Data from China suggest no survival benefit of two antiviral drugs in elderly COVID patients

News brief
Older patient in dark hospital room
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An observational study in eClinicalMedicine suggests that the antiviral drugs azvudine and nirmatrelvir/ritonavir (Paxlovid) were similarly ineffective in preventing death in elderly patients hospitalized for COVID-19 in China, although the authors acknowledge that the findings may be subject to confounding factors and bias.

Azvudine has conditional approval for treatment of viral diseases such as COVID-19 and AIDS in China but isn't approved for use in the United States, where Paxlovid is approved for treatment of mild or moderate COVID-19 in high-risk adults.

Researchers from the Chinese PLA General Hospital in Beijing evaluated the electronic medical records of 249 COVID-19 patients with an average age of 91.4 years hospitalized in December 2022 and January 2023. Of all patients, 128 received azvudine, 66 were given Paxlovid, and 55 received no antiviral. Average follow-up was 84 days.

"The proportion of severe illness and death caused by COVID-19 among the elderly is the highest among all age groups, and elderly patients are commonly accompanied by multi-disease and multi-reuse drugs," the study authors noted, adding that caution must be taken when prescribing drugs for these patients.

Potential confounding factors, bias

A total of 77 patients (31%) died during follow-up. Neither antiviral demonstrated a survival benefit, with a Cox analysis of all-cause death showing a 0.73 risk of death in the azvudine group and 0.80 in Paxlovid recipients compared with no antiviral treatment.

The proportion of severe illness and death caused by COVID-19 among the elderly is the highest among all age groups, and elderly patients are commonly accompanied by multi-disease and multi-reuse drugs.

The researchers noted several potential reasons for the lack of clinical benefit, including the advanced age, chronic illness burden, and disease severity among participants and inadequate study power to detect differences.

"Finally, the cause of selection bias cannot be ruled out because patients with more severe clinical presentations may have been preferentially selected by clinicians to receive nirmatrelvir/ritonavir," they wrote. "In that case, patients who received nirmatrelvir/ritonavir would be expected to have worse outcomes, which could obscure a potential therapeutic benefit of nirmatrelvir/ritonavir."

CDC tracking BA.2.87.1 SARS-CoV-2 variant

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The Centers for Disease Control and Prevention (CDC) recently announced that it is monitoring a newly identified SARS-CoV-2 variant called BA.2.87.1 from South Africa that has mutations that may pose a risk of immune escape, but so far there's no sign that it is spreading widely.

SARS-CoV-2 virus
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South African scientists have identified nine BA.2.87.1 sequences in samples that were collected between September and December of 2023. No cases have been identified outside of South Africa. "The fact that only nine cases have been detected in one country since the first specimen was collected in September suggests it does not appear to be highly transmissible – at least so far," the CDC said in a February 9 statement.

South African cases reported from three provinces

In South Africa, though, the cases were reported from three provinces over 3 months, suggesting that BA.2.87.1 can spread among people, the CDC said.

The CDC said it is monitoring BA.2.87.1 because it has more than 30 changes in the spike protein compared to XBB.1.5, the variant covered by the current monovalent vaccine. The CDC said variants with multiple spike protein changes could increase the potential for immune escape from earlier infection or vaccination. Experience with BA.2.86 and its JN.1 offshoot was a reminder that a variant's ability to transmit can change quickly over time.

BA.2.87.1 isn't fueling a detectable increase in South Africa's COVID cases, the CDC said. So far, it's not clear how well the current vaccine would protect against BA.2.87.1, but the group added that recent experience with the JN.1 variant suggests that the current COVID vaccine can help protect against a diverse range of variants.

The European Centre for Disease Prevention and Control (ECDC) is also tracking BA.2.87.1 as a variant under monitoring (VUM).

Chinese study finds excessive antibiotic use for chronic obstructive pulmonary disease

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A large-scale, population-based study in China reports that chronic obstructive pulmonary disease (COPD) patients were nearly eight times more likely to use antibiotics than the general population and received nearly twice as many antibiotic prescriptions, researchers reported late last week in the Journal of Antimicrobial Chemotherapy.

Using prescription data and survey responses from participants aged 40 years and older in a cohort of residents from Shanghai's Songjian District, researchers with Fudan University assessed correlations between COPD, the percentage of antibiotic use, and the average rate of prescribing of different types of antibiotics compared with the general population. While antibiotics are commonly used to manage acute exacerbations of COPD in China, there are concerns that some of this use is inappropriate and that frequent antibiotic use in COPD patients is creating a vicious cycle of antimicrobial-resistant infections that require more antibiotics.

High-priority group for stewardship efforts

A total of 34,576 people were included in the study, 1,594 (4.6%) of whom were COPD patients. Over 6 years of follow-up, the percentage of antibiotic use for COPD patients was 98.4%, which was 7.88 (95% confidence interval [CI], 5.24 to 11.85) times that for non-COPD patients after adjusting for potential confounders. The prescribing rate was 3,220 prescriptions per 1,000 person-years for COPD patients, which was 1.96 (95% CI, 1.87 to 2.06) times that for non-COPD patients.

