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Phenotype and specificity of T cells in primary human cytomegalovirus infection during pregnancy: IL-7Rpos long-term memory phenotype is associated with protection from vertical transmission.

ABSTRACT: Congenital human cytomegalovirus (HCMV) infection is the major cause of birth defects and a precise definition of the HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection during pregnancy. In this study, a high throughput method was used to define the frequency of CD4+ and CD8+ T cells specific for four HCMV proteins in the naïve compartment of seronegative subjects and the effector/memory compartments of subjects with primary/remote HCMV infection. The naïve repertoire displayed comparable frequencies of T cells that were reactive with HCMV structural (pp65, gB and the pentamer gHgLpUL128L) and non-structural (IE-1) proteins. Whereas, following natural infection, the majority of effector/memory CD4+ and CD8+ T cells recognized either gB or IE-1, respectively, and pp65. The pattern of T cell reactivity was comparable at early and late stages of infection and in pregnant women with primary HCMV infection transmitting or not transmitting the virus to the fetus. At an early stage of primary infection, about 50% of HCMV-reactive CD4+ T cells were long-term IL-7Rpos memory cells, while 6-12 months later, the frequency of these cells increased to 70%, approaching 100% in remote infections. In contrast, only 10-20% of HCMV-specific CD8+ T cells were long-term memory cells up to 12 months after infection onset, thereafter increasing to 70% in remote infections. Interestingly, a significantly higher frequency of HCMV-specific CD4+ T cells with a long-term IL-7Rpos memory phenotype was observed in non-transmitting compared to transmitting women. These findings indicate that immunodominance in HCMV infection is not predetermined in the naïve compartment, but is the result of virus-host interactions and suggest that prompt control of HCMV infection in pregnancy is associated with the rapid development of long-term IL-7Rpos memory HCMV-specific CD4+ T cells and a low risk of virus transmission to the fetus.

SUBMITTER: Mele F

PROVIDER: S-EPMC5675411 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Phenotype and specificity of T cells in primary human cytomegalovirus infection during pregnancy: IL-7Rpos long-term memory phenotype is associated with protection from vertical transmission.

Mele Federico F Fornara Chiara C Jarrossay David D Furione Milena M Arossa Alessia A Spinillo Arsenio A Lanzavecchia Antonio A Gerna Giuseppe G Sallusto Federica F Lilleri Daniele D

PloS one 20171107 11

Congenital human cytomegalovirus (HCMV) infection is the major cause of birth defects and a precise definition of the HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection during pregnancy. In this study, a high throughput method was used to define the frequency of CD4+ and CD8+ T cells specific for four HCMV proteins in the naïve compartment of seronegative subjects and the effector/memory compartments of subjects with primary/remote HCMV in ...[more]

PMID: 29112951

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Project description:BackgroundSince its emergence in December 2019, COVID-19 has spread to over 210 countries, with an estimated mortality rate of 3-4%. Little is understood about its effects during pregnancy.AimsTo describe the current understanding of COVID-19 illness in pregnant women, to describe obstetric outcomes and to identify gaps in the existing knowledge.MethodsMedline Ovid, EMBASE, World Health Organization COVID-19 research database and Cochrane COVID-19 in pregnancy spreadsheet were accessed on 18/4, 18/5 and 23/5 2020. Articles were screened via Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The following were excluded: reviews, opinion pieces, guidelines, articles pertaining solely to other viruses, single case reports.ResultsSixty articles were included in this review. Some pregnant participants may have been included in multiple publications, as admission dates overlap for reports from the same hospital. However, a total of 1287 confirmed SARS-CoV-2 positive pregnant cases are reported. Where universal testing was undertaken, asymptomatic infection occurred in 43.5-92% of cases. In the cohort studies, severe and critical COVID-19 illness rates approximated those of the non-pregnant population. Eight maternal deaths, six neonatal deaths, seven stillbirths and five miscarriages were reported. Nineteen neonates were SARS-CoV-2 positive, confirmed by reverse transcription polymerase chain reaction of nasopharyngeal swabs. [Correction added on 2 September 2020, after first online publication: the number of neonates indicated in the preceding sentence has been corrected from 'Thirteen' to 'Nineteen'.] CONCLUSIONS: Where universal screening was conducted, SARS-CoV-2 infection in pregnancy was often asymptomatic. Severe and critical disease rates approximate those in the general population. Vertical transmission is possible; however, it is unclear whether SARS-CoV-2 positive neonates were infected in utero, intrapartum or postpartum. Future work should assess risks of congenital syndromes and adverse perinatal outcomes where infection occurs in early and mid-pregnancy.

Project description:BackgroundReports on the occurrence and outcome of Visceral Leishmaniasis (VL) in pregnant women is rare in published literature. The occurrence of VL in pregnancy is not systematically captured and cases are rarely followed-up to detect consequences of infection and treatment on the pregnant women and foetus.MethodsA review of all published literature was undertaken to identify cases of VL infections among pregnant women by searching the following database: Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials; World Health Organization Global Index Medicus: LILACS (Americas); IMSEAR (South-East Asia); IMEMR (Eastern Mediterranean); WPRIM (Western Pacific); ClinicalTrials.gov; and the WHO International Clinical Trials Registry Platform. Selection criteria included any clinical reports describing the disease in pregnancy or vertical transmission of the disease in humans. Articles meeting pre-specified inclusion criteria and non-primary research articles such as textbook, chapters, letters, retrospective case description, or reports of accidental inclusion in trials were also considered.ResultsThe systematic literature search identified 272 unique articles of which 54 records were included in this review; a further 18 records were identified from additional search of the references of the included studies or from personal communication leading to a total of 72 records (71 case reports/case series; 1 retrospective cohort study; 1926-2020) describing 451 cases of VL in pregnant women. The disease was detected during pregnancy in 398 (88.2%), retrospectively confirmed after giving birth in 52 (11.5%), and the time of identification was not clear in 1 (0.2%). Of the 398 pregnant women whose infection was identified during pregnancy, 346 (86.9%) received a treatment, 3 (0.8%) were untreated, and the treatment status was not clear in the remaining 49 (12.3%). Of 346 pregnant women, Liposomal amphotericin B (L-AmB) was administered in 202 (58.4%) and pentavalent antimony (PA) in 93 (26.9%). Outcomes were reported in 176 pregnant women treated with L-AmB with 4 (2.3%) reports of maternal deaths, 5 (2.8%) miscarriages, and 2 (1.1%) foetal death/stillbirth. For PA, outcomes were reported in 88 of whom 4 (4.5%) died, 24 (27.3%) had spontaneous abortion, 2 (2.3%) had miscarriages. A total of 26 cases of confirmed, probable or suspected cases of vertical transmission were identified with a median detection time of 6 months (range: 0-18 months).ConclusionsOutcomes of VL treatment during pregnancy is rarely reported and under-researched. The reported articles were mainly case reports and case series and the reported information was often incomplete. From the studies identified, it is difficult to derive a generalisable information on outcomes for pregnant women and babies, although reported data favours the usage of liposomal amphotericin B for the treatment of VL in pregnant women.

Dataset Information

Phenotype and specificity of T cells in primary human cytomegalovirus infection during pregnancy: IL-7Rpos long-term memory phenotype is associated with protection from vertical transmission.

Publications

Phenotype and specificity of T cells in primary human cytomegalovirus infection during pregnancy: IL-7Rpos long-term memory phenotype is associated with protection from vertical transmission.

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