Abstract
Introduction
We are delighted to author this critical article on COVID-19 and diabetes in the ATTD 2020 Yearbook. It is thought-provoking to remember the last conference (13th International Conference on Advanced Technologies & Treatments for Diabetes in February 2020) held in Madrid, Spain. It is especially hard to believe that it was the last sizable (attended by nearly 4000 participants) international in-person conference. It is shocking to witness the venue utilized for the 2020 ATTD Conference being converted into a makeshift hospital for COVID-19 patients just a few months later. At the time of this writing, it is still unknown whether we will have an in-person meeting for the next ATTD Conference to be held in February 2021 in Paris, France. All the data presented in this article will be outdated by the time this manuscript is read. The data in this manuscript was collected in August 2020, and many of the findings will be quite different by February 2021.
Coronaviruses are a large family of viruses that are enveloped-positive-strain RNA viruses. There are many pathogenic coronaviruses found in humans, specifically severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory virus coronavirus (MERS-CoV), and the current novel SARS-CoV-2 virus, commonly referred to as COVID-19, which has caused a global pandemic. The primary mode of transmission for COVID-19 is human-to-human contact, and it is frequently spread by asymptomatic carriers, some of which are found to be “super spreaders.” The COVID-19 infection started in Wuhan, China, in December 2019 and later spread to Europe, the United States, and the rest of the world.
Since December 2019, the COVID-19 outbreak has affected more than 212 countries, translating to more than 20 million cases of the virus worldwide at the time of this writing, with >5 million cases in the United States alone. Other countries reporting higher numbers of COVID-19 patients are Brazil and India. More than 700,000 people have died from COVID-19 across the globe; specifically, in the United States and South America there have been more than 8 million cases reported, with a total of 370,000 deaths due to the virus. The exact prevalence of the infection is currently unknown. However, it is commonly believed that ∼60%–70% of the population will need to be infected for herd immunity to be effective.
Research demonstrates that nearly one-third of patients with severe COVID-19 who are admitted to the intensive care units (ICUs) in the United States have diabetes. The incidence of diabetes and hypertension in ICU patients with COVID-19 is about two-fold higher than in non-ICU patients. Specifically, the prevalence of diabetes is about three-fold higher in COVID-19 patients with severe complications than that of nonsevere cases (about 16% vs. 5.7%, respectively). Patients with diabetes (both type 1 and type 2) face a higher risk of morbidity and mortality associated with COVID-19. Recent United Kingdom National Health Service (UK NHS) data illustrate that people with type 1 diabetes and poor glucose control (HbA1c above 8.5%) have a 3.5-fold higher risk of death from COVID-19 than those without diabetes, whereas among individuals with type 2 diabetes and poor glucose control there is a two-time higher risk of death from COVID-19 than those without diabetes.
The COVID-19 global pandemic has affected healthcare (clinical and research) enormously, with devastating consequences physically, socially, and economically. The global economic impact of COVID-19 is unspeakable, with the world seeing drastically reduced gross domestic product growth, recession-level impacts, and the possibility of entering another depression. The healthcare impact, as it relates to diabetes, has been enormous, in turn, affecting not only clinical care but clinical research as well. Since many localities had stay-at-home, safer-at-home, or other lockdown orders, most of the economy came to a screeching halt. Unfortunately, these social distancing restrictions have affected many chronic conditions, like diabetes, adversely. Of all the catastrophic results from the pandemic, a silver lining may be the emergence of telehealth and virtual care as an alternative way to deliver ongoing and efficient care to patients with diabetes.
As one can imagine, it has been difficult to choose only a handful of abstracts for this article, as there have been thousands of manuscripts written since the pandemic started. In this opening article of the ATTD 2020 Yearbook on the COVID-19 pandemic and diabetes, we plan to discuss the following topics: Testing for the virus (antigens, reverse-transcription polymerase chain reaction [RT-PCR], and antibodies) Associated morbidity and mortality with COVID-19 Emerging medications for possible use in COVID-19 patients The role of virtual or telehealth through emerging technologies like continuous glucose monitors (CGM), insulin pumps, and hybrid closed-loop systems Treatment options with convalescent serum from patients who recovered from COVID-19 infections Possible COVID-19 vaccinations
Zainol Rashid Z, Othman SN, Abdul Samat MN, Ali UK, Wong KK
Xiang F, Wang X, He X, Peng Z, Yang B, Zhang J, Zhou Q, Ye H, Ma Y, Li H, Wei X, Cai P, Ma W-L
Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Spijker R, Taylor-Phillips S, Adriano A, Beese S, Dretzke J, Ferrante di Ruffano L, Harris IM, Price MJ, Dittrich S, Emperador D, Hooft L, Leeflang MM, Van den Bruel A, Cochrane COVID-19 Diagnostic Test Accuracy Group
Robbiani DF, Gaebler C, Muecksch F, Lorenzi JCC, Wang Z, Cho A, Agudelo M, Barnes CO, Gazumyan A, Finkin S, Hagglof T, Oliveira TY, Viant C, Hurley A, Hoffmann HH, Millard KG, Kost RG, Cipolla M, Gordon K, Bianchini F, Chen ST, Ramos V, Patel R, Dizon J, Shimeliovich I, Mendoza P, Hartweger H, Nogueira L, Pack M, Horowitz J, Schmidt F, Weisblum Y, Michailidis E, Ashbrook AW, Waltari E, Pak JE, Huey-Tubman KE, Koranda N, Hoffman PR, West AP Jr, Rice CM, Hatziioannou T, Bjorkman PJ, Bieniasz PD, Caskey M, Nussenzweig MC
Peters AL, Garg SK
Shah K, Tiwaskar M, Chawla P, Kale M, Deshmane R, Sowani A
Toubiana J, Poirault C, Corsia A, Bajolle F, Fourgeaud J, Angoulvant F, Debray A, Basmaci R, Salvador E, Biscardi S, Frange P, Chalumeau M, Casanova J-L, Cohen JF, Slimane A
Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, Bonanomi E, D'Antiga L
Galerius J, Sun Y, Platt J, Zucker J, Baldwin M, Hripcsak G, Labella A, Manson DK, Kubin C, Barr RG, Sobieszczyk ME, Schluger NW
Reynolds HR, Adhikari S, Pulgarin C, Troxel AB, Iturrate E, Johnson SB, Hausvater A, Newman JD, Berger JS, Bangalore S, Katz SD, Fishman GI, Kunichoff D, Chen Y, Ogedegbe G, Hochman JS
Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, Feldt T, Green G, Green ML, Lescure F-X, Nicastri E, Oda R, Yo K, Quiros-Roldan E, Studemeister A, Redinski J, Ahmed S, Bernett J, Chelliah D, Chen D, Chihara S, Cohen SH, Cunningham J, D'Arminio Monforte A, Ismail S, Kato H, Lapadula G, L'Her E, Maeno T, Majumder S, Massari M, Mora-Rillo M, Mutoh Y, Nguyen D, Verweij E, Zoufaly A, Osinusi AO, DeZure A, Zhao Y, Zhong L, Chokkalingam A, Elboudwarej E, Telep L, Timbs L, Henne I, Sellers S, Cao H, Tan SK, Winterbourne L, Desai P, Mera R, Gaggar A, Myers RP, Brainard DM, Childs R, Flanigan T
Selvaraj V, Dapaah-Afriyie K, Finn A, Flanigan TP
Murphy HR
Garg SK, Rodbard D, Hirsch IB, Forlenza GP
Jones MS, Goley AL, Alexander BE, Keller SB, Caldwell MM, Buse JB
Diagnostic performance of COVID-19 serology assay
Zainol Rashid Z, Othman SN, Abdul Samat MN, Ali UK, Wong KK
Universiti Kebangsaan Malaysia Medical Centre, Faculty of Medicine, Department of Medical Microbiology & Immunology, Kuala Lumpur, Malaysia
Background
The World Health Organization (WHO) declared COVID-19 a world pandemic on March 12, 2020. Using respiratory samples, suspected cases can be confirmed by nucleic acid assays with real-time PCR. Serology tests are comparatively easier to perform, but their usefulness may be limited by their performance and because antibodies can appear later in the course of the disease. The goal of this paper is to describe the performance data on serological assays for COVID-19.
