By Marie Rosenthal, MS, and Ethan Covey

Researchers found that an addition to injected COVID-19 vaccines could enhance their effectiveness and provide “border protection” in areas like the nose and mouth. Other researchers found that cognitive deficits could be more widespread than originally realized; no surprise, patients who were on mechanical ventilation suffered the most. There were higher rates of bloodstream infections during the pandemic, but rates of respiratory infections—other than COVID-19—plummeted. And who knew wastewater could actually be helpful in diagnosing the disease?

Many With COVID-19 Appear to Have Cognitive Deficits

A new study of more than 80,000 people found evidence of cognitive deficits in those who recovered from COVID-19.

The research found that those with more severe COVID-19 symptoms scored lower on an online series of tests, with performance on reasoning and problem-solving tasks being most affected. Further analysis of the data indicated that those who received mechanical ventilation had the greatest impairment on cognitive tasks (EClinicalMedicine 2021; 101044. doi:10.1016/j.eclinm.2021.101044).

A series of online tests developed by Adam Hampshire, PhD, a neuroscientist at Imperial College London, had been opened to the general public just before the pandemic for the BBC2 Horizon's Great British Intelligence test. 

In early 2020, the study team extended the questionnaires to gather information on SARS-CoV-2 infection, the symptoms experienced and the need for hospitalization.

Of the 81,337 participants who provided complete data, 12,689 suspected they had COVID-19. Participants reported a range of severity of illness, with many experiencing respiratory symptoms while recuperating at home (n=3,559). Nearly 200 were hospitalized (n=192) and about one-fourth of them (n=44) required mechanical ventilation.

The time since onset of illness was one to six months, meaning the study could not draw definitive conclusions about whether these effects on cognition were long-lasting.

The study found a relationship between deficits in overall cognitive performance and severity of respiratory symptoms. The research also found that not all areas of thinking ability correlated in the same way with COVID-19 illness and that some abilities were spared, which included emotional discrimination and working memory. In comparison, executive-level tasks that required skills in reasoning and problem solving seemed to show the greatest deficit.

To understand the magnitude of the deficits, the researchers compared the pattern of scores on the tests with cognitive changes that occur for other reasons. The effects in participants hospitalized with mechanical ventilation were similar to the average cognitive decline seen over a period of 10 years of aging and equivalent to a seven-point difference in IQ.

The researchers carried out a series of checks to ensure the cognitive deficits were associated with COVID-19 and not explicable by other variables. These included separating out those who had a confirmed positive test for SARS-CoV-2 and demonstrating that the cognitive deficits were indeed greater in those with positive tests. Further checks suggested the results were not due to a minority with pre-existing conditions or ongoing symptoms of COVID-19. Analysis also indicated it was unlikely that the results could be explained by the possibility that those who contracted more severe COVID-19 disease were less cognitively capable before they were ill.

“Going forward, it would be valuable to bring together brain imaging and cognitive tests with other information on mental health and everyday function, ideally in studies that track people’s trajectories for months or even years. To really know what the long-term effects are for people will require people to be followed up over time,” Dr. Hampshire said.

Higher Rates of BSI During Pandemic

Bloodstream infection was found at higher rates in patients during the COVID-19 pandemic—particularly among those in the ICU—when compared with the prepandemic period, according to a new study presented at the 31st European Congress of Clinical Microbiology & Infectious Diseases (abstract 563).

“It has been reported that certain viruses come predisposed to bacterial superinfection,” said Maria Angeles Orellana-Miguel, MD, of the Department of Clinical Microbiology, Hospital Universitario 12 de Octubre, in Madrid. “Some studies have suggested that SARS-CoV-2 can enhance colonization and attachment of bacteria to host tissue, and could increase tissue destruction, which might increase the risk of blood infection and sepsis.”

However, Dr. Orellana-Miguel noted, reports of bacterial coinfection and superinfection in COVID-19 patients are limited.

