• Low utilisation of bronchoscopy to assess COVID-19 respiratory infection: a multicenter experience

      Mahmood, Kamran; Abbott, Matt; Van Nostrand, Keriann; Bechara, Rabih; Gonzalez, Anne V; Brucker, Amanda; Green, Cynthia L; Polage, Christopher R; Department of Medicine (BMJ, 2021-07-23)
      Objective For the diagnosis of COVID-19, the yield of nasopharyngeal (NP) swabs is unclear, and bronchoalveolar lavage (BAL) is obtained to confirm the diagnosis. We assessed the utilisation of bronchoscopy for COVID-19 diagnosis in a multicenter study and compared the diagnostic yield of BAL versus NP swabs. Methods This retrospective study included all patients who were admitted with clinical presentation concerning for COVID-19 and underwent BAL from 1 March to 31 July 2020 at four tertiary care centres in North America. We also compared concordance of BAL with NP swabs for diagnosis of COVID-19 infection. Results Fifty-three patients, with clinical suspicion for COVID-19 and admitted for respiratory failure, underwent bronchoscopy to collect BAL for SARS-CoV-2 testing. During the same period, 2039 bronchoscopies were performed on patients not infected with COVID-19. Of 42 patients with NP swabs and BAL collected within ≤7 days, 1 was NP swab negative but positive by BAL for SARSCoV-2 (n=1/42 (2.4%)). Across a wide array of testing platforms, the overall agreement between NP swabs and BAL results was 97.6% (95% CI: 93.0% to 100%) with Cohen’s k of 0.90 (95% CI: 0.69 to 1.00). The sensitivity, specificity, positive and negative predictive values of NP swabs compared with BAL were 83.3% (95% CI: 53.5% to 100%), 100%, 100% and 97.3% (95% CI: 92.1% to 100%), respectively. Conclusions BAL was used infrequently to assess COVID-19 in busy institutions. NP swabs have a high concordance with BAL for COVID-19 testing, but negative NP swabs should be confirmed with BAL when clinical suspicion is high.
    • Making a Difference: Adaptation of the Clinical Laboratory in Response to the Rapidly Evolving COVID-19 Pandemic

      Sahajpal, Nikhil S.; Mondal, Ashis K.; Ananth, Sudha; Njau, Allan; Fulzele, Sadanand; Ahaluwalia, Pankaj; Chaubey, Alka; Hegde, Madhuri; Rojiani, Amyn M.; Kolhe, Ravindra; et al. (Sage, 2021-06-29)
      The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, led to unprecedented demands assigned to clinical diagnostic laboratories worldwide, forcing them to make significant changes to their regular workflow as they adapted to new diagnostic tests and sample volumes. Herein, we summarize the modifications/adaptation the laboratory had to exercise to cope with rapidly evolving situations in the current pandemic. In the first phase of the pandemic, the laboratory validated 2 reverse transcription polymerase chain reaction–based assays to test ∼1000 samples/day and rapidly modified procedures and validated various preanalytical and analytical steps to overcome the supply chain constraints that would have otherwise derailed testing efforts. Further, the pooling strategy was validated for wide-scale population screening using nasopharyngeal swab samples and saliva samples. The translational research arm of the laboratory pursued several initiatives to understand the variable clinical manifestations that this virus presented in the population. The phylogenetic evolution of the virus was investigated using next-generation sequencing technology. The laboratory has initiated the formation of a consortium that includes groups investigating genomes at the level of large structural variants, using genome optical mapping via this collaborative global effort. This article summarizes our journey as the laboratory has sought to adapt and continue to positively contribute to the unprecedented demands and challenges of this rapidly evolving pandemic.
    • The Molecular Basis of COVID-19 Pathogenesis, Conventional and Nanomedicine Therapy

      Kouhpayeh, Shirin; Shariati, Laleh; Boshtam, Maryam; Rahimmanesh, Ilnaz; Mirian, Mina; Esmaeili, Yasaman; Najaflu, Malihe; Khanahmad, Negar; Zeinalian, Mehrdad; Trovato, Maria; et al. (MDPI, 2021-05-21)
      In late 2019, a new member of the Coronaviridae family, officially designated as “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), emerged and spread rapidly. The Coronavirus Disease-19 (COVID-19) outbreak was accompanied by a high rate of morbidity and mortality worldwide and was declared a pandemic by the World Health Organization in March 2020. Within the Coronaviridae family, SARS-CoV-2 is considered to be the third most highly pathogenic virus that infects humans, following the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). Four major mechanisms are thought to be involved in COVID-19 pathogenesis, including the activation of the renin-angiotensin system (RAS) signaling pathway, oxidative stress and cell death, cytokine storm, and endothelial dysfunction. Following virus entry and RAS activation, acute respiratory distress syndrome develops with an oxidative/nitrosative burst. The DNA damage induced by oxidative stress activates poly ADP-ribose polymerase-1 (PARP-1), viral macrodomain of non-structural protein 3, poly (ADP-ribose) glycohydrolase (PARG), and transient receptor potential melastatin type 2 (TRPM2) channel in a sequential manner which results in cell apoptosis or necrosis. In this review, blockers of angiotensin II receptor and/or PARP, PARG, and TRPM2, including vitamin D3, trehalose, tannins, flufenamic and mefenamic acid, and losartan, have been investigated for inhibiting RAS activation and quenching oxidative burst. Moreover, the application of organic and inorganic nanoparticles, including liposomes, dendrimers, quantum dots, and iron oxides, as therapeutic agents for SARS-CoV-2 were fully reviewed. In the present review, the clinical manifestations of COVID-19 are explained by focusing on molecular mechanisms. Potential therapeutic targets, including the RAS signaling pathway, PARP, PARG, and TRPM2, are also discussed in depth.
    • Nanobased Platforms for Diagnosis and Treatment of COVID-19: From Benchtop to Bedside

