Challenges in hyperglycemia management in critically ill patients with COVID-19.

Hyperglycemia is commonly associated with adverse outcomes especially in patients requiring intensive care unit stay. Data from the corona virus disease 2019 (COVID-19) pandemic indicates that individuals with diabetes appear to be at similar risk for COVID-19 infection to those without diabetes but are more likely to experience increased morbidity and mortality. The proposed hypothesis for hyperglycemia in COVID-19 include insulin resistance, critical illness hyperglycemia (stress- induced hyperglycemia) secondary to high levels of hormones like cortisol and catecholamines that counteract insulin action, acute cytokine storm and pancreatic cell dysfunction. Diabetic patients are more likely to have severe hyperglycemic complications including diabetic ketoacidosis and hyperosmolar hyperglycemic state. Management of hyperglycemia in COVID-19 is often complicated by use of steroids, prolonged total parenteral or enteral nutrition, frequent acute hyperglycemic events, and restrictions with fluid management due to acute respiratory distress syndrome. While managing hyperglycemia special attention should be paid to mode of insulin delivery, frequency of glucose monitoring based on patient and caregiver safety thereby minimizing exposure and conserving personal protective equipment. In this article we describe the pathophysiology of hyperglycemia, challenges encountered in managing hyperglycemia, and review some potential solutions to address them.

Kidney disease and COVID-19 disease severity-systematic review and meta-analysis.

We aimed to identify prevalence and association of comorbid chronic kidney disease (CKD), acute kidney injury (AKI) and utilization prevalence of continuous renal replacement therapy (CRRT) in COVID-19-hospitalized patients as a function of severity status. With the ongoing struggle across the globe to combat COVID-19 disease, published literature has described the role of kidney disease in COVID-19 patients based on single/multicenter experiences across the globe. We extracted data from observational studies describing comorbid CKD, AKI and CRRT and outcomes and severity of COVID-19-hospitalized patients from December 1, 2019-August 20, 2020 following PRISMA guidelines. Severity of COVID-19 includes intensive care unit admission, oxygen saturation < 90%, invasive mechanical ventilation utilization, in-hospital admission and mortality. Meta-analysis was performed using a random-effects model to calculate pooled estimates, and forest plots were created. In total, 29 studies with 15,017 confirmed COVID-19 patients were included. The overall prevalence of AKI was 11.6% [(430/3693)], comorbid CKD 9.7% [(1342/13,728)] and CRRT 2.58% [(102/3946)] in our meta-analysis. We also found higher odds of comorbid CKD (pooled OR: 1.70; 95%CI: 1.21-2.40; p = 0.002), AKI (8.28; 4.42-15.52; p < 0.00001) and utilization of CRRT (16.90; 9.00-31.74; p < 0.00001) in patients with severe COVID-19 disease. Conclusion Our meta-analysis suggests that comorbid CKD, AKI and utilization of CRRT were significantly associated with COVID-19 disease severity. Clinicians should focus on early triaging of COVID-19 patients with comorbid CKD and at risk for AKI to prevent complication and mortality.

Outcomes of COVID-19 Complications and their Possibilities as Potential Triggers of Stroke.

INTRODUCTION: There is limited literature on coronavirus disease 2019 (COVID -19) complications such as thromboembolism, cardiac complications etc. as possible trigger for stroke. Hence, we aim to evaluate the prevalence and outcomes of COVID-19 related cardiovascular complications and secondary infection and their possibility as potential triggers for the stroke. METHODS: Data from observational studies describing the complications [acute cardiac injury (ACI), cardiac arrhythmias (CA), disseminated intravascular coagulation (DIC), septic shock, secondary infection] and outcomes of COVID-19 hospitalized patients from December 1, 2019 to June 30, 2020, were extracted following PRISMA guidelines. Adverse outcomes defined as intensive care units, oxygen saturation less than 90%, invasive mechanical ventilation, severe disease, and in-hospital mortality. The odds ratio and 95% confidence interval were obtained, and forest plots were created using random-effects models. A short review of these complications as triggers of stroke was conducted. RESULTS: 16 studies with 3480 confirmed COVID-19 patients, prevalence of ACI [38%vs5.9%], CA [26%vs5.3%], DIC [4%vs0.74%], septic shock [18%vs0.36%], and infection [30%vs12.5%] was higher among patients with poor outcomes. In meta-analysis, ACI [aOR:9.93(95%CI:3.95-25.00], CA [7.52(3.29-17.18)], DIC [7.36(1.24-43.73)], septic shock [30.12(7.56-120.10)], and infection [10.41(4.47-24.27)] had higher odds of adverse outcomes. Patients hospitalized with acute ischemic stroke and intracerebral hemorrhage, had complications like pulmonary embolism, venous thromboembolism, DIC, etc. and had poor outcomes CONCLUSION: The complications like acute cardiac injury, cardiac arrhythmias, DIC, septic shock, and secondary infection had poor outcomes. Patients with stroke were having history of these complications. Long term monitoring is required in such patients to prevent stroke and mitigate adverse outcomes.

