Diagnosis, management, and outcomes of venous thromboembolism in COVID-19 positive patients: a role for direct anticoagulants?

Coronavirus disease 2019 (COVID-19) has been associated with an increased risk of thromboembolic complications due to systemic coagulation activation. Little is known about the role of direct anticoagulants (DOACs) in COVID-19 related thrombosis. In this audit we sought to distinguish COVID-19 hospitalised patients with a diagnosis of venous thromboembolism (VTE) and record their outcomes over a period of 3 months (01/02/2020-30/04/2020). A total of 1583 patients were diagnosed with laboratory proven COVID-19 disease. Amongst them, 38 patients (0.82%) suffered VTE (median age 68 years, male/female: 20/18). VTE was the presenting symptom on admission in 71%. Pulmonary embolism was diagnosed in 92% of patients; 5 patients required intensive care and 3 underwent thrombolysis. 27 patients received initial treatment with unfractionated heparin/low molecular weight heparin (LMWH) while 10 were treated with direct anticoagulants (DOACs). After a median follow up of 25 days, 29 (76%) patients were alive while 5 were still hospitalised. Most patients (83%) were discharged on DOACs, no VTE recurrence or bleeding was recorded post-discharge. Our results suggest that direct anticoagulants could be a safe and effective treatment option in selected COVID-19 positive patients who have suffered venous thromboembolism.

Enhanced MERS coronavirus surveillance of travelers from the Middle East to England.

During the first year of enhanced MERS coronavirus surveillance in England, 77 persons traveling from the Middle East had acute respiratory illness and were tested for the virus. Infection was confirmed in 2 travelers with acute respiratory distress syndrome and 2 of their contacts. Patients with less severe manifestations tested negative.

Stewardship: it's going viral.

Introduction: Historically, antimicrobial stewardship (AMS) has considered the judicious use of antibiotics. AMS is widely adopted across Europe and the US; recently antifungal AMS is gaining momentum but antiviral AMS has been little described. Here we describe the introduction of AMS virology reviews at University Hospitals Birmingham (UHBFT); a novel concept and an opportunity to broaden the beneficial aspects of AMS to virology, termed anti-viral stewardship (AVS). Method: In June 2022, a UK supply issue with aciclovir injection (ACV IV) was announced. In order to review and preserve parenteral ACV for those in greatest need, UHBFT pharmacist and virologists implemented a specialist review for patients prescribed more than 48 hours of treatment. This review initially lasted 10 weeks and data was collected on the advice offered, whether it was accepted, and time required completing the review. Results: AVS rounds halved IV ACV consumption, compared to pre or post intervention levels, with more than half of patients advised to stop or switch to oral therapy. Diagnostics and sampling guidance was offered in one quarter of reviews, whilst the remaining interventions were more stewardship focused. In almost all cases stewardship advice was readily accepted by clinical teams. Due to positive feedback from clinicians and its effective management of supply, the anti-viral stewardship (AVS) programme was re-introduced in June 2023. Conclusions: Antiviral AMS rounds provide an opportunity to optimise sampling, diagnosis and improve patient management. Introduction of regular AVS at UHBFT are now well established and plan to be implemented in other hospitals.

Recurrent SARS-CoV-2 mutations in immunodeficient patients.

Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunodeficient patients are an important source of variation for the virus but are understudied. Many case studies have been published which describe one or a small number of long-term infected individuals but no study has combined these sequences into a cohesive dataset. This work aims to rectify this and study the genomics of this patient group through a combination of literature searches as well as identifying new case series directly from the COVID-19 Genomics UK (COG-UK) dataset. The spike gene receptor-binding domain and N-terminal domain (NTD) were identified as mutation hotspots. Numerous mutations associated with variants of concern were observed to emerge recurrently. Additionally a mutation in the envelope gene, T30I was determined to be the second most frequent recurrently occurring mutation arising in persistent infections. A high proportion of recurrent mutations in immunodeficient individuals are associated with ACE2 affinity, immune escape, or viral packaging optimisation. There is an apparent selective pressure for mutations that aid cell-cell transmission within the host or persistence which are often different from mutations that aid inter-host transmission, although the fact that multiple recurrent de novo mutations are considered defining for variants of concern strongly indicates that this potential source of novel variants should not be discounted.

Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers.

