Publications by authors named "Michael G Ison"

158 Publications

Changing Trends in Mortality Among Solid Organ Transplant Recipients Hospitalized for Covid-19 During the Course of the Pandemic.

Am J Transplant 2021 Sep 12. Epub 2021 Sep 12.

Transplant Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, USA.

Mortality among patients hospitalized for Covid-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for Covid-19, we compared 28-day mortality between early 2020 (3/1/20-6/19/20) and late 2020 (6/20/20-12/31/20). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1,435/1,616 (88.8%) SOTR and 971/1,435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (P<0.001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%] and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46-0.98, P=0.016). Between the early and late periods, corticosteroids (≥ 6mg dexamethasone/day) and remdesivir use increased (62/571 [10.9%] vs. 243/402 [61.5%], P <0.001 and 50/571 [8.8%] vs. 213/402 [52.2%], P<0.001, respectively) and hydroxychloroquine and IL-6/IL-6 receptor inhibitor use decreased (329/571 [60.0%] vs. 4/492 [1.0 %], P <0.001 and 73/571 [12.8%] vs. 5/402 [1.2%], P <0.001, respectively). Mortality among SOTR hospitalized for Covid-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study.
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http://dx.doi.org/10.1111/ajt.16840DOI Listing
September 2021

Influenza polymerase inhibitor resistance: Assessment of the current state of the art - A report of the isirv Antiviral group.

Antiviral Res 2021 10 4;194:105158. Epub 2021 Aug 4.

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Victoria, Australia. Electronic address:

It is more than 20 years since the neuraminidase inhibitors, oseltamivir and zanamivir were approved for the treatment and prevention of influenza. Guidelines for global surveillance and methods for evaluating resistance were established initially by the Neuraminidase Inhibitor Susceptibility Network (NISN), which merged 10 years ago with the International Society for influenza and other Respiratory Virus Diseases (isirv) to become the isirv-Antiviral Group (isirv-AVG). With the ongoing development of new influenza polymerase inhibitors and recent approval of baloxavir marboxil, the isirv-AVG held a closed meeting in August 2019 to discuss the impact of resistance to these inhibitors. Following this meeting and review of the current literature, this article is intended to summarize current knowledge regarding the clinical impact of resistance to polymerase inhibitors and approaches for surveillance and methods for laboratory evaluation of resistance, both in vitro and in animal models. We highlight limitations and gaps in current knowledge and suggest some strategies for addressing these gaps, including the need for additional clinical studies of influenza antiviral drug combinations. Lessons learned from influenza resistance monitoring may also be helpful for establishing future drug susceptibility surveillance and testing for SARS-CoV-2.
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http://dx.doi.org/10.1016/j.antiviral.2021.105158DOI Listing
October 2021

A surrogate virus neutralization test to quantify antibody-mediated inhibition of SARS-CoV-2 in finger stick dried blood spot samples.

Sci Rep 2021 07 28;11(1):15321. Epub 2021 Jul 28.

Institute for Policy Research, Northwestern University, Evanston, USA.

The spike protein of SARS-CoV-2 engages the human angiotensin-converting enzyme 2 (ACE2) receptor to enter host cells, and neutralizing antibodies are effective at blocking this interaction to prevent infection. Widespread application of this important marker of protective immunity is limited by logistical and technical challenges associated with live virus methods and venous blood collection. To address this gap, we validated an immunoassay-based method for quantifying neutralization of the spike-ACE2 interaction in a single drop of capillary whole blood, collected on filter paper as a dried blood spot (DBS) sample. Samples are eluted overnight and incubated in the presence of spike antigen and ACE2 in a 96-well solid phase plate. Competitive immunoassay with electrochemiluminescent label is used to quantify neutralizing activity. The following measures of assay performance were evaluated: dilution series of confirmed positive and negative samples, agreement with results from matched DBS-serum samples, analysis of results from DBS samples with known COVID-19 status, and precision (intra-assay percent coefficient of variation; %CV) and reliability (inter-assay; %CV). Dilution series produced the expected pattern of dose-response. Agreement between results from serum and DBS samples was high, with concordance correlation = 0.991. Analysis of three control samples across the measurement range indicated acceptable levels of precision and reliability. Median % surrogate neutralization was 46.9 for PCR confirmed convalescent COVID-19 samples and 0.1 for negative samples. Large-scale testing is important for quantifying neutralizing antibodies that can provide protection against COVID-19 in order to estimate the level of immunity in the general population. DBS provides a minimally-invasive, low cost alternative to venous blood collection, and this scalable immunoassay-based method for quantifying inhibition of the spike-ACE2 interaction can be used as a surrogate for virus-based assays to expand testing across a wide range of settings and populations.
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http://dx.doi.org/10.1038/s41598-021-94653-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319431PMC
July 2021

Genetic regulation of nonsense-mediated decay underlies association with risk of severe COVID-19.

medRxiv 2021 Jul 13. Epub 2021 Jul 13.

Genomic regions have been associated with COVID-19 susceptibility and outcomes, including the chr12q24.13 locus encoding antiviral proteins OAS1-3. Here, we report genetic, functional, and clinical insights into genetic associations within this locus. In Europeans, the risk of hospitalized vs. non-hospitalized COVID-19 was associated with a single 19Kb-haplotype comprised of 76 variants included in a 95% credible set within a large genomic fragment introgressed from Neandertals. The risk haplotype was also associated with impaired spontaneous but not treatment-induced SARS-CoV-2 clearance in a clinical trial with pegIFN-λ1. We demonstrate that two exonic variants, rs10774671 and rs1131454, affect splicing and nonsense-mediated decay of . We suggest that genetically-regulated loss of expression contributes to impaired spontaneous clearance of SARS-CoV-2 and elevated risk of hospitalization for COVID-19. Our results provide the rationale for further clinical studies using interferons to compensate for impaired spontaneous SARS-CoV-2 clearance, particularly in carriers of the risk haplotypes.
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http://dx.doi.org/10.1101/2021.07.09.21260221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288155PMC
July 2021

Antibodies, boosters, and optimizing SARS-CoV-2 vaccines for transplantation: A call for more research.