COVID-19 Outcomes Amongst Patients With Pre-existing Cardiovascular Disease and Hypertension.

INTRODUCTION:  Coronavirus disease 2019 (COVID-19) has multiorgan involvement and its severity varies with the presence of pre-existing risk factors like cardiovascular disease (CVD) and hypertension (HTN). Therefore, it is important to evaluate their effect on outcomes of COVID-19 patients. The objective of this meta-analysis and meta-regression is to evaluate outcomes of COVID-19 amongst patients with CVD and HTN. METHODS: English full-text observational studies having data on epidemiological characteristics of patients with COVID-19 were identified searching PubMed from December 1, 2019, to July 31, 2020, following Meta-analysis Of Observational Studies in Epidemiology (MOOSE) protocol. Studies having pre-existing CVD and HTN data that described outcomes including mortality and invasive mechanical ventilation (IMV) utilization were selected. Using random-effects models, risk of composite poor outcomes (meta-analysis) and isolated mortality and IMV utilization (meta-regression) were evaluated. Pooled prevalence of CVD and HTN, correlation coefficient (r) and odds ratio (OR) were estimated. The forest plots and correlation plots were created using random-effects models. RESULTS: Out of 29 studies (n=27,950) that met the criteria, 28 and 27 studies had data on CVD and HTN, respectively. Pooled prevalence of CVD was 18.2% and HTN was 32.7%. In meta-analysis, CVD (OR: 3.36; 95% CI: 2.29-4.94) and HTN (OR: 1.94; 95% CI: 1.57-2.40) were associated with composite poor outcome. In age-adjusted meta-regression, pre-existing CVD was having significantly higher correlation of IMV utilization (r: 0.28; OR: 1.3; 95% CI: 1.1-1.6) without having any association with mortality (r: -0.01; OR: 0.9; 95% CI: 0.9-1.1) among COVID-19 hospitalizations. HTN was neither correlated with higher IMV utilization (r: 0.01; OR: 1.0; 95% CI: 0.9-1.1) nor correlated with higher mortality (r: 0.001; OR: 1.0; 95% CI: 0.9-1.1). CONCLUSION: In age-adjusted analysis, though we identified pre-existing CVD as a risk factor for higher utilization of mechanical ventilation, pre-existing CVD and HTN had no independent role in increasing mortality.

Emerging therapeutics in the management of COVID-19.

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) pandemic has placed a tremendous burden on healthcare systems globally. Therapeutics for treatment of the virus are extremely inconsistent due to the lack of time evaluating drug efficacy in clinical trials. Currently, there is a deficiency of published literature that comprehensively discusses all therapeutics being considered for the treatment of COVID-19. A review of the literature was performed for articles related to therapeutics and clinical trials in the context of the current COVID-19 pandemic. We used PubMed, Google Scholar, and Clinicaltrials.gov to search for articles relative to the topic of interest. We used the following keywords: "COVID-19", "therapeutics", "clinical trials", "treatment", "FDA", "ICU", "mortality", and "management". In addition, searches through the references of retrieved articles was also performed. In this paper, we have elaborated on the therapeutic strategies that have been hypothesized or trialed to-date, the mechanism of action of each therapeutic, the clinical trials finished or in-process that support the use of each therapeutic, and the adverse effects associated with each therapeutic. Currently, there is no treatment that has been proven to provide significant benefit in reducing morbidity and mortality. There are many clinical trials for numerous different therapeutic agents currently underway. By looking back and measuring successful strategies from previous pandemics in addition to carrying out ongoing research, we provide ourselves with the greatest opportunity to find treatments that are beneficial.

Utilization of extracorporeal membrane oxygenation during the COVID-19 pandemic.

