{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T05:29:50Z","timestamp":1765344590822,"version":"3.46.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypokalemia is common in patients hospitalized with coronavirus disease 2019 (COVID-19) and is associated with mortality, disease progression and severity. Increased aldosterone levels were previously suggested to be the main cause of potassium loss in this population. We aimed to assess the effects of the latest morning plasma aldosterone levels on changes in serum potassium during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used dynamic generalized estimating equations (GEEs) on longitudinal data (3 weeks) from an adequately sized (159 patients) platform trial evaluating therapeutics for COVID-19 during the first wave of infections in Vienna, Austria. We adjusted for important confounding variables (GEE A, 106 patients) and conducted sensitivity analyses by including medications with the potential to confound the analysis (GEE B, 82 patients) and by modeling an exponential decay of effects on potassium over time (GEE C, 82 patients). Furthermore, we explored the relationship descriptively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The median potassium concentration was 3.8 (quartile 1: 3.5, quartile 3: 4.0) mmol\/L, and hypokalemia (&amp;lt;3.5 mmol\/L) was present in 15.7% of patients at the first blood draw compared to 21.6% throughout the 3-week observation period. The median aldosterone concentration was 45.0 (20.0, 104.0) pmol\/L and was below the lower limit of quantitation (20 pmol\/L) in 32.4% of samples. Aldosterone was not associated with changes in potassium neither in GEE A [base-10 logarithm of aldosterone,\n                      <jats:italic>\u03b2<\/jats:italic>\n                      : \u22120.008 (95% CI: \u22120.074, 0.057),\n                      <jats:italic>p<\/jats:italic>\n                      -value: 0.805], in GEE B [\n                      <jats:italic>\u03b2<\/jats:italic>\n                      : 0.013 (\u22120.064, 0.090),\n                      <jats:italic>p<\/jats:italic>\n                      -value: 0.739], nor in GEE C [\n                      <jats:italic>\u03b2<\/jats:italic>\n                      : 0.001 (\u22120.078, 0.075),\n                      <jats:italic>p<\/jats:italic>\n                      -value: 0.971].\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Aldosterone levels were low and were not associated with potassium changes in patients hospitalized with COVID-19 during the first wave of the SARS-CoV-2 pandemic.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1706679","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T05:25:33Z","timestamp":1765344333000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma aldosterone is low in patients hospitalized with COVID-19 and not associated with changes in serum potassium levels: post hoc observational analyses of clinical trial data"],"prefix":"10.3389","volume":"16","author":[{"given":"Simon","family":"Krenn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"H\u00f6dlmoser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amelie","family":"Kurnikowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Jorge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farsad","family":"Eskandary","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Heinze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Hecking","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Reindl-Schwaighofer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e2262","DOI":"10.1002\/rmv.2262","article-title":"Epidemiology, prognosis and management of potassium disorders in Covid-19","volume":"32","author":"Noori","year":"2022","journal-title":"Rev Med Virol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.jdmv.2021.10.006","article-title":"Relationship between kalemia and intensive care unit admission or death in hospitalized COVID-19 patients: A cohort study","volume":"47","author":"Gu\u00e9don","year":"2022","journal-title":"JMV-J M\u00e9decine Vasc"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2020.09.033","article-title":"Hypokalemia as a sensitive biomarker of disease severity and the requirement for invasive mechanical ventilation requirement in COVID-19 pneumonia: A case series of 306 Mediterranean patients","volume":"100","author":"Moreno-P\u00e9rez","year":"2020","journal-title":"Int J Infect Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26082","article-title":"Correlation between the variables collected at admission and progression to severe cases during hospitalization among patients with COVID-19 in Chongqing","volume":"92","author":"Duan","year":"2020","journal-title":"J Med Virol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0271132","article-title":"Assessment of hypokalemia and clinical