Utility of COVID-19 antigen testing in the emergency department.

BACKGROUND: The BinaxNOW coronavirus disease 2019 (COVID-19) Ag Card test (Abbott Diagnostics Scarborough, Inc.) is a lateral flow immunochromatographic point-of-care test for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein antigen. It provides results from nasal swabs in 15 minutes. Our purpose was to determine its sensitivity and specificity for a COVID-19 diagnosis. METHODS: Eligible patients had symptoms of COVID-19 or suspected exposure. After consent, 2 nasal swabs were collected; 1 was tested using the Abbott RealTime SARS-CoV-2 (ie, the gold standard polymerase chain reaction test) and the second run on the BinaxNOW point of care platform by emergency department staff. RESULTS: From July 20 to October 28, 2020, 767 patients were enrolled, of which 735 had evaluable samples. Their mean (SD) age was 46.8 (16.6) years, and 422 (57.4%) were women. A total of 623 (84.8%) patients had COVID-19 symptoms, most commonly shortness of breath (n = 404; 55.0%), cough (n = 314; 42.7%), and fever (n = 253; 34.4%). Although 460 (62.6%) had symptoms ≤7 days, the mean (SD) time since symptom onset was 8.1 (14.0) days. Positive tests occurred in 173 (23.5%) and 141 (19.2%) with the gold standard versus BinaxNOW test, respectively. Those with symptoms >2 weeks had a positive test rate roughly half of those with earlier presentations. In patients with symptoms ≤7 days, the sensitivity, specificity, and negative and positive predictive values for the BinaxNOW test were 84.6%, 98.5%, 94.9%, and 95.2%, respectively. CONCLUSIONS: The BinaxNOW point-of-care test has good sensitivity and excellent specificity for the detection of COVID-19. We recommend using the BinasNOW for patients with symptoms up to 2 weeks.

Gastric Aspergillosis in a COVID-19 Patient.

The SARS-CoV-2 virus, which causes Coronavirus-19 infection (COVID-19), frequently elicits the development of depressed immunity, therefore, opportunistic infections. Opportunistic organisms are commonly present in the human body without causing critical illness. However, they can also lead to pathologic illness when a person is immunocompromised. Aspergillosis is among the many opportunistic infections. Even though this infection primarily involves the respiratory system and is less likely to be found in the gastrointestinal tract, we report a case of a COVID-19 individual that developed massive gastrointestinal bleeding whose condition deteriorated, and the pathological examination revealed gastric aspergillosis. Although not common, gastric aspergillosis should be considered while treating patients with COVID-19 who present gastrointestinal symptoms.

Evaluation of the potential of Rejuveinix plus dexamethasone against sepsis.

Aim: Our main objectives were to compare the effects of Rejuveinix (RJX), dexamethasone (DEX) and their combination on the severity of sepsis and survival outcome in an animal model of fatal sepsis. Methods: We used the LPS plus D-galactosamine mouse model of sepsis to compare the anti-inflammatory activities of RJX, dexamethasone and a combination of RJX plus DEX. Additionally, we examined the clinical feasibility and tolerability of combining RJX with DEX in COVID-19 patients in a clinical phase I study. Data were analyzed using standard methods. Results & conclusion: RJX exhibited potent anti-inflammatory activity in the murine sepsis model. The combination of RJX plus DEX was more effective than either agent alone, decreased the inflammatory cytokine responses and associated organ damage, and improved the survival outcome in mice. In the phase I clinical study, RJX plus DEX was well tolerated by COVID-19 patients.

Call for a Global Vaccine Plan to Combat Current and Future Pandemics: One for ALL and ALL for One.

The emergence of SARS-CoV-2 in late December 2019 has taken the world by storm. In March 2020, the World Health Organization (WHO) named this virus COVID-19. To date, it has infected approximately 186 million people worldwide and is attributed as the cause of death of more than 5 million people (and this number is only increasing.) The global effort to develop vaccines and therapeutics occurred at the fastest pace yet, with several vaccines' approval under emergency authorization use. There are also several post-marketing side effects, including myocarditis, cerebral venous embolism, and Guillain Barre Syndrome. Global vaccine disparity complicates the control of pandemic challenges. Several highly infectious variants have emerged, and more variants are feared to emerge if global vaccination plans are not developed soon.

