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Research in brief

Full-dose anticoagulation in COVID-19 patients Full-dose anticoagulation lowers the risk of blood-clotting complications compared with standard-dose prophylactic anticoagulation, according to a clinical trial in critically ill COVID-19 patients across the USA. The study did not include a control group, and the time from symptom onset to starting antiviral therapy varied among the patients. For more on baseline SARS-CoV-2 antigen levels and illness severity see Ann Intern Med 2022;published online Aug 30. https://doi.org/10.7326/m22-0924 For more on full-dose anticoagulation and COVID-19 see Circulation 2022;published online Aug 29. https://doi.org/10.1161/circulationaha.122.061533 For more on COVID-19 antiviral combinations see J Infect 2022;published online July 31. https://doi.org/10.1016/j.jinf.2022.07.023 For more on dolutegravir-based ART and pregnancy see N Engl J Med 2022;387: 799–809 For more on HBV and HDV treatment see Gut 2022;published online Aug 17. https://doi.org/10.1136/gutjnl-2022-327216 For more on tecovirimat and monkeypox see JAMA 2022;published online Aug 22. https://doi.org/10.1001/jama.2022.15336 For more on an injectable tuberculosis treatment see Nat Commun 2022;13: 4455

Baseline SARS-CoV-2 antigen levels linked to illness severity A study has found that the amount of SARS-CoV-2 antigen measured in the blood of patients hospitalised with COVID-19 is associated with illness severity and other clinical outcomes. High blood antigen levels also correlated with some known risk factors for worse illness, such as being male. The ACTIV-3 trial enrolled people hospitalised with COVID-19 between August, 2020, and November, 2021, in the USA. Participants contributed a baseline blood sample and were then randomly assigned to receive either an experimental COVID-19 therapeutic or placebo. All participants received the antiviral remdesivir unless contraindicated. In this followup analysis, researchers examined 2540 participant baseline blood samples for SARS-CoV-2 antigen levels.

Full-dose anticoagulation in COVID-19 patients
Full-dose anticoagulation lowers the risk of blood-clotting complications compared with standard-dose prophylactic anticoagulation, according to a clinical trial in critically ill COVID-19 patients across the USA. In 390 patients who were randomly assigned to an anticoagulation course, the risk of venous or arterial clotting complications was 44% lower among patients who received the full dose compared with the standard dose. Fatal or life-threatening bleeding, the primary safety endpoint, occurred in four patients in the full-dose group compared with one patient in the standard-dose group.

COVID-19 antiviral combinations show promise
Researchers have found promising new antiviral combination therapies against COVID-19 in cell culture experiments. They tested the sensitivity of different SARS-CoV-2 omicron and delta viruses to combinations of the four currently approved antiviral drugsremdesivir, molnupiravir, nirmatrelvir, and aprotinin-with interferon beta 1b, an antiviral naturally produced in the body. They found that interferon combinations with molnupiravir, nirmatrelvir, and aprotinin were much more effective than interferon combinations with remdesivir. The researchers said interferon combinations with the other three antivirals should be clinically tested.

Dolutegravir-based ART effective in pregnancy
A study has found that dolutegravirbased antiretroviral therapies (ARTs) for HIV-1 were more effective in pregnant people than some other ART regimens. The observational study compared dolutegravir use in pregnancy with atazanavir-ritonavir, darunavirritonavir, raltegravir, and elvitegravircobicistat, which are commonly used ART regimens in the USA and Europe. About half of the participants started ART before conception. At delivery, 96·7% of participants who received dolutegravir were virally suppressed, compared with 84·0%, 90·1%, 89·2%, and 89·8% of those who received atazanavir-ritonavir, darunavirritonavir, raltegravir, and elvitegravircobicistat, respectively. Limited data are available on the effectiveness and safety of dolutegravir in pregnancy, a once-daily regimen that has been shown to be less likely to induce resistance than other ARTs.

Potential new treatment against HBV and HDV
A new treatment against both hepatitis B virus (HBV) and hepatitis D virus (HDV) has shown good results in animal models. The treatment has two stages: a DNA-based vaccine is administered that activates antibodies and T cells against both viruses, and then repeated doses of a proteinbased vaccine are given. When the treatment was given to mice carrying parts of HBV and HDV, which resembles chronic HBV infection, the animals produced antibodies and T cells at high levels. Also, antibodies from treated mice were able to protect mice carrying human liver cells against simultaneous infection with HBV and HDV, and these antibodies were able to protect mice with chronic HBV infection against HDV infection.

Tecovirimat potentially effective for monkeypox
The antiviral tecovirimat appears to be effective in the treatment of monkeypox symptoms and skin lesions based on research in 25 patients with monkeypox who were given the antiviral. On average, patients in the study had symptoms or lesions for 12 days before starting antiviral treatment. Patients were treated for 2 weeks, except for one patient who was treated for 21 days. On day 7 of therapy, 40% of patients had healed lesions. By day 21, 92% had healed and were painfree. The study did not include a control group, and the time from symptom onset to starting antiviral therapy varied among the patients.

Long-lasting injectable tuberculosis treatment
A long-acting injectable formulation of the antituberculosis drug rifabutin has been developed, and in animals models one injection was shown to last for at least 4 months. The current standard treatment requires a daily drug regimen. Researchers combined rifabutin with biodegradable polymers and non-toxic solvents that solidify in the body after subcutaneous injection and they added a compound to increase the amount of rifabutin that could be included. In mouse models, a solidified implant slowly eroded over the course of 16 weeks. It also prevented infection in mice that were exposed to tuberculosis.