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COVID-19 Research
Show moreBackground & aims: Multiple gastrointestinal (GI) symptoms, including diarrhea, nausea/vomiting, and abdominal pain, as well as liver enzyme abnormalities, have been variably reported in patients with coronavirus disease 2019 (COVID-19). This document provides best practice statements and recommendations for consultative management based on a systematic review and meta-analysis of international data on GI and liver manifestations of COVID-19. Methods: We performed a systematic literature search to identify published and unpublished studies using OVID Medline and preprint servers (medRxiv, LitCovid, and SSRN) up until April 5, 2020; major journal sites were monitored for US publications until April 19, 2020. We pooled the prevalence of diarrhea, nausea, vomiting, and abdominal pain, as well as liver function tests abnormalities, using a fixed-effect model and assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. Results: We identified 118 studies and used a hierarchal study selection process to identify unique cohorts. We performed a meta-analysis of 47 studies including 10,890 unique patients. Pooled prevalence estimates of GI symptoms were as follows: diarrhea 7.7% (95% confidence interval [CI], 7.2%-8.2%), nausea/vomiting 7.8% (95% CI, 7.1%-8.5%), and abdominal pain 2.7% (95% CI, 2.0%-3.4%). Most studies reported on hospitalized patients. The pooled prevalence estimates of elevated liver abnormalities were as follows: aspartate transaminase 15.0% (95% CI, 13.6%-16.5%) and alanine transaminase 15.0% (95% CI, 13.6%-16.4%). When we compared studies from China to studies from other countries in subgroup analyses, diarrhea, nausea/vomiting, and liver abnormalities were more prevalent outside of China, with diarrhea reported in 18.3% (95% CI, 16.6%-20.1%). Isolated GI symptoms were reported rarely. We also summarized the Gl and liver adverse effects of the most commonly utilized medications for COVID-19. Conclusions: GI symptoms are associated with COVID-19 in <10% of patients. In studies outside of China, estimates are higher. Further studies are needed with standardized GI symptoms questionnaires and liver function test checks on admission to better quantify and qualify the association of these symptoms with COVID-19. Based on findings from our meta-analysis, we provide several Best Practice Statements for the consultative management of COVID-19. Keywords: COVID-19; Gastrointestinal and Liver Manifestations.
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Show moreEssential workers during the COVID-19 pandemic face heightened levels of anxiety and depression due to increased work demands, lack of adequate personal protective equipment, fear of contracting the virus, and fear of spreading it to loved ones. This is a time of urgent need for mental health support for workers affected by the pandemic crisis. Clinicians may employ empirically supported interventions derived from cognitive behavioral therapy (CBT) and related therapies. Psychological First Aid, an evidence-based crisis intervention, may be utilized to emphasize basic needs and support, but is intended as an acute disaster intervention. Given that a pandemic is an ongoing and prolonged stressor, additional CBT-informed interventions are likely needed to fully support essential workers during these times. It is recommended that clinicians help essential worker clients meet their basic needs by modifying health and sleep habits where possible and helping them advocate for their needs using interpersonal effectiveness skills. Empathic listening, validation of the crisis at hand, and values clarification can aid the therapeutic relationship, help them feel a renewed sense of purpose and meaning in their careers and with their families, and facilitate behavior change consistent with chosen values. Self-monitoring through a daily diary can help clients focus their thoughts and recognize maladaptive patterns in their thoughts and behaviors. In tandem with these techniques, behavioral activation and coping strategies including relaxation, distress tolerance, and acceptance promote engaging in positive and adaptive activities. Finally, therapists can help clients reduce anxiety related to the pandemic by helping them limit information intake.
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Show moreDigestive manifestations appear to be common in patients with coronavirus disease 2019 (COVID19). Gastroenterologists will invariably come into contact with infected patients, and the risk of intraprocedural exposure is well established. Recommendations have been issued to guide personal protective equipment (PPE) use and the triage of procedural urgency, among other operational considerations. In response, institutions providing gastroenterology and endoscopy services have taken urgent action to protect patients and staff, but the uptake and extent of these practice changes in North America is unknown. We conducted a survey of gastroenterology and endoscopy practices to assess the response to the COVID-19 pandemic across the continent.
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Show moreEmerging results indicate that an uncontrolled host immune response, leading to a life-threatening condition called cytokine release syndrome (also termed “cytokine storm”), is the major driver of pathology in severe COVID-19. In this pandemic, considerable effort is being focused on identifying host genomic factors that increase susceptibility or resistance to the complications of COVID-19 and translating these findings to improved patient care. In this regard, the chemokine receptor-ligand nexus has been reported as potentially important in severe COVID-19 disease pathogenesis and its treatment. Valuable genomic insights into the chemokine receptor-ligand nexus have been gained from HIV infection and disease progression studies. Applying that knowledge, together with newly discovered potential host genomic factors associated with COVID-19, may lead to a more comprehensive understanding of the pathogenesis and treatment outcomes in COVID-19 patients.