Low versus high dose anticoagulation in patients with Coronavirus 2019 pneumonia at the time of admission to critical care units: A multicenter retrospective cohort study in the Beaumont healthcare system.

PURPOSE: Coagulopathy is common in patients with COVID-19. The ideal approach to anticoagulation remains under debate. There is a significant variability in existing protocols for anticoagulation, and these are mostly based on sporadic reports, small studies, and expert opinion. MATERIALS AND METHODS: This multicenter retrospective cohort study evaluated the association between anticoagulation dose and inpatient mortality among critically ill COVID-19 patients admitted to the intensive care units (ICUs) or step-down units (SDUs) of eight Beaumont Healthcare hospitals in Michigan, USA from March 10th to April 15th, 2020. RESULTS: Included were 578 patients with a median age of 64 years; among whom, 57.8% were males. Most patients (n = 447, 77.3%) received high dose and one in four (n = 131, 22.7%) received low dose anticoagulation. Overall mortality rate was 41.9% (n = 242). After adjusting for potential confounders (age, sex, race, BMI, ferritin level at hospital admission, intubation, comorbidities, mSOFA, and Padua score), administration of high anticoagulation doses at the time of ICU/SDU admission was associated with decreased inpatient mortality (OR 0.564, 95% CI 0.333-0.953, p = 0.032) compared to low dose. CONCLUSION: Treatment with high dose anticoagulation at the time of ICU/SDU admission was associated with decreased adjusted mortality among critically ill adult patients with COVID-19.

Pancreatic Pseudocysts as a Late Manifestation of COVID-19.

The novel coronavirus disease has caused an ongoing pandemic since the end of 2019. It is a transmissible infection caused by the SARS-CoV-2 virus. The highly infectious nature of this illness is based mostly throughout the respiratory tract. However, this virus can affect all systems of the human body, such as the gastrointestinal tract. We report a case of pancreatic pseudocysts as a late manifestation of COVID-19.

"MATH+" Multi-Modal Hospital Treatment Protocol for COVID-19 Infection: Clinical and Scientific Rationale.

In December 2019, coronavirus disease 2019 (COVID-19), a severe respiratory illness caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The greatest impact that COVID-19 had was on intensive care units (ICUs), given that approximately 20% of hospitalized cases developed acute respiratory failure (ARF) requiring ICU admission. Based on the assumption that COVID-19 represented a viral pneumonia and no anti-coronaviral therapy existed, nearly all national and international health care societies recommended "supportive care only" avoiding other therapies outside of randomized controlled trials, with a specific prohibition against the use of corticosteroids in treatment. However, early studies of COVID-19-associated ARF reported inexplicably high mortality rates, with frequent prolonged durations of mechanical ventilation (MV), even from centers expert in such supportive care strategies. These reports led the authors to form a clinical expert panel called the Front-Line COVID-19 Critical Care Alliance (www.flccc.net). The panel collaboratively reviewed the emerging clinical, radiographic, and pathological reports of COVID-19 while initiating multiple discussions among a wide clinical network of front-line clinical ICU experts from initial outbreak areas in China, Italy, and New York. Based on the shared early impressions of "what was working and what wasn't working", the increasing medical journal publications and the rapidly accumulating personal clinical experiences with COVID-19 patients, a treatment protocol was created for the hospitalized patients based on the core therapies of methylprednisolone, ascorbic acid, thiamine, heparin and non-antiviral co-interventions (MATH+). This manuscript reviews the scientific and clinical rationale behind MATH+ based on published in-vitro, pre-clinical, and clinical data in support of each medicine, with a special emphasis of studies supporting their use in the treatment of patients with viral syndromes and COVID-19 specifically.

The Ichikado CT score as a prognostic tool for coronavirus disease 2019 pneumonia: a retrospective cohort study.