Methods
We reviewed multiple reports and kit inserts on the diagnostic performance of commercially available rapid tests from various manufacturers. Only preliminary data are currently available.
Results
From a total of nine rapid detection test (RDT) kits, three kits offer total antibody detection while six kits offer combination SARS-CoV-2 IgM and IgG detection in two separate test lines. All kits use whole blood, serum, or plasma samples and are based on colloidal gold-labeled immunochromatography principle and one-step method, with results obtained within 15 minutes. The sensitivity for both IgM and IgG tests ranges between 72.7% and 100%, while specificity ranges between 98.7% and 100%. Also reviewed in this paper are two immunochromatography processes using nasopharyngeal or throat swab for detection of COVID-19 specific antigen.
Conclusions
There is a great deal to determine regarding the value of serological testing in COVID-19 diagnosis and monitoring. More comprehensive evaluations of this form of testing are rapidly under way. The use of serology methods requires appropriate interpretation of the results and understanding of the strengths and limitations of such tests.
Antibody detection and dynamic characteristics in patients with COVID-19
Xiang F1, Wang X1, He X1, Peng Z2, Yang B1, Zhang J1, Zhou Q1, Ye H3, Ma Y1, Li H1, Wei X1, Cai P4, Ma W-L1
1Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 2School of Urban Design, Wuhan University, Wuhan, China; 3Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 4Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Background
The corona virus disease 2019 (COVID-19), which is caused by the corona virus 2 (SARS-CoV-2), has been rapidly spreading nationwide and abroad. A serologic test to identify antibody dynamics and response to SARS-CoV-2 was developed.
Methods
Nucleic acid testing by RT-PCR for SARS-CoV-2 was the gold standard for COVID-19 diagnosis. At 3–40 days after symptom onset, the antibodies against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay (ELISA) based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19. The serodiagnostic power of the specific IgM and IgG antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and consistency rate.
Results
As early as the fourth day after symptom onset, the seroconversion of specific IgM and IgG antibodies was observed. In patients confirmed with COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 77.3% (51/66), 100%, 100%, 80.0%, and 88.1%, respectively, and those of IgG were 83.3.3% (55/66), 95.0%, 94.8%, 83.8%, and 88.9%, respectively. In patients suspected with COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 87.5% (21/24), 100%, 100%, 95.2%, and 96.4%, respectively, and those of IgG were 70.8% (17/24), 96.6%, 85.0%, 89.1%, and 88.1%, respectively. Both antibodies that performed well in serodiagnosis for COVID-19 rely on great specificity.
Conclusions
The antibodies against SARS-CoV-2 can be detected in the middle and later stage of the illness. Antibody detection may play an important role in the diagnosis of COVID-19 as an approach that complements viral nucleic acid assays.
Antibody tests for identification of current and past infection with SARS-CoV-2
Deeks JJ1,2, Dinnes J1,2, Takwoingi Y1,2, Davenport C1,2, Spijker R3,4, Taylor-Phillips S1,5, Adriano A1, Beese S1, Dretzke J1, Ferrante di Ruffano L1, Harris IM1, Price MJ1,2, Dittrich S6, Emperador D6, Hooft L4, Leeflang MM7,8, Van den Bruel A9; Cochrane COVID-19 Diagnostic Test Accuracy Group
1Test Evaluation Research Group, Institute of Applied Health Research, University of Birmingham, Birmingham, UK; 2 NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK; 3Medical Library, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health, Amsterdam, Netherlands; 4Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; 5Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK; 6FIND, Geneva, Switzerland; 7Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands; 8Biomarker and Test Evaluation Programme (BiTE), Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; 9Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
Background
SARS-CoV-2 virus and the resulting COVID-19 pandemic pose important diagnostic concerns. Several strategies are available to diagnose current infection, rule out infection, identify patients in need of care escalation, or test for previous infection and immune response. Serology tests that detect the antibodies to SARS-CoV-2 aim to identify prior SARS-CoV-2 infection and may help confirm current infection.
Methods
This paper aims to assess the diagnostic accuracy of antibody tests to determine if a person in the community or in primary or secondary care has SARS-CoV-2 infection, or has had SARS-CoV-2 infection in the past, as well as the accuracy of antibody tests for use in seroprevalence surveys. We performed electronic searches in both the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we looked at repositories of COVID-19 publications and did not apply any language restrictions. We ran searches for this review iteration until April 27, 2020. We included test accuracy studies of any design that evaluated antibody tests (including enzyme-linked immunosorbent assays, chemiluminescence immunoassays, and lateral flow assays) in patients suspected of current or previous SARS-CoV-2 infection, or wherever tests were used to detect infection. We also included studies of patients either known to have, or not to have, SARS-CoV-2 infection. We included all reference standards to define the presence or absence of SARS-CoV-2 (including RT-PCR and clinical diagnostic criteria). We assessed potential bias and applicability of the studies using the QUADAS-2 tool. We extracted two-by-two contingency table data and presented sensitivity and specificity for each antibody (or combination of antibodies) using paired forest plots. We pooled data with random-effects logistic regression as appropriate, stratifying by time since post-symptom onset. We tabulated available data by test manufacturer. We have presented uncertainty in estimates of sensitivity and specificity using 95% confidence intervals (CIs).
