A new study based on surveys collected as part of the COVID Symptom Study Biobank in the United Kingdom suggests that generalized joint hypermobility (GJH), commonly known as being double jointed, may be linked to developing long COVID.

The connective tissue disorder is often thought of as a benign condition, but the authors said these findings suggest it may reflect a genotype more susceptible to fatigue and post-viral sequelae.

The survey was conducted in August 2022 and included 3,064 participants, of whom 81.4% reported ever having COVID-19. The survey respondents also completed a self-report questionnaire to detect GJH. Of the respondents who had COVID, 914 (37%) said they had not fully recovered from their last bout of COVID-19, and, of these, 269 (29%) had GJH.

Joint hypermobility tied to fatigue

While any COVID-19 infection was not associated with having GJH, GJH was significantly associated with non-recovery from COVID-19 at an adjusted odds ratio of 1.33 (95% confidence interval, 1.10 to 1.61).

GJH was also associated with increased levels of fatigue, one of the hallmark symptoms of long COVID.

An individual with GJH (an index of variant connective tissue structure) was approximately 30% more likely not to have recovered after initial COVID-19 infection

"In this large population-based study, an individual with GJH (an index of variant connective tissue structure) was approximately 30% more likely not to have recovered after initial COVID-19 infection," the authors said. "We propose that this linked through the fatigue level, suggesting that GJH may represent a subtype of those with persistent symptoms from COVID-19."

Nearly 7,000 excess tuberculosis (TB) deaths occurred in Europe in 2021 and 2022, during the COVID-19 pandemic, according to a report today from the World Health Organization (WHO) and the European Centre for Disease Prevention and Control (ECDC).

WHO and ECDC officials attribute the excess TB deaths that occurred in the WHO European Region from 2020 through 2022 to pandemic-related disruptions to TB services, which resulted in more people with undiagnosed and untreated TB. Had the pandemic not occurred, they said, TB mortality likely would have continued on the downward trend that began in 2013.

The overall TB death rate in the region fell overall 53% from 2013 through 2022, with an average decline of 8% per year, but it increased in 2021 and remained stable in 2022.

"Our latest report reveals a heart-breaking, entirely preventable situation—people affected by TB were not protected during the pandemic and 7,000 needlessly lost their lives because of disruptions to TB services," Hans Henri Kluge, MD, MPH, director of the WHO's European regional office, said in an ECDC press release.

Drug-resistant TB, low cure rates

The report also shows that while rifampicin-resistant/multidrug-resistant (RR/MDR)-TB cases fell by 6% from 2021 to 2022, the proportion of RR/MDR-TB among new (24%) and previously treated (54%) TB cases in the region exceeds the global average (3.3% and 17%, respectively).

In addition, on average of only 6 out of 10 and 7 out of 10 TB treatments using first-line medications cured the infection in European Union/European Economic Area and WHO European Region countries, respectively—the lowest rates observed in a decade and a possible sign of issues with treatment compliance and monitoring.

On a positive note, the more than 170,000 TB cases reported in the region in 2022 represented a 3.1% increase in the number of notified TB patients compared with 2021, a second year of recovery following a 24% drop in TB notifications in 2020. WHO and ECDC officials say this indicates TB services are recovering from the pandemic.

The officials say countries need to strengthen TB prevention, testing, and treatment services to get back on track.

A study conducted in four Nordic countries found that receipt of the measles, mumps, and rubella (MMR) vaccine was associated with an 11% reduced rate of antibiotic use in children under 2, researchers reported yesterday in the journal Vaccine.

Using national registries, Nordic researchers analyzed a cohort of 831,287 children under the age of 2 years in Denmark, Finland, Norway, and Sweden who had received a third dose of the diptheria-tetanus-acellular pertussis vaccine (DTaP) but had not yet received the MMR vaccine. They then investigated whether receipt of the MMR vaccine after a third DTaP dose was associated with reduced rates of antibiotic use compared with three DTaP doses.

The proportion of children in the study who had received a recorded dose of MMR vaccine before age 2 ranged from 78.6% in Finland to 96.2% in Norway. In all countries, receipt of MMR vaccine after the third DTaP dose was associated with reduced rates of antibiotic treatment, with an adjusted hazard ratio (aHR) of 0.92 (95% confidence interval [CI], 0.91 to 0.93) in Denmark, 0.92 (95% CI, 0.90 to 0.94) in Finland, 0.84 (95% CI, 0.82 to 0.85) in Norway, and 0.87 (95% CI, 0.85 to 0.90) in Sweden. The overall aHR for all countries was 0.89 (95% CI, 0.85 to 0.83). The results were similar for boys and girls.

Bias may explain some of the association

But the researchers also observed a lower rate of antibiotic treatments among children who had received three DTaP doses compared with two, with reductions ranging from 14% in Denmark to 29% in Sweden. The findings of this negative control analysis, they say, suggests the lower rate of antibiotic treatment associated with receipt of MMR vaccine is affected by residual confounding.

"The magnitude of the association in the negative control analysis does indicate that bias related to receiving vaccines according to recommendation may at least partly account for the observed beneficial association of MMR vaccination," the study authors wrote.

Noting that the Defense Logistics Agency (DLA) categorizes 27% of drugs on the US Food and Drug Administration's (FDA's) Essential Medicines List as "very high risk," a bipartisan group of senators has asked the Department of Defense (DoD) to release information on the implementation of measures to reduce risks to the military pharmaceutical supply chain.

In a March 18 letter to DoD Secretary Lloyd Austin III, a group led by Senators Elizabeth Warren (D-Mass) and Marco Rubio (R-Fla) asks the DoD to describe its progress in implementing Section 860 of the Fiscal Year 2023 National Defense Authorization Act (NDAA).

The NDAA stemmed from Warren and Rubio's Strengthening Supply Chains for Servicemembers and Security Act, which directed the DoD to develop guidelines for risk management of its pharmaceutical supply chain, report on supply chain risks, and establish a working group to develop policies for scarce-drug allocation.

Quality failures, single-source drugs, overseas plants

Reasons behind the shortages include quality failures, single-manufacturer drugs and ingredients, and the overseas location of a high proportion of drug makers supplying the US market—58% in 2022. "This exposes the drug supply chain to potential safety risks, as federal regulators have a reduced ability to conduct oversight in India, China, and other foreign countries," the senators wrote.

They cited a recent report that said, "Some generic versions of [tacrolimus, an immune suppressant given to prevent organ rejection], given to soldiers who have lost limbs in combat, might not work." Intas Pharmaceuticals, tacrolimus's Indian manufacturer, was also responsible for shortages of cancer drugs after an FDA investigation found serious deficiencies, forcing the plant to close, the letter noted.

This exposes the drug supply chain to potential safety risks, as federal regulators have a reduced ability to conduct oversight in India, China, and other foreign countries.

In addition to information on remediation actions, the senators asked the DoD to detail by April 1 all military supply chain disruptions, disclose whether it intends to release the findings of the Report on the Department of Defense Pharmaceutical Supply Chain Risks, and provide an update on the implementation of responsiveness testing of the DLA's contingency contracts for medications.