Am J Transplant 2021 Jul 9. Epub 2021 Jul 9.

Division of Infectious Diseases, Duke University, Durham, North Carolina, USA.

Despite emerging data suggesting reduced antibody responses among solid organ transplant recipients following SARS-CoV-2 vaccine, critical unanswered questions remain. The clinical implications of the reduced humoral response need to be assessed through prospective studies. Studies are likewise needed to inform which vaccine dosing strategies result in improved immunity and if such approaches maximize protection against severe infection in the vulnerable transplant population.
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http://dx.doi.org/10.1111/ajt.16758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441892PMC
July 2021

Outcomes of repeat kidney transplantation following prior graft failure secondary to BK nephropathy: A single-center retrospective study.

Transpl Infect Dis 2021 Aug 9;23(4):e13672. Epub 2021 Jul 9.

Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Background: BK virus is associated with development of nephropathy (BKVN) that can lead to graft failure after renal transplantation. There are limited data on rates of recurrence and outcomes of repeat renal transplantation after prior graft loss caused by BKVN.

Methods: After IRB approval, data on all patients who underwent a repeat renal transplantation after prior graft failure as a result of BKVN were identified. Data on management of patients prior to retransplantation, induction and maintenance immunosuppression, and key clinical and virologic outcomes were collected. Descriptive statistics were used for analysis.

Results: Thirteen patients were identified over a 13-year period, and follow-up of these patients occurred for a median of 4.7 years. Most patients have previous renal transplants removed prior to (7/13, 53.8%) or at the time of retransplantation (3/13, 23.1%). Close virologic monitoring of serum and urine, coupled with early immunosuppression minimization, was associated with few patients developing BK viruria above 1 × 10 c/mL (4/13, 30.8%), BK viremia above 10,000 c/mL (2/13, 15.4%), and biopsy-proven BKVN (1/12, 8.3%); most (8/13, 61.5%) developed BK viruria at any level. Renal function at 1 year post-retransplantation was generally excellent and only 1 patient developed graft failure caused by recurrent focal segmental glomerulosclerosis. In our review of the literature, 2 large observational studies of the UNOS database as well as our analysis of case reports showed excellent graft survival and very low rates of recurrent BKVN leading to graft loss.

Conclusions: Retransplantation after prior graft failure caused by BKVN generally has low rates of recurrence when coupled with close monitoring and early immunosuppression minimization. Removal of failed renal transplant may allow easier monitoring for recurrence.
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http://dx.doi.org/10.1111/tid.13672DOI Listing
August 2021

The Interplay Between Policy and COVID-19 Outbreaks in South Asia: Longitudinal Trend Analysis of Surveillance Data.

JMIR Public Health Surveill 2021 06 17;7(6):e24251. Epub 2021 Jun 17.

Buehler Center for Health Policy & Economics, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.

Background: COVID-19 transmission rates in South Asia initially were under control when governments implemented health policies aimed at controlling the pandemic such as quarantines, travel bans, and border, business, and school closures. Governments have since relaxed public health restrictions, which resulted in significant outbreaks, shifting the global epicenter of COVID-19 to India. Ongoing systematic public health surveillance of the COVID-19 pandemic is needed to inform disease prevention policy to re-establish control over the pandemic within South Asia.

Objective: This study aimed to inform public health leaders about the state of the COVID-19 pandemic, how South Asia displays differences within and among countries and other global regions, and where immediate action is needed to control the outbreaks.

Methods: We extracted COVID-19 data spanning 62 days from public health registries and calculated traditional and enhanced surveillance metrics. We use an empirical difference equation to measure the daily number of cases in South Asia as a function of the prior number of cases, the level of testing, and weekly shifts in variables with a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R.

Results: Traditional surveillance metrics indicate that South Asian countries have an alarming outbreak, with India leading the region with 310,310 new daily cases in accordance with the 7-day moving average. Enhanced surveillance indicates that while Pakistan and Bangladesh still have a high daily number of new COVID-19 cases (n=4819 and n=3878, respectively), their speed of new infections declined from April 12-25, 2021, from 2.28 to 2.18 and 3.15 to 2.35 daily new infections per 100,000 population, respectively, which suggests that their outbreaks are decreasing and that these countries are headed in the right direction. In contrast, India's speed of new infections per 100,000 population increased by 52% during the same period from 14.79 to 22.49 new cases per day per 100,000 population, which constitutes an increased outbreak.

Conclusions: Relaxation of public health restrictions and the spread of novel variants fueled the second wave of the COVID-19 pandemic in South Asia. Public health surveillance indicates that shifts in policy and the spread of new variants correlate with a drastic expansion in the pandemic, requiring immediate action to mitigate the spread of COVID-19. Surveillance is needed to inform leaders whether policies help control the pandemic.
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http://dx.doi.org/10.2196/24251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213065PMC
June 2021

Reply to Lapadula, et al.

Clin Infect Dis 2021 May 20. Epub 2021 May 20.

Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

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http://dx.doi.org/10.1093/cid/ciab468DOI Listing
May 2021

COVID-19 in hospitalized lung and non-lung solid organ transplant recipients: A comparative analysis from a multicenter study.

Am J Transplant 2021 08 24;21(8):2774-2784. Epub 2021 Jul 24.

Division of Infectious Disease, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York.

Lung transplant recipients (LTR) with coronavirus disease 2019 (COVID-19) may have higher mortality than non-lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with COVID-19 to compare mortality by 28 days between hospitalized LTR and non-lung SOTR. Multivariable logistic regression models were used to assess comorbidity-adjusted mortality among LTR vs. non-lung SOTR and to determine risk factors for death in LTR. Of 1,616 SOTR with COVID-19, 1,081 (66%) were hospitalized including 120/159 (75%) LTR and 961/1457 (66%) non-lung SOTR (p = .02). Mortality was higher among LTR compared to non-lung SOTR (24% vs. 16%, respectively, p = .032), and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0-2.6, p = .04). Among LTR, chronic lung allograft dysfunction (aOR 3.3, 95% CI 1.0-11.3, p = .05) was the only independent risk factor for mortality and age >65 years, heart failure and obesity were not independently associated with death. Among SOTR hospitalized for COVID-19, LTR had higher mortality than non-lung SOTR. In LTR, chronic allograft dysfunction was independently associated with mortality.
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http://dx.doi.org/10.1111/ajt.16692DOI Listing
August 2021

Long-Term Infectious Complications of Kidney Transplantation.

