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1.
Placenta ; 123: 12-23, 2022 06 01.
Article in English | MEDLINE | ID: covidwho-1815047

ABSTRACT

INTRODUCTION: The effect of SARS-CoV-2 severity or the trimester of infection in pregnant mothers, placentas, and infants is not fully understood. METHODS: A retrospective, observational cohort study in Chapel Hill, NC of 115 mothers with SARS-CoV-2 and singleton pregnancies from December 1, 2019 to May 31, 2021 via chart review to document the infants' weight, length, head circumference, survival, congenital abnormalities, hearing loss, maternal complications, and placental pathology classified by the Amsterdam criteria. RESULTS: Of the 115 mothers, 85.2% were asymptomatic (n = 37) or had mild (n = 61) symptoms, 13.0% had moderate (n = 9) or severe (n = 6) COVID-19, and 1.74% (n = 2) did not have symptoms recorded. Moderate and severe maternal infections were associated with increased C-section, premature delivery, infant NICU admission, and were more likely to occur in Type 1 (p = 0.0055) and Type 2 (p = 0.0285) diabetic mothers. Only one infant (0.870%) became infected with SARS-CoV-2, which was not via the placenta. Most placentas (n = 63, 54.8%) did not show specific histologic findings; however, a subset showed mild maternal vascular malperfusion (n = 26, 22.6%) and/or mild microscopic ascending intrauterine infection (n = 28, 24.3%). The infants had no identifiable congenital abnormalities, and all infants and mothers survived. DISCUSSION: Most mothers and their infants had a routine clinical course; however, moderate and severe COVID-19 maternal infections were associated with pregnancy complications and premature delivery. Mothers with pre-existing, non-gestational diabetes were at greatest risk of developing moderate or severe COVID-19. The placental injury patterns of maternal vascular malperfusion and/or microscopic ascending intrauterine infection were not associated with maternal COVID-19 severity.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Premature Birth , Female , Humans , Immunoglobulin G , Infant , Infectious Disease Transmission, Vertical , Mothers , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/pathology , Premature Birth/epidemiology , Premature Birth/pathology , Retrospective Studies , SARS-CoV-2
2.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333686

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has now caused over 2 million deaths worldwide and continues to expand. Currently, much is unknown about functionally neutralizing human antibody responses and durability to SARS-CoV-2. Using convalescent sera collected from 101 COVID-19 recovered individuals 21-212 days after symptom onset with forty-eight additional longitudinal samples, we measured functionality and durability of serum antibodies. We also evaluated associations between individual demographic and clinical parameters with functional neutralizing antibody responses to COVID-19. We found robust antibody durability out to six months, as well as significant positive associations with the magnitude of the neutralizing antibody response and male sex. We also show that SARS-CoV-2 convalescent neutralizing antibodies are higher in individuals with cardio-metabolic comorbidities. SIGNIFICANCE: In this study we found that neutralizing antibody responses in COVID-19 convalescent individuals vary in magnitude but are durable and correlate well with RBD Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex. We also show for the first time, that higher convalescent antibody titers in male donors are associated with increased age and symptom grade. Furthermore, cardio-metabolic co-morbidities are associated with higher antibody titers independently of sex. Here, we present an in-depth evaluation of serologic, demographic, and clinical correlates of functional antibody responses and durability to SARS-CoV-2.

3.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-333608

ABSTRACT

SARS-CoV-2 seroprevalence was low (<1%) in this large population of healthcare workers (HCWs) across the state of Tennessee (n=11,787) in May-June 2020. Among those with PCR results, 81.5% of PCR and antibody test results were concordant. SARS-CoV-2 seroprevalence was higher among HCWs working in high-community-transmission regions and among younger workers. IMPORTANCE: These results may be seen as a baseline assessment of SARS-CoV-2 seroprevalence among HCWs in the American South during a period of growth, but not yet saturation, of infections among susceptible populations. In fact, this period of May-June 2020 was marked by the extension of renewed and sustained community-wide transmission after mandatory quarantine periods expired in several more populous regions of Tennessee. Where community transmission remains low, HCWs may still be able to effectively mitigate SARS-CoV-2 transmission, preserving resources for populations at high risk of severe disease, and these sorts of data help highlight such strategies.