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Show moreThe pandemic associated with Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV2) and its disease named COVID-19 challenged the scientific community to discover effective therapeutic solutions in a short period. Repurposing existing drugs is one viable approach that emphasizes speed during these urgent times. Famotidine, a class A G protein-coupled receptor antagonist used for the treatment of gastroesophageal reflux was recently identified in an in silico screening. Additionally, a recent retrospective clinical report showed that the treatment with famotidine provided a good outcome in patients infected with SARS-CoV2. A clinical trial testing effectiveness of famotidine in combination with hydroxychloroquine is currently ongoing in the United States (US). In the 1990s, famotidine was described as an antiviral agent against human immunodeficiency virus (HIV). Interestingly, some HIV protease inhibitors are presently being used against SARS-CoV2. However, it is not clear if famotidine could be effective against SARS-CoV2. Thus, by using a computational analysis, we aimed to examine if the antiviral effect of famotidine could be related to the inhibition of proteases involved in the virus replication. Our results showed that famotidine could interact within the catalytic site of the three proteases associated with SARS-CoV2 replication. However, weak binding affinity of famotidine to these proteases suggests that a successful famotidine therapy could likely be achieved only in combination with other antiviral drugs. Finally, analysis of famotidine’s pharmacokinetic parameters indicated that its effect against SARS-CoV2 infection could be reached only upon intravenous administration. This work will contribute to the pharmacological knowledge of famotidine as an antiviral agent against SARS-CoV2.
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Show moreRATIONALE AND OBJECTIVES: Predictive models and anecdotal articles suggest radiology practices were losing 50-70% of their normal imaging volume during the COVID-19 pandemic. Using actual institutional data, we investigated the change in imaging utilization and revenue during this public health crisis. MATERIALS AND METHODS: Imaging performed within the 8-week span between March 8-April 30, 2020 was categorized into the COVID-19 healthcare crisis timeframe. The first week of this date range and the 10 weeks prior were used to derive the normal practice expected volume. A rolling seven-day total value was used for volume tracking and comparison. Total imaging utilization was derived and organized by patient setting (outpatient, inpatient, emergency) and imaging modality (X-ray, CT, Mammography, MRI, Nuclear Medicine/PET, US). The three highest volume hospitals were analyzed. Revenue information was collected from the hospital billing system. RESULTS: System-wide imaging volume decreased by 55% between April 7-13, 2020. Outpatient exams decreased by 68% relative to normal practice. Emergency exams decreased by 48% and inpatient exams declined by 31%. Mammograms and nuclear medicine scans were the most affected modalities, decreasing by 93% and 61%, respectively. The main campus hospital experienced less relative imaging volume loss compared to the other smaller and outpatient-driven hospitals. At its lowest point, the technical component revenue from main campus imaging services demonstrated a 49% negative variance from normal practice. CONCLUSION; The trends and magnitude of the actual imaging utilization data presented will help inform evidence-based decisions for more accurate volume predictions, policy changes, and institutional preparedness for current and future pandemics.
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Show moreThe global pandemic of COVID-19 is colliding with the epidemic of opioid use disorders (OUD) and other substance use disorders (SUD) in the United States (US). Currently, there is limited data on risks, disparity, and outcomes for COVID-19 in individuals suffering from SUD. This is a retrospective case-control study of electronic health records (EHRs) data of 73,099,850 unique patients, of whom 12,030 had a diagnosis of COVID-19. Patients with a recent diagnosis of SUD (within past year) were at significantly increased risk for COVID-19 (adjusted odds ratio or AOR = 8.699 [8.411–8.997], P < 10(−30)), an effect that was strongest for individuals with OUD (AOR = 10.244 [9.107–11.524], P < 10(−30)), followed by individuals with tobacco use disorder (TUD) (AOR = 8.222 ([7.925–8.530], P < 10(−30)). Compared to patients without SUD, patients with SUD had significantly higher prevalence of chronic kidney, liver, lung diseases, cardiovascular diseases, type 2 diabetes, obesity and cancer. Among patients with recent diagnosis of SUD, African Americans had significantly higher risk of COVID-19 than Caucasians (AOR = 2.173 [2.01–2.349], P < 10(−30)), with strongest effect for OUD (AOR = 4.162 [3.13–5.533], P < 10(−25)). COVID-19 patients with SUD had significantly worse outcomes (death: 9.6%, hospitalization: 41.0%) than general COVID-19 patients (death: 6.6%, hospitalization: 30.1%) and African Americans with COVID-19 and SUD had worse outcomes (death: 13.0%, hospitalization: 50.7%) than Caucasians (death: 8.6%, hospitalization: 35.2%). These findings identify individuals with SUD, especially individuals with OUD and African Americans, as having increased risk for COVID-19 and its adverse outcomes, highlighting the need to screen and treat individuals with SUD as part of the strategy to control the pandemic while ensuring no disparities in access to healthcare support.
