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."

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.

• Japan's Institute for Infectious Disease yesterday reported the country's first known case of human-to-human transmission of severe fever with thrombocytopenia syndrome (SFTS), a disease primarily spread by ticks but in very rare instances has spread from infected animals or people. Doctors described the findings yesterday in an online report that was translated and posted by FluTrackers, an infectious disease news message board. An emergency department (ED) doctor contracted the virus in April 2023 after evaluating a man in his 90s who had fever, lack of appetite, and difficulty moving. The medical team suspected SFTS, and the patient was hospitalized but died 3 days later. The ED doctor helped care for the patient in the hospital and had removed the patient's indwelling venous catheter. Eleven days after the ED visit, the doctor began having symptoms and tested positive for SFTS virus. He had no recent history of tick bites and didn't have pets.
• The umbrella group that manages the oral cholera vaccine stockpile yesterday called for urgent actions to slow an unprecedented multiyear global surge in cholera cases. In a statement, the International Coordinating Group (ICG) on Vaccine Provision said investments are needed to improve access to safe water, sanitation and hygiene, testing, and detecting outbreaks quickly. The group also said more efforts are needed to improve access to healthcare and fast-track more production of oral cholera vaccine, for which there is a severe shortage. Global production is estimated at between 37 million and 50 million doses this year but is still inadequate to meet supply. Currently, no new manufacturers are expected to come online before 2025. The hardest-hit countries include the Democratic Republic of the Congo, Ethiopia, Haiti, Somalia, Sudan, Syria, Zambia, and Zimbabwe.