The ongoing outbreak of severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2, or coronavirus disease 2019 (COVID-19)] was declared a pandemic by the World Health Organization on March 11, 2020. Worldwide, more than 65 million people have been infected with this SARS-CoV-2 virus, and over 1.5 million people have died due to the viral illness. Although a tremendous amount of medical progress has been made since its inception, there continues to be ongoing research regarding the pathophysiology, treatments, and vaccines. While a vast majority of those infected develop only mild to moderate symptoms, about 5% of people have severe forms of infection resulting in respiratory failure, myocarditis, septic shock, or multi-organ failure. Despite maximal cardiopulmonary support and invasive mechanical ventilation, mortality remains high. Extracorporeal membrane oxygenation (ECMO) remains a valid treatment option when maximal conventional strategies fail. Utilization of ECMO in the pandemic is challenging from both resource allocation and ethical standpoints. This article reviews the rationale behind its use, current status of utilization, and future considerations for ECMO in critically ill COVID-19 patients.

Mortal remains disposal in the wake of the COVID-19 pandemic.

When dealing with infectious disease-related deaths, it is important to handle the remains of the deceased in a respectful and safe manner. There is no known evidence of SARS-CoV-2 transmission through handling of COVID-19 victim remains. However, guidelines recommend appropriate precautions to ensure safety from any potential risk. Discussions of safe and dignified postmortem care in COVID-19 cases can guide future decision making to encourage safety, dignity, and respect for all.

Habit Mimics the Illness: EVALI During the Era of the COVID-19 Pandemic.

Globally, health care providers have been challenged to provide adequate care during the coronavirus disease-2019 (COVID-19) pandemic. Due to the ever changing and rapidly evolving nature of the novel coronavirus, there is increased public anxiety and knowledge gaps that have created major dilemmas in health care delivery. In this environment, there is tremendous pressure on clinicians to diagnose each and every case of COVID-19. This has led to a situation in which clinicians are primed to suspect all respiratory illness is due to COVID-19 infection until proven otherwise. Because of this, providers may misdiagnose patients who have illnesses that are distinct from COVID-19 but present in a similar manner. In the current article, we present the case of e-cigarette- and vaping-associated acute lung injury (EVALI) mimicking pneumonia secondary to the novel coronavirus. It is unknown if vaping puts patients at higher risk of respiratory failure if coinfected with COVID-19. Therefore, exposure history in patients presenting with pneumonia-like syndrome is important. Physicians should be aware of the overlap between these conditions and should pay particular attention during history taking to distinguish EVALI from COVID-19 pneumonia.

COVID-19 and Hypercoagulability: A Review.

Thrombotic complications of the novel coronavirus (COVID-19) are a concerning aspect of the disease, due to the high incidence in critically ill patients and poor clinical outcomes. COVID-19 predisposes patients to a hypercoagulable state, however, the pathophysiology behind the thrombotic complications seen in this disease is not well understood. Several mechanisms have been proposed and the pathogenesis likely involves a host immune response contributing to vascular endothelial cell injury, inflammation, activation of the coagulation cascade via tissue factor expression, and shutdown of fibrinolysis. Treatments targeting these pathways may need to be considered to improve clinical outcomes and decrease overall mortality due to thrombotic complications. In this review, we will discuss the proposed pathophysiologic mechanisms for thrombotic complications in COVID-19, as well as treatment strategies for these complications based on the current literature available.

Gastrointestinal implications in COVID-19.

Believed to have originated from a local Huanan Seafood Wholesale Market in Wuhan, Hubei Province in China, the COVID-19 has had an unprecedented and catastrophic impact on humanity, with the WHO declaring it a global pandemic. Although the first case of COVID-19 was reported in December 2019, the primary source and intermediate host have not been confirmed, but human-to-human transmission has been universally accepted. The main mode of transmission of the virus is through respiratory droplets along with prominent respiratory system involvement. However, fecal-oral transmission due to the shedding of the virus in the gastrointestinal (GI) tract may continue for up to 10 weeks after respiratory clearance and is fast becoming important. SARS-CoV-2 shows a high affinity to ACE2 receptors, making sites of high ACE2 receptor expression, such as lungs, GI tract, brain, kidneys, heart, liver and immune system, a prime target for infection. Through this literature review, we aim to summarize the current knowledge of immunological pathways that contribute to the disease with a focus specifically on the GI tract involvement. We direct attention to the pathophysiological mechanism of involvement of the GI tract leading to symptomatic manifestations, track GI organ-specific viral loads to compare and contrast with other organ systems. We briefly detail specific treatment strategies from a GI disease standpoint and mention special considerations when there is involvement of the GI tract.

Telemedicine, the current COVID-19 pandemic and the future: a narrative review and perspectives moving forward in the USA.

