• Acute Kidney Injury and Advanced Kidney Disease in the COVID-19 Pandemic: Proceedings From a National Kidney Foundation Symposium

      . Hirsch, Jamie S; Ikizler, Talat Alp; Sharma, Shuchita; Mohammed, Azeem; Department of Radiology and Imaging (Elsevier, 2021-04-17)
      The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented and historic public health crisis that continues to expand and evolve. The National Kidney Foundation held a 2-part continuing medical education live virtual symposium on July 16 and July 24, 2020, to address the multiple challenges of COVID-19 in the context of advanced chronic kidney disease. Faculty addressed the pathophysiology, impact, risks, and management of COVID-19 as it relates to advanced kidney disease. Testing, risk mitigation, and inpatient and outpatient management were also addressed. This concise review addresses major findings of the symposium along with certain updates regarding vaccinations since then. These findings include: (1) severe COVID-19 infection has been associated with acute kidney injury, (2) it is essential to prevent and actively manage acute kidney injury to decrease mortality in these critically ill patients, (3) management of patients with advanced kidney disease should be geared toward minimizing their risk for exposure while making sure they are receiving adequate treatments, and (4) patients with kidney disease, especially ones in advanced stages, should be prioritized for vaccination.
    • COVID-19 RT-PCR diagnostic assay sensitivity and SARS-CoV-2 transmission: A missing link?

      Sahahjpal, Nikhil Shri; Hon, Ephrem Chin Lip; Dallaire, Stephanie; Williams, Colin; Ananth, Sudha; Mondal, Ashis K; Rojiani, Amyn M; Hegde, Madhuri; Kolhe, Ravindra; Department of Pathology (medRxiv, 2021-03-26)
      Background The sensitivity of commercially available RT-PCR assays varies over 10,000 fold, ranging from 10 to 20,000 viral copies/ml. The reporting of high Ct value results has been under scrutiny, as the clinical significance of these values is not yet completely understood. The early detection of infected individuals (high Ct results) in the pre-symptomatic phase of the disease using highly sensitive RT-PCR methods has been argued as a strategy to prevent transmission, while on the contrary, the reporting of high Ct has been criticized as false-positive results causing unnecessary testing and having several negative implications. The purpose of this study was to verify the presence of SARS-CoV-2 genomes in samples with a wide range of RT-PCR Ct values including samples with high Ct (37 to 42) using next-generation sequencing (NGS). Methods The study evaluated a total of 547 previously positive samples tested with the PerkinElmer® New Coronavirus Nucleic Acid Detection RT-PCR kit. The samples included in this study ranged from Ct values of 17-42, with 44 samples having a Ct > 37. Of the 547 samples, 149 were sequenced using PerkinElmer NEXTFLEX Variant-Seq SARS-CoV2 assay on NovaSeq 6000, and 398 samples were sequenced using Illumina SARS-CoV-2 respiratory viral panel kits using the NextSeq 500/550 system. Results Between the two clinical laboratories, a total of ~1.95 million samples were tested using the FDAEUA PerkinElmer® New Coronavirus RT-PCR assay. Of the 1.95 million samples, ~1.72 million were negative, ~250,000 positive, and ~16,500 in the range of 37-42. Of the 547 samples sequenced, the percentage of sequencing reads that aligned to the SARS-CoV-2 Wuhan-hu-1 reference genome (NC_045512.2) ranged from 25.5% to 99.69%. All samples sequenced showed high sequence specificity to the SARS-CoV-2 virus. Low Ct samples showed complete uniform coverage across the entire 29kb SAR-CoV-2 genome. The average coverage in samples with high Ct (>37) was found to be 55.5% (range 16.1-99.2%). However, as sample Ct increased, a gradual decrease in coverage uniformity was observed for few samples. Conclusion This study demonstrates for the first time that the viral RNA is present in the high Ct value range of 37- 42 and the sequence is unique to SARS-CoV-2 confirmed using two separate sequencing assays. This confirms that the detected Ct values are reflective of the presence of the SARS-CoV2 virus and they are not an artifact or contamination. In light of the recent work highlighting the majority of transmission being pre-symptomatic/ asymptomatic, and high Ct results being observed at both the early and late phases of infection warrants further investigation into the clinical utility of high Ct results to curtail the spread of the virus.
    • Human security as biosecurity

      Albert, Craig; Baez, Amado; Rutland, Joshua; Department of Social Sciences (Cambridge University Press (CUP), 2021-01-19)
      Research within security studies has struggled to determine whether infectious disease (ID) represents an existential threat to national and international security. With the emergence of SARS-CoV-2 (COVID-19), it is imperative to reexamine the relationship between ID and global security. This article addresses the specific threat to security from COVID-19, asking, “Is COVID-19 a threat to national and international security?” To investigate this question, this article uses two theoretical approaches: human security and biosecurity. It argues that COVID-19 is a threat to global security by the ontological crisis posed to individuals through human security theory and through high politics, as evidenced by biosecurity. By viewing security threats through the lens of the individual and the state, it becomes clear that ID should be considered an international security threat. This article examines the relevant literature and applies the theoretical framework to a case study analysis focused on the United States.
    • The Effects of the COVID-19 Pandemic on Trauma Presentations in a Level One Trauma Center