Clin J Am Soc Nephrol 2021 Apr 20. Epub 2021 Apr 20.

Division of Pediatric Infectious Diseases, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio

Infections remain a common complication of solid-organ transplantation. Most infections in the first month after transplant are typically health care-associated infections, whereas late infections, beyond 6-12 months, are community-acquired infections. Opportunistic infections most frequently present in the first 12 months post-transplant and can be modulated on prior exposures and use of prophylaxis. In this review, we summarize the current epidemiology of postkidney transplant infections with a focus on key viral (BK polyomavirus, cytomegalovirus, Epstein-Barr virus, and norovirus), bacterial (urinary tract infections and colitis), and fungal infections. Current guidelines for safe living post-transplant are also summarized. Literature supporting prophylaxis and vaccination is also provided.
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http://dx.doi.org/10.2215/CJN.15971020DOI Listing
April 2021

Latin America and the Caribbean SARS-CoV-2 Surveillance: Longitudinal Trend Analysis.

JMIR Public Health Surveill 2021 04 27;7(4):e25728. Epub 2021 Apr 27.

Buehler Center for Health Policy and Economics, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.

Background: The COVID-19 pandemic has placed unprecedented stress on economies, food systems, and health care resources in Latin America and the Caribbean (LAC). Existing surveillance provides a proxy of the COVID-19 caseload and mortalities; however, these measures make it difficult to identify the dynamics of the pandemic and places where outbreaks are likely to occur. Moreover, existing surveillance techniques have failed to measure the dynamics of the pandemic.

Objective: This study aimed to provide additional surveillance metrics for COVID-19 transmission to track changes in the speed, acceleration, jerk, and persistence in the transmission of the pandemic more accurately than existing metrics.

Methods: Through a longitudinal trend analysis, we extracted COVID-19 data over 45 days from public health registries. We used an empirical difference equation to monitor the daily number of cases in the LAC as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. COVID-19 transmission rates were tracked for the LAC between September 30 and October 6, 2020, and between October 7 and 13, 2020.

Results: The LAC saw a reduction in the speed, acceleration, and jerk for the week of October 13, 2020, compared to the week of October 6, 2020, accompanied by reductions in new cases and the 7-day moving average. For the week of October 6, 2020, Belize reported the highest acceleration and jerk, at 1.7 and 1.8, respectively, which is particularly concerning, given its high mortality rate. The Bahamas also had a high acceleration at 1.5. In total, 11 countries had a positive acceleration during the week of October 6, 2020, whereas only 6 countries had a positive acceleration for the week of October 13, 2020. The TAC displayed an overall positive trend, with a speed of 10.40, acceleration of 0.27, and jerk of -0.31, all of which decreased in the subsequent week to 9.04, -0.81, and -0.03, respectively.

Conclusions: Metrics such as new cases, cumulative cases, deaths, and 7-day moving averages provide a static view of the pandemic but fail to identify where and the speed at which SARS-CoV-2 infects new individuals, the rate of acceleration or deceleration of the pandemic, and weekly comparison of the rate of acceleration of the pandemic indicate impending explosive growth or control of the pandemic. Enhanced surveillance will inform policymakers and leaders in the LAC about COVID-19 outbreaks.
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http://dx.doi.org/10.2196/25728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083950PMC
April 2021

SARS-CoV-2 Surveillance System in Canada: Longitudinal Trend Analysis.

JMIR Public Health Surveill 2021 05 10;7(5):e25753. Epub 2021 May 10.

Buehler Center for Health Policy and Economics, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.

Background: The COVID-19 global pandemic has disrupted structures and communities across the globe. Numerous regions of the world have had varying responses in their attempts to contain the spread of the virus. Factors such as public health policies, governance, and sociopolitical climate have led to differential levels of success at controlling the spread of SARS-CoV-2. Ultimately, a more advanced surveillance metric for COVID-19 transmission is necessary to help government systems and national leaders understand which responses have been effective and gauge where outbreaks occur.

Objective: The goal of this study is to provide advanced COVID-19 surveillance metrics for Canada at the country, province, and territory level that account for shifts in the pandemic including speed, acceleration, jerk, and persistence. Enhanced surveillance identifies risks for explosive growth and regions that have controlled outbreaks successfully.

Methods: Using a longitudinal trend analysis study design, we extracted 62 days of COVID-19 data from Canadian public health registries for 13 provinces and territories. We used an empirical difference equation to measure the daily number of cases in Canada as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R.

Results: We compare the week of February 7-13, 2021, with the week of February 14-20, 2021. Canada, as a whole, had a decrease in speed from 8.4 daily new cases per 100,000 population to 7.5 daily new cases per 100,000 population. The persistence of new cases during the week of February 14-20 reported 7.5 cases that are a result of COVID-19 transmissions 7 days earlier. The two most populous provinces of Ontario and Quebec both experienced decreases in speed from 7.9 and 11.5 daily new cases per 100,000 population for the week of February 7-13 to speeds of 6.9 and 9.3 for the week of February 14-20, respectively. Nunavut experienced a significant increase in speed during this time, from 3.3 daily new cases per 100,000 population to 10.9 daily new cases per 100,000 population.

Conclusions: Canada excelled at COVID-19 control early on in the pandemic, especially during the first COVID-19 shutdown. The second wave at the end of 2020 resulted in a resurgence of the outbreak, which has since been controlled. Enhanced surveillance identifies outbreaks and where there is the potential for explosive growth, which informs proactive health policy.
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http://dx.doi.org/10.2196/25753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112542PMC
May 2021

Real-World Experience of Bamlanivimab for COVID-19: A Case-Control Study.

