BackgroundA standardised approach to assessing COVID-19 survivors has not been established, largely due to the paucity of data on medium- and long-term sequelae. Interval chest radiograph is recommended following community-acquired pneumonia, however its utility in monitoring recovery from COVID-19 pneumonia remains unclear.MethodsProspective single-centre observational cohort study. Patients hospitalised with severe COVID-19 pneumonia (admission duration ≥48 h and oxygen requirement ≥40% or critical care admission) underwent face-to-face assessment 4–6 weeks post-discharge. Primary outcome: radiological resolution of COVID-19 pneumonitis (Radiographic Assessment of Lung Oedema score <5). Secondary outcomes: clinical outcomes, symptom questionnaires, mental health screening (Trauma Screening Questionnaire, GAD-7, PHQ-9), physiological testing (4-metre gait speed (4MGS), 1-minute sit-to-stand test (STS)).Results119 patients assessed between 3rd June and 2nd July 2020 at median (IQR) 61 (51–67) days post-discharge. Mean±sd age 58.7±14.4 years, body mass index 30.0 (25.9–35.2) kg·m−2, 62% male, 68% ethnic minority. Despite radiographic resolution of pulmonary infiltrates in 87%, mMRC breathlessness scores were above pre-COVID baseline in 46% and patients reported persistent fatigue (68%), sleep disturbance (57%) and breathlessness (32%). Screening thresholds were breached for post-traumatic stress disorder (25%), anxiety (22%) and depression (18%). 4MGS was slow (<0.8 m·s−1) in 38%, 35% desaturated by ≥4% during STS. Of 56 thoracic computed tomography scans performed, 75% demonstrated COVID-related interstitial and/or airways disease.ConclusionsPersistent symptoms, adverse mental health outcomes and physiological impairment are common 2 months after severe COVID-19 pneumonia. Follow-up chest radiograph is a poor marker of recovery, therefore holistic face-to-face assessment is recommended to facilitate early recognition and management of post-COVID sequelae.

Through the use of a quantitative solution hybridization assay with 32P-labeled cDNA probes, we found that mevinolin, an inhibitor of cholesterol synthesis, elevates the level of mRNA for the low density lipoprotein receptor in livers of hamsters and rabbits. In hamsters the maximal effect (3-fold increase) occurred at 0.1% mevinolin in the diet for 10 days. The same dose produced a maximal induction (10-fold) of mRNA levels for 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme of cholesterol synthesis, and a maximal decrease (80%) in plasma cholesterol. The drug lowered the level of all cholesterol-carrying lipoproteins in plasma. In normal rabbits, mevinolin produced a 90% reduction in plasma low density lipoprotein-cholesterol levels, which was associated with a 2.5-fold increase in low density lipoprotein receptor mRNA levels. A similar induction of receptor mRNA occurred in livers of Watanabe-heritable hyperlipidemic rabbits, although the plasma cholesterol was not reduced to normal, presumably because the receptors produced by the mutant mRNA function poorly. These data are consistent with the hypothesis that mevinolin and other inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase lower plasma cholesterol levels in part by stimulating production of mRNA for the low density lipoprotein receptor in liver.

Pharmacologic doses of 17a-ethinyl estradiol are known to increase the number of low density lipoprotein (LDL) receptors in livers of rats, thereby producing a profound fall in plasma cholesterol levels. We now report that ethinyl estradiol exerts the same effect in livers of male and female rabbits and that the increase in receptor number is correlated with a 6-to 8-fold increase in the levels of receptor mRNA. Receptor protein was measured by ligand blotting, and mRNA levels were measured by a quantitative solution hybridization/Si nuclease protection assay using uniformly 32P-labeled single-stranded cDNA probes. These experiments demonstrate that pharmacologic induction of the mRNA for the LDL receptor in liver can lead to increased LDL receptor levels and a fall in plasma cholesterol in experimental animals.Regulation of the activity of the low density lipoprotein (LDL) receptor in liver constitutes a potential mechanism by which dietary and hormonal agents may alter plasma cholesterol levels (1). LDL receptors remove LDL and its precursor, intermediate density lipoprotein (IDL), from plasma (2). In rodent species (rabbits, hamsters, and rats), approximately 70% of the body's LDL receptors are expressed on liver cells (3-6). When these receptors are reduced in number, lipoprotein-bound cholesterol accumulates in plasma (7-10); conversely, an increase in hepatic receptors profoundly lowers plasma cholesterol levels (11-13).In tissue culture cells such as human fibroblasts, the number ofLDL receptors is dictated by the amount of mRNA for the receptor (14). When cultured cells have an overabundance ofcholesterol, the amount ofreceptor mRNA declines, the synthesis of LDL receptors is reduced, and the uptake of LDL is diminished (1,14). Conversely, when cultured cells have an increased requirement for cholesterol, they produce increased amounts of LDL receptor mRNA (14). No quantitative estimates of the mRNA for the LDL receptor in animal livers have been made. Whether changes in mRNA levels underlie regulation of the LDL receptor in the liver is also unknown.A dramatic induction of LDL receptor activity occurs in livers of rats treated with pharmacologic doses of 17a-ethinyl estradiol (11, 12). This demonstration followed the observation of Hay et al. (15), who showed that pharmacologic doses of ethinyl estradiol lead to a profound drop in the total plasma cholesterol level in rats. Kovanen et al. (11) and Chao et al. (12) showed that the fall in cholesterol was attributable to a marked increase in the number of LDL receptors in the liver, with consequent rapid clearance oflipoproteins from plasma.The present studies were designed to reveal whether high doses of ethinyl estradiol raise hepatic LDL receptor levels by producing an increase in the amount of LDL receptor mRNA. We turned from the rat to the rabbit because of the availability of a cDNA probe for the rabbit LDL receptor (T.Y., M.S.B., J.L.G., and D. W. Russell, unpublished data). Kushwaha and Hazzard have shown that estrogens decrease the pl...

Background. Coronavirus disease 2019 (COVID-19) had a significant impact on the National Health Service in the United Kingdom (UK), with over 35 000 cases reported in London by July 30, 2020. Detailed hospital-level information on patient characteristics, outcomes, and capacity strain is currently scarce but would guide clinical decision-making and inform prioritisation and planning. Methods. We aimed to determine factors associated with hospital mortality and describe hospital and ICU strain by conducting a prospective cohort study at a tertiary academic centre in London, UK. We included adult patients admitted to the hospital with laboratory-confirmed COVID-19 and followed them up until hospital discharge or 30 days. Baseline factors that are associated with hospital mortality were identified via semiparametric and parametric survival analyses. Results. Our study included 429 patients: 18% of them were admitted to the ICU, 52% met criteria for ICU outreach team activation, and 61% had treatment limitations placed during their admission. Hospital mortality was 26% and ICU mortality was 34%. Hospital mortality was independently associated with increasing age, male sex, history of chronic kidney disease, increasing baseline C-reactive protein level, and dyspnoea at presentation. COVID-19 resulted in substantial ICU and hospital strain, with up to 9 daily ICU admissions and 41 daily hospital admissions, to a peak census of 80 infected patients admitted in the ICU and 250 in the hospital. Management of such a surge required extensive reorganisation of critical care services with expansion of ICU capacity from 69 to 129 beds, redeployment of staff from other hospital areas, and coordinated hospital-level effort. Conclusions. COVID-19 is associated with a high burden of mortality for patients treated on the ward and the ICU and required substantial reconfiguration of critical care services. This has significant implications for planning and resource utilisation.

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