Macrolides, lincosamides, streptogramins, quinolones, and other beta-lactams were the most commonly used antibiotics by COPD patients. Except for aminoglycosides, both the percentage of antibiotic use and the rate of antibiotic prescribing for all antibiotics were increased in COPD patients, who were 1.34 (95% CI, 1.20 to 1.50) times more likely to be prescribed a maximum of two antibiotics and 2.77 (95% CI, 2.47 to 3.11) times more likely to use antibiotics intravenously.

The study authors say the findings suggest COPD patients are a high-priority group for the management of antibiotic use in communities.

Study: COVID-19 raises risk of heart attack in HIV patients

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A large study in Spain finds that COVID-19 is associated with a 30% increased risk of major cardiovascular events in people with HIV during the year following infection. The study is published in Clinical Microbiology and Infection.

Using a population of people in Catalonia with HIV (PWH) who had a documented COVID-19 infection, plus PWH with no COVID infections, the authors of the study estimated the incidence rate (IR) of a first cardiovascular event (CVE) after COVID-19 during an average follow-up period of 243 days.

Included were 4,199 PWH with and 14,004 PWH without COVID-19 infections, 82% of all study subjects were men, and the average age was 47. Overall, 211 PWH with COVID-19 and 621 without developed CVE, the authors said, with an IR of 70.2 and 56.8 per 1,000 person-years, respectively.

Even mild infections pose risk

COVID-19 was associated with a 30% increased subsequent risk of CVE (adjusted hazard ratio, 1.30; 95% confidence interval, 1.09 to 1.55). Risk was highest in the 6 months following acute infection, and there was no association with COVID-19 severity and subsequent CVE, suggesting that even mild to moderate infections increased the risk.

"Even while the absolute rates of CVE in PWH have significantly declined in recent years, they continue to have a 1.5-2-fold greater relative risk compared to individuals without HIV," the authors wrote. "Therefore, the confirmation that the incidence of major CVE is increased the year following COVID-19 in PWH, including those non-hospitalized or without prior CVE, deserves major awareness."

The authors said reasons for the increased risk are unknown and multifactorial. Earlier studies have suggested PWH have elevated levels of T-cell and inflammatory markers after COVID-19.

Cambodia reports fourth H5N1 avian flu case of the year

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Cambodia has reported its fourth human H5N1 avian flu case of the year, the brother of a 9-year-old boy who recently died from his H5N1 infection, according to a statement from the country's health ministry that was translated and posted by Avian Flu Diary, an infectious disease news blog.

H5N1 virus particles
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The latest confirmed case is a 16-year-old boy who didn't have respiratory symptoms. The boy and his deceased younger brother are from Kratie province in northeastern Cambodia. The health ministry didn't say if the teen had any other symptoms, but it said it continues to track contacts and has distributed oseltamivir to close contacts of confirmed cases.

Earlier report noted poultry deaths

The current statement didn't have any details about the teen's exposure. The ministry statement last week announcing his brother's illness and death said poultry had died at the patient's home and that dead birds were eaten.

Cambodia has now reported 10 human H5N1 cases since 2023, part of rise in cases that follows a decade-long lapse in cases. The country's recent cases have involved an older H5N1 clade (2.3.2.1c) that is known to circulate in the country's poultry. It is different than the newer H5N1 clade (2.3.4.4b) that is circulating widely in wild birds and poultry in multiple world regions, with sporadic detections in mammals and humans.

Quick takes: Listeria recalls expand, CDC mpox vaccine reminder, Oregon plague case

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  • Several US food companies have issued recalls because they contain cheese and dairy ingredients made by a California company at the center of an investigation into a multistate Listeria monocytogenes outbreak. In an outbreak update, the Centers for Disease Control and Prevention lists 61 foods on a recall list, which include the earlier recalled products from Rizo-Lopez Foods, plus several other products from other companies that used Rizo-Lopez Food ingredients. The list of foods containing potentially tainted ingredients includes items such as meal kits, salad kits, layered tips, and salad dressings. The number of outbreak illnesses remains at 26 cases, 2 of them fatal, from 11 states.
  • Though mpox cases in the United States have declined sharply since the outbreak peak in the summer of 2022, small clusters of cases continue to be reported, prompting a vaccination reminder today from the Centers for Disease Control and Prevention (CDC). In October 2023, the CDC recommended that people in risk groups ages 18 and older receive two doses of the Jynneos vaccine to reduce the risk of continued transmission. However, in a Clinician Outreach and Communication Activity (COCA) e-mail notice today, the CDC said only one in four of the approximately 2 million eligible people have received two doses. It urged clinicians to remain diligent about taking patients' sexual histories and recommending Jynneos to those who are eligible. A recent surveillance update said 169 mpox cases have been reported in US so far this year.
  • In Oregon, public health officials in Deschutes County have reported a human plague infection in a person who likely contracted the disease from his or her symptomatic pet cat. The case marks Oregon's first human plague case since 2015, according to a statement. The patient's illness was identified early in the disease, posing a low risk to the community. A report from NBC News quoting a county health official said the patient was hospitalized with a draining abscess that progressed to the bloodstream but has responded well to antibiotic treatment. Investigators have found no other cases. The disease can spread to people or animals through a bite from an infected flea or contact with an animal infected with Yersinia pestis. In central Oregon, the animals most likely to carry plague are squirrels and chipmunks, but mice and other rodents can all carry the bacteria.

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