Clin Infect Dis 2021 Apr 13. Epub 2021 Apr 13.

Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Background: COVID-19 has strained healthcare systems with patient hospitalizations and deaths. Anti-spike monoclonal antibodies, including bamlanivimab, have demonstrated reduction in hospitalization rates in clinical trials, yet real-world evidence is lacking.

Methods: We conducted a retrospective case-control study across a single healthcare system of non-hospitalized patients, age 18 years or older, with documented positive SARS-CoV-2 testing, risk factors for severe COVID-19, and referrals for bamlanivimab via emergency use authorization. Cases were defined as patients who received bamlanivimab; contemporary controls had a referral order placed but did not receive bamlanivimab. The primary outcome was 30-day hospitalization rate from initial positive SARS-CoV-2 PCR. Descriptive statistics, including Chi-square and Mann-Whitney U test, were performed. Multivariable logistic regression was used for adjusted analysis to evaluate independent associations with 30-day hospitalization.

Results: Between November 20, 2020 and January 19, 2021, 218 patients received bamlanivimab (cases) and 185 were referred but did not receive drug (controls). Thirty-day hospitalization rate was significantly lower among patients who received bamlanivimab (7.3% v 20.0%, RR 0.37, 95% CI 0.21-0.64, p<0.001), and the number needed to treat was 8. On logistic regression, odds of hospitalization were increased in patients not receiving bamlanivimab and with a higher number of pre-specified comorbidities (OR 4.19 CI: 1.31-2.16, p<0.001; OR 1.68, CI: 2.12-8.30, p<0.001, respectively).

Conclusion: Ambulatory patients with COVID-19 who received bamlanivimab had a lower 30-day hospitalization than control patients in real-world experience. We identified receipt of bamlanivimab and fewer comorbidities as protective factors against hospitalization.
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http://dx.doi.org/10.1093/cid/ciab305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083260PMC
April 2021

The future of SARS-CoV-2 vaccines in transplant recipients: To be determined.

Am J Transplant 2021 08 19;21(8):2629-2630. Epub 2021 Apr 19.

Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

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http://dx.doi.org/10.1111/ajt.16598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250727PMC
August 2021

Surveillance of the Second Wave of COVID-19 in Europe: Longitudinal Trend Analyses.

JMIR Public Health Surveill 2021 04 28;7(4):e25695. Epub 2021 Apr 28.

Buehler Center for Health Policy and Economics, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.

Background: The COVID-19 pandemic has severely impacted Europe, resulting in a high caseload and deaths that varied by country. The second wave of the COVID-19 pandemic has breached the borders of Europe. Public health surveillance is necessary to inform policy and guide leaders.

Objective: This study aimed to provide advanced surveillance metrics for COVID-19 transmission that account for weekly shifts in the pandemic, speed, acceleration, jerk, and persistence, to better understand countries at risk for explosive growth and those that are managing the pandemic effectively.

Methods: We performed a longitudinal trend analysis and extracted 62 days of COVID-19 data from public health registries. We used an empirical difference equation to measure the daily number of cases in Europe as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R.

Results: New COVID-19 cases slightly decreased from 158,741 (week 1, January 4-10, 2021) to 152,064 (week 2, January 11-17, 2021), and cumulative cases increased from 22,507,271 (week 1) to 23,890,761 (week 2), with a weekly increase of 1,383,490 between January 10 and January 17. France, Germany, Italy, Spain, and the United Kingdom had the largest 7-day moving averages for new cases during week 1. During week 2, the 7-day moving average for France and Spain increased. From week 1 to week 2, the speed decreased (37.72 to 33.02 per 100,000), acceleration decreased (0.39 to -0.16 per 100,000), and jerk increased (-1.30 to 1.37 per 100,000).

Conclusions: The United Kingdom, Spain, and Portugal, in particular, are at risk for a rapid expansion in COVID-19 transmission. An examination of the European region suggests that there was a decrease in the COVID-19 caseload between January 4 and January 17, 2021. Unfortunately, the rates of jerk, which were negative for Europe at the beginning of the month, reversed course and became positive, despite decreases in speed and acceleration. Finally, the 7-day persistence rate was higher during week 2 than during week 1. These measures indicate that the second wave of the pandemic may be subsiding, but some countries remain at risk for new outbreaks and increased transmission in the absence of rapid policy responses.
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http://dx.doi.org/10.2196/25695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080962PMC
April 2021

Patterns and persistence of SARS-CoV-2 IgG antibodies in Chicago to monitor COVID-19 exposure.

JCI Insight 2021 05 10;6(9). Epub 2021 May 10.

Center for Genetic Medicine and.

BACKGROUNDEstimates of seroprevalence to SARS-CoV-2 vary widely and may influence vaccination response. We ascertained IgG levels across a single US metropolitan site, Chicago, from June 2020 through December 2020.METHODSParticipants (n = 7935) were recruited through electronic advertising and received materials for a self-sampled dried-blood spot assay through the mail or a minimal contact in-person method. IgG against the receptor-binding domain of SARS-CoV-2 was measured using an established highly sensitive and highly specific assay.RESULTSOverall seroprevalence was 17.9%, with no significant difference between method of contact. Only 2.5% of participants reported having had a diagnosis of COVID-19 based on virus detection, consistent with a 7-fold greater exposure to SARS-CoV-2 measured by serology than that detected by viral testing. The range of IgG level observed in seropositive participants from this community survey overlapped with the range of IgG levels associated with COVID-19 cases having a documented positive PCR test. From a subset of those who participated in repeat testing, half of seropositive individuals retained detectable antibodies for 3 to 4 months.CONCLUSIONQuantitative IgG measurements with a highly specific and sensitive assay indicated more widespread exposure to SARS-CoV-2 than observed by viral testing. The range of IgG concentrations produced from these asymptomatic exposures was similar to IgG levels occurring after documented nonhospitalized COVID-19, which were considerably lower than those produced from hospitalized COVID-19 cases. The differing ranges of IgG response, coupled with the rate of decay of antibodies, may influence response to subsequent viral exposure and vaccine.FundingNational Science Foundation grant 2035114, NIH grant 3UL1TR001422-06S4, NIH National Center for Advancing Translational Sciences grants UL1 TR001422 and UL1 TR002389, Dixon Family Foundation, Northwestern University Cancer Center (NIH grant P30 CA060553), and Walder Foundation's Chicago Coronavirus Assessment Network.
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http://dx.doi.org/10.1172/jci.insight.146148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262291PMC
May 2021

SARS-CoV-2 Vaccination and Solid Organ Transplant Patients: Data Needed to Inform Safety and Efficacy.

