Repeat COVID infections appear to predispose patients to disease, death

Repeat SARS-CoV-2 infections confer significant additional risk of adverse multi-organ medical conditions and poor outcomes such as hospitalization, diabetes, kidney disease, mental illness, death, and diseases affecting the lungs, heart, brain, blood, and musculoskeletal systems, suggests a study published yesterday in Nature Medicine.

Researchers at Washington University and the Veterans Affairs (VA) St. Louis Health Care System used the VA's national healthcare database to estimate the risk of poor 6-month outcomes among 443,588 veterans who had one COVID-19 infection, 40,947 infected at least twice, and 5,334,729 uninfected controls from Mar 1, 2020, to Apr 6, 2022. Of those with at least two infections, most had two or three, and a few had four.

Compared with patients with no reinfection, repeat infection was tied to more than double the risk of death (hazard ratio [HR], 2.17) and more than three times the risk of hospitalization (HR, 3.32). Such patients were 3.5 times more likely to develop lung disease, 3.0 times more likely to have new-onset heart conditions, and 1.6 times more likely to have neurologic disease.

The greatest risks were in the 30 days after infection but were still evident at 6 months. The cumulative risks of repeat infection rose by the number of infections. "Reducing overall burden of death and disease due to SARS-CoV-2 will require strategies for reinfection prevention," the authors wrote.

In a Washington University news release, senior author Ziyad Al-Aly, MD, clinical epidemiologist at the university's medical school, said he has observed in recent months "an air of invincibility among people who have had COVID-19 or their vaccinations and boosters, and especially among people who have had an infection and also received vaccines."

But the research shows the potential detriment of serial infections, he said: "Without ambiguity, our research showed that getting an infection a second, third or fourth time contributes to additional health risks.… Going into the winter season, people should be aware of the risks and practice vigilance to reduce their risk of infection or reinfection."
Nov 10 Nat Med study
Nov 10 Washington University news release

High blood pressure linked to greater risk of severe COVID-19

In a study in PLOS One of more than 16,000 infected people in the United Kingdom, high blood pressure was found to be associated with a 22% higher odds of severe COVID-19, though successfully reducing blood pressure through medication was linked with a corresponding reduction in risk.

The study looked at medical records from the UK Biobank, a longitudinal prospective study initiated in 2006 that has recruited more than 500,000 men and women aged from 40 to 69 years. It included 16,134 peopleo who tested positive for COVID-19. Of those, 22% (3,584) developed severe COVID-19, and 40% (6,517) had high blood pressure.

All COVID-19 records from March 2020 through April 2021 were included in the study. The authors defined severe COVID-19 as a case that required hospitalization.

High blood pressure was associated with 22% higher odds of severe COVID-19 (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.12 to 1.33) compared with normal blood pressure.

In those taking blood pressure medication, elevated systolic blood pressure (SBP) showed a dose-response relationship with severe COVID-19 (150 to 159 mm Hg vs 120 to 129 OR, 1.91; 95% CI, 1.44 to 2.53; >180 mm Hg versus 120 to 129 OR, 1.93; 95% CI, 1.06 to 3.51).

Angiotensin-converting enzyme inhibitors or angiotensin-II receptor blockers were not associated with altered risk of severe COVID-19, the authors said.

"Even though the mortality rate due to COVID-19 has been hugely reduced over the last year due to mutation, vaccination and effective treatments, this study highlights the importance of hypertension as a risk factor for COVID-19," the authors concluded. "Our data suggest that further research is needed into the mechanisms driving hypertension as a risk factor for COVID-19 in case of novel, more severe strains or other viruses in the future."
Nov 9 PLOS One study

COVID-19 cases rise in Australia, decline in Europe

As Australia approaches its summer season, a new wave of COVID-19 activity is under way, according to official and media reports.

Norelle Sherry, MBBS, with the Doherty Institute, told Australia's ABC News this week that the wave is driven by multiple Omicron offshoots. BA.5 is still dominant, but scientists are also detecting the BA.5-descendent BQ.1 and the Omicron recombinant virus XBB. "We're actually in more of a COVID soup—not my original phrase, but I think it's definitely apt," she told ABC.

