Health outcomes 3 months and 6 months after molnupiravir treatment for COVID-19 for people at higher risk in the community (PANORAMIC): a randomised controlled trial

Background: No randomised controlled trials have yet reported on the effectiveness of molnupiravir on longer term outcomes for COVID-19. The PANORAMIC trial found molnupiravir reduced time to recovery in acute COVID-19 over 28 days. We aimed to report the effect of molnupiravir treatment for COVID-19 on wellbeing, severe and persistent symptoms, new infections, health care and social service use, medication use, and time off work at 3 months and 6 months post-randomisation. Methods: This study is a follow-up to the main analysis, which was based on the first 28 days of follow-up and has been previously reported. For this multicentre, primary care, open-label, multi-arm, prospective randomised controlled trial conducted in the UK, participants were eligible if aged at least 50 years, or at least 18 years with a comorbidity, and unwell 5 days or less with confirmed COVID-19 in the community. Participants were randomly assigned to the usual care group or molnupiravir group plus usual care (800 mg twice a day for 5 days), which was stratified by age (<50 years or ≥50 years) and vaccination status (at least one dose: yes or no). The primary outcome was hospitalisation or death (or both) at 28 days; all longer term outcomes were considered to be secondary outcomes and included self-reported ratings of wellness (on a scale of 0–10), experiencing any symptom (fever, cough, shortness of breath, fatigue, muscle ache, nausea and vomiting, diarrhoea, loss of smell or taste, headache, dizziness, abdominal pain, and generally feeling unwell) rated as severe (moderately bad or major problem) or persistent, any health and social care use, health-related quality of life (measured by the EQ-5D-5L), time off work or school, new infections, and hospitalisation. Findings: Between Dec 8, 2021, and April 27, 2022, 25 783 participants were randomly assigned to the molnupiravir plus usual care group (n=12 821) or usual care group (n=12 962). Long-term follow-up data were available for 23 008 (89·2%) of 25 784 participants with 11 778 (91·9%) of 12 821 participants in the molnupiravir plus usual care group and 11 230 (86·6%) of 12 963 in the usual care group. 22 806 (99·1%) of 23 008 had at least one previous dose of a SARS-CoV-2 vaccine. Any severe (3 months: adjusted risk difference –1·6% [–2·6% to –0·6%]; probability superiority [p(sup)]>0·99; number needed to treat [NNT] 62·5; 6 months: –1·9% [–2·9% to –0·9%]; p(sup)>0·99, NNT 52·6) or persistent symptoms (3 months: adjusted risk difference –2·1% [–2·9% to –1·5%]; p(sup)>0·99; NNT 47·6; 6 months: –2·5% [–3·3% to –1·6%]; p(sup)>0·99; NNT 40) were reduced in severity, and health-related quality of life (measured by the EQ-5D-5L) improved in the molnupiravir plus usual care group at 3 months and 6 months (3 months: adjusted mean difference 1·08 [0·65 to 1·53]; p(sup)>0·99; 6 months: 1·09 [0·63 to 1·55]; p(sup)>0·99). Ratings of wellness (3 months: adjusted mean difference 0·15 (0·11 to 0·19); p(sup)>0·99; 6 months: 0·12 (0·07 to 0·16); p(sup)>0·99), experiencing any more severe symptom (3 months; adjusted risk difference –1·6% [–2·6% to –0·6%]; p(sup)=0·99; 6 months: –1·9% [–2·9% to –0·9%]; p(sup)>0·99), and health-care use (3 months: adjusted risk difference –1·4% [–2·3% to –0·4%]; p(sup)>0·99; NNT 71·4; 6 months: –0·5% [–1·5% to 0·4%]; p(sup)>0·99; NNT 200) had high probabilities of superiority with molnupiravir treatment. There were significant differences in persistence of any symptom (910 [8·9%] of 10 190 vs 1027 [11%] of 9332, NNT 67) at 6 months, and reported time off work at 3 months (2017 [17·9%] of 11 274 vs 2385 [22·4%] of 10 628) and 6 months (460 [4·4%] of 10 562 vs 527 [5·4%] of 9846; NNT 100). There were no differences in hospitalisations at long-term follow-up. Interpretation: In a vaccinated population, people treated with molnupiravir for acute COVID-19 felt better, experienced fewer and less severe COVID-19 associated symptoms, accessed health care less often, and took less time off work at 6 months. However, the absolute differences in this open-label design are small with high numbers needed to treat

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial

Background: The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population. Methods: PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031. Findings: Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir. Interpretation: Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial

BackgroundThe safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population.MethodsPANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031.FindingsBetween Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir.InterpretationMolnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community