The retrospective study analyzed the number of blood cultures ordered and corresponding results from March 1, 2020 through April 27, 2020, and during the same period in 2019. A total of 6,007 and 4,671 blood cultures corresponding to 2,086 and 1,647 patients were analyzed from the 2019 and 2020 periods, respectively. The numbers corresponded to a blood culture-per-patient rate of 2.88 during 2019, and a slightly lower rate of 2.83 during 2020.

Yet, while there was an overall decrease in blood cultures ordered during the COVID-19 period, there was an increase in the percentage of positivity (13% vs. 17.4%) and contamination (5.4% vs. 8.8%). Additionally, more male than female patients had positive blood cultures during the pandemic period (53.5% vs. 61.5%).

There was a significant increase in rates of coagulase-negative Staphylococcus (CNS) during the pandemic period, and it was the most frequently isolated microorganism in patients with a positive SARS-CoV-2 polymerase chain reaction (PCR) test. Comparatively, there was a decrease in Enterobacterales, although they remained the most frequently isolated pathogens in patients who were untested or had negative SARS-CoV-2 PCR results.

Respiratory Virus Spread Historically Low During Pandemic, Yet Rising

The circulation of respiratory viruses in the United States has been at historically low levels during the COVID-19 pandemic.

However, rates have varied among viruses, and many have returned to prepandemic levels, even exhibiting atypical, offseason spread (MMWR Morb Mortal Wkly Rep 2021;70:1013-1019).

“This report describes how respiratory viruses, like flu, spread at historically low levels during the first year and a half of the COVID-19 pandemic, likely because of measures used to stop the spread of COVID-19, which include staying home,” said Sonja J. Olsen, PhD, an epidemiologist with the Influenza Division, National Center for Immunization and Respiratory Diseases, CDC. “However, spread of some of these viruses is now increasing, and there could be more widespread respiratory circulation this fall and winter.”

The study focused on virologic data available from U.S. laboratories through the U.S. World Health Organization Collaborating Laboratories System and the CDC’s National Respiratory and Enteric Virus Surveillance System, and focused on influenza activity from Oct. 3, 2020 to May 22, 2021, and activity of other respiratory viruses from Jan. 4, 2020 to May 22, 2021.

From October 2020 through the end of the survey period, U.S. influenza activity was lower than at any time since 1997, when public data became available. In clinical specimens, 0.2% tested positive for influenza, as did 0.05% of specimens tested at public health laboratories.

Like flu, respiratory syncytial virus (RSV) circulated at historically low levels throughout 2020. However, rates of RSV have been increasing across the country since April 2021. Activity of common human coronaviruses and parainfluenza viruses decreased during 2020, but have since bounced back to prepandemic levels—including rates of activity that contrast with typical seasonal trends. Rhinoviruses and enteroviruses remained at low levels through May 2020, but have since risen to near-prepandemic levels.

The epidemiologists of the report noted that clinicians need to be aware of how these various viruses have rebounded and the potential for further spread caused by decreases in COVID-19 mitigation practices.

“It is important to continue everyday preventive actions, like avoiding close contact with people who are sick, staying home when sick, covering coughs and sneezes, and frequent handwashing,” Dr. Olsen said. “In addition, influenza vaccination for persons 6 months and older will be important in preventing flu.”

Not So Wasted Wastewater

By monitoring wastewater, scientists at the University of California, San Diego School of Medicine detected 85% of COVID-19 cases on campus—wastewater samples tested positive before most individual cases were diagnosed. 

The researchers have been screening wastewater from campus buildings for signs of the virus since the summer of 2020, thinking the information could help prevent outbreaks (mSystems2021 Aug 10. doi:10.1128/mSystems.00793-21).

Now they have data to back it up: Screening for SARS-CoV-2 in wastewater, the team showed they can detect even a single infected, asymptomatic person living or working in a large building. Notification to occupants of each building with positive wastewater increased COVID-19 testing rates by as much as 13-fold. Once an occupant tested positive, isolation and contact tracing helped prevent further spread of the virus.

“University campuses especially benefit from wastewater surveillance as a means to avert COVID-19 outbreaks, as they're full of largely asymptomatic populations and are potential hot spots for transmission that necessitate frequent diagnostic testing,” said first author Smruthi Karthikeyan, PhD, an environmental engineer and postdoctoral researcher at UC San Diego School of Medicine.