In a related development, a Princess Cruise ship that traveled on a 12-day trip to New Zealand with 4,300 guests and crew on board will disembark in Sydney tomorrow with 800 people positive for COVID-19, the Sydney Morning Herald reported today. New South Wales health officials classified the ship outbreak as high impact, its highest level, meaning the ship isn't able to maintain its critical services due to staff or resource shortages.

In other global developments, the European Centre for Disease Prevention and Control (ECDC) in its latest weekly update said COVID-19 cases and deaths continue to decline in the region and that hospitalizations are declining or stable. BA.5 is still dominant, and the proportion of BQ.1 is at 18.1%, up from 11.3% the previous week.

The European Medicines Agency (EMA) yesterday announced the approval of Sanofi's adjuvanted vaccine that includes the spike protein of the Beta variant to be used as a booster for adults previously vaccinated with mRNA or adenovirus vaccines.

Also, China—experiencing a rise in COVID activity—has relaxed some of its measures, according to Reuters. It cut the quarantine period for contacts by 2 days and eased fines for airlines carrying passengers who test positive for COVID.
Nov 9 ABC News story
Nov 11 Sydney Morning Herald story
Nov 10 ECDC update
Nov 10 EMA announcement
Nov 11 Reuters story

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

COVID-19 mitigation measures tied to fewer infant bacterial infections

A study of 97 hospitals in the United States and Canada found that the incidence of urinary tract infection (UTI) and invasive bacterial infection (IBI) in infants with fever fell to pre-pandemic levels by early 2022, researchers reported yesterday in Pediatrics.

The multicenter cross-sectional study, conducted from November 2020 through March 2022, included full-term, previously healthy, well-appearing infants 8 to 60 days old who visited an emergency department or were hospitalized with a temperature of 38°C (100.4°F) or higher. Because single-center studies have suggested a higher proportion of infants with UTI and IBI in the months following the beginning of the COVID-19 pandemic, the researchers wanted to examine UTI and IBI prevalence in a larger, more geographically diverse population over the course of the pandemic. They also aimed to determine if there was any association between COVID-19 prevalence and the odds of an infant having UTI and IBI.

Of the 9,112 infants included in the study, 603 (6.6%) had UTI, 163 (1.8%) had bacteremia without meningitis, and 43 (0.5%) had bacterial meningitis. UTI prevalence decreased from 11.2% in November 2020 to 3.0% in January 2022. IBI prevalence was highest in February 2021 (6.1%) and decreased to 0.4% in January 2022.

There was a significant downward monthly trend for odds of UTI (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.91 to 0.94) and IBI (OR, 0.90; 95% CI, 0.87 to 0.93). For every 5% increase in COVID-19 prevalence in the month of presentation, the odds of an infant having UTI (OR, 0.97; 95% CI, 0.96 to 0.98) or bacteremia without meningitis decreased (OR, 0.94; 95% CI, 0.88 to 0.99).

"The prevalence estimates from our study demonstrate that the risk of UTI, bacteremia, and bacterial meningitis among febrile infants is higher in time periods when respiratory viral infections are likely of low prevalence, potentially because of pandemic mitigation measures, but then return to baseline risk, or lower, when these measures end," the study authors wrote. "With the potential for future pandemics, understanding the impact of mitigation measures upon bacterial infection prevalence in febrile infants is a key component to informed decision-making between clinicians and parents."
Nov 10 Pediatrics study

CDC: Healthcare-associated infections continued to climb in 2021

A new report from the Centers for Disease Control and Prevention (CDC) shows that healthcare-associated infections (HAIs) in US hospitals remain elevated above pre–COVID-19 pandemic levels.

Findings from the review of quarterly 2021 National Healthcare Safety Network data show continued increases in the quarterly standardized infections ratios (SIRs) for central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated events (VAEs), and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia compared with 2019. The report analyzed data from acute care hospitals, critical access hospitals, inpatient rehabilitation facilities, and long-term acute care hospitals.

