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Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome.

ABSTRACT: We present a multivariate metabotyping approach to assess the functional recovery of nonhospitalized COVID-19 patients and the possible biochemical sequelae of "Post-Acute COVID-19 Syndrome", colloquially known as long-COVID. Blood samples were taken from patients ca. 3 months after acute COVID-19 infection with further assessment of symptoms at 6 months. Some 57% of the patients had one or more persistent symptoms including respiratory-related symptoms like cough, dyspnea, and rhinorrhea or other nonrespiratory symptoms including chronic fatigue, anosmia, myalgia, or joint pain. Plasma samples were quantitatively analyzed for lipoproteins, glycoproteins, amino acids, biogenic amines, and tryptophan pathway intermediates using Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Metabolic data for the follow-up patients (n = 27) were compared with controls (n = 41) and hospitalized severe acute respiratory syndrome SARS-CoV-2 positive patients (n = 18, with multiple time-points). Univariate and multivariate statistics revealed variable patterns of functional recovery with many patients exhibiting residual COVID-19 biomarker signatures. Several parameters were persistently perturbed, e.g., elevated taurine (p = 3.6 × 10^-3 versus controls) and reduced glutamine/glutamate ratio (p = 6.95 × 10^-8 versus controls), indicative of possible liver and muscle damage and a high energy demand linked to more generalized tissue repair or immune function. Some parameters showed near-complete normalization, e.g., the plasma apolipoprotein B100/A1 ratio was similar to that of healthy controls but significantly lower (p = 4.2 × 10^-3) than post-acute COVID-19 patients, reflecting partial reversion of the metabolic phenotype (phenoreversion) toward the healthy metabolic state. Plasma neopterin was normalized in all follow-up patients, indicative of a reduction in the adaptive immune activity that has been previously detected in active SARS-CoV-2 infection. Other systemic inflammatory biomarkers such as GlycA and the kynurenine/tryptophan ratio remained elevated in some, but not all, patients. Correlation analysis, principal component analysis (PCA), and orthogonal-partial least-squares discriminant analysis (O-PLS-DA) showed that the follow-up patients were, as a group, metabolically distinct from controls and partially comapped with the acute-phase patients. Significant systematic metabolic differences between asymptomatic and symptomatic follow-up patients were also observed for multiple metabolites. The overall metabolic variance of the symptomatic patients was significantly greater than that of nonsymptomatic patients for multiple parameters (χ² p = 0.014). Thus, asymptomatic follow-up patients including those with post-acute COVID-19 Syndrome displayed a spectrum of multiple persistent biochemical pathophysiology, suggesting that the metabolic phenotyping approach may be deployed for multisystem functional assessment of individual post-acute COVID-19 patients.

SUBMITTER: Holmes E

PROVIDER: S-EPMC8147448 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThis study aimed to estimate potential undetected cancers over the first 2 years of the COVID-19 pandemic in Catalonia.MethodsCancer incidence was compared between pre-pandemic (2019) and pandemic (March 2020-January 2022) periods in the Catalan Pathology Registry (CPR) according to sex, age, and tumor site. The correlation between cancer diagnosis and COVID-19 health care workload was also evaluated by means of the Pearson's correlation coefficient (R). The expected incident cancers (E) during the pandemic were estimated by applying 2019 CPR cancer incidence specific rates by sex and 5-year age groups to the 2020 and 2021 Catalan population pyramids. CPR incident cancers were considered observed (O). Standardized incidence ratios (SIR) and 95% confidence intervals (CIs) were calculated using the O/E ratio.ResultsAfter two pandemic years, cancer diagnosis decreased by 12% (SIR 0.88, 95% CI 0.87-0.89), or ∼7700 undetected cancers (13 000 with nonmelanoma skin cancer). Without nonmelanoma skin cancer, 72% of the cancer underdiagnosis was generated in 2020. Diagnoses decreased more in men (whole pandemic -14%; 2020 -21%; 2021 -8%) than in women (-9%, -19%, -3%, respectively), dropping significantly overall in all pandemic waves but the fifth (first -37%, second -16%, third -8%, fourth -6%, fifth -2%, sixth -6%), and across all adult age groups. In the first wave, CPR cancer diagnosis was inversely correlated with COVID-19 caseload in primary care (R -0.91, 95% CI -0.97 to -0.75) and occupancy in conventional hospital wards (R -0.91, 95% CI -0.99 to -0.48) and intensive care (R -0.91, 95% CI 95% -0.98 to -0.70).ConclusionsOur study evaluated the overall pandemic impact on cancer diagnosis on a large scale and with minimal selection bias, showing that as of February 2022, cancer detection in Catalonia had not yet recovered to pre-pandemic levels. Pending cancer incidence data from population-based cancer registries, early CPR data could inform the development of Spanish cancer control plans.

Project description:BackgroundNo effective oral therapy exists for early coronavirus disease 2019 (COVID-19).ObjectiveTo investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients.DesignRandomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668).SettingInternet-based trial across the United States and Canada (40 states and 3 provinces).ParticipantsSymptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset.InterventionOral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo.MeasurementsSymptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue scale. The primary end point was change in overall symptom severity over 14 days.ResultsOf 491 patients randomly assigned to a group, 423 contributed primary end point data. Of these, 341 (81%) had laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or epidemiologically linked exposure to a person with laboratory-confirmed infection; 56% (236 of 423) were enrolled within 1 day of symptoms starting. Change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, -0.27 point [95% CI, -0.61 to 0.07 point]; P = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P < 0.001). With placebo, 10 hospitalizations occurred (2 non-COVID-19-related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29).LimitationOnly 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages.ConclusionHydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19.Primary funding sourcePrivate donors.

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Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome.

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