Rates of COVID-19 rebound were similar among hospitalized patients infected with the Omicron BA.2.2 variant who did and didn't receive oral antiviral drugs, and relapse wasn't tied to worse clinical outcomes, suggests a study published yesterday in The Lancet Infectious Diseases.

Rebound is a re-emergence of symptoms and an uptick in viral load after a period of recovery. The antiviral drug nirmatrelvir-ritonavir (Paxlovid) was associated with COVID-19 rebound in some previous research, while some newer research has concluded that it is not unique to Paxlovid.

This University of Hong Kong–led study evaluated rates of viral rebound and death, intensive care unit (ICU) admission, and mechanical ventilation among 4,592 adults who didn't require supplemental oxygen from Feb 26 to Jul 3, 2022.

Participants were hospitalized within 3 days of COVID-19 diagnosis and were receiving Paxlovid or the antiviral drug molnupiravir twice daily for 5 days, or no antiviral treatment.

Risk factors for rebound

Viral rebound occurred in 16 of 242 (6.6%) of patients given Paxlovid, 27 of 563 (4.8%) of molnupiravir recipients, and 170 of 3,787 (4.5%) of untreated participants. Impaired immune status was a risk factor for viral rebound, regardless of treatment status (Paxlovid odds ratio [OR], 7.37; molnupiravir OR, 3.05; control, 2.21).

Risk factors for rebound among Paxlovid recipients included age 18 to 65 years (OR, 3.09), greater chronic condition burden (OR, 6.02), and simultaneous receipt of corticosteroids (OR, 7.51).

Viral rebound was not tied to increased probability of death, ICU admission, or mechanical ventilation.

Among molnupiravir recipients, increased odds of rebound were linked to age 18 to 65 years (OR, 2.68) and concomitant corticosteroids (OR, 3.11). Viral rebound was not tied to increased probability of death, ICU admission, or mechanical ventilation (Paxlovid adjusted OR [aOR], 1.90; molnupiravir aOR, 1.05; no treatment aOR, 1.27).

The study "emphasises the importance of continuing to offer antivirals to individuals with COVID-19 who are at increased risk of progression to severe COVID-19," Nicola Petrosillo, MD, of Rome's Fondazione Policlinico Universitario, said in a related commentary.

The World Health Organization (WHO) has abandoned plans for the second phase of its study into the origins of the SARS-CoV-2 virus because of challenges it faced doing key studies in China, Nature reported today, citing Maria Van Kerkhove, PhD, the WHO's technical lead for COVID-19.

An international team led by the WHO spent 4 weeks in China in January 2021 investigating the source of the virus. They published their full findings in March 2021, which covered four possibilities, with a jump to humans from an intermediate animal carrier most likely. While pressing China for more transparency, the group planned on doing a second phase of the study.

The study into the origins of the virus, however, has been hampered by multilayered political tensions. In July, the WHO sent a proposed outline for the second phase of the study to China, which included sampling at wild-animal markets and audits of labs in the Wuhan area, but China rejected the plans, according to Nature.

Bat sampling continues

Other efforts are still under way to learn new clues about the initial spread, such as sampling in bats, as well as testing of archived wastewater and blood samples, Nature reported, adding that researchers say too much time has passed to gather some data that would help better identify the source.

On Twitter today, Peter Daszak, PhD, who was part of the earlier WHO joint mission and is the president of EcoHealth Alliance, said, intense politicization derailed phase 2 of the study. "A constant barrage of media harassment, driven by polarized politics has effectively halted scientific progress. We're left with ZERO new data - just intrigue, rumor, hearsay & vindictive political posturing."

In the summer of 2021, the WHO established a permanent group called the Scientific Advisory Group for Origins of Novel Pathogens (SAGO) to continue the search for the source of SARS-CoV-2 and other novel pathogens.

The company said the trial is also intended to support licensing in Europe and Brazil.

Regional health officials in Cameroon today announced that two suspected Marburg cases have been identified, both of whom live in the same community that borders Equatorial Guinea, which declared an outbreak yesterday.

Reuters, quoting a regional health official who took part in a meeting today in Cameroon's capital, said the two suspected case-patients are a boy and a girl, both 16 years old. Neither had traveled to Equatorial Guinea. Authorities have identified 42 of their contacts, and further contact tracing is under way.

