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COVID-19 Research
Show moreObjective: To investigate a cluster of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in employees working on 1 floor of a hospital administration building. Methods: Contact tracing was performed to identify potential exposures and all employees were tested for SARS-CoV-2. Whole-genome sequencing was performed to determine the relatedness of SARS-CoV-2 samples from infected personnel and from control cases in the health-care system with coronavirus disease 2019 (COVID-19) during the same period. Carbon dioxide levels were measured during a workday to assess adequacy of ventilation; readings >800 parts per million (ppm) were considered an indication of suboptimal ventilation. To assess the potential for airborne transmission, DNA-barcoded aerosols were released, and real-time polymerase chain reaction was used to quantify particles recovered from air samples in multiple locations. Results: Between December 22, 2020, and January 8, 2021, 17 coworkers tested positive for SARS-CoV-2, including 13 symptomatic and 4 asymptomatic individuals. Of the 5 cluster SARS-CoV-2 samples sequenced, 3 were genetically related, but these employees denied higher-risk contacts with one another. None of the sequences from the cluster were genetically related to the 17 control sequences of SARS-CoV-2. Carbon dioxide levels increased during a workday but never exceeded 800 ppm. DNA-barcoded aerosol particles were dispersed from the sites of release to locations throughout the floor; 20% of air samples had >1 log10 particles. Conclusions: In a hospital administration building outbreak, sequencing of SARS-CoV-2 confirmed transmission among coworkers. Transmission occurred despite the absence of higher-risk exposures and in a setting with adequate ventilation based on monitoring of carbon dioxide levels.
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Show moreIn this review, we summarize the current status of nucleic acid and antigen testing required for diagnosing SARS-CoV-2 infection and COVID-19 disease. Nucleic acid amplification (NAAT) and antigen-detection (Ag) tests occupy a critically important frontline of defense against SARS-CoV-2 in clinical and public health settings. In early stages of this outbreak, we observed that identifying the causative agent of a new illness of unknown origin was greatly accelerated by characterizing the nucleic acid signature of the novel coronavirus. Results from nucleic acid sequencing led to the development of highly sensitive RT-PCR testing for use in clinical settings and to informing best practices for patient care, and in public health settings to the development of strategies for protecting populations. As the current COVID-19 pandemic has evolved, we have seen how NAAT performance has been used to guide and optimize specimen collection, inform patient triage decisions, reveal unexpected clinical symptoms, clarify risks of transmission within patient care facilities, and guide appropriate treatment strategies. For public health settings during the earliest stages of the pandemic, NAATs served as the only tool available for studying the epidemiology of this new disease by identifying infected individuals, studying transmission patterns, modeling population impacts, and enabling disease control organizations and governments to make challenging disease mitigation recommendations to protect the expanding breadth of populations at risk. With time, the nucleic acid signature has provided the information necessary to understand SARS-CoV-2 protein expression for further development of antigen-based point-of-care (POC) diagnostic tests. The advent of massive parallel sequencing (ie, next generation sequencing) has afforded the characterization of this novel pathogen, informed the sequences best adapted for RT-PCR assays, guided vaccine production, and is currently used for tracking and monitoring SARS-CoV-2 variants.
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Show moreSeveral recent reports have raised concern that infected coworkers may be an important source of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) acquisition by healthcare personnel. In a suspected outbreak among emergency department personnel, sequencing of SARS-CoV-2 confirmed transmission among coworkers. The suspected 6-person outbreak included 2 distinct transmission clusters and 1 unrelated infection.
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Show moreWe report 2 episodes of potential SARS-CoV-2 transmission from infected van drivers to passengers despite masking and physical distancing. Whole-genome sequencing confirmed relatedness of driver and passenger SARS-CoV-2. With the heater operating, fluorescent microspheres were transported by airflow >3 meters from the front to the back of the van.