Overall, CLABSIs rose by 7% from 2020 to 2021, CAUTIs increased 5%, VAEs climbed by 12%, and hospital-onset MRSA bacteremia rose by 14%. The largest increases were seen in intensive care units. Among other HAIs, surgical-site infections saw no significant changes from 2020 to 2021, and hospital-onset Clostridioides difficile infections fell by 3%.

While the increases in CLABSIs, CAUTIs, VAEs, and MRSA bacteremia are notably smaller than those observed in 2020, when hospitals across the country were overwhelmed with COVID-19 patients, they reflect the continued strain that the pandemic has placed on US hospitals, the CDC said.

"In 2021, the nation and the world continued to experience unprecedented challenges due to the COVID-19 pandemic, which impacted surveillance for and incidence of HAIs," the report authors wrote. "Compared to pre-pandemic years, hospitals across the nation experienced higher than usual hospitalizations and shortages in healthcare personnel and equipment, which may have resulted in deterioration in multiple patient safety metrics since the beginning of the pandemic."

On a positive note, the report also shows that, compared with the 2015 national SIRs, 49 states performed better on at least two infections, 33 performed better on three infection types, and 20 performed better on four infection types.

According to the CDC, approximately 1 in 31 US hospital patients, and 1 in 43 nursing home residents, acquires at least one infection linked to their healthcare each day. 
Nov 4 CDC HAI progress report

Unneeded antibiotics for respiratory infections tied to harm, higher costs

Originally published by CIDRAP News Nov 10

A study of more than 3 million patients with bacterial and viral respiratory infections found that inappropriate antibiotic prescriptions were associated with increased risk of adverse events and higher healthcare costs, researchers reported today in Clinical Infectious Diseases.

The study, conducted by researchers with the Washington University School of Medicine in St. Louis and the Pew Charitable Trusts, used data from the MarketScan Commercial Database to analyze antibiotic exposure among adults aged 18 to 64 years who were diagnosed as having a bacterial or viral infection from April 2016 through September 2018.

They analyzed inappropriate versus appropriate prescriptions, focusing on the relationship between inappropriate antibiotics and adverse drug events and 30-day attributable expenditures. Inappropriate antibiotics were defined as non–guideline-recommended antibiotics for bacterial infections and any antibiotic for viral infections.

Among 3,294,598 eligible adults (median age, 43 years; 41% male), there were 1,656,960 bacterial respiratory infections and 1,637,638 viral respiratory infections. The proportion of adults with bacterial infections who received inappropriate antibiotics differed by infection, ranging from 43% (sinusitis) to 56% (pharyngitis), while inappropriate antibiotics for viral infections ranged from 7% (influenza) to 66% (bronchitis).

Analysis of different infections found that inappropriate antibiotics for pharyngitis were associated with an increased risk of Clostridioides difficile infection (hazard ratio [HR], 2.90; 95% CI, 1.31 to 6.40) and nausea/vomiting/abdominal pain (HR, 1.10; 95% CI, 1.03 to 1.08), while an increased of vulvovaginal candidiasis was linked to inappropriate antibiotics for viral upper respiratory infections (HR, 1.24; 95% CI, 1.14 to 1.34 ) and non-suppurative otitis media (ear infection; HR, 1.39; 95% CI, 1.09 to 1.77).

The mean 30-day total attributable expenditure for inappropriate antibiotics for bacterial infections ranged from $18 (sinusitis) to $67 (pharyngitis) and from –$53 (bronchitis) to $49 (influenza) for viral infections.

"These results support the need for increased outpatient antibiotic stewardship efforts to discourage antibiotic prescribing for viral infections, encourage appropriate selection of guideline-recommended antibiotics for bacterial infections, and reduce antibiotic-related harms and expenditures," the study authors concluded.
Nov 9 Clin Infect Dis abstract

Trial supports shorter regimens for resistant TB

Originally published by CIDRAP News Nov 8

A clinical trial conducted in seven countries found that two shortened, bedaquiline-containing regimens had superior efficacy in treating rifampicin-resistant tuberculosis (TB) compared with a 9-month injectable-containing regimen, with fewer cases of hearing loss, investigators reported today in The Lancet.