Yesterday the World Health Organization (WHO) detailed a Marburg outbreak in Equatorial Guinea, the country's first, with 9 deaths and 16 suspected cases reported. So far, one of eight samples tested in Senegal was positive for Marburg virus, a close relative of Ebola. The virus cases a hemorrhagic fever similar to Ebola.

Emergency meeting

The WHO today convened an emergency meeting of its Marburg experts to review possible vaccines and treatments and look at research priorities for Equatorial Guinea's outbreak.

No approved vaccines or treatments exist, but two vaccines are in phase 1 clinical trials. One vaccine is from the Sabin Vaccine Institute and the other from Janssen (Johnson & Johnson).

In West Africa's Ebola outbreak, advanced clinical trials took place for Merck's VSV-EBOV vaccine, which was found to be highly effective. In Uganda's recent Sudan Ebola outbreak, officials had hoped to do similar trials for candidate vaccines against that subtype, but cases  declined rapidly before the studies could begin.

Decades of conflict in Iraq have contributed to a "catastrophic" rise in antimicrobial resistance (AMR) in the country, according to a commentary published yesterday in BMJ Global Health.

In a review of literature on AMR and wars in Iraq going back to the 1980s, a team led by researchers with the American University of Beirut explore the underinvestigated role that these conflicts have played in spiking rates of resistance in pathogens such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae in Iraq. They note that while war and the treatment of soldiers' injuries with antibiotics have been implicated in the emergence of AMR as far back as the 1940s, current armed conflicts and the resistance-inducing properties of non-antibiotic antimicrobials, such as heavy metals used in ammunition and explosives, need further exploration.

"Contemporary conflicts, waged in urban and industrialised landscapes, pressure microbes with selective environments that contain unique combinations and concentrations of toxic heavy metals and antibiotics, while simultaneously providing niches and dissemination routes for microbial pathogens," the authors wrote.

Looking at literature from the Iran-Iraq war (1980-1988) through the US invasion and occupation (2003-2011) and the ISIS conflict (2014-2017), the authors conclude that this selective pressure has been exacerbated by the high number of wounded soldiers and civilians, the use of broad-spectrum antibiotics for war wounds, the dismantling of healthcare infrastructures, the loss of healthcare workers, the deterioration of infection control measures, and lack of access to proper water, sanitation, and hygiene (WASH).

"Taken together, a destroyed healthcare infrastructure, inappropriate microbial therapies, limited resources, high heavy metal contamination in humans and the environment, and lack of WASH, combined, likely play instrumental roles in the catastrophic rise of AMR in Iraq and, by extension, regionally and globally," they wrote.

The authors say clinical, microbiologic, ethnographic, and environmental research is needed to conclusively establish the role that these multiple conflicts have played in the rise of multidrug-resistant organisms, and that understanding these links is essential for global response.

The Pan American Health Organization (PAHO) yesterday issued an epidemiologic alert about elevated chikungunya activity in the Americas, which urged countries to prepare their healthcare systems to handle the medical management of it and other mosquito-borne diseases.

The group said cases were up sharply in 2022 compared to the previous year, with 13 countries reporting chikungunya infections. There were more than 271,000 illnesses last year, 95 of them fatal. For comparison, the region reported about 137,000 cases in 2021, 12 if them fatal. During the first 4 weeks of 2023, PAHO received reports of 30,707 cases, including 14 deaths.

PAHO warned that countries in the Southern Cone will face summer temperatures in the first half of 2023, which could put an increased arbovirus burden on health systems in affected areas. Another factor is a lot of susceptible people, given that the last large outbreak occurred 8 years ago, in 2014.

Chikungunya is spread by Aedes aegypti and Aedes albopictus mosquitoes, which are common in the Americas and also carry dengue virus. The main symptoms are joint pain, which can persist. The disease isn't typically fatal, but vulnerable groups such as newborns and seniors are at higher risk for severe disease.

There are currently no vaccines or treatments.

Chikungunya vaccine trial enrollment

Valneva, a pharmaceutical company based in France, today announced that it completed enrollment for the phase 3 trial of its candidate single-dose chikungunya vaccine. The trial will take place in 754 adolescents in Brazil, and the first results are expected in the middle of 2023.

The trial, funded by the Coalition for Epidemic Preparedness and Response (CEPI), is intended to support a label extension for a possible initial regulatory approval from the US Food and Drug Administration (FDA). The company completed a rolling submission to the FDA in December 2022.