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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 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 morePURPOSE: To illustrate the change in emergency department (ED) imaging utilization at a multicenter health system in the state of Ohio during the COVID-19 pandemic. METHODS: A retrospective observational study was conducted assessing ED imaging volumes between March 1, 2020, and May 11, 2020, during the COVID-19 crisis. A rolling 7-day total value was used for volume tracking and comparison. Total imaging utilization in the ED was compared with new COVID-19 cases in our region. Utilization was first categorized by modality and then by plain films and computed tomography (CT) scans grouped by body part. CT imaging of the chest was specifically investigated by assessing both CT chest only exams and CT chest, abdomen, and pelvis (C/A/P) exams. Ultimately, matching pair-wise statistical analysis of exam volumes was performed to assess significance of volume change. RESULTS: Our multicenter health system experienced a 46% drop in imaging utilization (p < 0.0001) during the pandemic. Matching pair-wise analysis showed a statistically significant volume decrease by each modality and body part. The exceptions were non-contrast chest CT, which increased (p = 0.0053), and non-trauma C/A/P CT, which did not show a statistically significant volume change (p = 0.0633). CONCLUSION: ED imaging utilization trends revealed through actual health system data will help inform evidence-based decisions for more accurate volume predictions and therefore institutional preparedness for current and future pandemics.
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Show moreRNA viruses are major threats to global society and mass outbreaks can cause long-lasting damage to international economies. RNA and related retro viruses represent a large and diverse family that contribute to the onset of human diseases such as AIDS; certain cancers like T cell lymphoma; severe acute respiratory illnesses as seen with COVID-19; and others. The hallmark of this viral family is the storage of genetic material in the form of RNA, and upon infecting host cells, their RNA genomes reprogram the cellular environment to favor productive viral replication. RNA is a multifunctional biomolecule that not only stores and transmits heritable information, but it also has the capacity to catalyze complex biochemical reactions. It is therefore no surprise that RNA viruses use this functional diversity to their advantage to sustain chronic or lifelong infections. Efforts to subvert RNA viruses therefore requires a deep understanding of the mechanisms by which these pathogens usurp cellular machinery. Here, we briefly summarize several experimental techniques that individually inform on key physicochemical features of viral RNA genomes and their interactions with proteins. Each of these techniques provide important vantage points to understand the complexities of virus-host interactions, but we attempt to make the case that by integrating these and similar methods, more vivid descriptions of how viruses reprogram the cellular environment emerges. These vivid descriptions should expedite the identification of novel therapeutic targets.
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Show moreBACKGROUND: Coronaviruses infect numerous animal species causing a variety of illnesses including respiratory, neurologic and enteric disease. Human coronaviruses (HCoV) are mainly associated with respiratory tract disease but have been implicated in enteric disease. OBJECTIVES: To investigate the frequency of coronaviruses in stool samples from children and adults with gastrointestinal illness by RT-PCR. STUDY DESIGN: Clinical samples submitted for infectious diarrhea testing were collected from December 2007 through March 2008. RNA extraction and RT-PCR was performed for stools negative for Clostridium difficile using primer sets against HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1. Clinical data from samples positive for coronaviruses were reviewed and recorded. RESULTS: Samples from 479 patients were collected including 151 pediatric (<= 18yrs), and 328 adults (> 18yrs). Of these samples, 4 patients (1.3%, 2 adult; 2 pediatric) screened positive for the presence of a coronavirus. All detected coronaviruses were identified as HCoV-HKU1. No stools screened positive for either HCoV-229E, HCoV-NL63 or HCoV-OC43. All HCoV-HKU1 positive samples occurred between mid January to mid February. Clinical manifestations from HCoV-HKU1 positive patients included diarrhea, emesis and respiratory complaints. Three (75%) patients were admitted to the hospital with a median length of stay of 6 days. CONCLUSIONS: Coronaviruses as a group are not commonly identified in stool samples of patients presenting with gastrointestinal illness. HCoV-HKU1 can be identified in stool samples from children and adults with gastrointestinal disease, with most individuals having respiratory findings as well. No stool samples screened positive for HCoV-NL63, HCoV-229E, or HCoV-OC43.