Transplantation 2021 Mar 10. Epub 2021 Mar 10.

Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, Illinois Division of Infectious Diseases, Johns Hopkins University, Baltimore, Maryland Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania Division of Infectious Diseases, University of California, San Francisco, San Francisco, California Division of Pediatric Infectious Diseases, Vanderbilt University, Nashville, Tennessee Division of Infectious Diseases, University of Michigan, Ann Arbor, Michigan Vaccine and Infectious Diseases Division, Fred Hutch Cancer Research Center and Division of Infectious Diseases, University of Washington, Seattle, Washington Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts Division of Infectious Diseases, Duke University, Durham, North Carolina.

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http://dx.doi.org/10.1097/TP.0000000000003747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429513PMC
March 2021

Testing deceased organ donors for infections: An organ procurement organization survey.

Am J Transplant 2021 05 11;21(5):1924-1930. Epub 2021 Mar 11.

Northwestern University Transplant Outcomes Research Collaborative, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Organ procurement organizations (OPO) test potential deceased organ donors for infectious diseases required by policy, but many also perform testing for additional infections. The current state of donor testing in the United States is unknown. We sent an IRB approved survey to all 57 U.S. OPOs using REDCap. Descriptive statistics were performed. From the 57 OPOs, we received 46 (80.7%) unique responses with all 11 United Network of Organ Sharing regions represented. Forty of 46 (87%) OPO respondents consulted an Infectious Diseases physician when needed. Eighteen of 46 (39%) tested for West Nile virus (WNV) and 17 of 18 (94%) tested year-round. Eleven of 46 (23.9%) tested for Strongyloides infection while 17 of 46 (37%) tested for Chagas disease. All OPOs performed prospective nucleic acid testing (NAT) for HIV, hepatitis B and hepatitis C on all donors. OPO testing of additional infections has increased since prior surveys but remains variable. Standardization of organ donor infectious diseases evaluation should be considered.
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http://dx.doi.org/10.1111/ajt.16552DOI Listing
May 2021

Surveillance Metrics of SARS-CoV-2 Transmission in Central Asia: Longitudinal Trend Analysis.

J Med Internet Res 2021 02 3;23(2):e25799. Epub 2021 Feb 3.

Buehler Center for Health Policy and Economics, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.

Background: SARS-CoV-2, the virus that caused the global COVID-19 pandemic, has severely impacted Central Asia; in spring 2020, high numbers of cases and deaths were reported in this region. The second wave of the COVID-19 pandemic is currently breaching the borders of Central Asia. Public health surveillance is necessary to inform policy and guide leaders; however, existing surveillance explains past transmissions while obscuring shifts in the pandemic, increases in infection rates, and the persistence of the transmission of COVID-19.

Objective: The goal of this study is to provide enhanced surveillance metrics for SARS-CoV-2 transmission that account for weekly shifts in the pandemic, including speed, acceleration, jerk, and persistence, to better understand the risk of explosive growth in each country and which countries are managing the pandemic successfully.

Methods: Using a longitudinal trend analysis study design, we extracted 60 days of COVID-19-related data from public health registries. We used an empirical difference equation to measure the daily number of cases in the Central Asia region as a function of the prior number of cases, level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R.

Results: COVID-19 transmission rates were tracked for the weeks of September 30 to October 6 and October 7-13, 2020, in Central Asia. The region averaged 11,730 new cases per day for the first week and 14,514 for the second week. Infection rates increased across the region from 4.74 per 100,000 persons to 5.66. Russia and Turkey had the highest 7-day moving averages in the region, with 9836 and 1469, respectively, for the week of October 6 and 12,501 and 1603, respectively, for the week of October 13. Russia has the fourth highest speed in the region and continues to have positive acceleration, driving the negative trend for the entire region as the largest country by population. Armenia is experiencing explosive growth of COVID-19; its infection rate of 13.73 for the week of October 6 quickly jumped to 25.19, the highest in the region, the following week. The region overall is experiencing increases in its 7-day moving average of new cases, infection, rate, and speed, with continued positive acceleration and no sign of a reversal in sight.

Conclusions: The rapidly evolving COVID-19 pandemic requires novel dynamic surveillance metrics in addition to static metrics to effectively analyze the pandemic trajectory and control spread. Policy makers need to know the magnitude of transmission rates, how quickly they are accelerating, and how previous cases are impacting current caseload due to a lag effect. These metrics applied to Central Asia suggest that the region is trending negatively, primarily due to minimal restrictions in Russia.
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http://dx.doi.org/10.2196/25799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861038PMC
February 2021

SARS-CoV-2 Wave Two Surveillance in East Asia and the Pacific: Longitudinal Trend Analysis.

J Med Internet Res 2021 02 1;23(2):e25454. Epub 2021 Feb 1.

Buehler Center for Health Policy and Economics, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.

Background: The COVID-19 pandemic has had a profound global impact on governments, health care systems, economies, and populations around the world. Within the East Asia and Pacific region, some countries have mitigated the spread of the novel coronavirus effectively and largely avoided severe negative consequences, while others still struggle with containment. As the second wave reaches East Asia and the Pacific, it becomes more evident that additional SARS-CoV-2 surveillance is needed to track recent shifts, rates of increase, and persistence associated with the pandemic.