Results
We included 57 publications reporting on a total of 54 study cohorts with 15,976 samples, of which 8526 were from cases of SARS-CoV-2 infection. Studies were conducted in Asia (n=38), Europe (n=15), and the United States and China (n=1). We identified data from 25 commercial tests and numerous in-house assays, a small fraction of the 279 antibody assays listed by the Foundation for Innovative Diagnostics. More than half (n=28) of the studies included were only available as preprints. Our concerns included risk of bias as well as applicability. Common issues included the following: use of multigroup designs (n=29); inclusion of only COVID-19 cases (n=19); lack of blinding of the index test (n=49) and reference standard (n=29); differential verification (n=22); and the lack of clarity about participant numbers, characteristics, and study exclusions (n=47). Most studies (n=44) only included patients who were hospitalized because of suspected or confirmed COVID-19 infection. There were no studies exclusively in asymptomatic participants. Two-thirds of the studies (n=33) defined COVID-19 cases based on RT-PCR results alone, disregarding the potential for false-negative RT-PCR results. We perceived evidence of the selective publication of study findings by omission of the identity of tests (n=5). We observed substantial heterogeneity in sensitivities of IgA, IgM, and IgG antibodies, or combinations thereof, for results aggregated across various time periods post-symptom onset (range 0% to 100% for all target antibodies). Therefore, we based our main results on the 38 studies that stratified results by the time since symptom onset. The numbers of individuals contributing data to each study each week are small and are usually not based on tracking the same groups of patients over time. Pooled results for IgG, IgM, IgA, total antibodies, and IgG/IgM all showed low sensitivity during the first week since onset of symptoms (all less than 30.1%), rising in the second week and reaching their highest values in the third week. The combination of IgG/IgM had a sensitivity of 30.1% (95% CI 21.4 to 40.7) for 1 to 7 days, 72.2% (95% CI 63.5 to 79.5) for 8 to 14 days, and 91.4% (95% CI 87.0 to 94.4) for 15 to 21 days. Estimates of accuracy beyond 3 weeks are based on smaller sample sizes and fewer studies. For 21 to 35 days, pooled sensitivities for IgG/IgM were 96.0% (95% CI 90.6 to 98.3). Insufficient studies exist to estimate sensitivity of tests beyond 35 days post-symptom onset. Summary specificities (provided in 35 studies) exceeded 98% for all target antibodies with confidence intervals no more than 2 percentage points wide. False-positive results were more common where COVID-19 had been suspected and ruled out, but numbers were small and the difference was within the range of chance. Assuming a prevalence of 50%, a value considered possible in healthcare workers who have suffered respiratory symptoms, we would anticipate that 43 (28 to 65) would be missed and 7 (3 to 14) would be falsely positive in 1000 people undergoing IgG/IgM testing at days 15 to 21 post-symptom onset. At a prevalence of 20%, a likely value in surveys in high-risk settings, 17 (11 to 26) would be missed per 1000 people tested and 10 (5 to 22) would be falsely positive. At a lower prevalence of 5%, a likely value in national surveys, 4 (3 to 7) would be missed per 1000 tested, and 12 (6 to 27) would be falsely positive. Analyses showed small differences in sensitivity among assay type, but methodological concerns and sparse data prevent comparisons among test brands.
Conclusions
The sensitivity of antibody tests is too low in the first week since symptom onset to have a primary role for the diagnosis of COVID-19, but they may still have a role complementing other testing in individuals presenting later, when RT-PCR tests are negative or are not done. Antibody tests are likely to have a useful role for detecting previous SARS-CoV-2 infection if used 15 or more days after symptom onset. However, the duration of antibody rises is currently unknown, and we discovered very little data beyond 35 days post-symptom onset. Therefore, we are uncertain about the usefulness of these tests for seroprevalence surveys for public health management purposes. Concerns about high risk of bias and applicability make it likely that the accuracy of tests when used in clinical care will be lower than reported in the included studies. Sensitivity has mainly been evaluated in hospitalized patients, so it is unclear whether the tests are able to detect lower antibody levels likely seen with milder and asymptomatic COVID-19 disease. The design, execution, and reporting of studies of the accuracy of COVID-19 tests necessitates considerable improvement. Studies must report data on sensitivity disaggregated by time since symptom onset. COVID-19-positive cases that are RT-PCR-negative should be included as well as those confirmed RT-PCR, in accordance with the World Health Organization (WHO) and China National Health Commission of the People's Republic of China (CDC) case definitions. We were only able to obtain data from a small proportion of available tests, and action is needed to ensure that all results of test evaluations are accessible in the public domain to prevent selective reporting. This is a fast-moving field, and we plan ongoing updates of this living systematic review.
Convergent antibody responses to SARS-CoV-2 in convalescent individuals
Robbiani DF1, Gaebler C1, Muecksch F2, Lorenzi JCC1, Wang Z1, Cho A1, Agudelo M1, Barnes CO3, Gazumyan A1, Finkin S1, Hagglof T1, Oliveira TY1, Viant C1, Hurley A4, Hoffmann HH5, Millard KG1, Kost RG6, Cipolla M1, Gordon K1, Bianchini F1, Chen ST1, Ramos V1, Patel R1, Dizon J1, Shimeliovich I1, Mendoza P1, Hartweger H1, Nogueira L1, Pack M1, Horowitz J1, Schmidt F2, Weisblum Y2, Michailidis E5, Ashbrook AW5, Waltari E7, Pak JE7, Huey-Tubman KE3, Koranda N3, Hoffman PR3, West AP Jr3, Rice CM5, Hatziioannou T2, Bjorkman PJ3, Bieniasz PD2,8, Caskey M1, Nussenzweig MC1,8
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY; 2Laboratory of Retrovirology, The Rockefeller University, New York, NY; 3Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA; 4Hospital Program Direction, The Rockefeller University, New York, NY; 5Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY; 6Hospital Clinical Research Office, The Rockefeller University, New York, NY; 7Chan Zuckerberg Biohub, San Francisco, CA; 8Howard Hughes Medical Institute, The Rockefeller University, New York, NY
Background
During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2.