      Bidram, Elham; Esmaeili, Yasaman; Amini, Abbas; Sartorius, Rossella; Tay, Franklin R.; Shariati, Laleh; Makvandi, Pooyan; The Graduate School (American Chemical Society (ACS), 2021-05-12)
      Human respiratory viral infections are the leading cause of morbidity and mortality around the world. Among the various respiratory viruses, coronaviruses (e.g., SARSCoV-2) have created the greatest challenge and most frightening health threat worldwide. Human coronaviruses typically infect the upper respiratory tract, causing illnesses that range from common cold-like symptoms to severe acute respiratory infections. Several promising vaccine formulations have become available since the beginning of 2021. Nevertheless, achievement of herd immunity is still far from being realized. Social distancing remains the only effective measure against SARS-CoV-2 infection. Nanobiotechnology enables the design of nanobiosensors. These nanomedical diagnostic devices have opened new vistas for early detection of viral infections. The present review outlines recent research on the effectiveness of nanoplatforms as diagnostic and antiviral tools against coronaviruses. The biological properties of coronavirus and infected host organs are discussed. The challenges and limitations encountered in combating SARS-CoV-2 are highlighted. Potential nanodevices such as nanosensors, nanobased vaccines, and smart nanomedicines are subsequently presented for combating current and future mutated versions of coronaviruses.
    • A Narrative Review of Factors Historically Influencing Telehealth Use across Six Medical Specialties in the United States

      Rangachari, Pavani; Mushiana, Swapandeep S.; Herbert, Krista; Department of Interdisciplinary Health Sciences; Department of Family Medicine (MDPI, 2021-05-08)
      Prior to the COVID-19 pandemic, studies in the US have identified wide variations in telehealth use across medical specialties. This is an intriguing problem, because the US has historically lacked a standardized set of telehealth coverage and reimbursement policies, which has posed a barrier to telehealth use across all specialties. Although all medical specialties in the US have been affected by these macro (policy-level) barriers, some specialties have been able to integrate telehealth use into mainstream practice, while others are just gaining momentum with telehealth during COVID-19. Although the temporary removal of policy (coverage) restrictions during the pandemic has accelerated telehealth use, uncertainties remain regarding future telehealth sustainability. Since macro (policy-level) factors by themselves do not serve to explain the variation in telehealth use across specialties, it would be important to examine meso (organizational-level) and micro (individual-level) factors historically influencing telehealth use across specialties, to understand underlying reasons for variation and identify implications for widespread sustainability. This paper draws upon the existing literature to develop a conceptual framework on macro-meso-micro factors influencing telehealth use within a medical specialty. The framework is then used to guide a narrative review of the telehealth literature across six medical specialties, including three specialties with lower telehealth use (allergy-immunology, family medicine, gastroenterology) and three with higher telehealth use (psychiatry, cardiology, radiology) in the US, in order to synthesize themes and gain insights into barriers and facilitators to telehealth use. In doing so, this review addresses a gap in the literature and provides a foundation for future research. Importantly, it helps to identify implications for ensuring widespread sustainability of telehealth use in the post-pandemic future.
    • Next-Generation Sequencing (NGS) in COVID-19: A Tool for SARS-CoV-2 Diagnosis, Monitoring New Strains and Phylodynamic Modeling in Molecular Epidemiology

      John, Goldin; Sahajpal, Nikhil Shri; Mondal, Ashis K.; Ananth, Sudha; Williams, Colin; Chaubey, Alka; Rojiani, Amyn M.; Kolhe, Ravindra; Department of Pathology (MDPI, 2021-07-30)
      This review discusses the current testing methodologies for COVID-19 diagnosis and explores next-generation sequencing (NGS) technology for the detection of SARS-CoV-2 and monitoring phylogenetic evolution in the current COVID-19 pandemic. The review addresses the development, fundamentals, assay quality control and bioinformatics processing of the NGS data. This article provides a comprehensive review of the obstacles and opportunities facing the application of NGS technologies for the diagnosis, surveillance, and study of SARS-CoV-2 and other infectious diseases. Further, we have contemplated the opportunities and challenges inherent in the adoption of NGS technology as a diagnostic test with real-world examples of its utility in the fight against COVID-19.
    • The Potential of Lung Epithelium Specific Proteins as Biomarkers for COVID-19-Associated Lung Injury