BACKGROUND: The relationship between computed tomography (CT) and prognosis of patients with COVID-19 pneumonia remains unclear. We hypothesized that the Ichikado CT score, obtained in the first 24 h of hospital admission, is an independent predictor for all-cause mortality during hospitalization in patients with COVID-19 pneumonia. METHODS: Single-center retrospective cohort study of patients with confirmed COVID-19 pneumonia admitted at our institution between March 20th, 2020 and October 31st, 2020. Patients were enrolled if, within 24 h of admission, a chest CT scan, an arterial blood gas, a complete blood count, and a basic metabolic panel were performed. Two independent radiologists, who were blinded to clinical data, retrospectively evaluated the chest CT scans following a previously described qualitative and quantitative CT scoring system. The primary outcome was all-cause in-hospital mortality or survival to hospital discharge. Secondary outcomes were new requirements for invasive mechanical ventilation and hospital length of stay. Cox regression models were used to test the association between potential independent predictors and all-cause mortality. RESULTS: Two hundred thirty-five patients, 197 survivors and 38 nonsurvivors, were studied. The median Ichikado CT score for nonsurvivors was significantly higher than survivors (P < 0.001). An Ichikado CT score of more than 172 enabled prediction of mortality, with a sensitivity of 84.2% and a specificity of 79.7%. Multivariate analysis identified Ichikado CT score (HR, 7.772; 95% CI, 3.164-19.095; P < 0.001), together with age (HR, 1.030; 95% CI, 1.030-1.060; P = 0.043), as independent predictors of all-cause in-hospital mortality. CONCLUSIONS: Ichikado CT score is an independent predictor of both requiring invasive mechanical ventilation and all-cause mortality in patients hospitalized with COVID-19 pneumonia. Further prospective evaluation is necessary to confirm these findings. TRIAL REGISTRATION: The WCG institutional review board approved this retrospective study and patient consent was waived due to its non-interventional nature (Identifier: 20210799).

A scoping review of the pathophysiology of COVID-19.

COVID-19 is a highly heterogeneous and complex medical disorder; indeed, severe COVID-19 is probably amongst the most complex of medical conditions known to medical science. While enormous strides have been made in understanding the molecular pathways involved in patients infected with coronaviruses an overarching and comprehensive understanding of the pathogenesis of COVID-19 is lacking. Such an understanding is essential in the formulation of effective prophylactic and treatment strategies. Based on clinical, proteomic, and genomic studies as well as autopsy data severe COVID-19 disease can be considered to be the connection of three basic pathologic processes, namely a pulmonary macrophage activation syndrome with uncontrolled inflammation, a complement-mediated endothelialitis together with a procoagulant state with a thrombotic microangiopathy. In addition, platelet activation with the release of serotonin and the activation and degranulation of mast cells contributes to the hyper-inflammatory state. Auto-antibodies have been demonstrated in a large number of hospitalized patients which adds to the end-organ damage and pro-thrombotic state. This paper provides a clinical overview of the major pathogenetic mechanism leading to severe COVID-19 disease.

Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19.

BACKGROUND: After COVID-19 emerged on U.S shores, providers began reviewing the emerging basic science, translational, and clinical data to identify potentially effective treatment options. In addition, a multitude of both novel and repurposed therapeutic agents were used empirically and studied within clinical trials. AREAS OF UNCERTAINTY: The majority of trialed agents have failed to provide reproducible, definitive proof of efficacy in reducing the mortality of COVID-19 with the exception of corticosteroids in moderate to severe disease. Recently, evidence has emerged that the oral antiparasitic agent ivermectin exhibits numerous antiviral and anti-inflammatory mechanisms with trial results reporting significant outcome benefits. Given some have not passed peer review, several expert groups including Unitaid/World Health Organization have undertaken a systematic global effort to contact all active trial investigators to rapidly gather the data needed to grade and perform meta-analyses. DATA SOURCES: Data were sourced from published peer-reviewed studies, manuscripts posted to preprint servers, expert meta-analyses, and numerous epidemiological analyses of regions with ivermectin distribution campaigns. THERAPEUTIC ADVANCES: A large majority of randomized and observational controlled trials of ivermectin are reporting repeated, large magnitude improvements in clinical outcomes. Numerous prophylaxis trials demonstrate that regular ivermectin use leads to large reductions in transmission. Multiple, large "natural experiments" occurred in regions that initiated "ivermectin distribution" campaigns followed by tight, reproducible, temporally associated decreases in case counts and case fatality rates compared with nearby regions without such campaigns. CONCLUSIONS: Meta-analyses based on 18 randomized controlled treatment trials of ivermectin in COVID-19 have found large, statistically significant reductions in mortality, time to clinical recovery, and time to viral clearance. Furthermore, results from numerous controlled prophylaxis trials report significantly reduced risks of contracting COVID-19 with the regular use of ivermectin. Finally, the many examples of ivermectin distribution campaigns leading to rapid population-wide decreases in morbidity and mortality indicate that an oral agent effective in all phases of COVID-19 has been identified.