      Devarakonda, Aditya K.; Wehrle, Chase J.; Chibane, Fairouz L.; Drevets, Peter D.; Fox, Elizabeth D.; Lawson, Andrew G. (SAGE Publications, 2020-11-24)
      Background: Over 28 million confirmed cases of COVID-19 have been reported to date, resulting in over 900 000 deaths. With an increase in awareness regarding the virus, the behavior of general population has changed dramatically. As activities such as driving and hospital presentation patterns have changed, our study aimed to assess the differences in trauma case variables before and during the COVID-19 pandemic. Methods: Trauma data for the period of March 1st-June 15th were compared for the years 2015-2019 (pre-COVID) and 2020 (COVID). The data were analyzed across the following categories: injury severity score, injury mechanism, motor vehicle crashes (MVCs) vs. other blunt injuries, alcohol involvement, and length of hospital stay. Results: The median injury severity score pre-COVID and during COVID was 9, representing no change. There was no difference in overall distribution of mechanism of injury; however, there was a significant decrease in the percentage of MVCs pre-COVID (36.39%) vs. COVID (29.6%, P < .05). Alcohol was significantly more likely to be involved in trauma during COVID-19 (P < .05). The mean hospital stay increased from 3.87-5.4 days during COVID-19 (P < .05). Discussion: We saw similar results to prior studies in terms of there being no change in trauma severity. Our observation that motor vehicle collisions have decreased is consistent with current data showing decreased use of motor vehicles during the pandemic. We also observed an increase in alcohol-related cases which are consistent with the reported changes in alcohol consumption since the pandemic began.
    • Cannabidiol (CBD) modulation of apelin in acute respiratory distress syndrome

      Salles, Évila Lopes; Khodadadi, Hesam; Jarrahi, Abbas; Ahluwalia, Meenakshi; Paffaro Jr, Valdemar Antonio; Costigliola, Vincenzo; Yu, Jack C.; Hess, David C.; Dhandapani, Krishnan M.; Baban, Babak; et al. (Wiley, 2020-08-28)
      Considering lack of target-specific antiviral treatment and vaccination for COVID-19, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve COVID-19-infected patient outcomes. In a follow-up study to our recent findings indicating the potential of Cannabidiol (CBD) in the treatment of acute respiratory distress syndrome (ARDS), here we show for the first time that CBD may ameliorate the symptoms of ARDS through up-regulation of apelin, a peptide with significant role in the central and peripheral regulation of immunity, CNS, metabolic and cardiovascular system. By administering intranasal Poly (I:C), a synthetic viral dsRNA, while we were able to mimic the symptoms of ARDS in a murine model, interestingly, there was a significant decrease in the expression of apelin in both blood and lung tissues. CBD treatment was able to reverse the symptoms of ARDS towards a normal level. Importantly, CBD treatment increased the apelin expression significantly, suggesting a potential crosstalk between apelinergic system and CBD may be the therapeutic target in the treatment of inflammatory diseases such as COVID-19 and many other pathologic conditions.
    • Clinical validation of innovative, low cost, kit-free, RNA processing protocol for RT-PCR based COVID-19 testing

      Sahajpal, Nikhil Shri; Mondal, Ashis K; Njau, Allan; Ananth, Sudha; Kothandaraman, Arvind; Hegde, Madhuri; Chaubey, Alka; Padala, Sandeep; Kota, Vamsi; Caspary, Kevin; et al. (medRxiv, 2020-07-30)
      The current gold-standard molecular diagnosis for COVID-19 is based on a multi-step assay involving RNA-extraction and RT-PCR analysis for the detection of SARS-CoV-2. RNA34 extraction step has been a major rate-limiting step in implementing high-throughput screening for COVID-19 during this pandemic. Moreover, clinical laboratories are facing several challenges that include cost, reagents, instrumentation, turn-around time, trained personnel, and supply-chain constraints to efficiently implement and sustain testing. Cognizant of these limitations, we evaluated the extraction-free methods described in the literature and have developed an innovative, simplified and easy protocol employing limited reagents to extract RNA for subsequent RT-PCR analysis. Nasopharyngeal-swab samples were subjected to the following individual conditions: 65°C for 15 minutes; 80°C for 5 minutes; 90°C for 5 minutes or 80°C for 1 minute, and processed for direct RT-PCR. These groups were also compared with a supplemental protocol adding isopropanol-ethanol-water elution steps followed by RT-PCR assay. The direct RT-PCR assay did not detect SARS-CoV-2 within the various temperature incubation only groups, whereas, the 90°C for 5 minutes-isopropanol-ethanol-water method was found to be comparable to the FDA-EUA method. Evaluation of the performance metrics for 100 clinical samples demonstrated a sensitivity of 94.2% and a specificity of 100%. The limit of detection was ascertained to be ~40 copies/ml by absolute-quantification. The protocol presented for this assay employs limited reagents and yields results with high sensitivity. Additionally, it presents a simplified methodology that would be easier to implement in laboratories in limited resource countries in order to meet the high current COVID-19 testing needs.