prognosis in Patients with COVID-19 in Yangzhou, China","volume":"17","author":"Yin","year":"2022","journal-title":"PLoS One"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1177\/0004563220922255","article-title":"Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19)","volume":"57","author":"Lippi","year":"2020","journal-title":"Ann Clin Biochem Int J Lab Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.11122","article-title":"Assessment of hypokalemia and clinical characteristics in patients with coronavirus disease 2019 in wenzhou, China","volume":"3","author":"Chen","year":"2020","journal-title":"JAMA Netw Open"},{"key":"B8","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1186\/s12879-020-05242-w","article-title":"Correlation analysis between disease severity and clinical and biochemical characteristics of 143 cases of COVID-19 in Wuhan, China: a descriptive study","volume":"20","author":"Wang","year":"2020","journal-title":"BMC Infect Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s40620-022-01429-3","article-title":"Negative prognostic impact of electrolyte disorders in patients hospitalized for Covid-19 in a large multicenter study","volume":"36","author":"Genovesi","year":"2023","journal-title":"J Nephrol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.50965","article-title":"Association between average plasma potassium levels and 30-day mortality during hospitalization in patients with COVID-19 in Wuhan, China","volume":"18","author":"Liu","year":"2021","journal-title":"Int J Med Sci"},{"key":"B11","doi-asserted-by":"publisher","first-page":"58","DOI":"10.4103\/abr.abr_178_21","article-title":"Identification of high death risk coronavirus disease-19 patients using blood tests","volume":"11","author":"Zadeh Hosseingholi","year":"2022","journal-title":"Adv BioMed Res"},{"key":"B12","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1055\/s-0042-1742631","article-title":"Early biochemical markers in predicting the clinical outcome of COVID-19 patients admitted in tertiary care hospital","volume":"14","author":"Prasad","year":"2022","journal-title":"J Lab Physicians"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.30476\/IJMS.2021.47835","article-title":"Risk factors for the mortality in hospitalized patients with COVID-19: A brief report","volume":"46","author":"Sami","year":"2021","journal-title":"Iran J Med Sci"},{"key":"B14","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.puhe.2021.11.007","article-title":"Clinical features, risk factors and a prediction model for in-hospital mortality among diabetic patients infected with COVID-19: data from a referral centre in Iran","volume":"202","author":"Kabootari","year":"2022","journal-title":"Public Health"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2021.11.001","article-title":"Individual outcome prediction models for patients with COVID-19 based on their first day of admission to the intensive care unit","volume":"100","author":"Rigo-Bonnin","year":"2021","journal-title":"Clin Biochem"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41440-020-0476-3","article-title":"Downregulation of ACE2 induces overstimulation of the renin\u2013angiotensin system in COVID-19: should we block the renin\u2013angiotensin system","volume":"43","author":"Silhol","year":"2020","journal-title":"Hypertens Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.47906","article-title":"Newly diagnosed hypokalemic periodic paralysis triggered by COVID-19","volume":"15","author":"Schulte","year":"2023","journal-title":"Cureus"},{"key":"B18","doi-asserted-by":"publisher","first-page":"luaf151","DOI":"10.1210\/jcemcr\/luaf151","article-title":"Severe and intractable hypokalemia in a patient with new-onset type 1 diabetes and COVID-19 infection","volume":"3","author":"Sj\u00f6holm","year":"2025","journal-title":"JCEM Case Rep"},{"key":"B19","doi-asserted-by":"publisher","first-page":"23","DOI":"10.5049\/EBP.2020.18.2.23","article-title":"Hypertension and electrolyte disorders in patients with COVID-19","volume":"18","author":"Lim","year":"2020","journal-title":"Electrolytes Blood Press"},{"key":"B20","doi-asserted-by":"publisher","first-page":"108132","DOI":"10.1016\/j.diabres.2020.108132","article-title":"COVID-19, diabetes mellitus and ACE2: The conundrum","volume":"162","author":"Pal","year":"2020","journal-title":"Diabetes Res Clin Pract"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202101-0142LE","article-title":"ACE2 elevation in severe COVID-19","volume":"203","author":"Reindl-Schwaighofer","year":"2021","journal-title":"Am J Respir Crit Care Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpaa169","article-title":"Serum ACE2, angiotensin II, and aldosterone levels are unchanged in patients with COVID-19","volume":"34","author":"Rieder","year":"2021","journal-title":"Am J