Stethoscope - An essential diagnostic tool or a relic of the past?

Rene Laennec came up with the idea of a stethoscope in 1816 to avoid the embarrassment of performing immediate auscultation on women. Soon many doctors around the world started using this tool because of its increased accuracy and ease of use. Stethoscopes hold great significance in the medical community. However, is the importance placed on stethoscopes justified today? We now have devices like portable ultrasound machines that make it much easier to visualize the body. These devices offset their higher initial cost by reducing downstream costs due to their greater accuracy and their capability of detecting diseases at an earlier stage. Also, because of the COVID-19 pandemic, new ways are being investigated to reduce the transmission of diseases. Stethoscopes being a possible vector for infectious agents coupled with the advent of newer devices that can visualize the body with greater accuracy put into question the continued use of stethoscopes today. With that said, the use of stethoscopes to diagnose diseases is still crucial in places where buying these new devices is not yet possible. The stethoscope is a great symbol of medicine, but its use needs to be in line with what is best for the patient.

COVID-19 Associated Spontaneous Pneumothorax and Pneumopericardium: A Case Report.

Novel coronavirus 2019 (COVID-19) has been one of the largest and most devastating global pandemics of our time. There have been several complications of this disease that have also proven to be debilitating and deadly. While primarily affecting the respiratory system, some cases presented with uncommon complications such as pneumopericardium and spontaneous pneumothorax. We present a case of an elderly female diagnosed with COVID-19 found to have both spontaneous pneumothorax and pneumopericardium. She had a complicated hospital course and ultimately succumbed to her illness. While the pathogenesis of these conditions is not yet fully understood, further studies are needed to help clinicians develop treatment and prevention strategies to improve patient outcomes.

The time to offer treatments for COVID-19.

Background: COVID-19 has several overlapping phases. Treatments to date have focused on the late stage of disease in hospital. Yet, the pandemic is by propagated by the viral phase in out-patients. The current public health strategy relies solely on vaccines to prevent disease.Methods: We searched the major national registries, pubmed.org, and the preprint servers for all ongoing, completed and published trial results.Results: As of 2/15/2021, we found 111 publications reporting findings on 14 classes of agents, and 9 vaccines. There were 62 randomized controlled studies, the rest retrospective observational analyses. Only 21 publications dealt with outpatient care. Remdesivir and high titer convalescent plasma have emergency use authorization for hospitalized patients in the U.S.A. There is also support for glucocorticoid treatment of the COVID-19 respiratory distress syndrome. Monoclonal antibodies are authorized for outpatients, but supply is inadequate to treat all at time of diagnosis. Favipiravir, ivermectin, and interferons are approved in certain countries.Expert Opinion: Vaccines and antibodies are highly antigen specific, and new SARS-Cov-2 variants are appearing. We call on public health authorities to authorize treatments with known low-risk and possible benefit for outpatients in parallel with universal vaccination.

The Importance of Understanding the Stages of COVID-19 in Treatment and Trials.

COVID-19, caused by SARS-CoV-2, continues to be a major health problem since its first description in Wuhan, China, in December 2019. Multiple drugs have been tried to date in the treatment of COVID-19. Critical to treatment of COVID-19 and advancing therapeutics is an appreciation of the multiple stages of this disease and the importance of timing for investigation and use of various agents. We considered articles related to COVID-19 indexed on PubMed published January 1, 2020-November 15, 2020, and considered papers on the medRxiv preprint server. We identified relevant stages of COVID-19 including three periods: pre-exposure, incubation, and detectable viral replication; and five phases: the viral symptom phase, the early inflammatory phase, the secondary infection phase, the multisystem inflammatory phase, and the tail phase. This common terminology should serve as a framework to guide when COVID-19 therapeutics being studied or currently in use is likely to provide benefit rather than harm.

Clinical and Scientific Rationale for the "MATH+" Hospital Treatment Protocol for COVID-19.

