COVID-19 antibodies may linger for at least 7 months, study suggests

COVID-19 antibodies remained 7 months' post-infection, with some even increasing in levels, according to a follow-up study of 578 healthcare workers at the Hospital Clínic at Barcelona. The results, which were published today in Nature Communications, also include evidence that exposure to common cold coronaviruses may contribute to some cross protection.

The cohort submitted four different blood samples from March to October 2020, which were assessed for Immunoglobulin (Ig) A, IgM, and IgG antibodies to six different SARS-CoV-2 antigens as well as the presence of antibodies against four human coronaviruses (HCoVs). By month 6 post-symptom onset (PSO), 16.4% of the cohort had tested seropositive for COVID-19 at least once, and the researchers were able to look at kinetic curves based on samples from 76 symptomatic participants at a maximum of 7.7 PSO.

Overall, IgG levels were steady for spike protein (S) antigens and for IgA up to 230 days PSO, with 71% and 69% of participants remaining seropositive 6 months PSO, respectively. S-related IgG levels increased after 150 days in 73.9% of people, the researchers add, and plasma neutralizing capacity increased from symptom onset until day 80 but then remained stable up to 250 days PSO.

Comparatively, only 34% of participants were seropositive for IgM after 6 months, and even less (26%) were seropositive for nucleocapsid-related IgG. The researchers note that all IgA and IgM appeared to peak within the first month but then decline to 30% and 23.5% seropositivity at 1 and 3 months PSO.

"Importantly, we observed a trend towards higher levels of antibodies against HCoVs N proteins at baseline in those participants who did not become infected with SARS-CoV-2, suggesting some level of cross-protection against infection," the researchers write. Furthermore, data showed that asymptomatic COVID-19 patients had higher anti-HCoV IgG and IgA levels.

"Although cross-protection by pre-existing immunity to common cold coronaviruses remains to be confirmed, this could help explain the big differences in susceptibility to the disease within the population," said study lead Carlota Dobaño, PhD, in a Barcelona Institute for Global Health (ISIGlobal) press release.
Aug 6 Nat Comm study
Aug 6 ISI Global press release

Long COVID-19 in hospitalized patients affected mental, physical health

Lingering symptoms affected most COVID-hospitalized patients mentally or physically 6 months post-discharge, according to a study yesterday in the Journal of General Internal Medicine.

The researchers surveyed 126 people who completed a 1-month and 6-month survey after being discharged from a New York University hospital from Apr 15 to May 30, 2020. All had needed at least some supplemental oxygen, and most (60%) were male, with the median age of 62 years. Almost three out of four people (74%) were still experiencing worse health compared with baseline functions and reported an average of 7.1 symptoms. Furthermore, some had even required an emergency department visit (15%) or hospital readmission (8%).

Compared with their average summary scores via the 100-point PROMIS Global Health-10 instrument, overall physical health was still worse (45.2 vs 53.7 pre-COVID) as was mental health (47.4 vs 54.2). Shortness of breath affected 63% of the cohort, and 9% of 124 patients without pre-COVID oxygen requirements still needed supplemental oxygen post-discharge. Those who had needed intensive care unit (ICU) treatment were more likely to report lingering health issues, but PROMIS Global Health-10 outcomes and shortness of breath measurements were still similar to the overall group.

Fatigue (85%), muscle weakness (46%), memory difficulties (41%), and brain fog (37%) were also commonly reported.

"In conclusion, we found that patients discharged after hospitalization for severe COVID-19 still experience symptoms that may affect their quality of life even 6 months after discharge. Support and treatment are needed to return these patients back to their pre-COVID baseline," write the researchers.
Aug 5 J Gen Int Med study

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

Declining susceptibility to azithromycin found in German gonorrhea samples

Analysis of Neisseria gonorrhoea samples from diagnostic laboratories throughout Germany shows a significant decrease in susceptibility to azithromycin, one of the two remaining antibiotics recommended for gonorrhea infections, German researchers reported yesterday in Eurosurveillance.

The analysis of 3,253 N gonorrhoea isolates collected from January 2014 through May 2021 noted a substantial increase in the proportion of isolates with an azithromycin minimum inhibitory concentration (MIC) value higher than 1 mg/L (above the epidemiologic cut-off), rising from 1.3% of isolates in 2014 to 12.2% in 2020. Preliminary data for 2021 showed the proportion with an azithromycin MIC >1 climbing to 20.7%, but those data have yet to be confirmed.

"According to our current observations and data described by others, we may not be fully able to rely on azithromycin as a therapeutic agent for the treatment of gonorrhoea," the researchers from Germany's Robert Koch Institute wrote. 

Only two isolates—one from 2015, the other from 2018—were found to be resistant to ceftriaxone, the other antibiotic recommended for gonorrhea. Dual therapy consisting of azithromycin and ceftriaxone has been the standard treatment for gonorrhea infections in Germany since 2013, but the authors note that ceftriaxone monotherapy has become the preferred treatment in well-controlled settings where adherence can be guaranteed.
Aug 5 Eurosurveill study

Indonesian drug outlets often dispense antibiotics without prescription

Originally published by CIDRAP News Aug 5

A study involving simulated patients found that dispensing antibiotics without a prescription is common in Indonesian drug stores and pharmacies, despite regulations against it, researchers reported this week in BMJ Global Health.