Hypertens"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2020.07.006","article-title":"Letter to the Editor - Circulating plasma levels of angiotensin II and aldosterone in patients with coronavirus disease 2019 (COVID-19): A preliminary report","volume":"63","author":"Henry","year":"2020","journal-title":"Prog Cardiovasc Dis"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/00365513.2021.1926536","article-title":"Serum ACE activity and plasma ACE concentration in patients with SARS-CoV-2 infection","volume":"81","author":"Henry","year":"2021","journal-title":"Scand J Clin Lab Invest"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.04.003","article-title":"Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China","volume":"98","author":"Su","year":"2020","journal-title":"Kidney Int"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2506","DOI":"10.1038\/s41467-021-22781-1","article-title":"Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 infection","volume":"12","author":"Diao","year":"2021","journal-title":"Nat Commun"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.07.019","article-title":"SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule","volume":"98","author":"Werion","year":"2020","journal-title":"Kidney Int"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.04.043","article-title":"SARS-CoV-2 N protein induces hypokalemia in acute kidney injury mice via ENaC-dependent mechanism","volume":"33","author":"Zhang","year":"2025","journal-title":"Mol Ther"},{"key":"B29","doi-asserted-by":"publisher","first-page":"587","DOI":"10.12688\/f1000research.24441.2","article-title":"Electrolyte disturbances in SARS-CoV-2 infection","volume":"9","author":"Mabillard","year":"2020","journal-title":"F1000Research"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/hvaa001","article-title":"Measurement of equilibrium angiotensin II in the diagnosis of primary aldosteronism","volume":"66","author":"Guo","year":"2020","journal-title":"Clin Chem"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kws412","article-title":"The table 2 fallacy: presenting and interpreting confounder and modifier coefficients","volume":"177","author":"Westreich","year":"2013","journal-title":"Am J Epidemiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.07.034","article-title":"Acute and chronic regulation of aldosterone production","volume":"350","author":"Hattangady","year":"2012","journal-title":"Mol Cell Endocrinol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.14882","article-title":"Sex differences in electrolyte imbalances caused by SARS-CoV-2: A cross-sectional study","volume":"75","author":"Pani","year":"2021","journal-title":"Int J Clin Pract"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-020-01996-4","article-title":"Hypokalemia in patients with COVID-19","volume":"25","author":"Alfano","year":"2021","journal-title":"Clin Exp Nephrol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2017.07.035","article-title":"Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system","volume":"245","author":"Nilsson","year":"2017","journal-title":"Int J Cardiol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/78.1.72","article-title":"Total body potassium differs by sex and race across the adult age span","volume":"78","author":"He","year":"2003","journal-title":"Am J Clin Nutr"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e220190","DOI":"10.1530\/EC-22-0190","article-title":"Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay","volume":"11","author":"Wiegand","year":"2022","journal-title":"Endocr Connect"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/path.5471","article-title":"Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19)","volume":"251","author":"Bourgonje","year":"2020","journal-title":"J Pathol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2315","DOI":"10.3390\/jcm9072315","article-title":"The plasmatic aldosterone and C-reactive protein levels, and the severity of Covid-19: the dyhor-19 study","volume":"9","author":"Villard","year":"2020","journal-title":"J Clin Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.121.18295","article-title":"Dysregulation of ACE (Angiotensin-converting enzyme)-2 and renin-angiotensin peptides in SARS-CoV-2 mediated mortality and end-organ injuries","volume":"79","author":"Wang","year":"2022","journal-title":"Hypertension"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1706679\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T05:25:34Z","timestamp":1765344334000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1706679\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,10]]},"references-count":41,"alternative-id":["10.3389\/fendo.2025.1706679"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1706679","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,10]]},"article-number":"1706679"}}