In December 2019, COVID-19, a severe respiratory illness caused by the new coronavirus SARS-CoV-2 (COVID-19) emerged in Wuhan, China. The greatest impact that COVID-19 had was on intensive care units (ICUs), given that approximately 20% of hospitalized cases developed acute respiratory failure (ARF) requiring ICU admission. Based on the assumption that COVID-19 represented a viral pneumonia and no anti-coronaviral therapy existed, nearly all national and international health care societies' recommended "supportive care only" avoiding other therapies outside of randomized controlled trials, with a specific prohibition against the use of corticosteroids in treatment. However, early studies of COVID-19-associated ARF reported inexplicably high mortality rates, with frequent prolonged durations of mechanical ventilation (MV), even from centers expert in such supportive care strategies. These reports led the authors to form a clinical expert panel called the Front-Line COVID-19 Critical Care Alliance (www.flccc.net). The panel collaboratively reviewed the emerging clinical, radiographic, and pathological reports of COVID-19 while initiating multiple discussions among a wide clinical network of front-line clinical ICU experts from initial outbreak areas in China, Italy, and New York. Based on the shared early impressions of "what was working and what wasn't working," the increasing medical journal publications and the rapidly accumulating personal clinical experiences with COVID-19 patients, a treatment protocol was created for the hospitalized patients based on the core therapies of methylprednisolone, ascorbic acid, thiamine, heparin and co-interventions (MATH+). This manuscript reviews the scientific and clinical rationale behind MATH+ based on published in-vitro, pre-clinical, and clinical data in support of each medicine, with a special emphasis of studies supporting their use in the treatment of patients with viral syndromes and COVID-19 specifically. The review concludes with a comparison of published multi-national mortality data with MATH+ center outcomes.

COVID-19 Coexisting With the Human Immunodeficiency Virus: A Case Report.

The newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has impacted the world dramatically, forcing the medical community to quickly and effectively find ways to manage coronavirus disease 2019 (COVID-19). The COVID-19 pandemic has shown many similarities to the human immunodeficiency virus pandemic in 1981, from the fear of treating patients for a virus we have little knowledge of, to analyzing how the levels of CD4+ are affected in both diseases. Declining numbers of CD4+ levels are classically seen with HIV patients, however, given the immune response of our bodies, these levels have also been seen to decrease during an active COVID-19 infection. Besides, there is speculation that people living with HIV are at a higher risk for mortality if infected with SARS-CoV-2. Therefore, the interaction of these two viruses can create a syndemic culture, and thus, the need to monitor and treat patients with human immunodeficiency virus and COVID-19 cautiously.

MATH+ protocol for the treatment of SARS-CoV-2 infection: the scientific rationale.

INTRODUCTION: COVID-19 disease progresses through a number of distinct phases. The management of each phase is unique and specific. The pulmonary phase of COVID-19 is characterized by an organizing pneumonia with profound immune dysregulation, activation of clotting, and a severe microvascular injury culminating in severe hypoxemia. The core treatment strategy to manage the pulmonary phase includes the combination of methylprednisolone, ascorbic acid, thiamine, and heparin (MATH+ protocol). The rationale for the MATH+ protocol is reviewed in this paper. AREAS COVERED: We provide an overview on the pathophysiological changes occurring in patients with COVID-19 respiratory failure and a treatment strategy to reverse these changes thereby preventing progressive lung injury and death. EXPERT OPINION: While there is no single 'Silver Bullet' to cure COVID-19, we believe that the severely disturbed pathological processes leading to respiratory failure in patients with COVID-19 organizing pneumonia will respond to the combination of Methylprednisone, Ascorbic acid, Thiamine, and full anticoagulation with Heparin (MATH+ protocol).We believe that it is no longer ethically acceptable to limit management to 'supportive care' alone, in the face of effective, safe, and inexpensive medications that can effectively treat this disease and thereby reduce the risk of complications and death.

Covid-19-induced hepatic encephalopathy: A case report

By the end of December 2019, a single stranded ribonucleic acid (RNA) virus, Coronavirus, was said to be responsible for an outbreak of respiratory infections of unknown origin in Wuhan, China. Globally, this virus has caused over 160,000 deaths and is expected to increase as the pandemic continues. The majority of patients with the coronavirus disease 2019 (COVID-19) infection present symptomatically with fever, shortness of breath, or cough;however, given that the Coronavirus targets the angiotensin converting enzyme 2 receptors (ACE2), it has been suspected that the virus also exhibits neuroinvasive effects. We present a case of a 32-year-old man with a one-week history of progressive shortness of breath, myalgias, arthralgias, fever peaks, who tested positive for COVID-19 and developed acute hepatic encephalopathy with altered mental status.