Methods
Here we report on 149 COVID-19 convalescent individuals.
Results
Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titers: less than 1:50 in 33% and below 1:1000 in 79%, while only 1% showed titers above 1:5000. Antibody sequencing revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50 values) as low as single-digit nanograms per milliliter.
Conclusions
Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.
Comment
The above four abstracts describe different serological assays for COVID-19 antibodies. There are currently two antibody assays against SARS-CoV-2–IgM and IgG. In the early stages of COVID-19 pathogenesis, the antibody response may not be significantly detected; however, after 10–14 days of infection, there is a significant IgG antibody observed in patients who are COVID-19 positive via RT-PCR. At the time of this writing, the definitive test for diagnosing a patient with COVID-19 is the RT-PCR test for the virus. Yet, after a few days, the presence of COVID-19 antibodies indirectly reflects past infection (symptomatic or asymptomatic). There are numerous antibody assays available in the marketplace, many of which have not been vetted by proper studies even though approved by the U.S. Food and Drug Administration (FDA), as they were authorized on an emergency basis. Thus, the sensitivity and specificity of these assays are currently being challenged. Also, we do not currently know the duration of the neutralizing antibody response as measured by the assays because most of the studies have recorded only up to two or three months past the initial infection. It is possible that by the end of 2020, we will learn more about this antibody response and duration within the system.
The silver lining to COVID-19: avoiding diabetic ketoacidosis admissions with telehealth
Peters AL1, Garg SK2
1Keck School of Medicine of the University of Southern California, Los Angeles, CA; 2Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, CO
Background
The Stay at Home order in Colorado and The Stay Safe at Home order in California during the COVID-19 pandemic have compelled most endocrinologists/diabetologists to provide diabetes care remotely via telehealth. This could ultimately provide better access to diabetes healthcare in certain circumstances. However, healthcare disparities continue to challenge the availability of diabetes technology for underserved communities. We report our experiences using telehealth to effectively provide diabetes care to two patients and subsequently prevent hospital admissions.
Methods
Two adult patients with type 1 diabetes (T1D)–one new onset and the other with established T1D–are presented using telehealth facilitated by Clarity Software and the “Share” feature with the use of Dexcom G6 continuous glucose monitoring (CGM) for management of diabetic ketosis and hyperglycemia.
Results
Both patients were managed effectively via remote services despite having a higher risk of diabetic ketoacidosis (DKA). Glucose data shared through CGM facilitated frequent adjustments to insulin doses, increased fluid and carbohydrate intake, and prevention of hospital admissions in both cases. In the case of a patient with new-onset T1D, most of the education was handled remotely by certified diabetes care and education specialists.
Conclusions
Acute diabetes complications like DKA increase morbidity and mortality and add to the costs of the healthcare system. The current pandemic of COVID-19 has allowed newer ways (with the help of newer technologies) to manage high-risk patients with T1D and DKA via telehealth and may result in lasting benefits to patients with T1D.
Hypoglycemia at the time of Covid-19 pandemic
Shah K1, Tiwaskar M2, Chawla P3, Kale M4, Deshmane R5, Sowani A6
1Diabetes & Thyroid Care Center, India; 2Shilpa Medical Research Centre, India; 3Lina Diabetes Care and Mumbai Diabetes Research Centre, India; 4Dr Kale's Diabetes and Psychiatry Clinic, India; 5Shree Mahalaxmi Diabetic Care Centre, India; 6Diabetes Specialty Centre, India
Background
Hypoglycemia is the most critical factor to be addressed in glycemic management of diabetes in order to avoid further complications. The new coronavirus strain (COVID-19) pandemic has resulted in lockdowns that have further complicated concerns surrounding hypoglycemia due to limited access to food, outpatient clinics, pathological services, and medicines.
Aim
To assess the contributing factors related to the risk of hypoglycemia during April–May 2020 lockdown in people with type 2 diabetes mellitus.
Methodology
We analyzed the data retrospectively from 146 patients with type 2 diabetes mellitus (T2DM) who presented with symptoms suggestive of hypoglycemia to the emergency department (ED) during lockdown.
Results
The majority of patients were male (90/146) with a mean age of 59.88±10.09 years and a mean random blood glucose level of 57.67±9.00 mg/dL. Two-thirds of patients (70.83%) had level 1 hypoglycemia, while level 2 hypoglycemia was reported in 29.16% of patients. A combination of metformin and sulfonylureas (SU) was most commonly associated with the risk of hypoglycemia (65.75%), followed by insulin (33.56%). Subjects who received insulin reported a lower blood glucose value (50.75±8.20 mg/dL) as compared to those receiving a combination of metformin and SU (60.95±7.10 mg/dl); 33.56% of patients who had received prophylaxis hydroxychloroquine (HCQ) 400 mg twice a day along with the routine antihyperglycemic agents without their dose adjustment reported hypoglycemia. Patients with hypertension, microvascular and macrovascular complications, and those coexistent with one another had a higher propensity for the risk of hypoglycemia (46.58%, 33.56%, 23.29%, and 32.88% respectively).
Conclusions
The COVID-19 lockdown has been shown to influence the risk of hypoglycemia in patients with T2DM, especially in those taking SU, insulin, and HCQ, and particularly in patients with associated comorbidities. Patient education, support, and telemedicine play a pivotal role in preventing hypoglycemia.
