Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Review of \u3ci\u3eThe Indian Southwest: 1580-1830: Ethnogenesis and Reinvention\u3c/i\u3e By Gary Clayton Anderson

This is the most lucid and detailed examination of the political economy of the Southern Plains. At the center of that economy roamed the buffalo; but once Europeans arrived, horses, cattle, firearms, captives, and manufactured goods helped power it. Bonds of kinship and reciprocity drew all peoples in and around the Southern Plains into it, including Pueblos and Spaniards in New Mexico; Spaniards and Mexicans in Texas; Jumanos, Apaches, Wichitas, and Comanches on the Plains; and Caddos and the French in Louisiana. Still, the Plains could be a hard environment, with long droughts and epidemics of European diseases, both of which decimated populations. For any single people to meet these challenges and dominate the economy would require it to change its society, its culture, and itself as well. Between 1580 and 1830, several peoples rose up to command the economy only to falter or be pushed aside. The Jumanos, an agricultural people of South Texas, controlled it initially but were absorbed by the Apaches, who first learned to use the horse to their advantage. The Nortefios (Wichitas and Caddos) drove the Apaches from the Plains. On their heels came the Comanches, who developed a high mobility and other societal changes, allowing them to dominate until 1830. And therein lay the paradox: to control the Southern Plains\u27s political economy meant being altered by it. Horses, guns, and manufactured goods- status goods -not only changed peoples\u27 physical culture, but brought about an increasingly stratified social structure. Seniors controlled status goods and only sparingly doled them out to juniors. Some Comanches possessed hundreds of horses, others none. The need for forage brought smaller bands. Men took more wives to tan more hides to acquire more status goods. The people themselves also changed through what Anderson terms ethnogenesis. Control required a large population, and to achieve this and replenish those killed by disease and drought Southern Plains peoples, particularly the Comanches, captured then assimilated a variety of other peoples. This political economy unraveled about 1830 as Americans and removed Indians entered the Plains. These people, geared toward agricultural capitalism, were unwilling to make kinship or uphold reciprocal obligations. Once again, Southern Plains Indians would have to remake themselves. Anderson has done strong, innovative work here, employing previously unused primary sources from France, Spain, and Mexico to bring new insights to the Indian Southern Plains. His volume sets the bar for future Plains histories

Strangers for family : gifts, reciprocity, and kinship in Caddoan-Euroamerican relations, 1685-1835

Vita.Prior to regular contact with Europeans, the Caddoans created a complex, hierarchical, and highly organized society which participated in a far-flung trade with other native peoples. As they came into contact with other Indians, the Caddoans' kin-ordered mode of production allowed them to incorporate these strangers and their goods into Caddoan society. In their lands in what became Louisiana, Texas, Arkansas, and Oklahoma, the Caddoans often adopted foreign ideas, tools, and goods and then adapted them to Caddoan ways. With the coming of the French and Spanish after 1685, Caddoan society found itself under tremendous pressures, such as a dependency on manufactured goods and population loss from disease and increased warfare. The Caddoans found that their kin-ordered mode of production worked equally as well with Europeans. For successful diplomacy and trade, Europeans found they had to work within this Caddoan system in which gift-exchange established fictive and affinal kinships. From these kinships, the Caddoans expected the Europeans to uphold a host of reciprocal obligations, such provide loyalty, advice, protection, and of course, more gifts of valuable manufactured goods. As long as the Europeans needed these native peoples as military allies and as trade partners who provided hides and horses for their mercantilist empires, the Caddoans could remain politically and economically independent. Still, loss of land as well as population decreases from disease and warfare forced alterations in Caddoan society. Despite these changes, the Caddoans continually chose traditionally Caddoan ways to deal with them. Though Caddoan communities coalesced, they maintained their class, lineage, and leadership systems. Only with the coming of United States and the advent of agricultural capitalism did the Caddoans find themselves losing their political and economic independence. Rather than hides, Americans desired Caddoan land, so they pushed them off the land. In 1835, the United States government forced the Caddoans to cede their land in Louisiana and move west

Strangers for family : gifts, reciprocity, and kinship in Caddoan-Euroamerican relations, 1685-1835

Vita.Prior to regular contact with Europeans, the Caddoans created a complex, hierarchical, and highly organized society which participated in a far-flung trade with other native peoples. As they came into contact with other Indians, the Caddoans' kin-ordered mode of production allowed them to incorporate these strangers and their goods into Caddoan society. In their lands in what became Louisiana, Texas, Arkansas, and Oklahoma, the Caddoans often adopted foreign ideas, tools, and goods and then adapted them to Caddoan ways. With the coming of the French and Spanish after 1685, Caddoan society found itself under tremendous pressures, such as a dependency on manufactured goods and population loss from disease and increased warfare. The Caddoans found that their kin-ordered mode of production worked equally as well with Europeans. For successful diplomacy and trade, Europeans found they had to work within this Caddoan system in which gift-exchange established fictive and affinal kinships. From these kinships, the Caddoans expected the Europeans to uphold a host of reciprocal obligations, such provide loyalty, advice, protection, and of course, more gifts of valuable manufactured goods. As long as the Europeans needed these native peoples as military allies and as trade partners who provided hides and horses for their mercantilist empires, the Caddoans could remain politically and economically independent. Still, loss of land as well as population decreases from disease and warfare forced alterations in Caddoan society. Despite these changes, the Caddoans continually chose traditionally Caddoan ways to deal with them. Though Caddoan communities coalesced, they maintained their class, lineage, and leadership systems. Only with the coming of United States and the advent of agricultural capitalism did the Caddoans find themselves losing their political and economic independence. Rather than hides, Americans desired Caddoan land, so they pushed them off the land. In 1835, the United States government forced the Caddoans to cede their land in Louisiana and move west