Digital technologies in the public-health response to COVID-19.

Digital technologies are being harnessed to support the public-health response to COVID-19 worldwide, including population surveillance, case identification, contact tracing and evaluation of interventions on the basis of mobility data and communication with the public. These rapid responses leverage billions of mobile phones, large online datasets, connected devices, relatively low-cost computing resources and advances in machine learning and natural language processing. This Review aims to capture the breadth of digital innovations for the public-health response to COVID-19 worldwide and their limitations, and barriers to their implementation, including legal, ethical and privacy barriers, as well as organizational and workforce barriers.

Towards an ultra-rapid smartphone- connected test for infectious diseases.

The development is reported of an ultra-rapid, point-of-care diagnostic device which harnesses surface acoustic wave (SAW) biochips, to detect HIV in a finger prick of blood within 10 seconds (sample-in-result-out). The disposable quartz biochip, based on microelectronic components found in every consumer smartphone, is extremely fast because no complex labelling, amplification or wash steps are needed. A pocket-sized control box reads out the SAW signal and displays results electronically.

Correction: Novel decay dynamics revealed for virus-mediated drug activation in cytomegalovirus infection.

[This corrects the article DOI: 10.1371/journal.ppat.

Novel decay dynamics revealed for virus-mediated drug activation in cytomegalovirus infection.

Human cytomegalovirus (CMV) infection is a substantial cause of morbidity and mortality in immunocompromised hosts and globally is one of the most important congenital infections. The nucleoside analogue ganciclovir (GCV), which requires initial phosphorylation by the viral UL97 kinase, is the mainstay for treatment. To date, CMV decay kinetics during GCV therapy have not been extensively investigated and its clinical implications not fully appreciated.

Cytomegalovirus in pregnancy and the neonate.

Congenital cytomegalovirus (CMV) remains a leading cause of disability in children. Understanding the pathogenesis of infection from the mother via the placenta to the neonate is crucial if we are to produce new interventions and provide supportive mechanisms to improve the outcome of congenitally infected children. In recent years, some major goals have been achieved, including the diagnosis of primary maternal CMV infection in pregnant women by using the anti-CMV IgG avidity test and the diagnosis and prognosis of foetal CMV infection by using polymerase chain reaction real-time tests to detect and quantify the virus in amniotic fluid.

Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy.

Background: To help decide when to start and when to stop pre-emptive therapy for cytomegalovirus infection, we conducted two open-label randomized controlled trials in renal, liver and bone marrow transplant recipients in a single centre where pre-emptive therapy is indicated if viraemia exceeds 3000 genomes/ml (2520 IU/ml) of whole blood.

Methods: Patients with two consecutive viraemia episodes each below 3000 genomes/ml were randomized to continue monitoring or to immediate treatment (Part A). A separate group of patients with viral load greater than 3000 genomes/ml was randomized to stop pre-emptive therapy when two consecutive levels less than 200 genomes/ml (168 IU/ml) or less than 3000 genomes/ml were obtained (Part B).

CMV infected or not CMV infected: that is the question.

Cytomegalovirus (CMV) infection is widespread in the human population. Normally, in adolescents and adults, prior exposure to CMV can readily be determined by IgG assays. However, in individuals where antibody production is impaired, such as patients with common variable immunodeficiency disease or in the very young where maternal antibodies are present, diagnosis of CMV infection is problematic using such assays.

The "silent" global burden of congenital cytomegalovirus.

Human cytomegalovirus (CMV) is a leading cause of congenital infections worldwide. In the developed world, following the virtual elimination of circulating rubella, it is the commonest nongenetic cause of childhood hearing loss and an important cause of neurodevelopmental delay. The seroprevalence of CMV in adults and the incidence of congenital CMV infection are highest in developing countries (1 to 5% of births) and are most likely driven by nonprimary maternal infections.

Acute cytomegalovirus infection is associated with increased frequencies of activated and apoptosis-vulnerable T cells in HIV-1-infected infants.

Cytomegalovirus (CMV) coinfection is associated with infant HIV-1 disease progression and mortality. In a cohort of Kenyan HIV-infected infants, the frequencies of activated (CD38(+) HLA-DR(+)) and apoptosis-vulnerable (CD95(+) Bcl-2(-)) CD4(+) and CD8(+) T cells increased substantially during acute CMV infection. The frequency of activated CD4(+) T cells was strongly associated with both concurrent CMV coinfection (P = 0.

Importance of the cytomegalovirus seropositive recipient as a contributor to disease burden after solid organ transplantation.

Background: The incidence of cytomegalovirus (CMV) syndrome/disease after adult solid organ transplantation in the era effective antiviral therapy has not been fully assessed.