Kawasaki-like multisystem inflammatory syndrome in children during the Covid-19 pandemic in Paris, France: prospective observational study
Toubiana J1,2, Poirault C1, Corsia A3, Bajolle F4, Fourgeaud J5, Angoulvant F6, Debray A1, Basmaci R7, Salvador E3, Biscardi S8, Frange P9, Chalumeau M1,10, Casanova J-L11,12, Cohen JF1,10, Slimane Allali1
1Department of General Paediatrics and Paediatric Infectious Diseases, Necker-Enfants Malades University Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Université de Paris, Paris, France; 2Institut Pasteur, Biodiversity and Epidemiology of Bacterial Pathogens, Paris, France; 3Paediatric Intensive Care Unit, Necker-Enfants Malades University Hospital, AP-HP, Université de Paris, Paris, France; 4M3C-Necker-Enfants Malades University Hospital, Université de Paris, Paris, France; 5Virology Laboratory, Necker-Enfants Malades University Hospital, AP-HP, Université de Paris, Paris, France; 6Pediatric Emergency Department, Necker-Enfants Malades University Hospital, AP-HP; INSERM, Centre de Recherche des Cordeliers, UMRS 1138, Université de Paris, Paris, France; 7Pediatric and Emergency Unit, Louis Mourier Hospital, Université de Paris, Paris, France; 8Pediatric Emergency Unit, Hôpital Intercommunal, Créteil, France; 9Department of Clinical Microbiology, Necker-Enfants Malades University Hospital, AP-HP, EHU 7328 PACT, Imagine Institute, Université de Paris, Paris, France; 10Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Centre of Research in Epidemiology and Statistics, INSERM, Université de Paris, Paris, France; 11Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Imagine Institute, Pediatric Hematology and Immunology Unit, Necker-Enfants Malades Hospital, AP-HP, Université de Paris, Paris, France; 12St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, Howard Hughes Medical Institute, New York, NY
Background
To explain the features of children and adolescents affected by an outbreak of Kawasaki-like multisystem inflammatory syndrome and to assess a potential temporal association with SARS-CoV-2 infection.
Methods
This was a prospective observational study at a pediatric department of a university hospital in Paris, France. Twenty-one children and adolescents (aged ≤18 years) with attributes of Kawasaki disease were admitted to the hospital between April 27 and May 11, 2020. They were followed up on until discharge by May 15, 2020. The primary outcomes included clinical and biological data, imaging and echocardiographic findings, treatment, and outcomes. Nasopharyngeal swabs were prospectively tested for SARS-CoV-2 using RT-PCR, and blood samples were tested for IgG antibodies to the virus.
Results
The children and adolescents (median age 7.9 [range 3.7–16.6] years) were admitted with characteristics of Kawasaki disease over a 15-day period, 12 (57%) of which were of African ancestry. Twelve (57%) presented with Kawasaki disease shock syndrome and 16 (76%) with myocarditis; 17 (81%) required intensive care support. All 21 patients had obvious gastrointestinal symptoms during the early stage of illness as well as high levels of inflammatory markers. Nineteen (90%) showed evidence of recent SARS-CoV-2 infection (positive RT-PCR result in 8/21, positive IgG antibody detection in 19/21). All 21 patients received intravenous immunoglobulin, and 10 (48%) patients also received corticosteroids. The clinical outcome was favorable in all patients. Moderate coronary artery dilations were detected in 5 (24%) of the patients during hospital stay. By May 15, 2020, after 8 (5–17) days in the hospital, all patients were discharged.
Conclusions
The ongoing outbreak of Kawasaki-like multisystem inflammatory syndrome among children and adolescents in the Paris area might be related to SARS-CoV-2. An unusually high proportion of the affected children and adolescents in this study had gastrointestinal symptoms and Kawasaki disease shock syndrome and were of African ancestry.
An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study
Verdoni L1, Mazza A1, Gervasoni A1, Martelli L1, Ruggeri M1, Ciuffreda M2, Bonanomi E3, D'Antiga L1
1Paediatric Department, Hospital Papa Giovanni XXIII, Bergamo, Italy; 2Paediatric Cardiology, Hospital Papa Giovanni XXIII, Bergamo, Italy; 3Paediatric Intensive Care Unit, Hospital Papa Giovanni XXIII, Bergamo, Italy
Background
The Bergamo province has been extensively affected by the SARS-CoV-2 epidemic, hence it is a natural observatory of virus manifestations in the general population. After a recent outbreak of Kawasaki disease, we aimed to evaluate incidence and characteristics of patients with Kawasaki-like disease that were diagnosed at the time of the SARS-CoV-2 epidemic.
Methods
All patients diagnosed with a Kawasaki-like disease at our center in the past 5 years were divided according to symptomatic presentation before (group 1) or after (group 2) the start of the SARS-CoV-2 epidemic. Kawasaki-like presentations were handled as Kawasaki disease according to the indications of the American Heart Association. Kawasaki disease shock syndrome (KDSS) was defined by the presence of circulatory dysfunction, and macrophage activation syndrome (MAS) determined by the Paediatric Rheumatology International Trials Organisation criteria. Current or previous infection was determined by reverse-transcriptase quantitative PCR in nasopharyngeal and oropharyngeal swabs and by serological qualitative test detecting SARS-CoV-2 IgM and IgG, respectively.
Results
Group 1 included 19 patients (7 boys, 12 girls, aged 3.0 years [SD 2.5]) diagnosed between January 1, 2015, and February 17, 2020. Group 2 comprised 10 patients (7 boys, 3 girls, aged 7.5 years [SD 3.5]) diagnosed between February 18 and April 20, 2020; 8 of 10 were positive for IgG or IgM, or both. The two groups differed in disease incidence (group 1 vs group 2, 0.3 vs 10 per month), mean age (3.0 vs 7.5 years), cardiac involvement (2 of 19 vs 6 of 10), KDSS (0 of 19 vs 5 of 10), MAS (0 of 19 vs 5 of 10), and the need for adjunctive steroid treatment (3 of 19 vs 8 of 10; all P<0.01).
Conclusions
In the previous month we found a 30-fold increased incidence of Kawasaki-like disease. Children diagnosed after the SARS-CoV-2 epidemic began showing evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and displayed features of MAS. The SARS-CoV-2 epidemic was correlated with high incidence of a severe form of Kawasaki disease. A similar outbreak of Kawasaki-like disease is expected to occur in other countries experiencing the SARS-CoV-2 epidemic.
Comment
Mortality from COVID-19 has been reported to be disproportionately higher among those with diabetes and among minority subgroups like African Americans in the United States. There is no indication that genetics plays an essential role in this increased mortality. These disparities can be related to a lack of access to quality care, resources, loss of health insurance, poor glucose control, and/or a delay in seeking medical advice. The subsequent four abstracts emphasize the evolving complications of COVID-19-related hypoglycemia, diabetic ketoacidosis (DKA), and Kawasaki-like multisystem inflammatory syndrome reported in children.
Unfortunately, many patients who had existing type 1 or type 2 diabetes avoided seeking medical care due to a fear of contracting COVID-19, even though they had severe hypoglycemia or DKA associated with hyperglycemia. In the first abstract, we report how DKA can be effectively managed remotely through telehealth using CGM technologies (Dexcom G6).