Stem cell transplantation is used widely in the management of a range of diseases of the hemopoietic system. Patients are immunosuppressed profoundly in the early posttransplant period, and reactivation of cytomegalovirus (CMV) remains a significant cause of morbidity and mortality. Adoptive transfer of donor-derived CMV-specific CD8+ T cell clones has been shown to reduce the rate of viral reactivation; however, the complexity of this approach severely limits its clinical application. We have purified CMV-specific CD8+ T cells from the blood of stem cell transplant donors using staining with HLA-peptide tetramers followed by selection with magnetic beads. CMV-specific CD8+ cells were infused directly into nine patients within 4 h of selection. Median cell dosage was 8.6 x 10(3)/kg with a purity of 98% of all T cells. CMV-specific CD8+ T cells became detectable in all patients within 10 d of infusion, and TCR clonotype analysis showed persistence of infused cells in two patients studied. CMV viremia was reduced in every case and eight patients cleared the infection, including one patient who had a prolonged history of CMV infection that was refractory to antiviral therapy. This novel approach to adoptive transfer has considerable potential for antigen-specific T cell therapy.

Correlation between Cepheid GeneXpert and Abbott M2000 assays for HIV viral load measurements.

Measurement of HIV viral load (VL) is the best indicator of success of antiretroviral therapy. We investigated the correlation between results by the Cepheid GeneXpert and a standard of care VL assay (Abbott M2000). This was a prospective study of people living with HIV who attended the department for routine VL measurement with the Abbott M2000. Consenting patients agreed to provide one extra blood sample for VL measurement with the Cepheid GeneXpert assay. One hundred patients consented to participate in the study. There were 18 patients with VL ≥ 40 copies/mL and 75 patients with VL < 40 copies on both assays. The two assays had 93% agreement, with a kappa of 0.79 (p < 0.001). Treating VL as a continuous variable found measurements to be significantly higher on the Cepheid GeneXpert assay than the Abbott (p = 0.002). Analysis of samples with VL ≥ 40 copies/mL on either assay (n = 25) found the mean difference between the two assays to be 0.31 log10 copies/mL (95% limits of agreement: -0.63, 1.25). Whilst the measurements on the two assays are relatively highly correlated, there is a clear bias, with the Cepheid GeneXpert tending to give higher VL values.

Swine flu: a Birmingham experience.

By the beginning of July 2009 the West Midlands had seen more cases of novel H1N1 influenza (swine flu) than any other region in the U.K. Over a three-week period almost 850 people presented to Heartlands Hospital with flu-like symptoms. Of those admitted 52 adults were subsequently confirmed as having H1N1 infection. Most were younger than 30 and not from traditional influenza risk groups. The main risk factor for severe disease was asthma, and to a lesser extent pregnancy and obesity. Seven patients were admitted to intensive care and five developed an acute lung injury requiring prolonged admission. Two patients required extra corporeal membrane oxygenation and one died. Despite increased workload normal clinical services were unaffected. The hospital was not closed to admissions nor was it paralysed by staff absence. With a predicted second wave expected at the end of 2009, efforts to maintain effective community assessment remain crucial.

Impact of a PCR point of care test for influenza A/B on an acute medical unit in a large UK teaching hospital: results of an observational, pre and post intervention study.

Background: Influenza viruses is a leading cause of acute respiratory infection, placing a significant burden on healthcare. To reduce hospital transmission, patients clinically suspected of having influenza are isolated and offered empirical antiviral treatment. Here we report the use of a point of care test (POCT) for influenza viruses in an acute medical unit (AMU) at Queen Elizabeth Hospital Birmingham for patients presenting with influenza-like illness. Methods: A PCR POCT was installed on AMU in Dec 17 - Mar 18 (period 2) and used to test any patient with influenza-like illness. We conducted an evaluation against influenza virus's data collected between Dec 16-Mar 17 (period 1) where no POCT was used. Four outcomes were measured: length of stay, oseltamivir utilisation, time to isolation and in-hospital cases of influenza viruses. Results: There were 51 confirmed influenza virus cases in period 1 vs 666 in period 2. During period 2, the length of stay of patients presenting with influenza-like illness (2.4 vs 7.9 days) and time to isolation from receipt of a positive result (0.09 vs 1.26 days) was significantly shorter. The time to initial receipt of antivirals for patients with influenza virus was significantly quicker in period 2 (0.59 vs 1.1 days) and the total number of influenza virus cases identified after 72 h of admission was significantly lower (9% vs 51%). Discussion: Following introduction of the POCT, there was an increase in appropriately targeted oseltamivir prescribing, shorter time to isolation, proportionally less post-72-h influenza virus cases and a reduction in length of stay of patients presenting with influenza-like illness. Conclusions: Routine use of POCTs for viruses should be introduced into diagnostic pathways for acute respiratory illness, especially at the front door of hospitals.