4.
Open Forum Infectious Diseases ; 8(SUPPL 1):S731, 2021.
Article in English | EMBASE | ID: covidwho-1746305

ABSTRACT

Background. We report on a 56 year-old male with prolonged COVID-19 pneumonia who initially improved with dexamethasone and intubation but quickly decompensated. Clinical and radiologic features were consistent with VAP. Tracheal aspirate cultures grew carbapenem-resistant Enterobacter cloacae;meropenem (MEM) MIC was >8 ug/ml (resistant) while ceftazidime-avibactam (CZA) MIC was 2/4 ug/ml (susceptible). Lateral flow antigen assay detected a KPC enzyme. The patient was treated with CZA with steady improvement in respiratory function over the next two weeks. He then experienced an episode of tachycardia, prompting repeat culture. At this point the patient had been extubated: sputum culture grew KPC+ E. cloacae that now showed CZA-resistance (MIC >8/4 ug/ml) and paradoxical decrease in MEM MIC (4 ug/ml);meropenem-vaborbactam (< 2/8 ug/ml) was susceptible. Methods. The pre- & post-CZA therapy E. cloacae isolates underwent whole genome sequencing using the Illumina 150bp paired end protocol;sequences were quality trimmed and compared. Results. A point mutation in the plasmid blaKPC3 gene was identified in the post-CZA therapy isolate, an R163S mutation in the omega loop of the enzyme. ompC and ompF porin genes were analyzed to rule-out decreased influx as a mechanism for CZA-resistance: the pre- and post-CZA isolates had identical porin sequences. Conclusion. This case highlights emerging mutations within KPC carbapenemases that lead to resistance to 'last-line' antimicrobials like CZA. The presumptive mechanism is increased KPC active site promiscuity due to increased omega loop flexibility, allowing increased ceftazidime binding and hydrolysis, and decreased avibactam binding and beta lactamase inhibition. Paradoxically, MEM susceptibility improves after such omega loop mutations, likely due to decreased active site binding affinity, a 'seesaw' effect between MEM and CZA. While authors have reported MEM MICs falling into the 'susceptible' category after an omega loop variant, these bacteria invariably develop secondary mutations leading to MEM treatment failure. Fortunately, given our patient's improved respiratory status, the post-CZA E. cloacae isolate was felt to reflect colonization and the patient was discharged home without antimicrobial therapy.

6.
Muscle & Nerve ; 64:S25-S25, 2021.
Article in English | Web of Science | ID: covidwho-1507506
7.
J Clin Microbiol ; : Jcm0081121, 2021.
Article in English | PubMed | ID: covidwho-1299217

ABSTRACT

Background: SARS-CoV-2 is a novel positive-sense single stranded RNA virus that has caused a recent pandemic. Most patients have a mild disease course, while approximately 20 percent have moderate-to-severe disease, often requiring hospitalization and, in some cases, care in the intensive care unit. Results: By investigating a perceived increased rate of indeterminate QuantiFERON®-TB Gold Plus results in hospitalized COVID patients, we demonstrate that severely ill COVID-19 patients have at least a 6-fold reduction of interferon-gamma (IFN-γ) levels compared to control patients. What is more, over sixty percent of these severely ill COVID-19 patients' peripheral T-cells were found to be unable to produce measurable IFN-γ when stimulated with phytohemagglutinin (PHA), a potent IFN-γ mitogen, reflected by an indeterminate QuantiFERON®-TB Gold Plus. This defect of IFN-γ production was independent of absolute lymphocyte counts and immunosuppressive therapy. It was associated with increased levels of IL-6, which was a predictor of patient outcomes for our cohort when measured early in the course of disease. Finally, in a subset of COVID-19 patients, we found elevated IL-10 levels, in addition to IL-6 elevation. Conclusions: In addition to finding a significant limitation of IGRA testing severely ill COVID-19 patients, these data provide evidence that many of these patients demonstrate a focused Th2 immune response with inhibition of IFN-γ signaling and, in many cases, significant elevations of IL-6.

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