Objective: To determines the incidence of CMV syndrome/disease after solid organ transplantation in the UK.

Study Design: A retrospective analysis of 1807 solid organ transplants from 12 UK solid organ transplant centres representing 32.

Influence of cytomegalovirus infection on immune cell phenotypes in patients with common variable immunodeficiency.

Background: A subset of patients with common variable immunodeficiency (CVID) have debilitating inflammatory complications strongly associated with cytomegalovirus (CMV) infection and a hyperproliferative CMV-specific T-cell response.

Objectives: We studied the T-cell response to CMV and the global effect of this virus on immune effector cell populations in patients with CVID.

Methods: Antibody staining, peptide stimulation, and proliferation assays were used to profile CMV-specific T-cell function.

Differential decay kinetics of human cytomegalovirus glycoprotein B genotypes following antiviral chemotherapy.

Background: The impact of different cytomegalovirus (HCMV) glycoprotein B (gB) genotypes on pathogenesis remains controversial.

Objectives: To investigate the effect of gB genotypes either as single infections or as part of multiple infections on the early kinetics of response to ganciclovir therapy.

Methods: Patients (n=239) enrolled in a study of intravenous ganciclovir or valganciclovir for the treatment of HCMV disease were analysed by a gB genotype specific PCR to quantify the amount of each gB genotype present at initiation of therapy (baseline, day 0) and at days 3, 7, 14 and 21 post therapy.

Summary of the British Transplantation Society Guidelines for the Prevention and Management of CMV Disease After Solid Organ Transplantation.

The third edition of the British Transplantation Society Guidelines for the Prevention and Management of CMV Disease after Solid Organ Transplantation was published in March 2011. This article summarizes the important changes and advances in management in this rapidly evolving field. The pros and cons of universal, or targeted anti-cytomegalovirus (CMV) prophylaxis, and pre-emptive anti-CMV therapy are discussed, especially with respect to advances in CMV polymerase chain reaction monitoring.

Cytomegalovirus quantification: where to next in optimising patient management?

Background: Over the years quantification of cytomegalovirus (HCMV) load in blood has become a mainstay of clinical management helping direct deployment of antiviral therapy, assess response to therapy and highlight cases of drug resistance.

Aims: The review focuses on a brief historical perspective of HCMV quantification and the ways in which viral load is being used to improve patient management.

Methods: A review of the published literature and also personal experience at the Royal Free Hospital.

Inflammation in common variable immunodeficiency is associated with a distinct CD8(+) response to cytomegalovirus.

Background: Common variable immunodeficiency is the most common primary immunodeficiency. A subset of patients has debilitating inflammatory complications.

Objectives: We investigated the role of cytomegalovirus (CMV), and the T-cell response targeted at this virus, in this inflammatory disease.

Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial.

Background: Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia is detected in allograft recipients. Values of viral load correlate with development of end-organ disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vaccine-induced immunity could do likewise.

Immunotherapy and vaccination after transplant: the present, the future.

Vaccination and adoptive immunotherapy for herpes virus infections has become an attractive option for the control of a virus family that negatively affects transplantation. In the future, enhanced ability to select antigen-specific T cells without significant in vitro manipulation should provide new opportunities for refining and enhancing adoptive immunotherapeutic approaches. This article focuses on advances in the area of vaccinology for some of these infections and in the use of adoptive immunotherapy.

Human cytomegalovirus (HCMV) replication kinetics in stem cell transplant recipients following anti-HCMV therapy.

Background: Cytomegalovirus (HCMV) remains an important infection following stem cell transplantation (SCT) and is managed via pre-emptive therapy. In some patients HCMV loads continue to increase after therapy and they experience multiple episodes of replication.

Objectives: To identify the risk factors associated with failure to immediately control HCMV replication after antiviral therapy and for recurrence of replication.

Sequential mutations associated with adaptation of human cytomegalovirus to growth in cell culture.

Mutations that occurred during adaptation of human cytomegalovirus to cell culture were monitored by isolating four strains from clinical samples, passaging them in various cell types and sequencing ten complete virus genomes from the final passages. Mutational dynamics were assessed by targeted sequencing of intermediate passages and the original clinical samples. Gene RL13 and the UL128 locus (UL128L, consisting of genes UL128, UL130 and UL131A) mutated in all strains.

Immunotherapy and vaccination after transplant: the present, the future.

Vaccination and adoptive immunotherapy for herpes virus infections has become an attractive option for the control of a virus family that negatively affects transplantation. In the future, enhanced ability to select antigen-specific T cells without significant in vitro manipulation should provide new opportunities for refining and enhancing adoptive immunotherapeutic approaches. This article focuses on advances in the area of vaccinology for some of these infections and in the use of adoptive immunotherapy.