Thermolytic Grafting of Polystyrene to Porous Silicon

Inert-atmosphere thermolysis of polystyrene, preloaded into a porous silicon (pSi) template, generates a composite in which styrenic fragments are chemically grafted via Si C bonds to the surface of the pore walls. The quantity of styrenic material in the pores, and thus the final porosity of the composites, is controlled by the amount of polystyrene initially loaded into the pSi host and the time and temperature of thermolysis. For a host template with a porosity of 64 +/- 1%, the porosity of the resulting composite can be varied from 10 to 50%. The composites are significantly more hydrophobic than bulk polystyrene, displaying water contact angles ranging from 110 to 138 degrees compared to a value of 89 for a pure polystyrene film. The contact angle follows the Cassie rule for porosity values up to 40%, increasing with increasing porosity. For composite porosity values >40%, the contact angle is observed to decrease, and this correlates with increasing silicon oxide content and a decrease in hydrophobicity. The stability of the grafted composite material in aqueous base (>pH 12) is enhanced with increasing styrenic content

Dynamic Motion of Organic Spacer Cations in Ruddlesden–Popper Lead Iodide Perovskites Probed by Solid-State NMR Spectroscopy

International audienceLayered hybrid organic–inorganic perovskites such as the lead halide Ruddlesden–Popper (RP) series are solution-processable two-dimensional (2D) materials with tunable optoelectronic properties. Dynamic interactions between the ionic perovskite substructure and organic spacer cations impact optoelectronic properties relevant for device applications. Here, the static and dynamic structures of linear alkylammonium and aromatic spacers in lead iodide RP phases (n = 1) are characterized at ambient temperatures using solid-state NMR (ssNMR) spectroscopy and compared with previously reported crystal structures derived from X-ray diffraction. Rigid and flexible sites of spacers are distinguished by examining 13C{1H} and 15N{1H} cross-polarization magic-angle spinning (CP-MAS) signal intensity build-up. Different trends in site-specific rigidity are observed for short and long alkylammonium spacers. Short spacers (e.g., butylammonium) are attached by strong affinity interactions to lead iodide octahedra, whereas longer spacers (e.g., dodecylammonium) are more rigid within the RP interlayer than near the octahedral surface. Phenethylammonium and butylammonium spacers are similarly rigid, and we estimate that the local reorientation time scale of phenyl rings is 10–100 μs by 2D 13C CP-variable contact (CP-VC) experiments. These ssNMR results indicate that the interplay between spacer interactions with lead iodide octahedra (Coulombic and hydrogen-bonding) and van der Waals forces between spacers is responsible for a variety of site-specific dynamics and local structural distortions at intermediate time scales (microsecond to millisecond). This study demonstrates a general method to characterize nanoscale structures and site-specific dynamics that contribute to structural and electronic disorder in functional optoelectronic RP phases

Layered Hybrid Lead Iodide Perovskites with Short Interlayer Distances

Layered hybrid perovskites comprise modular components that are individually highly tunable, resulting in materials with a range of structures and properties. In these layered materials, the usual assumption is of two-dimensional electronic behavior, because of the relatively large separations between the inorganic layers. Here, we report two layered hybrid lead iodide perovskites that possess unusually short interlayer distances: (IPA)_{2}(MA)Pb_{2}I_{7} and (ACA)(MA)PbI_{4} (IPA = isopropylammonium, MA = methylammonium, ACA = acetamidinium). These compounds are prepared from mixing small organic cations, where they crystallize in a Ruddlesden–Popper type structure and a structure with alternating cations in the interlayer space, respectively. The crystal structures are compared in detail with related structures, and electronic structures are analyzed using density functional theory based calculations. Time-resolved microwave conductivity measurements are employed to provide insight into charge transport in these compounds. This work exemplifies the unusual templating role of small organic cations in the layered halide compounds

Layered Hybrid Lead Iodide Perovskites with Short Interlayer Distances

Layered hybrid perovskites comprise modular components that are individually highly tunable, resulting in materials with a range of structures and properties. In these layered materials, the usual assumption is of two-dimensional electronic behavior, because of the relatively large separations between the inorganic layers. Here, we report two layered hybrid lead iodide perovskites that possess unusually short interlayer distances: (IPA)_{2}(MA)Pb_{2}I_{7} and (ACA)(MA)PbI_{4} (IPA = isopropylammonium, MA = methylammonium, ACA = acetamidinium). These compounds are prepared from mixing small organic cations, where they crystallize in a Ruddlesden–Popper type structure and a structure with alternating cations in the interlayer space, respectively. The crystal structures are compared in detail with related structures, and electronic structures are analyzed using density functional theory based calculations. Time-resolved microwave conductivity measurements are employed to provide insight into charge transport in these compounds. This work exemplifies the unusual templating role of small organic cations in the layered halide compounds

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial

Background The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population. Methods PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031. Findings Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir. Interpretation Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community