Objective: The goal of this study is to provide advanced surveillance metrics for COVID-19 transmission that account for speed, acceleration, jerk, persistence, and weekly shifts, to better understand country risk for explosive growth and those countries who are managing the pandemic successfully. Existing surveillance coupled with our dynamic metrics of transmission will inform health policy to control the COVID-19 pandemic until an effective vaccine is developed. We provide novel indicators to measure disease transmission.

Methods: Using a longitudinal trend analysis study design, we extracted 330 days of COVID-19 data from public health registries. We used an empirical difference equation to measure the daily number of cases in East Asia and the Pacific as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R.

Results: The standard surveillance metrics for Indonesia, the Philippines, and Myanmar were concerning as they had the largest new caseloads at 4301, 2588, and 1387, respectively. When looking at the acceleration of new COVID-19 infections, we found that French Polynesia, Malaysia, and the Philippines had rates at 3.17, 0.22, and 0.06 per 100,000. These three countries also ranked highest in terms of jerk at 15.45, 0.10, and 0.04, respectively.

Conclusions: Two of the most populous countries in East Asia and the Pacific, Indonesia and the Philippines, have alarming surveillance metrics. These two countries rank highest in new infections in the region. The highest rates of speed, acceleration, and positive upwards jerk belong to French Polynesia, Malaysia, and the Philippines, and may result in explosive growth. While all countries in East Asia and the Pacific need to be cautious about reopening their countries since outbreaks are likely to occur in the second wave of COVID-19, the country of greatest concern is the Philippines. Based on standard and enhanced surveillance, the Philippines has not gained control of the COVID-19 epidemic, which is particularly troubling because the country ranks 4th in population in the region. Without extreme and rigid social distancing, quarantines, hygiene, and masking to reverse trends, the Philippines will remain on the global top 5 list of worst COVID-19 outbreaks resulting in high morbidity and mortality. The second wave will only exacerbate existing conditions and increase COVID-19 transmissions.
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http://dx.doi.org/10.2196/25454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857528PMC
February 2021

Understanding the pharmacokinetics of Favipiravir: Implications for treatment of influenza and COVID-19.

EBioMedicine 2021 Jan 6;63:103204. Epub 2021 Jan 6.

Midwestern University, Colleges of Pharmacy and Graduate Studies, Departments of Pharmacy and Pharmacology, Pharmacometrics Center of Excellence, Downers Grove, IL USA; Northwestern Memorial Hospital, Chicago, IL, USA.

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http://dx.doi.org/10.1016/j.ebiom.2020.103204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785424PMC
January 2021

The limits of refusal: An ethical review of solid organ transplantation and vaccine hesitancy.

Am J Transplant 2021 08 23;21(8):2637-2645. Epub 2021 Jan 23.

Department of Pediatrics, University of Washington, School of Medicine, Seattle, Washington, USA.

Patients pursuing solid organ transplantation are encouraged to receive many vaccines on an accelerated timeline. Vaccination prior to transplantation offers the best chance of developing immunity and may expand the pool of donor organs that candidates can accept without needing posttransplant therapy. Furthermore, transplant recipients are at greater risk for acquiring vaccine-preventable illnesses or succumbing to severe sequelae of such illnesses. However, a rising rate of vaccine refusal has challenged transplant centers to address the phenomenon of vaccine hesitancy. Transplant centers may need to consider adopting a policy of denial of solid organ transplantation on the basis of vaccine refusal for non-medical reasons (i.e., philosophical or religious objections or personal beliefs that vaccines are unnecessary or unsafe). Arguments supporting such a policy are motivated by utility, stewardship, and beneficence. Arguments opposing such a policy emphasize justice and respect for persons, and seek to avoid worsening inequities or medical coercion. This paper examines these arguments and situates them within the special cases of pediatric transplantation, emergent transplantation, and living donation. Ultimately, a uniform national policy addressing vaccine refusal among transplant candidates is needed to resolve this ethical dilemma and establish a consistent, fair, and standard approach to vaccine refusal in transplantation.
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http://dx.doi.org/10.1111/ajt.16472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298607PMC
August 2021

SARS-CoV-2 Surveillance in the Middle East and North Africa: Longitudinal Trend Analysis.

J Med Internet Res 2021 01 15;23(1):e25830. Epub 2021 Jan 15.

Buehler Center for Health Policy and Economics, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.

Background: The COVID-19 pandemic has disrupted the lives of millions and forced countries to devise public health policies to reduce the pace of transmission. In the Middle East and North Africa (MENA), falling oil prices, disparities in wealth and public health infrastructure, and large refugee populations have significantly increased the disease burden of COVID-19. In light of these exacerbating factors, public health surveillance is particularly necessary to help leaders understand and implement effective disease control policies to reduce SARS-CoV-2 persistence and transmission.

Objective: The goal of this study is to provide advanced surveillance metrics, in combination with traditional surveillance, for COVID-19 transmission that account for weekly shifts in the pandemic speed, acceleration, jerk, and persistence to better understand a country's risk for explosive growth and to better inform those who are managing the pandemic. Existing surveillance coupled with our dynamic metrics of transmission will inform health policy to control the COVID-19 pandemic until an effective vaccine is developed.

Methods: Using a longitudinal trend analysis study design, we extracted 30 days of COVID-19 data from public health registries. We used an empirical difference equation to measure the daily number of cases in MENA as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel data model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R.

Results: The regression Wald statistic was significant (χ=859.5, P<.001). The Sargan test was not significant, failing to reject the validity of overidentifying restrictions (χ=16, P=.99). Countries with the highest cumulative caseload of the novel coronavirus include Iran, Iraq, Saudi Arabia, and Israel with 530,380, 426,634, 342,202, and 303,109 cases, respectively. Many of the smaller countries in MENA have higher infection rates than those countries with the highest caseloads. Oman has 33.3 new infections per 100,000 population while Bahrain has 12.1, Libya has 14, and Lebanon has 14.6 per 100,000 people. In order of largest to smallest number of cumulative deaths since January 2020, Iran, Iraq, Egypt, and Saudi Arabia have 30,375, 10,254, 6120, and 5185, respectively. Israel, Bahrain, Lebanon, and Oman had the highest rates of COVID-19 persistence, which is the number of new infections statistically related to new infections in the prior week. Bahrain had positive speed, acceleration, and jerk, signaling the potential for explosive growth.

