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      Clinical profile and outcomes in COVID-19 patients with diabetic ketoacidosis: A systematic review of literature

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          Abstract

          Background and aim

          To perform a systematic literature review and analyze the demographic/biochemical parameters and clinical outcomes of COVID-19 patients with diabetic ketoacidosis (DKA) and combined DKA/HHS (hyperglycemic hyperosmolar syndrome).

          Methods

          PubMed, Scopus, Embase, and Google Scholar databases were systematically searched till August 3, 2020 to identify studies reporting COVID-19 patients with DKA and combined DKA/HHS. A total of 19 articles reporting 110 patients met the eligibility criteria.

          Results

          Of the 110 patients, 91 (83%) patients had isolated DKA while 19 (17%) had DKA/HHS. The majority of the patients were male (63%) and belonged to black ethnicity (36%). The median age at presentation ranged from 45.5 to 59.0 years. Most of the patients (77%) had pre-existing type 2 diabetes mellitus. Only 10% of the patients had newly diagnosed diabetes mellitus. The median blood glucose at presentation ranged from 486.0 to 568.5 mg/dl, being higher in patients with DKA/HHS compared to isolated DKA. The volume of fluid replaced in the first 24 h was higher in patients with DKA/HHS in contrast to patients with DKA alone. The in-hospital mortality rate was 45%, with higher mortality in the DKA/HHS group than in the isolated DKA group (67% vs. 29%). pH was lower in patients who had died compared to those who were discharged.

          Conclusion

          DKA in COVID-19 patients portends a poor prognosis with a mortality rate approaching 50%. Differentiating isolated DKA from combined DKA/HHS is essential as the latter represents around one-fifth of the DKA cases and tends to have higher mortality than DKA alone.

          Highlights

          • •

            Occasional reports of diabetic ketoacidosis (DKA) have been reported in COVID-19.

          • •

            DKA is more common in males and in individuals with black ethnicity and pre-existing T2DM.

          • •

            DKA in COVID-19 portends a poor prognosis with mortality being higher in patients with combined DKA/HHS than isolated DKA.

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          Most cited references55

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          Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial

          Yeming Wang, Dingyu Zhang, Guanhua Du … (2021)
          Summary Background No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. Methods We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir–ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. Findings Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87–1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95–2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. Interpretation In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. Funding Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.
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            Epidemiological Characteristics of 2143 Pediatric Patients With 2019 Coronavirus Disease in China

            Yuanyuan Dong, Xi Mo, Yabin Hu … (2020)
            To identify the epidemiological characteristics and transmission patterns of pediatric patients with the 2019 novel coronavirus disease (COVID-19) in China.
            Article 0 comments Cited 1650 times – based on 0 reviews     Review now
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              Is Open Access

              Impact of sex and gender on COVID-19 outcomes in Europe

              Catherine Gebhard, Vera Regitz-Zagrosek, Hannelore Neuhauser … (2020)
              Background Emerging evidence from China suggests that coronavirus disease 2019 (COVID-19) is deadlier for infected men than women with a 2.8% fatality rate being reported in Chinese men versus 1.7% in women. Further, sex-disaggregated data for COVID-19 in several European countries show a similar number of cases between the sexes, but more severe outcomes in aged men. Case fatality is highest in men with pre-existing cardiovascular conditions. The mechanisms accounting for the reduced case fatality rate in women are currently unclear but may offer potential to develop novel risk stratification tools and therapeutic options for women and men. Content The present review summarizes latest clinical and epidemiological evidence for gender and sex differences in COVID-19 from Europe and China. We discuss potential sex-specific mechanisms modulating the course of disease, such as hormone-regulated expression of genes encoding for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) entry receptors angiotensin converting enzyme (ACE) 2 receptor and TMPRSS2 as well as sex hormone-driven innate and adaptive immune responses and immunoaging. Finally, we elucidate the impact of gender-specific lifestyle, health behavior, psychological stress, and socioeconomic conditions on COVID-19 and discuss sex specific aspects of antiviral therapies. Conclusion The sex and gender disparities observed in COVID-19 vulnerability emphasize the need to better understand the impact of sex and gender on incidence and case fatality of the disease and to tailor treatment according to sex and gender. The ongoing and planned prophylactic and therapeutic treatment studies must include prospective sex- and gender-sensitive analyses.
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                Author and article information

                Contributors
                Rimesh Pal
                Journal
                Journal ID (nlm-ta): Diabetes Metab Syndr
                Journal ID (iso-abbrev): Diabetes Metab Syndr
                Title: Diabetes & Metabolic Syndrome
                Publisher: Diabetes India. Published by Elsevier Ltd.
                ISSN (Print): 1871-4021
                ISSN (Electronic): 1878-0334
                Publication date PMC-release: 18 August 2020
                Publication date (Electronic): 18 August 2020
                Affiliations
                [a ]Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
                [b ]Department of Endocrinology, Institute of Post Graduate Medical Education and Research, Kolkata, 700007, India
                [c ]National Institute of Nursing Education, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
                [d ]Department of Hematology, Institute of Hematology and Transfusion Medicine, Medical College and Hospital, Kolkata, West Bengal, 700073, India
                Author notes
                [∗ ]Corresponding author. rimesh.ben@ 123456gmail.com
                [1]

                Contributed equally.

                Article
                Publisher ID: S1871-4021(20)30318-0
                DOI: 10.1016/j.dsx.2020.08.015
                PMC ID: 7434433
                PubMed ID: 32853901
                SO-VID: 4641d762-b04b-471f-9022-3c4fbbc27fb6
                Copyright © © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 5 August 2020
                Date accepted : 14 August 2020
                Categories
                Subject: Article

                Keywords: covid-19,diabetic ketoacidosis,hyperglycemic hyperosmolar syndrome,subcutaneous insulin therapy
                Data availability:
                Keywords: covid-19, diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome, subcutaneous insulin therapy

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