Researchers from Indonesia, Australia, and the United Kingdom recruited and trained 21 people to visit drug outlets (community pharmacies and drugstores) in urban and rural areas of Indonesia, simulate clinical symptoms of an infection or report on another person's symptoms, and record the details of the interaction. The standardized patients (SPs) presented three clinical scenarios: a parent of a child with diarrhea, an adult with presumptive tuberculosis (TB), and an adult with an upper respiratory tract infection (URTI). The primary outcome was dispensing an antibiotic without a prescription, or without the client requesting it.

The SPs made a total of 495 visits to 166 drug outlets, and antibiotic dispensing without a prescription occurred at 69% of visits. In addition, antibiotics were frequently dispensed with few or no instructions on proper use.

Compared with drugstores, dispensing without a prescription was more likely at standalone pharmacies (odds ratio [OR], 5.9; 95% confidence interval [CI], 3.2 to 10.8) and pharmacies attached to clinics (OR, 2.2; 95% CI, 1.2 to 3.9). The odds of an SP receiving an antibiotic without a prescription were five times higher for presumptive TB (OR, 5.7; 95% CI, 3.0 to 10.8) or URTI (OR, 5.2; 95% CI, 2.7 to 9.8) than for a child with diarrhea.

Interviews with a sample of pharmacists and drug outlet staff revealed that inappropriate antibiotic dispensing was driven by strong patient demand, unqualified drug sellers dispensing medication, competition between different types of drug outlets, pressure on staff from drug outlet owners, and weak enforcement of regulations.

Under Indonesian law, licensed pharmacists can dispense antibiotics only with a prescription, and drugstores are prohibited from selling antibiotics. The study authors say stronger enforcement of those laws will not fully solve the problem.

"A multifaceted approach should be considered, taking into account the profit-maximising motives of drug outlets, the high demand for antibiotics among clients, and the push from owners to compete with other outlets, including drug stores which dispense antibiotics despite being prohibited from selling this class of medication," they wrote. 
Aug 3 BMJ Glob Health study

Trial supports stopping antibiotics for RTIs when not needed

Originally published by CIDRAP News Aug 4

Discontinuing antibiotics for uncomplicated respiratory tract infections (RTIs) when a physician has determined that antibiotics aren't needed is a safe strategy for reducing unnecessary antibiotic use, according to the results of a randomized clinical trial published yesterday in Clinical Microbiology and Infection.

In the multi-center open-label trial, conducted in Spain, adults with RTIs who had been taking antibiotics for less than 3 days but were deemed by trial investigators to not need antibiotics were randomized 1:1 to either discontinue or continue antibiotic treatment. The primary outcome was duration of severe symptoms (the number of days scoring 5 or 6 on a 6-item Likert scale), and secondary outcomes included antibiotics taken, adverse events, patient satisfaction, and complications within 3 months.

A total of 467 patients were randomized to the two arms, and 409 were included in the final analysis. The mean duration of severe symptoms was 3.0 days for the patients assigned to the discontinuation arm and 2.8 days for those who continued antibiotic treatment (mean difference, 0.2 days; 95% CI, —0.1 to —0.4 days). The proportion of patients who continued taking antibiotics after the baseline visit was much lower in the discontinuation group (25.1% vs 90.1%).

Patients assigned to the continuation group had a higher risk of adverse events (relative risk [RR], 1.47; 95% CI, 0.80 to 2.71) but slightly higher levels of patient satisfaction and a lower need for further healthcare contact in the following 3 months (RR, 0.61; 95% CI, 0.28 to 1.37).

The investigators note that the results are in line with previous studies showing no differences in clinical outcomes between antibiotics and placebo for uncomplicated RTIs, and resemble those obtained with a delayed antibiotic prescribing strategy.

"Our results have shown that discontinuing an already initiated antibiotic treatment for uncomplicated RTI when the clinician considered that it was not indicated had no influence on the clinical outcomes of the patients," they wrote.
Aug 3 Clin Microbiol Infect study

Study examines ways to cut antibiotics in terminal cancer patients

Originally published by CIDRAP News Aug 3

A single-center study of terminal cancer patients found a high rate of antibiotic use within the last 30 days of life, with significantly lower use among those who asked for limited antimicrobial treatment, researchers reported yesterday in Open Forum Infectious Diseases.

Despite uncertain benefits and the risk of adverse events and antimicrobial resistance, antimicrobial use in patients with terminal cancer is frequently continued after transition to comfort care and discontinued less than 1 day prior to death. To determine whether completing a Physician Orders for Life Sustaining Treatment (POLST) form and an accompanying antimicrobial preferences document had any relationship with antimicrobial use at the end of life, researchers from the University of Washington and the Fred Hutchinson Cancer Research Center conducted a retrospective study of patients who died at the Seattle Cancer Care Alliance from Jan 1, 2016, through Jun 30, 2019.

