Publications

Scholarly Journals--Published

• Liu, T., Chen, Z., Chen, W., Chen, X., Hosseini, M., Yang, Z., Ho D, Turay D, Gheorghe CP, Jones W, Wang, C. (2021). A benchmarking study of SARS-CoV-2 whole-genome sequencing protocols using COVID-19 patient samples. iScience, 102892. doi:10.1016/j.isci.2021.102892 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging new type of coronavirus that is responsible for the COVID-19 pandemic and the unprecedented global health emergency. Whole-genome sequencing (WGS) of SARS-CoV-2 plays a critical role in understanding the disease. Performance variation exists across SARS-CoV-2 viral WGS technologies, but there is currently no benchmarking study comparing different WGS sequencing protocols. We compared seven different SARS-CoV-2 WGS library protocols using RNA from patient nasopharyngeal swab samples under two storage conditions with low and high viral inputs. We found large differences in mappability and genome coverage, and variations in sensitivity, reproducibility, and precision of single-nucleotide variant calling across different protocols. For certain amplicon-based protocols, an appropriate primer trimming step is critical for accurate single-nucleotide variant calling. We ranked the performance of protocols based on six different metrics. Our findings offer guidance in choosing appropriate WGS protocols to characterize SARS-CoV-2 and its evolution. (08/2021) (link)
• Yao, R., Martin, C. B., Haase, V. S., Tse, B. C., Nishino, M., Gheorghe, C., & Balli, K. (2021). Initial clinical characteristics of gravid severe acute respiratory syndrome coronavirus 2-positive patients and the risk of progression to severe coronavirus disease 2019. Am J Obstet Gynecol MFM, 3(4), 100365. doi:10.1016/j.ajogmf.2021.100365 Available data suggest that the obstetric population is particularly vulnerable to severe respiratory syndrome coronavirus 2 infection, with a variable clinical course leading to severe respiratory failure. However, established early warning scores designed to identify patients at risk of clinical deterioration were never validated in the obstetric population. OBJECTIVE: This retrospective cohort study sought to evaluate the initial clinical characteristics of pregnant patients diagnosed with severe acute respiratory syndrome coronavirus 2 infection and to develop a pregnancy-specific early warning score to identify patients at risk for clinical deterioration and requiring advanced respiratory support. STUDY DESIGN: This was a single center, retrospective cohort study of pregnant patients diagnosed with severe acute respiratory syndrome coronavirus 2 infection between April 2020 and December 2020. A total of 50 patients with severe acute respiratory syndrome coronavirus 2 infection between April 2020 and November 2020 were used to create the prediction model. Initial clinical characteristics identified at the time of diagnosis were compared between patients who required advanced respiratory support and those who were asymptomatic or had mild symptoms for those diagnosed during the period of April 2020 to November 2020. Risk factors associated with a requirement for advanced respiratory support were used to create the Obstetric Warning Score system. The Obstetric Warning Score system was then validated using 30 patients diagnosed with severe acute respiratory syndrome coronavirus 2 infection in December 2020. A receiver operating characteristic curve was generated to evaluate the test characteristics of the Obstetric Warning Score system compared with other scoring systems including the Early Warning Score, the National Early Warning Score 2, and the Maternal Early Warning Criteria. RESULTS: Women who required advanced respiratory support were more likely to present with dyspnea (100% vs 33.3%; P<.001), have a higher heart rate (113.4 beats per minute vs 93 beats per minute; P<.001), respiratory rate (23.5 breaths per minute vs 17.7 breaths per minute; P<.001), temperature (99.1 degrees F vs 98.3 degrees F; P=.004), and C-reactive protein level (7.4 mg/dL vs 2.4 mg/dL; P<.001). Furthermore, 88.2% of patients requiring advanced respiratory support showed chest x-ray findings consistent with pneumonia, compared with 20.0% of the patients not requiring advanced respiratory support (P<.001). All patients requiring advanced respiratory support presented with at least 1 coronavirus disease 2019 symptom, whereas only 51.5% of patients not requiring advanced respiratory support were symptomatic (P<.001). The Obstetrical Warning Score model allocated 1 point each for a hazard ratio of >100 beats per minute, temperature of >99.0 degrees F, C-reactive protein level of >2.0 mg/dL, respiratory rate between 20 and 24 breaths per minute, complaints of dyspnea, and a positive chest x-ray. A respiratory rate of >24 breaths per minute was assigned 2 points. The area under the curve for the Obstetric Warning Score system was 0.97 compared with 0.72 for the Early Warning Score system, 0.92 for the National Early Warning Score 2 system, and 0.85 for the Maternal Early Warning Criteria system. An Obstetric Warning Score of >/=3 was predictive of a requirement for advanced respiratory support with a sensitivity of 100%, specificity 64%, and a positive predictive value of 36%. CONCLUSION: The Obstetric Warning Score system presents a validated method for providers to identify pregnant patients who are at risk for respiratory failure and a requirement for advanced respiratory support. (07/2021) (link)
• Gheorghe, C. P., Boring, N., Mann, L., Donepudi, R., Lopez, S. M., Chauhan, S. P.,Papanna, R. (2020). Neonatal Outcomes and Maternal Characteristics in Monochorionic Diamniotic Twin Pregnancies: Uncomplicated versus Twin-to-Twin Transfusion Syndrome Survivors after Fetoscopic Laser Surgery. Fetal Diagn Ther, 47(2), 165-170. doi:10.1159/000500858 Preterm birth remains a major complication of fetal laser surgery (FLS) due to twin-to-twin transfusion syndrome (TTTS). Objectives: We tested the hypothesis that neonatal outcomes in fetuses born at >24 weeks are worse in TTTS survivors compared to uncomplicated monochorionic diamniotic (MCDA) twins. Methods: 196 patients with TTTS treated with laser therapy and 91 uncomplicated MCDA gestations were compared. Neonatal outcomes included respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal death. Risk factors assessed were TTTS, maternal age, maternal body mass index, race, premature prolonged rupture of membranes, stage of TTTS, parity, and gestational age (GA) at delivery. Results: GA at delivery was lower in the TTTS group (31.0 ± 4.6 vs. 33.5 ± 2.4 weeks, p < 0.001). RDS and TTN occurred at higher rates in the TTTS than in the uncomplicated MCDA group. After multivariate logistic regression, the only factor significantly associated with the composite adverse outcome was GA at delivery (OR 0.61; 95% CI: 0.58–0.7). Conclusion: TTTS twins treated with FLS are deliver 2.5 weeks earlier than uncomplicated MCDA twins. Respiratory complications were significantly higher in TTTS twins and were mainly the consequence of the early GA at delivery. (02/2020) (link)