      Almuntashiri, Sultan; James, Chelsea; Wang, Xiaoyun; Siddiqui, Budder; Zhang, Duo; Division of Infectious Diseases; Vascular Biology Center (MDPI, 2021-09-08)
      Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection was first reported in Wuhan, China, and was declared a pandemic by the World Health Organization (WHO) on 20 March 2020. The respiratory system is the major organ system affected by COVID-19. Numerous studies have found lung abnormalities in patients with COVID-19, including shortness of breath, respiratory failure, and acute respiratory distress syndrome. The identification of lung-specific biomarkers that are easily measurable in serum would be valuable for both clinicians and patients with such conditions. This review is focused on the pneumoproteins and their potential to serve as biomarkers for COVID-19-associated lung injury, including Krebs von den Lungen-6 (KL-6), surfactant proteins (SP-A, SP-B, SP-C, SP-D), and Clara cell secretory protein (CC16). The current findings indicate the aforementioned pneumoproteins may reflect the severity of pulmonary manifestations and could serve as potential biomarkers in COVID-19-related lung injury.
    • SalivaSTAT: Direct-PCR and Pooling of Saliva Samples Collected in Healthcare and Community Setting for SARS-CoV-2 Mass Surveillance

      Sahajpal, Nikhil S.; Mondal, Ashis K.; Ananth, Sudha; Njau, Allan; Ahluwalia, Pankaj; Newnam, Gary; Lozoya-Colinas, Adriana; Hud, Nicholas V.; Kota, Vamsi; Ross, Ted M.; et al. (MDPI, 2021-05-19)
      Objectives: Limitations of widespread current COVID-19 diagnostic testing exist in both the pre-analytical and analytical stages. To alleviate these limitations, we developed a universal saliva processing protocol (SalivaSTAT) that would enable an extraction-free RT-PCR test using commercially available RT-PCR kits. Methods: We optimized saliva collection devices, heat-shock treatment, and homogenization. Saliva samples (879) previously tested using the FDA-EUA method were reevaluated with the optimized SalivaSTAT protocol using two widely available commercial RT-PCR kits. A five-sample pooling strategy was evaluated as per FDA guidelines. Results: Saliva collection (done without any media) showed performance comparable to that of the FDA-EUA method. The SalivaSTAT protocol was optimized by incubating saliva samples at 95 ◦C for 30-min and homogenization, followed by RT-PCR assay. The clinical sample evaluation of 630 saliva samples using the SalivaSTAT protocol with PerkinElmer (600-samples) and CDC (30-samples) RT-PCR assay achieved positive (PPA) and negative percent agreements (NPAs) of 95.0% and 100%, respectively. The LoD was established as ~60–180 copies/mL by absolute quantification. Furthermore, a five-samplepooling evaluation using 250 saliva samples achieved a PPA and NPA of 92% and 100%, respectively. Conclusion: We have optimized an extraction-free RT-PCR assay for saliva samples that demonstrates comparable performance to FDA-EUA assay (Extraction and RT-PCR).
    • Tryptophan-Kynurenine Pathway in COVID-19-Dependent Musculoskeletal Pathology: A Minireview

      Vyavahare, Sagar; Kumar, Sandeep; Cantu, Nicholas; Kolhe, Ravindra; Bollag, Wendy B.; McGee-Lawrence, Meghan E.; Hill, William D.; Hamrick, Mark W.; Isales, Carlos M.; Fulzele, Sadanand; et al. (Hindawi, 2021-10-05)
      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), affecting multiple organ systems, including the respiratory tract and lungs. Several studies have reported that the tryptophan-kynurenine pathway is altered in COVID-19 patients. The tryptophan-kynurenine pathway plays a vital role in regulating inflammation, metabolism, immune responses, and musculoskeletal system biology. In this minireview, we surmise the effects of the kynurenine pathway in COVID-19 patients and how this pathway might impact muscle and bone biology.
    • Understanding the cycles of COVID-19 incidence: Principal Component Analysis and interaction of biological and socio-economic factors

      Duarte, Pablo; Riveros-Perez, Efrain; Department of Anesthesiology and Perioperative Medicine (Elsevier, 2021-06-01)
      The incidence curve of coronavirus disease 19 (COVID-19) shows cyclical patterns over time. We examine the cyclical properties of the incidence curves in various countries and use principal components analysis to shed light on the underlying dynamics that are common to all countries. We find that the cyclical series of 37 countries can be summarized in four principal components which explain over 90% of the variation. We also discuss the influence of complex interactions between biological viral natural history and socio-political reactions and measures adopted by different countries on the cyclical patterns exhibited by COVID-19 around the globe.