The usual manifestation of COVID-19 includes severe lung disease, resulting in acute respiratory failure in most adults. During the second week of the illness, as the viral load decreases, there is usually a significant increase in inflammation markers (cytokine storm). In contrast, while most children and adolescents with COVID-19 do not require any medical intervention, a small number of children present with a multisystem inflammatory response (Kawasaki-like syndrome, reported in the July 2020 issue of the New England Journal of Medicine [NEJM]). This Kawasaki-like multisystem inflammatory syndrome in children has recently been described in both Western Europe and the United States. It has been shown to take up to 10 days for these children to seek medical intervention, and nearly half of those diagnosed with this inflammatory response were of African descent. More than 70% of these patients had myocarditis and Kawasaki disease shock syndrome. The use of intravenous immunoglobulin and corticosteroids proved to mitigate further complications from the cytokine storm. In the United States, most of the children who reported a Kawasaki-like syndrome disorder were older (8 to 15 years old) and had a much higher rate of cardiac involvement. Features of macrophage activation syndrome as defined by the Pediatric Rheumatology International Trials Organization (PRINTO) are present at the time of clinical manifestation. Sadly, outbreaks of Kawasaki-like disease are expected in many other countries facing the COVID-19 pandemic.
Observational study of hydroxychloroquine in hospitalized patients with Covid-19
Galerius J1,2, Sun Y3, Platt J4, Zucker J1,2, Baldwin M1,2, Hripcsak G5, Labella A1,2, Manson DK1,2, Kubin C 1,2, Barr RG1,2,4, Sobieszczyk ME1,2, Schluger NW1,2,4
1Divisions of General Medicine, Infectious Diseases, and Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Mailman School of Public Health New York, NY; 2New York-Presbyterian Hospital-Columbia University Irving Medical Center, New York, NY; 2Department of Biostatistics, Mailman School of Public Health, New York, NY; 3 Department of Epidemiology, Mailman School of Public Health, New York, NY; 4Department of Biomedical Informatics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
Background
Hydroxychloroquine has been widely administered to patients with Covid-19 without great evidence to support its use.
Methods
We studied the correlation between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were gathered concerning consecutive patients hospitalized with Covid-19, not including those who were intubated, died, or discharged within 24 hours after presenting to the emergency department (study baseline). The primary endpoint was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighted according to the propensity score.
Results
Of 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. During a median follow-up of 22.5 days, 811 of the remaining 1376 patients (58.9%) received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presenting to the emergency department, and 85.9% within 48 hours. Patients being treated with hydroxychloroquine were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs 360). Overall, 346 patients (25.1%) had a primary endpoint event (180 patients were intubated, of whom 66 subsequently died and 166 died without intubation). Ultimately, there was no noteworthy association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses.
Conclusions
In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite endpoint of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are still necessary.
Renin-angiotensin-aldosterone system inhibitors and risk of Covid-19
Reynolds HR, Adhikari S, Pulgarin C, Troxel AB, Iturrate E, Johnson SB, Hausvater A, Newman JD, Berger JS, Bangalore S, Katz SD, Fishman GI, Kunichoff D, Chen Y, Ogedegbe G, Hochman JS
New York University (NYU) Grossman School of Medicine, New York, NY
Background
The possibility of an increased risk in patients who have taken medications that act on the renin-angiotensin-aldosterone system (RAAS) and are exposed to Covid-19 is a potential concern. This is because the viral receptor is angiotensin-converting enzyme 2 (ACE2).
Methods
We evaluated the relationship between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the probability of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had and patients who had not been treated with these medications, overall as well as in patients with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as substantial.
Results
Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no relationship between any individual medication class and an increased likelihood of testing positive. None of the medications assessed were associated with a substantial increase in the risk of severe illness among patients who tested positive.
Conclusions
We discovered that there is no substantial increase in the likelihood of testing positive for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.
Compassionate use of remdesivir for patients with severe Covid-19
Grein J1, Ohmagari N10, Shin D2, Diaz G16, Asperges E19, Castagna A20, Feldt T26, Green G3, Green ML17, Lescure F-X27,28, Nicastri E22, Oda R11, Yo K12, Quiros-Roldan E23, Studemeister A4, Redinski J4, Ahmed S31, Bernett J6, Chelliah D2, Chen D32, Chihara S18, Cohen SH7, Cunningham J33, D'Arminio Monforte A21, Ismail S8, Kato H13, Lapadula G24, L'Her E29, Maeno T14, Majumder S5, Massari M25, Mora-Rillo M34, Mutoh Y15, Nguyen D30, Verweij E35, Zoufaly A36, Osinusi AO9, DeZure A9, Zhao Y9, Zhong L9, Chokkalingam A9, Elboudwarej E9, Telep L9, Timbs L9, Henne I9, Sellers S9, Cao H9, Tan SK9, Winterbourne L9, Desai P9, Mera R9, Gaggar A9, Myers RP9, Brainard DM9, Childs R37, Flanigan T38
1Cedars-Sinai Medical Center, Los Angeles, CA; 2El Camino Hospital, Mountain View, CA; 3Sutter Santa Rosa Regional Hospital, Santa Rosa, CA; 4Regional Medical Center, San Jose, CA; 5Good Samaritan Hospital, San Jose, CA; 6John Muir Health, Walnut Creek, CA; 7UC Davis Health, Sacramento, CA; 8NorthBay Medical Center, Fairfield, CA; 9Gilead Sciences, Foster City, CA; 10the National Center for Global Health and Medicine, Tokyo, Japan; 11Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu City, Japan; 12Hiratsuka City Hospital, Hiratsuka, Japan; 13Yokohama City University Hospital, Yokohama, Japan; 14Gunma University Hospital, Gunma, Japan; 15Tosei General Hospital, Seto, Japan; 16Providence Regional Medical Center Everett, Everett, WA; 17University of Washington Medical Center-Northwest, Seattle, WA; 18Virginia Mason Medical Center, Seattle, WA; 19Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 20IRCCS, San Raffaele Scientific Institute, Milan, Italy; 21Azienda Socio Sanitaria Territoriale Spedali (ASST) Santi Paolo e Carlo, Department of Health Services, University of Milan, Milan, Italy; 22National Institute for Infectious Diseases, IRCCS, L. Spallanzani, Rome, Italy; 23Università degli Study of Brescia, ASST Civili di Brescia, Brescia, Italy; 24San Gerardo Hospital, ASST Monza, University of Milan-Bicocca, Monza, Italy; 25Azienda Unite Sanitarie Locali-IRCCS, Reggio Emilia, Italy; 26Universitätsklinikum Düsseldorf, Düsseldorf, Germany; 27Université de Paris, Infection, Antimicrobiens, Modélisation, Evolution (IAME), INSERM, Paris; 28Assistance Publique-Hôpitaux de Paris, Department of Infectious Diseases, Bichat Hospital, Paris; 29Centre Hospitalier Régional et Universitaire de Brest-La Cavale Blanche, Brest, France; 30Division of Infectious Diseases and Tropical Medicine, University Hospital of Bordeaux, Bordeaux, France; 31St. Alexius Medical Center, Hoffman Estates, IL; 32Mackenzie Health, Richmond Hill, ON, Canada; 33Columbia University Irving Medical Center, New York; 34Hospital Universitario La Paz-Carlos III, Instituto de Investigación Hospital Universitario La Paz, Madrid; 35Bernhoven Hospital, Uden, the Netherlands; 36Kaiser Franz Josef Hospital, Vienna; 37the U.S. Public Health Service Commissioned Corps, Washington, DC; 38Miriam Hospital, Providence, RI
Background
Remdesivir is a nucleotide analogue prodrug that inhibits viral RNA polymerases and has shown in vitro activity against SARS-CoV-2.