Wastewater screening is an integral part of UCSD’s Return to Learn program, an evidence-based approach that has allowed the university to offer on-campus housing, in-person classes and research opportunities throughout most of the pandemic.

Return to Learn relies on three pillars: risk mitigation, viral detection and intervention. With approximately 10,000 students on campus during the 2020-2021 academic year, the many components of the program kept COVID-19 case rates much lower than the surrounding community and compared with most college campuses, maintaining a positivity rate of less than 1% during that time. The Return to Learn program, including wastewater testing, has become a model for other universities, K-12 school districts and regions.

Every morning, seven days a week, a team of students and staff in matching tee shirts deploys across campus in golf carts to collect sewage samples from 126 collection robots set up to monitor 350 buildings. By 10 a.m., they return to the lab at the School of Medicine.

There, the team processes the samples with a different kind of robot that concentrates the virus using magnetic nanoparticles, then extracts RNA from the samples. PCR testing is used to search for the virus’ signature genes.

When the virus is detected, automated but targeted messages are sent through a campus-wide system to people associated with affected buildings, such as students, staff and faculty, recommending they be tested for the virus as soon as possible. The data are added to a public dashboard.

Since the program’s inception, the team has worked constantly to optimize the process, Dr. Karthikeyan said. The current automated approach dramatically reduced the sample-to-result turnaround time 20-fold: now five hours for 96 samples. By miniaturizing the samples, the researchers reduced processing costs to $13 per sample. 

Better ‘Border Protection’ During COVID-19

A simple addition to injected COVID-19 vaccines could enhance their effectiveness and provide “border protection” immunity in areas like the nose and mouth to supplement antibodies in the bloodstream, new research suggests (Proc Natl Acad Sci U S A 2021;118[34]:e2102435118. doi:10.1073/pnas.2102435118).

The strategy involves dampening the activity of elastase, an enzyme produced by some white blood cells when they're responding to the vaccine challenge. When highly active, elastase breaks down not just the pathogen—its job—but also degrades pieces of cells that participate in the immune response.

Research in mice showed that an experimental COVID-19 vaccine containing a compound to inhibit elastase stimulated a robust antibody response that included immunity in the nose and mouth, ultimately providing extra protection for airways and the gastrointestinal tract.

“Our approach is to improve ‘border control.’ The benefits are broad because in addition to providing protection in the bloodstream like most vaccines do, we also have excellent protection in the doors and windows of the body that communicate with the outside," said senior study author Prosper Boyaka, PhD, a professor and the chair of the Department of Veterinary Biosciences at The Ohio State University, in Columbus.

“If we protect the mucosal area where the pathogen enters, then even if you don't reach total immunity there, you limit the amount of pathogen that enters the body so the antibodies inside are more efficient at clearing the infection,” Dr. Boyaka said. 

The experimental vaccine was produced by packaging a segment of the SARS-CoV-2 spike protein as an antigen with the common vaccine ingredient aluminum salts and an enzyme inhibitor. The findings suggest this affordable design could be particularly helpful in developing countries, where cold storage needed for existing vaccines is a challenge, said Dr. Boyaka, also an investigator and the program director in Ohio State's Infectious Diseases Institute.

There is an irony to the use of aluminum salts in about 70% of the world's vaccines: While alum's presence enhances the immune response, it also recruits the white blood cells that secrete elastase.

Alum is inexpensive to obtain or produce and can be stored at room temperature, and is effective at promoting development of a bloodstream-based antibody response to vaccination. But it doesn't do much for cell-mediated immunity that improves protection against viruses and bacteria that use cells to reproduce, and can't generate a useful number of antibodies in the body's portals of entry for most pathogens: the nose, mouth and genitourinary tract.

The researchers found that suppressing elastase in a vaccine containing alum had the dual benefits of broadening and speeding up the antibody response in the bloodstream and triggering the specific types of antibodies needed for immune protection of mucous membranes.

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