Seroprevalence of maternal HIV, hepatitis B, and syphilis in a major maternity hospital in North Kordofan, Sudan.

Routine infectious diseases screening of Sudanese pregnant women has been patchy due to scarcity of healthcare resources and social stigma. We sought to determine the seroprevalence of HIV, hepatitis B, and syphilis among pregnant women attending antenatal care (ANC) at El Obeid Maternity Hospital in western Sudan. We also explored the association between these infections and a set of socio-demographic and maternal variables. Unlinked anonymous testing for HIV-1/2 antibodies, hepatitis B surface antigen, and Treponema pallidum antibodies was performed on residual blood samples collected during routine ANC (August 2016-March 2017). Seroprevalence of HIV was 1.13% (5/444; 95% CI 0.37-2.61%), hepatitis B 2.93% (13/444; 95% CI 1.57-4.95%), and syphilis 7.43% (33/444; 95% CI 5.17-10.28%). On bivariate analysis, there were no statistically significant associations between hepatitis B, syphilis, or a composite outcome including any of the three infections and age, stage of pregnancy, gravidity, parity, previous mode of delivery, history of blood transfusion, or husband polygamy. Urgent action is needed to scale up routine maternal screening for HIV, hepatitis B, and syphilis on an opt-out basis. Further research into the socio-demographic and behavioural determinants of these infections as well as their clinical outcomes is needed.

An audit of the results of the Roche Amplicor gonorrhoea test on female genital samples--a cheaper and more sensitive method than culture in an urban English population.

We report an audit of the use of the Roche Amplicor gonorrhoea test in an urban English genitourinary (GU) medicine clinic. A number of studies have shown polymerase chain reaction (PCR) to be more sensitive than culture in detecting Neisseria gonorrhoea (NG) in genital samples. PCR also offers benefits over culture in terms of samples transport and storage requirements but cannot produce antibiotic sensitivities. In this audit, the use of both methods within an algorithm has reduced the overall cost of NG detection by approximately 30%. In all, 4.2% (99 out of 2336) of the endocervical samples were positive, but only 69% (68 out of 99) of these were also positive by culture. Urine samples showed twice as many inhibitory results as positive results: 19 (3%) inhibitory and 10 (1.5%) positive out of 662 samples. The use of the GC PCR in this protocol has been cost-saving and has increased the sensitivity of GC detection, but some results have been difficult to interpret. We hope to remedy this by the introduction of confirmatory testing for discrepant PCR results.

Unexplained abnormal liver function in patients with primary antibody deficiency: could it be chronic hepatitis E infection?

Data from recent studies suggest rising incidence rate of hepatitis E virus (HEV) infection in the UK. HEV infection may take a severe and persistent course in immunocompromised patients, including transplant recipients on immunosuppressives, patients with HIV, haematological malignancies and in idiopathic CD4+ T lymphocytopenia. The prevalence of HEV in primary antibody deficiency (PAD) disorders is still unknown. The aim of this study was to investigate HEV infection in 27 patients with PAD with unexplained, persistently elevated liver enzymes. Although all the 27 patients tested negative for HEV-RNA, we would still strongly recommend that HEV should be considered in any immunodeficient patient with impaired liver function.

Safety and Efficacy of Antiviral Therapy for Prevention of Cytomegalovirus Reactivation in Immunocompetent Critically Ill Patients: A Randomized Clinical Trial.

Importance: Latent cytomegalovirus (CMV) infection is present in more than half the adult population, and a viral reactivation (ie, when the virus becomes measurable in body fluids such as blood) can occur in up to one-third of these individuals during episodes of critical illness. Objective: To determine whether antiviral therapy is safe and effective for preventing CMV reactivation in a general population of critically ill patients. Design, Setting, and Participants: A single-center, open-label, randomized, controlled clinical trial recruited 124 CMV-seropositive patients undergoing mechanical ventilation for at least 24 hours in the intensive care unit between January 1, 2012, and January 31, 2014. The mean baseline Acute Physiology and Chronic Health Evaluation II score of all patients was 17.6. Interventions: Patients were randomized to receive anti-CMV prophylaxis with valacyclovir hydrochloride (n = 34) or low-dose valganciclovir hydrochloride (n = 46) for up to 28 days to suppress viral reactivation, or to a control group with no intervention (n = 44). Main Outcomes and Measures: Time to first CMV reactivation in blood within the 28-day follow-up period following initiation of the study drug. Results: Among the 124 patients in the study (46 women and 78 men; mean [SD] age, 56.9 [16.9] years), viral reactivation in the blood occurred in 12 patients in the control group, compared with 1 patient in the valganciclovir group and 2 patients in the valacyclovir group (combined treatment groups vs control: hazard ratio, 0.14; 95% CI 0.04-0.50). Although this trial was not powered to assess clinical end points, the valacyclovir arm was halted prematurely because of higher mortality; 14 of 34 patients (41.2%) had died by 28 days, compared with 5 of 37 (13.5%) patients in the control arm at the point of the decision to halt this arm. Other safety end points showed similar outcomes between groups. Conclusions and Relevance: Antiviral prophylaxis with valacyclovir or low-dose valganciclovir suppresses CMV reactivation in patients with critical illness. However, given the higher mortality, a large-scale trial would be needed to determine the clinical efficacy and safety of CMV suppression. Trial Registration: clinicaltrials.gov Identifier: NCT01503918.