Conclusions: Static and dynamic public health surveillance metrics provide a more complete picture of pandemic progression across countries in MENA. Static measures capture data at a given point in time such as infection rates and death rates. By including speed, acceleration, jerk, and 7-day persistence, public health officials may design policies with an eye to the future. Iran, Iraq, Saudi Arabia, and Israel all demonstrated the highest rate of infections, acceleration, jerk, and 7-day persistence, prompting public health leaders to increase prevention efforts.
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http://dx.doi.org/10.2196/25830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813562PMC
January 2021

Donor-derived renal allograft mucormycosis in a combined liver and kidney transplantation: Case report and review of the literature.

Transpl Infect Dis 2021 Jun 14;23(3):e13534. Epub 2020 Dec 14.

Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Mucormycosis infrequently may present with isolated renal involvement. Among solid organ transplant recipients, renal allograft mucormycosis has been most often associated with medical tourism or transplantation outside of the western world. We report a case of an HIV/HCV co-infected woman who underwent simultaneous liver and kidney transplantation with a Public Health Service increased risk donor organ. 16 days after transplant, she developed massive hematuria and was found to have renal allograft Rhizopus spp. involvement, we surmise to have been from donor-derived infection. Therapy included nephrectomy, debridement, liposomal amphotericin B, and posaconazole with survival. We reviewed PubMed indexed, English-language cases of isolated renal mucormycosis in general, in HIV/AIDS, and from donor-derived renal allograft infections.
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http://dx.doi.org/10.1111/tid.13534DOI Listing
June 2021

Patterns and persistence of SARS-CoV-2 IgG antibodies in Chicago to monitor COVID-19 exposure.

medRxiv 2021 Mar 16. Epub 2021 Mar 16.

Center for Genetic Medicine, Northwestern University Feinberg School of Medicine.

Background: Estimates of seroprevalence to SARS-CoV-2 vary widely and may influence vaccination response. We ascertained IgG levels across a single US metropolitan site, Chicago, from June 2020 through December 2020.

Methods: Participants (n=7935) were recruited through electronic advertising and received materials for a self-sampled dried blood spot assay through the mail or a minimal contact in person method. IgG to the receptor binding domain of SARS-CoV-2 was measured using an established highly sensitive and highly specific assay.

Results: Overall seroprevalence was 17.9%, with no significant difference between method of contact. Only 2.5% of participants reported having had a diagnosis of COVID-19 based on virus detection, consistent with a 7-fold greater exposure to SARS-CoV-2 measured by serology than detected by viral testing. The range of IgG level observed in seropositive participants from this community survey overlapped with the range of IgG levels associated with COVID-19 cases having a documented positive PCR positive test. From a subset of those who participated in repeat testing, half of seropositive individuals retained detectable antibodies for 3-4 months.

Conclusions: Quantitative IgG measurements with a highly specific and sensitive assay indicate more widespread exposure to SARS-CoV-2 than observed by viral testing. The range of IgG concentration produced from these asymptomatic exposures is similar to IgG levels occurring after documented non-hospitalized COVID-19, which is considerably lower than that produced from hospitalized COVID-19 cases. The differing ranges of IgG response, coupled with the rate of decay of antibodies, may influence response to subsequent viral exposure and vaccine.
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http://dx.doi.org/10.1101/2020.11.17.20233452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685344PMC
March 2021

Dynamic Public Health Surveillance to Track and Mitigate the US COVID-19 Epidemic: Longitudinal Trend Analysis Study.

J Med Internet Res 2020 12 3;22(12):e24286. Epub 2020 Dec 3.

Buehler Center for Health Policy & Economics and Departments of Emergency Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.

Background: The emergence of SARS-CoV-2, the virus that causes COVID-19, has led to a global pandemic. The United States has been severely affected, accounting for the most COVID-19 cases and deaths worldwide. Without a coordinated national public health plan informed by surveillance with actionable metrics, the United States has been ineffective at preventing and mitigating the escalating COVID-19 pandemic. Existing surveillance has incomplete ascertainment and is limited by the use of standard surveillance metrics. Although many COVID-19 data sources track infection rates, informing prevention requires capturing the relevant dynamics of the pandemic.

Objective: The aim of this study is to develop dynamic metrics for public health surveillance that can inform worldwide COVID-19 prevention efforts. Advanced surveillance techniques are essential to inform public health decision making and to identify where and when corrective action is required to prevent outbreaks.

Methods: Using a longitudinal trend analysis study design, we extracted COVID-19 data from global public health registries. We used an empirical difference equation to measure daily case numbers for our use case in 50 US states and the District of Colombia as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R.

Results: Examination of the United States and state data demonstrated that most US states are experiencing outbreaks as measured by these new metrics of speed, acceleration, jerk, and persistence. Larger US states have high COVID-19 caseloads as a function of population size, density, and deficits in adherence to public health guidelines early in the epidemic, and other states have alarming rates of speed, acceleration, jerk, and 7-day persistence in novel infections. North and South Dakota have had the highest rates of COVID-19 transmission combined with positive acceleration, jerk, and 7-day persistence. Wisconsin and Illinois also have alarming indicators and already lead the nation in daily new COVID-19 infections. As the United States enters its third wave of COVID-19, all 50 states and the District of Colombia have positive rates of speed between 7.58 (Hawaii) and 175.01 (North Dakota), and persistence, ranging from 4.44 (Vermont) to 195.35 (North Dakota) new infections per 100,000 people.