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Show moreThe etiological agent of severe acute respiratory syndrome (SARS) has been identified as a novel coronavirus SARS-CoV. Similar to other coronaviruses, spike (S)-glycoprotein of the virus interacts with a cellular receptor and mediates membrane fusion to allow viral entry into susceptible target cells. Accordingly, S-protein plays an important role in virus infection cycle and is the primary target of neutralizing antibodies. To begin to understand its biochemical and immunological properties, we expressed both full-length and ectodomain of the protein in various primate cells. Our results show that the protein has an electrophoretic mobility of about 160–170 kDa. The protein is glycosylated with high mannose and/or hybrid oligosaccharides, which account for approximately 30 kDa of the apparent protein mass. The detection of S-protein by immunoassays was difficult using human convalescent sera, suggesting that the protein may not elicit strong humoral immune response in virus-infected patients. We were able to pseudotype murine leukemia virus particles with S-protein and produce SARS pseudoviruses. Pseudoviruses infected Vero E6 cells in a pH-independent manner and the infection could be specifically inhibited by convalescent sera. Consistent with low levels of antibodies against S-protein, neutralizing activity was weak with 50% neutralization titers ranging between 1:15 to 1:25. To facilitate quantifying pseudovirus-infected cells, which are stained blue with X-Gal, we devised an automated procedure using an ELISPOT analyzer. The high-throughput capacity of this procedure and the safety of using SARS pseudoviruses should make possible large-scale analyses of neutralizing antibody responses against SARS-CoV.
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Show moreBackground: Shortages of personal protective equipment (PPE) including N95 respirators are an urgent concern in the setting of the global COVID-19 pandemic. Decontamination of PPE could be useful to maintain adequate supplies, but there is uncertainty regarding the efficacy of decontamination technologies. Methods: A modification of the American Society for Testing and Materials standard quantitative carrier disk test method (ASTM E-2197-11) was used to examine the effectiveness of 3 methods, including ultraviolet-C (UV-C) light, a high-level disinfection cabinet that generates aerosolized peracetic acid and hydrogen peroxide, and dry heat at 70°C for 30 minutes. We assessed the decontamination of 3 commercial N95 respirators inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and bacteriophages MS2 and Phi6; the latter is an enveloped RNA virus used as a surrogate for coronaviruses. Three and 6 log10 reductions on respirators were considered effective for decontamination and disinfection, respectively. Results: UV-C administered as a 1-minute cycle in a UV-C box or a 30-minute cycle by a room decontamination device reduced contamination but did not meet criteria for decontamination of the viruses from all sites on the N95s. The high-level disinfection cabinet was effective for decontamination of the N95s and achieved disinfection with an extended 31-minute cycle. Dry heat at 70°C for 30 minutes was not effective for decontamination of the bacteriophages. Conclusions: UV-C could be useful to reduce contamination on N95 respirators. However, the UV-C technologies studied did not meet pre-established criteria for decontamination under the test conditions used. The high-level disinfection cabinet was more effective and met criteria for disinfection with an extended cycle. Keywords: N95 respirator; SARS-CoV-2; Ultraviolet-C; decontamination; peracetic acid.
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Show moreIdentifying emergent patterns of coronavirus disease 2019 (COVID-19) at the local level presents a geographic challenge. The need is not only to integrate multiple data streams from different sources, scales, and cadences, but to also identify meaningful spatial patterns in these data, especially in vulnerable settings where even small numbers and low rates are important to pinpoint for early intervention. This paper identifies a gap in current analytical approaches and presents a near-real time assessment of emergent disease that can be used to guide a local intervention strategy: Geographic Monitoring for Early Disease Detection (GeoMEDD). Through integration of a spatial database and two types of clustering algorithms, GeoMEDD uses incoming test data to provide multiple spatial and temporal perspectives on an ever changing disease landscape by connecting cases using different spatial and temporal thresholds. GeoMEDD has proven effective in revealing these different types of clusters, as well as the influencers and accelerators that give insight as to why a cluster exists where it does, and why it evolves, leading to the saving of lives through more timely and geographically targeted intervention.
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