The STREAM stage 2 trial randomized patients aged 15 years or older with rifampicin-resistant TB to receive one of four treatments: the long regimen (the 20-month regimen recommended by the World Health Organization from 2011 to 2018), the control regimen (a 9-month regimen with the second-line injectable kanamycin), the oral regimen (9 months with bedaquiline replacing the injectable), and the 6-month regimen (containing bedaquiline and supplemented with 8 weeks of kanamycin). The primary outcome was favorable status (negative cultures for Mycobacterium tuberculosis) at 76 weeks, with additional analysis of serious adverse events.

Of the 517 participants in the modified intention-to-treat (mITT) analysis, 133 of 187 (71%) on the control regimen had a favorable outcome, compared with 162 of 196 (83%) on the oral regimen, for a difference of 11 percentage points (95% CI, 2.9 to 19.0), adjusted for HIV status and randomization protocol. By 76 weeks, 108 of 202 (53%) participants in the control regimen and 106 of 211 (50%) allocated to the oral regimen had an adverse event of grade 3 or 4, with hearing loss more frequent among those who received the control regimen (18 [9%] vs 4 [2%]).

Of the 134 participants in the mITT population who were allocated to the 6-month regimen, 122 (91%) had a favorable outcome, compared with 87 of 127 (69%) assigned to the control regimen, for an adjusted difference of 22.2 percentage points. Six of 143 (4%) recipients of the 6-month regimen had grade 3 or 4 hearing loss.

"In conclusion, STREAM stage 2 has shown that two short-course, bedaquiline-containing regimens are not only non-inferior but superior to a 9-month injectable-containing regimen," the investigators wrote. "These two regimens offer promising treatment options for patients with MDR [multidrug-resistant] or rifampicin-resistant tuberculosis. However, safer and simpler alternatives are still needed."
Nov 8 Lancet study

Veterinary antibiotic sales continue to decline in United Kingdom

Originally published by CIDRAP News Nov 8

A report today from the United Kingdom's Veterinary Medicines Directorate (VMD) shows that sales of antibiotics for use in UK livestock continue to decline.

The data in the 2021 UK Veterinary Antibiotic Resistance and Sales Surveillance Report (UK-VARSS) show that sales of antibiotics for use in food-producing animals, adjusted by animal population, fell by 6% compared with 2020 and 55% compared with 2014. Sales of highest-priority critically important antibiotics (HP-CIAs), which are considered the most vital antibiotics for human medicine, fell by 18% compared with 2020 and 83% compared with 2014. They accounted for 0.4% of total antibiotic sales for livestock in 2020—a new low.

The report also showed that antibiotic usage, including use of HP-CIAs, in 2020 fell across most animal species, with some increases observed in turkeys, game birds, and salmon. Use of HP-CIAs in UK pigs has fallen by 97% since 2015, and by 96% in UK poultry since 2014.

Clinical surveillance of antimicrobial resistance (AMR) in Escherichia coli from animal species shows some encouraging trends as well. Of the HP-CIAs tested, resistance to fluoroquinolones and third-generation cephalosporins was low or not detected for any animal species tested in 2021. In addition, the number of Salmonella isolates from cattle, pigs, chickens, and turkeys that were fully susceptible to the panel of antibiotics tested increased in 2021.

But the report does note an increase in the percentage of pigs carrying extended-spectrum beta-lactamase (ESBL)/AmpC-producing E coli, which are resistant to third-generation cephalosporins.

"Surveillance of antibiotic consumption and antibiotic resistance is one of the central pillars of the work we do on AMR," VMD Head of AMR Policy and Surveillance Kitty Healy, PhD, MRCVS, wrote in the forward to the report. "It has the potential to be more valuable still as we strive to continuously enhance our own surveillance programmes, and to link them with similar programmes in people, food, the environment and beyond."
Nov 8 UK VARSS report

Study finds uncomplicated UTI antibiotics are frequently inappropriate

Originally published by CIDRAP News Nov 7

A study of electronic health record (EHR) data from a US hospital network found that more than a third of antibiotic prescriptions for uncomplicated urinary tract infections (uUTIs) were inappropriate or suboptimal, researchers reported late last week in Antimicrobial Resistance and Infection Control.