Conclusions: Standard surveillance techniques such as daily and cumulative infections and deaths are helpful but only provide a static view of what has already occurred in the pandemic and are less helpful in prevention. Public health policy that is informed by dynamic surveillance can shift the country from reacting to COVID-19 transmissions to being proactive and taking corrective action when indicators of speed, acceleration, jerk, and persistence remain positive week over week. Implicit within our dynamic surveillance is an early warning system that indicates when there is problematic growth in COVID-19 transmissions as well as signals when growth will become explosive without action. A public health approach that focuses on prevention can prevent major outbreaks in addition to endorsing effective public health policies. Moreover, subnational analyses on the dynamics of the pandemic allow us to zero in on where transmissions are increasing, meaning corrective action can be applied with precision in problematic areas. Dynamic public health surveillance can inform specific geographies where quarantines are necessary while preserving the economy in other US areas.
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http://dx.doi.org/10.2196/24286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717896PMC
December 2020

A clade of SARS-CoV-2 viruses associated with lower viral loads in patient upper airways.

EBioMedicine 2020 Dec 11;62:103112. Epub 2020 Nov 11.

Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. Electronic address:

Background: The rapid spread of SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19), has been accompanied by the emergence of distinct viral clades, though their clinical significance remains unclear. Here, we aimed to investigate the phylogenetic characteristics of SARS-CoV-2 infections in Chicago, Illinois, and assess their relationship to clinical parameters.

Methods: We performed whole-genome sequencing of SARS-CoV-2 isolates collected from COVID-19 patients in Chicago in mid-March, 2020. Using these and other publicly available sequences, we performed phylogenetic, phylogeographic, and phylodynamic analyses. Patient data was assessed for correlations between demographic or clinical characteristics and virologic features.

Findings: The 88 SARS-CoV-2 genome sequences in our study separated into three distinct phylogenetic clades. Clades 1 and 3 were most closely related to viral sequences from New York and Washington state, respectively, with relatively broad distributions across the US. Clade 2 was primarily found in the Chicago area with limited distribution elsewhere. At the time of diagnosis, patients infected with Clade 1 viruses had significantly higher average viral loads in their upper airways relative to patients infected with Clade 2 viruses, independent of disease severity.

Interpretation: These results show that multiple variants of SARS-CoV-2 were circulating in the Chicago area in mid-March 2020 that differed in their relative viral loads in patient upper airways. These data suggest that differences in virus genotype can impact viral load and may influence viral spread.

Funding: Dixon Family Translational Research Award, Northwestern University Clinical and Translational Sciences Institute (NUCATS), National Institute of Allergy and Infectious Diseases (NIAID), Lurie Comprehensive Cancer Center, Northwestern University Emerging and Re-emerging Pathogens Program.
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http://dx.doi.org/10.1016/j.ebiom.2020.103112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655495PMC
December 2020

Impact of Screening and Treatment of Ureaplasma spp on Hyperammonemia Syndrome in Lung Transplant Recipients: A Single Center Experience.

Clin Infect Dis 2020 Oct 17. Epub 2020 Oct 17.

Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Background: Infection with Ureaplasma species (spp) has been linked to fatal hyperammonemia syndrome (HS) in lung transplant recipients. We sought to characterize the epidemiology of Ureaplasma spp in candidates and donors and describe outcomes of antimicrobial therapy in preventing and treating HS.

Methods: Candidate testing for Ureaplasma spp was performed with urine culture and PCR pre-transplant. Positive candidates were treated with levofloxacin. Donor testing was performed with bronchoalveolar lavage culture and PCR intraoperatively. From 7/2014-2/2017 patients were treated according to results; from 2/2017-10/2018 recipients received empiric levofloxacin and azithromycin at transplant until testing returned negative. HS was defined as new onset altered mental status after transplant with ammonia > 200 µmol/L.

Results: 60 patients who underwent lung transplant were included. 80% (n = 48) of patients had negative screening tests in donor and candidate pre-lung transplant, 8.3% (n = 5) of recipients had positive Ureaplasma spp testing in urine pre-transplant, and 13.3% (n = 8) had positive donor BAL testing at the time of lung transplant. 3 patients developed HS a median of 7 days post-transplant; 2 died of HS. Recipients of organs with Ureaplasma spp who received empiric therapy did not develop HS. Donors with Ureaplasma spp were younger and more sexually active.

Conclusion: Donor-derived Ureaplasma spp in lung transplant was associated with HS. Screening lung donors for Ureaplasma spp might allow for targeted therapy to reduce risk for development of HS, but future confirmatory studies are needed.
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http://dx.doi.org/10.1093/cid/ciaa1570DOI Listing
October 2020

Ibrutinib for chronic lymphocytic leukemia in the setting of respiratory failure from severe COVID-19 infection: Case report and literature review.

EJHaem 2020 Sep 20. Epub 2020 Sep 20.

Division of Hematology/Oncology, Department of Medicine Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center Chicago Illinois.

Ibrutinib, a known Burton's tyrosine kinase (BTK) and interleukin-2 inducible T-cell kinase (ITK) inhibitor, is used for the treatment of B-cell disorders (chronic lymphocytic leukemia [CLL] and various other lymphomas) and chronic graft versus host disease following allogeneic hematopoietic cell transplantation. Because it is considered an immunosuppressant, continuation of ibrutinib is often debated when patients have an active infection, and this becomes an especially difficult decision in the setting of coronavirus disease 2019 (COVID-19). Here, we describe a patient with CLL who was on ibrutinib then developed severe COVID-19 infection requiring mechanical ventilation. We elected to continue ibrutinib the same day he was intubated, reasoning that BTK inhibition in myeloid immune cells has been shown to reduce or even reverse influenza-mediated acute lung injury and that ITK inhibition in T cells has correlated with reduction in viral replication, and therefore may have an advantage in this setting. Ibrutinib also has been shown to block Src family kinases, which potentially could result in reduction of viral entry and the inflammatory cytokine response in the lungs. The patient was extubated after 9 days with a complex hospital course and eventually discharged on room air. The only way to rationally inform these decisions and explore similar potentially promising leads in this pandemic is to conduct carefully done clinical trials.
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http://dx.doi.org/10.1002/jha2.98DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537222PMC
September 2020
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