A narrative review was conducted to examine the current state of the utilisation of telemedicine amid the current COVID-19 pandemic and to evaluate the benefits of continuing telemedicine usage in the future. A literature review was performed for articles related to telemedicine. Databases including PubMed, Google Scholar, Cochrane Library and Ovid MEDLINE were searched. Three reviewers independently performed article selection based on relevance to our topic. We included all articles between 1990 and 2020 related to telemedicine using the following keywords: 'telemedicine', 'telehealth', 'policy', 'COVID-19', 'regulation', 'rural', 'physical examination', 'future'. A total of 60 articles were identified, and through careful selection we narrowed the final number of articles to 42 based on relevance to our topic. Telemedicine has been rapidly evolving over the past several decades. Issues with regulation and reimbursement have prevented its full immersion into the healthcare system. During the current pandemic, Centers for Medicare and Medicaid services have expanded access to telemedicine services. The advantages of telemedicine moving forward include its cost-effectiveness, ability to extend access to specialty services and its potential to help mitigate the looming physician shortage. Disadvantages include lack of available technological resources in certain parts of the country, issues with security of patient data, and challenges in performing the traditional patient examination. It is critically important that changes are made to fully immerse telemedicine services into the healthcare landscape in order to be prepared for future pandemics as well as to reap the benefits of this service in the future.

Renal Transplant Recipient with Concurrent COVID-19 and Stenotrophomonas maltophilia Pneumonia Treated with Trimethoprim/Sulfamethoxazole Leading to Acute Kidney Injury: A Therapeutic Dilemma.

BACKGROUND Although coronavirus disease 2019 (COVID-19) manifests primarily as a lung infection, its involvement in acute kidney injury (AKI) is gaining recognition and is associated with increased morbidity and mortality. Concurrent infection, which may require administration of a potentially nephrotoxic agent, can worsen AKI and lead to poor outcomes. Stenotrophomonas maltophilia is a multidrug-resistant gram-negative bacillus associated with nosocomial infections, especially in severely immunocompromised and debilitated patients. Trimethoprim/sulfamethoxazole combination (TMP/SMX) is considered the treatment of choice but can itself lead to AKI, posing a significant challenge in the management of patients with concomitant COVID-19 and S. maltophilia pneumonia. CASE REPORT A 64-year-old male with end-stage renal disease and post renal transplant presented with severe respiratory symptoms of COVID-19 and was intubated upon admission. His renal functions were normal at the time of admission. The patient subsequently developed superimposed bacterial pneumonia with S. maltophilia requiring administration of TMP/SMX. However, TMP/SMX led to the development of AKI, which continued to worsen despite appropriate management including hemodialysis. This coincided with and most likely resulted in the patient's clinical deterioration and ultimate death. CONCLUSIONS The etiology of kidney disease involvement in patients with COVID-19 is still evolving and appears to be multifactorial. The condition can significantly worsen especially when nephrotoxic agents are given, probably due to a cumulative or synergistic effect. Great caution should be taken when administering nephrotoxic agents in the setting of COVID-19 as it can lead to adverse patient outcomes.

Epstein-Barr Virus Versus Novel Coronavirus-Induced Hemophagocytic Lymphohistocytosis: The Uncharted Waters.

Hemophagocytic lymphohistocytosis (HLH) is a hyperinflammatory syndrome characterized by fever, hepatosplenomegaly, and pancytopenia. It may be associated with genetic mutations or viral/bacterial infections, most commonly Epstein-Barr virus (EBV) and cytomegalovirus. As for the novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), also known as COVID-19 (coronavirus disease-2019), the cytokine storm it triggers can theoretically lead to syndromes similar to HLH. In this article, we report a case of a 28-year-old female who presented with high-grade fevers, found to have both SARS-CoV-2 and EBV infections, and eventually began to show signs of early HLH. To our knowledge, this is the first case reported in literature that raises the possibility of SARS-CoV-2-related HLH development.

COVID-19 and Acute Lupus Pneumonitis: Diagnostic and Treatment Dilemma.

In this article, we present a case of a young female patient with previously diagnosed lupus pneumonitis, now with a flare and new superimposed COVID-19 infection that was treated with intravenous steroids. On computed tomography scans, she had extensive interstitial lung fibrosis in addition to a positive COVID-19 polymerase chain reaction test requiring 6 L of oxygen via nasal cannula on admission. After administration of methylprednisolone, the patient improved and was weaned off her oxygen requirements and was discharged home.