Methods
Patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2, were provided remdesivir on a compassionate-use basis. Patients were those with confirmed SARS-CoV-2 infection who were receiving oxygen support or who had an oxygen saturation of 94% or less while they were breathing ambient air. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This study includes data from patients who received remdesivir from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day.
Results
Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) in oxygen-support class showed improvement, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. In all, 25 patients (47%) were discharged, and 7 patients (13%) died. Mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation.
Conclusions
In this cohort of patients treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Determination of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy.
Short-term dexamethasone in Sars-CoV-2 patients
Selvaraj V1,2, Dapaah-Afriyie K1,2, Finn A1,2, Flanigan TP2,3
1Division of Hospital Medicine, The Miriam Hospital, Providence, RI; 2Warren Alpert Medical School of Brown University, Providence, RI; 3Department of Infectious Diseases, Brown Medicine, Providence, RI
Background
Dexamethasone is a synthetic glucocorticoid that has anti-inflammatory and immunosuppressive properties. A hyperinflammatory response occurs in the clinical course of patients with pneumonia due to SARS-CoV-2. There has been no definitive therapy for COVID-19 to date. We looked at the charts of SARS-CoV-2 patients who had pneumonia and moderate to severely elevated c-reactive protein (CRP) and worsening hypoxemia who were treated with early, short-term dexamethasone.
Methods
The 21 patients positive for SARS-CoV-2 who were admitted to The Miriam Hospital in Providence, RI, and treated with a short course of dexamethasone, either alone or in addition to current investigative therapies, are discussed.
Results
Following the start of dexamethasone from mean initial levels of 129.52 to 40.73 mg/L at time of discharge, CRP levels decreased significantly. 71% percent of the patients were discharged home with a mean length of stay of 7.8 days. None of the patients needed escalation of care leading to mechanical ventilation. Two patients were transferred to inpatient hospice facilities due to persistent hypoxemia, which was in line with their documented goals of care.
Conclusions
A short course of systemic corticosteroids was well tolerated among inpatients with SARS-CoV-2 and hypoxic respiratory failure. Most patients had improved outcomes. This limited case series may not provide concrete evidence toward the benefit of corticosteroids in COVID-19; however, the patients' positive response to short-term corticosteroids shows that they may help blunt the severity of inflammation and prevent a severe hyperinflammatory phase. In turn, this could reduce the overall length of stay, ICU admissions, and healthcare costs.
Comment
The above four abstracts report different therapeutic options for patients affected by COVID-19. It is essential to highlight that there is currently no specific antiviral treatment that is truly effective in reducing the morbidity and mortality of COVID-19.
The first abstract is an observational study investigating the use of hydroxychloroquine, a drug commonly used for malaria. Initially, hydroxychloroquine was claimed to be useful for COVID-19 in smaller observational studies done in India and China. However, the large observational study presented above was conducted in the United States and demonstrated that the drug was not associated with either a lower or increased risk of composite endpoints of intubation or death. Thus, hydroxychloroquine is no longer recommended as an effective medication for COVID-19, though controversy continues.
The second abstract attempts to correlate the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and associated risk of COVID-19 because this virus was determined to react with ACE2 receptors on cells. After being internalized within the cell from ACE2 receptors, the virus polymerizes by rapidly multiplying and spreading systemically. Some researchers hypothesized that the use of ACE inhibitors might pose a high risk of adverse outcomes in patients affected by COVID-19. In this extensive database of 12,594 patients who tested positive for COVID-19, the authors demonstrated no substantial increase in the likelihood of susceptibility or risk of severe complications among the patients who tested positive and who regularly used up to five commonly prescribed antihypertensive medications.
The third abstract describes the compassionate use of remdesivir for patients with severe COVID-19. In this compassionate-use study of remdesivir, there was a significant clinical improvement observed in nearly 70% of the patients. A later, much larger randomized controlled trial (RCT) cosponsored by Gilead Sciences, Inc., and the National Institutes of Health (NIH) was done in the United States. It demonstrated that the hospital stay was significantly reduced among patients who received remdesivir (Biegel et al., N Engl J Med 2020; 383:1813–1826) with no effect on the overall mortality. As a result of these published findings through the RCT, the FDA authorized remdesivir on an emergency basis for patients with severe COVID-19 in the United States.
The last abstract highlights the use of dexamethasone in critically ill patients with COVID-19. A short course of systemic corticosteroids in patients with COVID-19-associated hypoxic respiratory failure is shown to reduce mortality rates, and most patients had improved clinical outcomes. The use of corticosteroids in extremely sick patients may result in reducing the length of stay, ICU admissions, and overall healthcare costs.
Managing diabetes in pregnancy before, during, and after COVID-19
Murphy HR1–3
1Diabetes in Pregnancy Team, Cambridge University Hospitals, Addenbrookes' Hospital, Cambridge, UK; 2Division of Women's Health, North Wing, St. Thomas' Campus, Kings College London, London, UK; 3Norwich Medical School, Bob Champion Research and Education Building, University of East Anglia, Norwich, UK
Background
Pregnant women with diabetes are identified as being more vulnerable to the severe effects of COVID-19 and advised to stringently follow social-distancing measures. Here, we review the management of diabetes in pregnancy before and during the lockdown.
