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      Hypotheses about sub-optimal hydration in the weeks before coronavirus disease (COVID-19) as a risk factor for dying from COVID-19

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          Abstract

          To address urgent need for strategies to limit mortality from coronavirus disease 2019 (COVID-19), this review describes experimental, clinical and epidemiological evidence that suggests that chronic sub-optimal hydration in the weeks before infection might increase risk of COVID-19 mortality in multiple ways. Sub-optimal hydration is associated with key risk factors for COVID-19 mortality, including older age, male sex, race-ethnicity and chronic disease. Chronic hypertonicity, total body water deficit and/or hypovolemia cause multiple intracellular and/or physiologic adaptations that preferentially retain body water and favor positive total body water balance when challenged by infection. Via effects on serum/glucocorticoid-regulated kinase 1 (SGK1) signaling, aldosterone, tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), aquaporin 5 (AQP5) and/or Na +/K +-ATPase, chronic sub-optimal hydration in the weeks before exposure to COVID-19 may conceivably result in: greater abundance of angiotensin converting enzyme 2 (ACE2) receptors in the lung, which increases likelihood of COVID-19 infection, lung epithelial cells which are pre-set for exaggerated immune response, increased capacity for capillary leakage of fluid into the airway space, and/or reduced capacity for both passive and active transport of fluid out of the airways. The hypothesized hydration effects suggest hypotheses regarding strategies for COVID-19 risk reduction, such as public health recommendations to increase intake of drinking water, hydration screening alongside COVID-19 testing, and treatment tailored to the pre-infection hydration condition. Hydration may link risk factors and pathways in a unified mechanism for COVID-19 mortality. Attention to hydration holds potential to reduce COVID-19 mortality and disparities via at least 5 pathways simultaneously.

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          COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up

          Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, we review the current understanding of the pathogenesis, epidemiology, management and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, and of those with preexisting thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.
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            Kidney disease is associated with in-hospital death of patients with COVID-19.

            In December 2019, a coronavirus 2019 (COVID-19) disease outbreak occurred in Wuhan, Hubei Province, China, and rapidly spread to other areas worldwide. Although diffuse alveolar damage and acute respiratory failure were the main features, the involvement of other organs needs to be explored. Since information on kidney disease in patients with COVID-19 is limited, we determined the prevalence of acute kidney injury (AKI) in patients with COVID-19. Further, we evaluated the association between markers of abnormal kidney function and death in patients with COVID-19. This was a prospective cohort study of 701 patients with COVID-19 admitted in a tertiary teaching hospital that also encompassed three affiliates following this major outbreak in Wuhan in 2020 of whom 113 (16.1%) died in hospital. Median age of the patients was 63 years (interquartile range, 50-71), including 367 men and 334 women. On admission, 43.9% of patients had proteinuria and 26.7% had hematuria. The prevalence of elevated serum creatinine, elevated blood urea nitrogen and estimated glomerular filtration under 60 ml/min/1.73m2 were 14.4, 13.1 and 13.1%, respectively. During the study period, AKI occurred in 5.1% patients. Kaplan-Meier analysis demonstrated that patients with kidney disease had a significantly higher risk for in-hospital death. Cox proportional hazard regression confirmed that elevated baseline serum creatinine (hazard ratio: 2.10, 95% confidence interval: 1.36-3.26), elevated baseline blood urea nitrogen (3.97, 2.57-6.14), AKI stage 1 (1.90, 0.76-4.76), stage 2 (3.51, 1.49-8.26), stage 3 (4.38, 2.31-8.31), proteinuria 1+ (1.80, 0.81-4.00), 2+∼3+ (4.84, 2.00-11.70), and hematuria 1+ (2.99, 1.39-6.42), 2+∼3+ (5.56,2.58- 12.01) were independent risk factors for in-hospital death after adjusting for age, sex, disease severity, comorbidity and leukocyte count. Thus, our findings show the prevalence of kidney disease on admission and the development of AKI during hospitalization in patients with COVID-19 is high and is associated with in-hospital mortality. Hence, clinicians should increase their awareness of kidney disease in patients with severe COVID-19.
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              Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 2020

