Wendy Thompson, PhD, of the University of Manchester, said in a press release. "As dental care provision returns to a 'new normal' in the COVID-19 era, it is important to ensure access to high-quality, urgent dental care and to optimize the use of antibiotics."
Nov 13 Br Dent J study
Nov 13 FDI World Dental Federation white paper
Nov 13 FDI World Dental Federation press release

Reports cites gaps in TB diagnosis, prevention, and treatment

A report published yesterday by the Stop TB Partnership and Médecins Sans Frontières highlights policy gaps that the two groups say are undermining progress in the fight against tuberculosis (TB), including drug-resistant (DR)-TB.

The Step Up for TB 2020 report, which examines the national TB policies of 37 high-burden countries and assesses the extent to which they align with World Health Organization (WHO) guidelines and recommendations, finds that many of the countries have outdated diagnostic, treatment, and prevention policies. For example, while more than 80% indicate they are able to use rapid molecular tests as the initial diagnostic test for TB, many countries have not implemented this policy at scale, and less than a quarter of the countries offer a comprehensive set of drug susceptibility testing methods to ensure TB patients aren't being treated with drugs against which their bacteria are resistant.

On treatment, the report finds that only 61% of countries are using the modified, shorter all-oral treatment for DR-TB recommended by the WHO, while nearly half are still using regimens containing the most toxic injectable medicines. Only 65% of countries have policies for the type of shorter TB preventive treatment that can help reduce the number of latent TB infections that develop into active infections, and only half of the countries surveyed screen household members of people who have TB.

"Earlier this year, the COVID-19 pandemic hit the world with devastating impact, and governments around the world quickly adopted new policies and laws in response," Lucica Ditiu, MD, executive director of the Stop TB Partnership, said in a press release. "Meanwhile, TB remains the top infectious disease killer, even though it is preventable and curable. To make matters worse, most countries still use outdated policies, practices, tools and treatment regimens."

The report calls for countries to make relevant policy reforms a central part of their national TB response to meet the United Nations 2022 TB targets. Among those targets are diagnosis and treatment of 40 million people who have active TB and 30 million who have latent TB infection.
Nov 16 Stop TB Partnership press release
Nov 16 Step Up for TB 2020 report

H5N8 avian flu strikes more poultry, wild birds in Europe

Three European countries—France, Germany, and Belgium—reported more highly pathogenic H5N8 avian flu outbreaks, according to official reports.

France's agriculture ministry said H5N8 was detected in the animal department of a garden center near Bastia in its Corsica region after abnormal deaths were reported in poultry. All of the remaining birds were destroyed. An examination of the virus suggests that it is related to the H5N8 strain isolated in the Netherlands, and investigations are under way to determine the source of the virus.

Germany reported more H5N8 detections in poultry and wild birds, according to the latest notifications from the World Organization for Animal Health (OIE). It reported three more events at poultry farms, all in Mecklenburg-Vorpommern state, which began between Nov 13 and Nov 16. Taken together, the virus killed 621 of 71,932 poultry, and the remaining birds were culled.

The country also reported more detections in wild birds in Schleswig-Holstein state, which involved 56 waterfowl found dead from Nov 6 to Nov 13.

Belgium reported its first H5N8 detections of the season in wild birds. Three outbreaks involved waterfowl, including mute swans, found dead between Nov 4 and Nov 7 at different locations in West Flanders province.
Nov 16 French agriculture ministry statement
Nov 16 OIE report on H5N8 in German poultry
Nov 16 OIE report on H5N8 in German wild birds
Nov 17 OIE report on H5N8 in Belgian wild birds

Chapare virus may travel through rodents, human body fluids

An assessment of an outbreak in Bolivia of hemorrhagic fever caused by the Chapare arenavirus points to rodents as a potential source and notes that the virus could be transferred by human body fluids, according to Centers for Disease Control and Prevention (CDC) researchers presenting at the American Society of Tropical Medicine & Hygiene (ASTMH) annual meeting.

The Chapare virus has symptoms similar to Ebola and caused five infections and three deaths near La Paz, Bolivia, in 2019. During the outbreak, three healthcare workers contracted the virus, with possible transmissions from saliva suctioning and resuscitation. Viral RNA was also found in the semen of one survivor 168 days after infection. Before that, the only confirmed Chapare case was in 2004 in the Chapare province of Bolivia.

While no one knows the origin of the virus, pigmy rice rats and small-eared pigmy rice rats that were found around the home of a 2019 patient carried viral RNA. Other arenaviruses, such as Lassa, are carried through rodents as well.

Since the 2019 outbreak, the Bolivian Center for Tropical Diseases (CENTROP) has tagged three possible Chapare virus cases, and scientists have noted that others may have been misclassified as dengue fever. To help track the virus, Bolivian health officials, CENTROP, the Pan American Health Organization, and the CDC collected samples to analyze the virus's genome sequencing and created a reverse-transcription polymerase chain reaction test.
Nov 16 ASTMH press release
Jul 18, 2019, CIDRAP 2019 outbreak coverage