Data on residual clinical damage after Coronavirus disease-2019 (COVID-19) are lacking. The aims of this study were to investigate whether COVID-19 leaves behind residual dysfunction, and identify patients who might benefit from post-discharge monitoring. All patients aged �18 years admitted to the Emergency Department (ED) for COVID-19, and evaluated at post-discharge follow-up between 7 April and 7 May, 2020, were enrolled. Primary outcome was need of follow-up, defined as the presence at follow-up of at least one among: respiratory rate (RR) >20 breaths/min, uncontrolled blood pressure (BP) requiring therapeutic change, moderate to very severe dyspnoea, malnutrition, or new-onset cognitive impairment, according to validated scores. Post-traumatic stress disorder (PTSD) served as secondary outcome. 185 patients were included. Median [interquartile range] time from hospital discharge to follow-up was 23 [20-29] days. 109 (58.9%) patients needed follow-up. At follow-up evaluation, 58 (31.3%) patients were dyspnoeic, 41 (22.2%) tachypnoeic, 10 (5.4%) malnourished, 106 (57.3%) at risk for malnutrition. Forty (21.6%) patients had uncontrolled BP requiring therapeutic change, and 47 (25.4%) new-onset cognitive impairment. PTSD was observed in 41 (22.2%) patients. At regression tree analysis, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO 2 /FiO 2) and body mass index (BMI) at ED presentation, and age emerged as independent predictors of the need of followup. Patients with PaO 2 /FiO 2 <324 and BMI �33 Kg/m 2 had the highest odds to require follow-up. Among hospitalised patients, age �63 years, or age <63 plus non-invasive ventilation or diabetes identified those with the highest probability to need follow-up. PTSD was independently predicted by female gender and hospitalisation, the latter being protective (odds ratio, OR, 4.03, 95% confidence interval, CI, 1.76 to 9.47, p 0.0011; OR 0.37, 95% CI

Abstract-The kidney plays an important role in salt and blood pressure (BP) homeostasis. In previous studies, variants in the genes for ␣-adducin (ADD1), WNK1, and NEDD4L, which all regulate renal sodium absorption, have been associated with increased BP. However, findings have been inconsistent. We tested whether this is because of physiological interactions between the effects of variants in these genes. We assessed the single and combined effects of the ADD1 (Gly460Trp), WNK1 (rs880054 A/G), and NEDD4L (rs4149601 G/A) polymorphisms on renal and BP response to an acute Na load (nϭ344 subjects), BP decrease after 1 month of treatment with 12.5 mg of hydrochlorothiazide (nϭ193), and ambulatory 24-hour BP (nϭ690). Individually, the variants showed modest effects on some of the studied phenotypes. We found the ADD1 Trp allele to be permissive for the effects of variants of the other genes. In combination, the same variants (ADD1 Trp/WNK1 GG/Nedd4L GAϩAA) showed a consistent effect on renal Na handling (Pϭ0.009) and acute BP response to a saline infusion (Pϭ0.021), BP lowering after thiazide treatment (Pϭ0.008), and nocturnal systolic BP (Pϭ0.044). Physiological interaction between the ADD1 and WNK1-NEDD4L pathways influences the effects of variants in these genes on sodium-related BP regulation. Relatively common alleles in the ADD1, WNK1, and NEDD4L genes when present in combination may have significant effects on renal sodium handling, BP, and antihypertensive response to thiazides. (Hypertension. 2008;52:366-372.)Key Words: hypertension Ⅲ genetic Ⅲ sodium transport Ⅲ kidney Ⅲ blood pressure Ⅲ tubular Ⅲ renal R egulation of body sodium and blood pressure (BP) is achieved through the interaction of several mechanisms, including sodium (Na) transport at the basolateral and luminal tubular cell membranes along specific nephron segments. Moreover, physical, nervous, and hormonal mechanisms modulate this constitutive capacity of tubular cells to transport Na according to the body's needs. 1 In fact, virtually all mendelian disorders leading to hypertension are caused by gene variants affecting salt reabsorption. 2 A comprehensive approach to the genetics of the regulation of body Na and BP should take into account the interactions among the underlying variety of gene polymorphisms. At present, this approach is not feasible globally for the prohibitive size of the cohort required. However, a contribution along this line may be provided by focusing on genes affecting luminal (WNK1 and NEDD4L) and basolateral transport of Na (Adducin) in patients whose BP is changed by maneuvers affecting body Na.These genes have been chosen for the following reasons: a missense mutation in the ␣-adducin (ADD1 Gly/Trp) gene has been shown to affect the function of the protein with the Trp allele resulting in greater renal Na-K pump activity in nephron segments proximal to the macula densa. 3,4 Results of association studies of the Trp allele with BP are conflicting when this allele is considered alone, 5 but they are much more consisten...

Background and objectivesHypertension is a common aging-related disorder. Salt intake is one of the main environmental factors contributing to the development of hypertension. Transgenic mice with one-half Klotho deficiency displayed a spontaneous BP increase and salt-sensitive hypertension in response to high sodium intake. Usually circulating levels of α-Klotho decrease with age, and this reduction may be stronger in patients with several aging-related diseases. This study aimed at exploring the association of Klotho with salt sensitivity in humans.Design, setting, participants, & measurementsThe role of Klotho polymorphisms and α-Klotho serum levels was evaluated in patients with hypertension who were treatment naive and underwent an acute salt-sensitivity test (discovery n=673, intravenous 2 L of 0.9% saline in 2 hours). Salt sensitivity was defined as a mean BP increase of >4 mm Hg at the end of the infusion. A total of 32 single nucleotide polymorphisms in the Klotho gene (KL), previously identified with a genome-wide association study, were used in the genetic analysis and studied for a pressure-natriuresis relationship.ResultsOf the patients with hypertension, 35% were classified as salt sensitive. The most relevant polymorphism associated with pressure natriuresis was the common missense single nucleotide polymorphism rs9536314, and the GG and GT genotypes were more represented among patients who were salt sensitive (P=0.001). Those carrying the G allele showed a less steep pressure-natriuresis relationship, meaning that a significant increase in mean BP was needed to excrete the same quantity of salt compared with patients who were salt resistant. KL rs9536314 also replicated the pressure-natriuresis association in an independent replication cohort (n=193) and in the combined analysis (n=866). There was an inverse relationship between circulating Klotho and mean BP changes after the saline infusion (r=−0.14, P=0.03). Moreover, circulating α-Klotho was directly related to kidney function at baseline eGFR (r=0.22, P<0.001).ConclusionsKL rs9536314 is associated with salt-sensitive hypertension in patients with hypertension who are treatment naive. Moreover, circulating α-Klotho levels were mainly related to diastolic BP changes at the end of a salt load and to eGFR as an expression of kidney aging.