Among the 1,295 patients identified for the study, 1,070 (83%) received one or more inpatient antibiotic within the last 30 days of life. The median total and intravenous (IV) antibiotic use was 1,077 and 677 days of therapy per 1,000 inpatient days, respectively. A total of 318 (24.6%) patients had a completed POLST form on file, and 120 (37.7%) of those were completed at least 30 days before death; 35/120 (29.2%) specified limited antimicrobial use, 55/120 (45.8%) specified full antimicrobial use, and 30/120 (25.8%) omitted antimicrobial preference.

Compared with those without a POLST, patients specifying limited antibiotic use at least 30 days before death had significantly lower total antimicrobial days of therapy (DOT; adjusted incidence rate ratio [IRR], 0.68; 95% CI, 0.49 to 0.95) and IV antibiotic DOT (IRR, 0.57; 95% CI, 0.38 to 0.86).

The study authors note that Washington is only 1 of 18 states that includes a separate section on antibiotics in their POLST forms.

"This supports our hypothesis that completion of the antimicrobial preferences section of the POLST form at an intermediate interval prior to death is associated with subsequent antimicrobial exposure in the 30 days prior to death," they wrote. They said states should include antimicrobial prescribing data on their POLST forms. 
Aug 2 Open Forum Infect Dis abstract

Stewardship steps tied to less antibiotic use in COVID-19 patients

Originally published by CIDRAP News Aug 3

A retrospective study of patients in Kentucky suggests antibiotic stewardship interventions may safely cut antibiotic use in COVID-19 patients, researchers reported yesterday in Infection Control and Hospital Epidemiology.

Among 173 patients who received antibiotics for COVID-19 from June through July 2020 at a community healthcare system in Louisville, 91 (52.6%) met criteria for early discontinuation of antibiotics, and 82 patients (47.7%) were in the late-discontinuation group. The decision to discontinue antibiotics in COVID-19 patients without bacterial co-infection was made by trained clinical pharmacists who were part of the hospital's antimicrobial stewardship (AMS) team. Among the outcomes evaluated by the study were the percentage of AMS recommendations accepted, length of antibiotic therapy, length of hospital stay, and mortality.

In early-antibiotic-discontinuation patients, 41.8% had an AMS intervention, with an 86.8% acceptance rate, while 29.3% of patients in the late-antibiotic-discontinuation group had an AMS intervention, with a 54.2% acceptance rate. The median antibiotic length of therapy was 3 days in the early-discontinuation group and 7 days in the late-discontinuation group.

The overall in-hospital mortality rate was 17.3%; inpatient mortality occurred in 14.3% of the early-discontinuation group and 20.7% in the late-discontinuation group. Median length of stay was similar in the two groups, at 7 and 9 days, respectively.

The study authors say the findings may add to prescriber confidence when discontinuing antibiotics in COVID-19 patients, and demonstrate that stewardship interventions may lead to shorter lengths of antibiotic therapy.

"AMS recommendations could be a key factor in promoting appropriate antibiotic use in COVID-19 patients," they wrote.
Aug 2 Infect Control Hosp Epidemiol abstract

Study: More than half of US outpatient antibiotics not tied to visit, infection

Originally published by CIDRAP News Aug 2

More than half of ambulatory antibiotic use among privately insured US patients over a 2-year period was not linked to a clinician visit or an infection, researchers reported yesterday in Open Forum Infectious Diseases.

Using a database of privately insured US patients, researchers from Brigham and Women's Hospital, Harvard Medical School, and Northwestern University's Feinberg School of Medicine found that of 22.3 million outpatient antibiotic prescriptions issued from Apr 1, 2016, through Jun 1, 2018, 31% (6.9 million) were non–visit-based, and 22% (4.9 million) were associated with a clinician visit that did not involve an infection-related diagnosis. Compared with children, adults had over twice as high a proportion of antibiotic fills that were not visit-based (34% vs 16%) and had higher rates of non-infection-related prescriptions.

A comparison across clinician specialties showed that the highest non–visit-based prescribing rate was among medical/surgical specialists (38%), followed by internists (28%) and family practitioners (20%), and the lowest rates were among pediatricians (10%) and nurses (16%).

In multivariable modeling, non–visit-based prescribing was associated with increasing patient age, with the odds of a non–visit-based prescription increasing 1% for each year of age, and was less likely for patients in the South, patients with more baseline clinical visits, and those with chronic lung disease.

The study authors note that the findings are similar to a study they conducted using older Medicaid data, as well as smaller prior studies, which suggests that non–visit-based and non–infection-related prescribing remains a problem.

"Prescriptions issued and filled in the absence of an in-person visit or without documentation of an infection raise particular problems, since antibiotic stewardship interventions may not reach the prescribing clinician at the time when a decision is being made," they wrote.

They add that further analysis is needed to identify the clinical decision points at which stewardship interventions could make a difference.
Aug 1 Open Forum Infect Dis abstract