Predominance of enterovirus B and echovirus 30 as cause of viral meningitis in a UK population.

BACKGROUND/OBJECTIVES: Enteroviruses are the most common cause of aseptic or lymphocytic meningitis, particularly in children. With reports of unusually severe neurological disease in some patients infected with enterovirus D68 in North America, and a recent increase in the number of paediatric enterovirus meningitis cases presenting in this UK Midlands population, a retrospective regional surveillance study was performed. STUDY DESIGN: Cerebrospinal fluid (CSF) samples received were tested using the polymerase chain reaction (PCR) for HSV-1/2, VZV, enteroviruses and parechoviruses. Enterovirus PCR positive CSF samples were sent for further serotyping. A phylogenetic tree was constructed of the echovirus 30 VP1 sequences, where sufficient sample remained for sequencing. RESULTS: The number of enterovirus positive CSFs from each year were: 21 (2008), 7 (2011), 53 (2012), 58 (2013) and 31 (2014). Overall, 163 of the 170 serotyped enteroviruses belonged to the species B (echovirus 5, 6, 7, 9, 11, 13, 16, 17, 18, 21, 25, 30; coxsackie B1, B2, B3, B4, B5, A9), with only 7 belonging to species A (coxsackie A2, A6, A16 and enterovirus 71). Echovirus 30 was the predominant serotype overall, identified in 43 (25.3%) of samples, with a significantly higher proportion in the adult age group (37.3%) compared to the infant age group (12.3%). Phylogenetic analysis showed that these UK Midlands echovirus 30 VP1 sequences clustered most closely with those from Europe and China. CONCLUSION: This study showed a continued predominance of echovirus 30 as a cause of viral meningitis, particularly in adults, though more surveillance is needed.

Active screening and surveillance in the United Kingdom for Middle East respiratory syndrome coronavirus in returning travellers and pilgrims from the Middle East: a prospective descriptive study for the period 2013-2015.

BACKGROUND: Over 25000 pilgrims from the UK visit Saudi Arabia every year for the Umrah and Hajj pilgrimages. The recent outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in South Korea and the continuing reports of MERS-CoV cases from Saudi Arabia highlight the need for active surveillance for MERS-CoV in returning pilgrims or travellers from the Middle East. Public Health England Birmingham Laboratory (PHEBL) is one of a few selected UK public health laboratories responsible for MERS-CoV screening in travellers returning to the UK from the Middle East who present to hospital with severe respiratory symptoms. The results of the PHEBL MERS-CoV screening and surveillance over the past 3 years is presented. METHODS: UK travellers/pilgrims who returned from the Middle East and presented to a hospital with respiratory symptoms were studied over the period February 1, 2013 to December 31, 2015. Patients with respiratory symptoms, who satisfied the Public Health England MERS-CoV case algorithm, were tested for MERS-CoV and other respiratory tract viruses on admission to hospital. RESULTS: Two hundred and two patients suspected of having MERS-CoV were tested. None of them had a laboratory-confirmed MERS-CoV infection. A viral aetiology was detected in half (50.3%) of the cases, with rhinoviruses, influenza A (H1N1 and H3N2), and influenza B being most frequent. Peak testing occurred following the annual Hajj season and in other periods of raised national awareness. CONCLUSIONS: Respiratory tract infections in travellers/pilgrims returning to the UK from the Middle East are mainly due to rhinoviruses, influenza A, and influenza B. Whilst MERS-CoV was not detected in the 202 patients studied, heightened awareness of the possibility of MERS-CoV and continuous proactive surveillance are essential to rapidly identify cases of MERS-CoV and other seasonal respiratory tract viruses such as avian influenza, in patients presenting to hospital. Early identification and isolation may prevent outbreaks in nosocomial settings.