              On March 18, 2020, this report was posted online as an MMWR Early Release. Globally, approximately 170,000 confirmed cases of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) have been reported, including an estimated 7,000 deaths in approximately 150 countries ( 1 ). On March 11, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic ( 2 ). Data from China have indicated that older adults, particularly those with serious underlying health conditions, are at higher risk for severe COVID-19–associated illness and death than are younger persons ( 3 ). Although the majority of reported COVID-19 cases in China were mild (81%), approximately 80% of deaths occurred among adults aged ≥60 years; only one (0.1%) death occurred in a person aged ≤19 years ( 3 ). In this report, COVID-19 cases in the United States that occurred during February 12–March 16, 2020 and severity of disease (hospitalization, admission to intensive care unit [ICU], and death) were analyzed by age group. As of March 16, a total of 4,226 COVID-19 cases in the United States had been reported to CDC, with multiple cases reported among older adults living in long-term care facilities ( 4 ). Overall, 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths associated with COVID-19 were among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years. In contrast, no ICU admissions or deaths were reported among persons aged ≤19 years. Similar to reports from other countries, this finding suggests that the risk for serious disease and death from COVID-19 is higher in older age groups. Data from cases reported from 49 states, the District of Columbia, and three U.S. territories ( 5 ) to CDC during February 12–March 16 were analyzed. Cases among persons repatriated to the United States from Wuhan, China and from Japan (including patients repatriated from cruise ships) were excluded. States and jurisdictions voluntarily reported data on laboratory-confirmed cases of COVID-19 using previously developed data collection forms ( 6 ). The cases described in this report include both COVID-19 cases confirmed by state or local public health laboratories as well as those with a positive test at the state or local public health laboratories and confirmation at CDC. No data on serious underlying health conditions were available. Data on these cases are preliminary and are missing for some key characteristics of interest, including hospitalization status (1,514), ICU admission (2,253), death (2,001), and age (386). Because of these missing data, the percentages of hospitalizations, ICU admissions, and deaths (case-fatality percentages) were estimated as a range. The lower bound of these percentages was estimated by using all cases within each age group as denominators. The corresponding upper bound of these percentages was estimated by using only cases with known information on each outcome as denominators. As of March 16, a total of 4,226 COVID-19 cases had been reported in the United States, with reports increasing to 500 or more cases per day beginning March 14 (Figure 1). Among 2,449 patients with known age, 6% were aged ≥85, 25% were aged 65–84 years, 18% each were aged 55–64 years and 45–54 years, and 29% were aged 20–44 years (Figure 2). Only 5% of cases occurred in persons aged 0–19 years. FIGURE 1 Number of new coronavirus disease 2019 (COVID-19) cases reported daily*,† (N = 4,226) — United States, February 12–March 16, 2020 * Includes both COVID-19 cases confirmed by state or local public health laboratories, as well as those testing positive at the state or local public health laboratories and confirmed at CDC. † Cases identified before February 28 were aggregated and reported during March 1–3. The figure is a histogram, an epidemiologic curve showing 4,226 coronavirus disease 2019 (COVID-19) cases, by date of case report, in the United States during February 12–March 16, 2020. Figure 2 Coronavirus disease 2019 (COVID-19) hospitalizations,* intensive care unit (ICU) admissions, † and deaths, § by age group — United States, February 12– March 16, 2020 * Hospitalization status missing or unknown for 1,514 cases. † ICU status missing or unknown for 2,253 cases. § Illness outcome or death missing or unknown for 2,001 cases. The figure is a bar chart showing the number of coronavirus disease 2019 (COVID-19) hospitalizations, intensive care unit admissions, and deaths, by age group, in the United States during February 12– March 16, 2020. Among 508 (12%) patients known to have been hospitalized, 9% were aged ≥85 years, 36% were aged 65–84 years, 17% were aged 55–64 years, 18% were 45–54 years, and 20% were aged 20–44 years. Less than 1% of hospitalizations were among persons aged ≤19 years (Figure 2). The percentage of persons hospitalized increased with age, from 2%–3% among persons aged ≤19 years, to ≥31% among adults aged ≥85 years. (Table). TABLE Hospitalization, intensive care unit (ICU) admission, and case–fatality percentages for reported COVID–19 cases, by age group —United States, February 12–March 16, 2020 Age group (yrs) (no. of cases) %* Hospitalization ICU admission Case-fatality 0–19 (123) 1.6–2.5 0 0 20–44 (705) 14.3–20.8 2.0–4.2 0.1–0.2 45–54 (429) 21.2–28.3 5.4–10.4 0.5–0.8 55–64 (429) 20.5–30.1 4.7–11.2 1.4–2.6 65–74 (409) 28.6–43.5 8.1–18.8 2.7–4.9 75–84 (210) 30.5–58.7 10.5–31.0 4.3–10.5 ≥85 (144) 31.3–70.3 6.3–29.0 10.4–27.3 Total (2,449) 20.7–31.4 4.9–11.5 1.8–3.4 * Lower bound of range = number of persons hospitalized, admitted to ICU, or who died among total in age group; upper bound of range = number of persons hospitalized, admitted to ICU, or who died among total in age group with known hospitalization status, ICU admission status, or death. Among 121 patients known to have been admitted to an ICU, 7% of cases were reported among adults ≥85 years, 46% among adults aged 65–84 years, 36% among adults aged 45–64 years, and 12% among adults aged 20–44 years (Figure 2). No ICU admissions were reported among persons aged ≤19 years. Percentages of ICU admissions were lowest among adults aged 20–44 years (2%–4%) and highest among adults aged 75–84 years (11%–31%) (Table). Among 44 cases with known outcome, 15 (34%) deaths were reported among adults aged ≥85 years, 20 (46%) among adults aged 65–84 years, and nine (20%) among adults aged 20–64 years. Case-fatality percentages increased with increasing age, from no deaths reported among persons aged ≤19 years to highest percentages (10%–27%) among adults aged ≥85 years (Table) (Figure 2). Discussion Since February 12, 4,226 COVID-19 cases were reported in the United States; 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths occurred among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years. These findings are similar to data from China, which indicated >80% of deaths occurred among persons aged ≥60 years ( 3 ). These preliminary data also demonstrate that severe illness leading to hospitalization, including ICU admission and death, can occur in adults of any age with COVID-19. In contrast, persons aged ≤19 years appear to have milder COVID-19 illness, with almost no hospitalizations or deaths reported to date in the United States in this age group. Given the spread of COVID-19 in many U.S. communities, CDC continues to update current recommendations and develop new resources and guidance, including for adults aged ≥65 years as well as those involved in their care ( 7 , 8 ). Approximately 49 million U.S. persons are aged ≥65 years ( 9 ), and many of these adults, who are at risk for severe COVID-19–associated illness, might depend on services and support to maintain their health and independence. To prepare for potential COVID-19 illness among persons at high risk, family members and caregivers of older adults should know what medications they are taking and ensure that food and required medical supplies are available. Long-term care facilities should be particularly vigilant to prevent the introduction and spread of COVID-19 ( 10 ). In addition, clinicians who care for adults should be aware that COVID-19 can result in severe disease among persons of all ages. Persons with suspected or confirmed COVID-19 should monitor their symptoms and call their provider for guidance if symptoms worsen or seek emergency care for persistent severe symptoms. Additional guidance is available for health care providers on CDC’s website (https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html). This report describes the current epidemiology of COVID-19 in the United States, using preliminary data. The findings in this report are subject to at least five limitations. First, data were missing for key variables of interest. Data on age and outcomes, including hospitalization, ICU admission, and death, were missing for 9%–53% of cases, which likely resulted in an underestimation of these outcomes. Second, further time for follow-up is needed to ascertain outcomes among active cases. Third, the initial approach to testing was to identify patients among those with travel histories or persons with more severe disease, and these data might overestimate the prevalence of severe disease. Fourth, data on other risk factors, including serious underlying health conditions that could increase risk for complications and severe illness, were unavailable at the time of this analysis. Finally, limited testing to date underscores the importance of ongoing surveillance of COVID-19 cases. Additional investigation will increase the understanding about persons who are at risk for severe illness and death from COVID-19 and inform clinical guidance and community-based mitigation measures.* The risk for serious disease and death in COVID-19 cases among persons in the United States increases with age. Social distancing is recommended for all ages to slow the spread of the virus, protect the health care system, and help protect vulnerable older adults. Further, older adults should maintain adequate supplies of nonperishable foods and at least a 30-day supply of necessary medications, take precautions to keep space between themselves and others, stay away from those who are sick, avoid crowds as much as possible, avoid cruise travel and nonessential air travel, and stay home as much as possible to further reduce the risk of being exposed ( 7 ). Persons of all ages and communities can take actions to help slow the spread of COVID-19 and protect older adults. † Summary What is already known about this topic? Early data from China suggest that a majority of coronavirus disease 2019 (COVID-19) deaths have occurred among adults aged ≥60 years and among persons with serious underlying health conditions. What is added by this report? This first preliminary description of outcomes among patients with COVID-19 in the United States indicates that fatality was highest in persons aged ≥85, ranging from 10% to 27%, followed by 3% to 11% among persons aged 65–84 years, 1% to 3% among persons aged 55-64 years, <1% among persons aged 20–54 years, and no fatalities among persons aged ≤19 years. What are the implications for public health practice? COVID-19 can result in severe disease, including hospitalization, admission to an intensive care unit, and death, especially among older adults. Everyone can take actions, such as social distancing, to help slow the spread of COVID-19 and protect older adults from severe illness.
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                Author and article information

                Journal
                Med Hypotheses
                Med. Hypotheses
                Medical Hypotheses
                The Authors. Published by Elsevier Ltd.
                0306-9877
                1532-2777
                2 September 2020
                2 September 2020
                Affiliations
                [a ]Hydration Science Lab, College of Health Solutions, Arizona State University, Phoenix, Arizona, USA
                [b ]Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, USA
                [c ]Neuroesthetics
                [d ]Department of Medicine, University of California, San Francisco, California, USA
                [e ]Department of Physiology, Eberhard Karls University, Tubingen 72074, Germany
                Author notes
                [* ]Corresponding author at: 631 Lyon St, San Francisco, CA, 94117, United States.
                Article
                S0306-9877(20)31946-0 110237
                10.1016/j.mehy.2020.110237
                7467030
                © 2020 The Authors

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