Methods
Majority of antenatal diabetes and obstetric visits are provided remotely, with pregnant women attending hospital clinics only for essential ultrasound scans and labor and delivery. Online resources for supporting women who are planning a pregnancy and for self-management of pregnant women with T1D who are using intermittent or continuous glucose monitoring are provided. Retinal screening procedures, intrapartum care, and the varying impact of lockdown on maternal glycemic control are considered. Alternative screening procedures for diagnosing hyperglycemia during pregnancy and gestational diabetes mellitus (GDM) are discussed. Case histories describe the remote initiation of insulin pump therapy and automated insulin delivery in T1D pregnancy.
Results
Initial feedback suggests that video consultations are well received and that the experiences for women requiring face-to-face visits are greatly improved. As the pandemic eases, formal evaluation of remote models of diabetes education and technology implementation, including women's views, will be important.
Conclusion
Research and audit activities will resume, and we will find new ways for pregnant women with diabetes to choose their preferred glucose monitoring and insulin delivery.
Managing new-onset type 1 diabetes during the COVID-19 pandemic: challenges and opportunities
Garg SK1, Rodbard D2, Hirsch IB3, Forlenza GP1
1Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, CO; 2Biomedical Informatics Consultants LLC, Potomac, MD; 3Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle, WA
Background
The current COVID-19 pandemic provides an incentive to expand considerably the use of telemedicine for high-risk patients with diabetes, and especially for the management of T1D. Telemedicine and digital medicine also offer critically important approaches to improve access, efficacy, efficiency, and cost-effectiveness of medical care for people with diabetes.
Methods
Two case reports are presented where telemedicine was used effectively and safely after day 1 in-person patient education. These aspects of the management of new-onset T1D patients (adult and pediatric) included ongoing diabetes education of the patient and family digitally. The patients used continuous glucose monitoring with commercially available analysis software (Dexcom Clarity and Glooko) to generate ambulatory glucose profiles and interpretive summary reports. The adult subject used multiple daily insulin injections; the pediatric patient used an insulin pump. The subjects were managed using a combination of e-mail, Internet via Zoom, and telephone calls.
Results
These two cases show the feasibility and effectiveness of the use of telemedicine in applications in which we had not used it previously: new-onset diabetes education and insulin dosage management.
Conclusions
The present case reports illustrate how telemedicine can be used safely and effectively for new-onset T1D training and education for both pediatric and adult patients and their families. The COVID-19 pandemic has acutely stimulated the expansion of the use of telemedicine and digital medicine. We conclude that telemedicine is an effective approach for the management of patients with new-onset T1D.
Inpatient transition to virtual care during COVID-19 pandemic
Jones MS1, Goley AL1, Alexander BE1, Keller SB1, Caldwell MM2, Buse JB1
1Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC; 2Department of Medicine, Tufts University, Boston, MA
Introduction
During the coronavirus disease 2019 (COVID-19) outbreak, novel approaches to diabetes care have been employed. Care in both the inpatient and outpatient setting has transformed considerably. Driven by the need to reduce the use of personal protective equipment and exposure for patients and providers alike, we transitioned inpatient diabetes management services to largely “virtual” or remotely provided care at our hospital.
Methods
Implementation of a diabetes comanagement service under the direction of the University of North Carolina division of endocrinology was initiated in July 2019. In response to the COVID-19 pandemic, the diabetes service was largely transitioned to a virtual care model in March 2020. Automatic consults for COVID-19 patients were implemented. Glycemic outcomes from before and after transition to virtual care were evaluated.
Results
Data over a 15-week period suggest that using virtual care for diabetes management in the hospital is feasible and can provide similar outcomes to traditional face-to-face care.
Conclusions
Automatic consults for COVID-19 patients ensure that patients with serious illness receive specialized diabetes care. Transitioning to virtual care models does not limit the glycemic outcomes of inpatient diabetes care and should be employed to reduce patient and provider exposure in the setting of COVID-19. These findings may have implications for reducing nosocomial infection in less challenging times and might address shortage of healthcare providers, especially in the remote areas.
Comment
Many new-onset patients with type 1 diabetes delayed seeking medical advice during COVID-19 because of the risk of getting infected. Many hospitals noted a higher number of patients presenting with DKA because of the delay in diagnosing type 1 diabetes. Similar concerns were noted by many of the physicians managing diabetes during pregnancy. However, in many instances, most diabetes could be effectively managed remotely by using newer technologies like CGM, insulin pumps, and hybrid closed-loop systems. In several instances, even the pump and CGM initiation were commenced remotely with no adverse outcomes. The last abstract in this section compares the experience of virtual care for the in-patient setting during the COVID-19 pandemic as compared to in-person, in-patient visits (pre-COVID 19). The authors conclude that virtual care gave a similar time in range (TIR) for blood sugar levels with no increase in time below range during the virtual care period, irrespective of how patients were treated (whether it was remotely or in-person). This in-patient care data was based on self-monitoring of blood glucose (SMBG) data. More recently, the FDA gave emergency authorization for the use of CGM in the in-patient setting. Many hospitals in New York and other parts of the United States are now using CGM to manage in-patients remotely in the in-patient setting.
Conclusion
It is almost incomprehensible to think that a viral infection from COVID-19 has brought nearly the entire world, economy, healthcare, travel, hospitality industry, and more to a standstill. Many Asian countries have managed the disease more effectively than the Western world. However, the exact data remains questionable from those places, in terms of total prevalence and death reporting accuracies. RT-PCR testing is susceptible to detecting the coronavirus and for diagnosing the disease using a nasal swab. In fact, many new assays measure only the COVID-19 spike protein, which correlates with COVID-19 disease.
There is no effective treatment available to date; however, the use of antiviral treatments, like remdesivir, reduce the overall morbidity and length of stay in the hospital. In critically ill patients, use of dexamethasone and convalescent serum may improve the clinical outcomes of these patients.
Worldwide, many companies are attempting to manufacture an effective and safe vaccine against SARS-CoV-2, lasting anywhere from a few months to years. The different platforms considered for possible vaccines include mRNA vaccine technology, attenuated virus therapies, attenuated spike protein, an antibody against the spike protein, or other neutralizing antibodies against COVID-19, etc. The exact dosing schedule for a vaccine and whether an annual booster dose will be needed to keep adequate levels of neutralizing antibodies is currently unknown. However, at the present moment, human-to-human transmission can be significantly reduced by conservative practices like social distancing, frequent hand washing, and the use of facial coverings or masks.
Footnotes
Author Disclosure Statement
No competing financial interests exist.