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Show moreBACKGROUND: Current prevention options for upper respiratory infections (URIs) are not optimal. We conducted a randomized, double-blinded, placebo-controlled pilot clinical trial to evaluate the safety and efficacy of ARMS-I™ (currently marketed as Halo™) in the prevention of URIs. METHODS: ARMS-I is patented novel formulation for the prevention and treatment of influenza, comprising a broad-spectrum antimicrobial agent (cetylpyridinium chloride, CPC) and components (glycerin and xanthan gum) that form a barrier on the host mucosa, thus preventing viral contact and invasion. Healthy adults (18–45 years of age) were randomized into ARMS-I or placebo group (50 subjects each). The drug was sprayed intra-orally (3× daily) for 75 days. The primary objectives were to establish whether ARMS-I decreased the frequency, severity or duration of URIs. Secondary objectives were to evaluate safety, tolerability, rate of virus detection, acceptability and adherence; effect on URI-associated absenteeism and medical visits; and effect of prior influenza vaccination on study outcomes. RESULTS: Of the 94 individuals who completed the study (placebo: n = 44, ARMS-I: n = 50), six presented with confirmed URI (placebo: 4, ARMS-I: 2), representing a 55% relative reduction, albeit this was statistically not significant). Influenza, coronavirus or rhinovirus were detected in three participants; all in the placebo group. Moreover, frequency of post-treatment exit visits was reduced by 55% in ARMS-I compared to the placebo group (N = 4 and 2, respectively). Fever was reported only in the placebo group. ARMS-I significantly reduced the frequency and severity of cough and sore throat, and duration of cough (P ≤ .019 for all comparisons). ARMS-I was safe, well tolerated, had high acceptability and high adherence to medication use. Medical visits occurred only in the placebo group while absenteeism did not differ between the two arms. Prior influenza vaccination had no effect on study outcome. CONCLUSIONS: This randomized proof-of-concept clinical trial demonstrated that ARMS-I tended to provide protection against URIs in the enrolled study participants, while reducing severity and duration of cough and sore throat. A clinical trial with a larger number of study participants is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02644135 (retrospectively registered). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-2177-8) contains supplementary material, which is available to authorized users.
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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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Show moreBecause people with asymptomatic SARS-CoV-2 infections are an important source of transmission, widespread testing has the potential to identify and isolate such individuals, quarantine their contacts, and prevent further spread. However, testing for a condition in a group with low disease prevalence may lead to numerous false positive results. This study quantifies the tradeoff between reducing transmission by true positives and unnecessary isolation and quarantine due to false positives.
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Show moreSevere acute respiratory syndrome (SARS) is caused by a novel coronavirus, SARS-CoV. Virus entry into cells is mediated through interactions between spike (S) glycoprotein and angiotensin-converting enzyme 2 (ACE2). Alanine scanning mutagenesis analysis was performed to identify determinants on ACE2 critical for SARS-CoV infection. Results indicated that charged amino acids between residues 22 and 57 were important, K26 and D30, in particular. Peptides representing various regions of ACE2 critical for virus infection were chemically synthesized and evaluated for antiviral activity. Two peptides (a.a. 22–44 and 22–57) exhibited a modest antiviral activity with IC(50) of about 50 μM and 6 μM, respectively. One peptide comprised of two discontinuous segments of ACE2 (a.a. 22–44 and 351–357) artificially linked together by glycine, exhibited a potent antiviral activity with IC(50) of about 0.1 μM. This novel peptide is a promising candidate as a therapeutic agent against this deadly emerging pathogen.
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Show moreBACKGROUND: Clusters of COVID‐19 cases amplify the pandemic and are critical targets for intervention, but comprehensive cluster‐level data are not collected systematically by federal or most state public health entities. This analysis characterizes COVID‐19 clusters among vulnerable populations housed in congregate living settings across an entire community and describes early mitigation efforts. METHODS: The Cuyahoga County Board of Health identified and interviewed COVID‐19 cases and exposed contacts, assessing possible connections to congregate living facilities within its jurisdiction from March 7, 2020, to May 15, 2020, during the first phase of the pandemic, while state of Ohio stay‐at‐home orders were in effect. A multi‐disciplinary team‐based response network was mobilized to support active case finding and develop facility‐focused containment strategies. RESULTS: We identified a cascade of 45 COVID‐19 clusters across community facilities (corrections, nursing, assisted living, intermediate care, extended treatment, shelters, group homes). Attack rates were highest within small facilities (P < .01) and large facilities requiring extensive support to implement effective containment measures. For 25 clusters, we identified an index case who frequently (88%) was a healthcare worker. Engagement of clinical, community, and government partners through public health coordination efforts created opportunities to rapidly develop and coordinate effective response strategies to support the facilities facing the dawning impact of the pandemic. CONCLUSIONS: Active cluster investigations can uncover the dynamics of community transmission affecting both residents of congregate settings and their caregivers and help to target efforts toward populations with ongoing challenges in access to detection and control resources.
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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 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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