CMV infection and management among pediatric solid organ transplant recipients.

2022

e14220

2022 Jan 06

1399-3046

<p><strong>BACKGROUND: </strong>Cytomegalovirus (CMV) is an important cause of morbidity and mortality in pediatric solid organ transplant (SOT) recipients. However, the impact of asymptomatic CMV infections (ie, DNAemia) on clinical outcomes is not well established.</p>

<p><strong>METHODS: </strong>We performed a retrospective cohort study of children undergoing first SOT at our institution from January 2012 to June 2018. We evaluated the epidemiology of CMV infections and performed multivariable Cox regression to assess the association between CMV DNAemia without disease or CMV disease (syndrome or end-organ disease) on negative outcomes (death, re-transplantation, or moderate/severe rejection) within the first year after SOT.</p>

<p><strong>RESULTS: </strong>Among 271 individuals, 43 (15.9%) developed ≥1 CMV infection during the first year after SOT. There were 56 unique CMV infections including 14 episodes of CMV disease. In 167 patients offered CMV prophylaxis, only 8 (4.8%) developed their first CMV DNAemia episode while on prophylaxis 32 developed CMV DNAemia after prophylaxis completion; only 1 episode of CMV disease occurred while on antiviral prophylaxis. When accounting for receipt of ATG, oral steroids, and number of immunosuppressives on a given day, CMV disease was more strongly associated with negative outcomes (Hazard Ratio (HR): 3.28, 95% CI: 0.73-14.64; p&nbsp;=&nbsp;.12) than CMV DNAemia without disease (HR 1.42, 95% CI: 0.19- 10.79; p&nbsp;=&nbsp;.74), although not to a statistically significant degree.</p>

<p><strong>CONCLUSIONS: </strong>Most CMV infections occurred after completion of antiviral prophylaxis. CMV disease was more strongly associated with negative outcomes than asymptomatic CMV DNAemia and should be the focus of CMV prevention practices.</p>

10.1111/petr.14220

Pediatr Transplant

34994041

Proteomic Profiling of MIS-C Patients Reveals Heterogeneity Relating to Interferon Gamma Dysregulation and Vascular Endothelial Dysfunction.

2021

2021 Apr 20

<p>Multi-system Inflammatory Syndrome in Children (MIS-C) is a major complication of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic in pediatric patients. Weeks after an often mild or asymptomatic initial infection with SARS-CoV-2 children may present with a severe shock-like picture and marked inflammation. Children with MIS-C present with varying degrees of cardiovascular and hyperinflammatory symptoms. We performed a comprehensive analysis of the plasma proteome of more than 1400 proteins in children with SARS-CoV-2. We hypothesized that the proteome would reflect heterogeneity in hyperinflammation and vascular injury, and further identify pathogenic mediators of disease. Protein signatures demonstrated overlap between MIS-C, and the inflammatory syndromes macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). We demonstrate that PLA2G2A is a key marker of MIS-C that associates with TMA. We found that IFNγ responses are dysregulated in MIS-C patients, and that IFNγ levels delineate clinical heterogeneity.</p>

10.1101/2021.04.13.21255439

medRxiv

33907759

Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations.

2020

6051-6063

2020 12 08

2473-9537

<p>Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory syndrome in children (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. We hypothesized that complement activation plays an important role in SARS-CoV-2 infection in children and sought to understand if TMA was present in these patients. We enrolled 50 hospitalized pediatric patients with acute SARS-CoV-2 infection (n = 21, minimal coronavirus disease 2019 [COVID-19]; n = 11, severe COVID-19) or MIS-C (n = 18). As a biomarker of complement activation and TMA, soluble C5b9 (sC5b9, normal 247 ng/mL) was measured in plasma, and elevations were found in patients with minimal disease (median, 392 ng/mL; interquartile range [IQR], 244-622 ng/mL), severe disease (median, 646 ng/mL; IQR, 203-728 ng/mL), and MIS-C (median, 630 ng/mL; IQR, 359-932 ng/mL) compared with 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL; P &lt; .001). Higher sC5b9 levels were associated with higher serum creatinine (P = .01) but not age. Of the 19 patients for whom complete clinical criteria were available, 17 (89%) met criteria for TMA. A high proportion of tested children with SARS-CoV-2 infection had evidence of complement activation and met clinical and diagnostic criteria for TMA. Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C.</p>

10.1182/bloodadvances.2020003471

Blood Adv

33290544

Convalescent plasma for pediatric patients with SARS-CoV-2-associated acute respiratory distress syndrome.

2020

e28693

2020 Sep 04

1545-5017

<p>There are no proven safe and effective therapies for children who develop life-threatening complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Convalescent plasma (CP) has demonstrated potential benefit in adults with SARS-CoV-2, but has theoretical risks.We present the first report of CP in children with life-threatening coronavirus disease 2019 (COVID-19), providing data on four pediatric patients with acute respiratory distress syndrome. We measured donor antibody levels and recipient antibody response prior to and following CP infusion. Infusion of CP was not associated with antibody-dependent enhancement (ADE) and did not suppress endogenous antibody response. We found CP was safe and possibly efficacious. Randomized pediatric trials are needed.</p>

10.1002/pbc.28693

Pediatr Blood Cancer

32885904

Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2.

2020

2020 Jul 30

1558-8238

<p><strong>BACKGROUND: </strong>Initial reports from the Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to Coronavirus Disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed Multisystem Inflammatory Syndrome in Children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology.</p>

<p><strong>METHODS: </strong>We prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data. Twenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8 and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. Cts and burr cells on blood smears also differentiated between patients with severe COVID-19 and those with MIS-C.</p>

<p><strong>CONCLUSION: </strong>Pediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and severe COVID-19.</p>

10.1172/JCI140970

J. Clin. Invest.

32730233

SARS-CoV-2 seroprevalence among parturient women in Philadelphia.

2020

2020 Jul 29

2470-9468

<p>Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important for determining SARS-CoV-2 exposures within both individuals and populations. We validated a SARS-CoV-2 spike receptor binding domain serological test using 834 pre-pandemic samples and 31 samples from COVID-19 recovered donors. We then completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate exposure to SARS-CoV-2 within the community.</p>

10.1126/sciimmunol.abd5709

Sci Immunol

32727884

SARS-CoV-2 Seroprevalence Among Parturient Women.

2020

2020 Jul 10

<p>Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important to determine exposure and immunity to SARS-CoV-2 within both individuals and populations. We completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We tested 834 pre-pandemic samples collected in 2019 and 15 samples from COVID-19 recovered donors to validate our assay, which has a ~1% false positive rate. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate seroprevalence within the community.</p>

10.1101/2020.07.08.20149179

medRxiv

32676623

The Cost of a Culture and Doctoring at a Distance.

2015

597-9

2015 Nov

2154-1663

10.1542/hpeds.2015-0083

Hosp Pediatr

26526807