Using EHR data from a large integrated delivery network in Mid-Atlantic states, researchers analyzed female patients ages 12 and over who had been diagnosed as having a uUTI, received one or more antibiotics, and had one or more urine cultures with an antibiotic susceptibility test from July 2016 through March 2020. The goals of the study were to examine the proportion of antibiotics that were inappropriate (not recommended according to Infectious Diseases Society of America guidelines) or suboptimal (switched within 28 days because of treatment failure) and the total healthcare costs 6 months after infection.

Among the 2,565 women with a uUTI included in the study, the most commonly prescribed antibiotics were nitrofurantoin (61%), trimethoprim-sulfamethoxazole (19%), and ciprofloxacin (15%). More than one third of patients (40.2%) had an isolate that was not susceptible to one or more antibiotics indicated for treating uUTI patients. In total, 66.6% of patients received appropriate antibiotic therapy, while 29.9% received inappropriate treatment and 11.9% received suboptimal treatment. Inappropriate prescribing was more common for patients with non-susceptible (48.2%) versus susceptible (23.5%) isolates.

Patients who received inappropriate or suboptimal antibiotics had greater all-cause and UTI-related costs compared with appropriately prescribed patients, with the greatest difference seen among patients with antibiotic non-susceptible isolates.

The study authors note that while the results should not be extrapolated to a regional level, the findings are in line with previous studies that have found high rates of inappropriate prescribing for uUTIs and higher treatment costs linked to antibiotic resistance.

"As the incidence of antibiotic resistance has significantly increased in the US among community-acquired uUTIs, it is critical to understand regional resistance rates through local community surveillance to inform and improve empiric prescribing," the study authors wrote. "More rapid diagnostic tests are needed in order to optimize prescribing accuracy and avoid manifestation of painful symptoms."
Nov 4 Antimicrob Resist Infect Control study

Survey gauges interest in milk with responsible antibiotic use label

Originally published by CIDRAP News Nov 7

A survey and follow-up experiment conducted by researchers at Cornell University's College of Veterinary Medicine found that consumers will buy milk with a label indicating responsible antibiotic use, but they won't pay significantly more for it than conventionally raised milk. The results of the survey were published last week in the Journal of Dairy Science.

In the telephone survey, conducted among a nationally representative, random sample of 1,000 adults, respondents were asked about their awareness of antibiotic resistance-related issues and whether they would be willing to buy responsible antibiotic use (RAU)-labeled milk. That designation, which would allow for antibiotics to be used in dairy cattle only for therapeutic purposes, does not currently exist, but it has been proposed as an alternative to organic milk. Organic dairy farmers can use antibiotics to treat their cattle with antibiotics if needed, but cannot then market their milk as organic, which has led to some concerns about animal welfare.

In the survey, 75.1% of respondents said they were aware of antibiotic resistance-related issues and 48.5% said they would buy RAU-labeled milk, while 8.4% said they would continue to buy organic milk and 22.3% said they would continue to buy conventionally raised milk. Respondents who said they would prefer RAU-labeled milk over conventional described themselves as younger, aware of issues with antibiotic use, politically moderate, and having higher education.

But in an experimental auction conducted at Cornell, a sample of 85 residents of Ithaca, New York, after receiving information on what the different labels entailed, were unwilling to pay a significant premium for the RAU-labeled milk compared with unlabeled milk, while the premium for organic milk remained (mean willingness to pay per half-gallon: $2.24 for organic milk vs $1.92 for RAU-labeled milk vs $1.86 for unlabeled milk).

"This result suggests that despite consumers' aversion to antibiotic use in milk production, a market could exist for simply reducing their administration in exchange for a price premium lower than for organic milk," the study authors wrote.
Nov 1 J Dairy Sci study