Clinical features and management of human monkeypox: a retrospective observational study in the UK.

BACKGROUND: Cases of human monkeypox are rarely seen outside of west and central Africa. There are few data regarding viral kinetics or the duration of viral shedding and no licensed treatments. Two oral drugs, brincidofovir and tecovirimat, have been approved for treatment of smallpox and have demonstrated efficacy against monkeypox in animals. Our aim was to describe the longitudinal clinical course of monkeypox in a high-income setting, coupled with viral dynamics, and any adverse events related to novel antiviral therapies. METHODS: In this retrospective observational study, we report the clinical features, longitudinal virological findings, and response to off-label antivirals in seven patients with monkeypox who were diagnosed in the UK between 2018 and 2021, identified through retrospective case-note review. This study included all patients who were managed in dedicated high consequence infectious diseases (HCID) centres in Liverpool, London, and Newcastle, coordinated via a national HCID network. FINDINGS: We reviewed all cases since the inception of the HCID (airborne) network between Aug 15, 2018, and Sept 10, 2021, identifying seven patients. Of the seven patients, four were men and three were women. Three acquired monkeypox in the UK: one patient was a health-care worker who acquired the virus nosocomially, and one patient who acquired the virus abroad transmitted it to an adult and child within their household cluster. Notable disease features included viraemia, prolonged monkeypox virus DNA detection in upper respiratory tract swabs, reactive low mood, and one patient had a monkeypox virus PCR-positive deep tissue abscess. Five patients spent more than 3 weeks (range 22-39 days) in isolation due to prolonged PCR positivity. Three patients were treated with brincidofovir (200 mg once a week orally), all of whom developed elevated liver enzymes resulting in cessation of therapy. One patient was treated with tecovirimat (600 mg twice daily for 2 weeks orally), experienced no adverse effects, and had a shorter duration of viral shedding and illness (10 days hospitalisation) compared with the other six patients. One patient experienced a mild relapse 6 weeks after hospital discharge. INTERPRETATION: Human monkeypox poses unique challenges, even to well resourced health-care systems with HCID networks. Prolonged upper respiratory tract viral DNA shedding after skin lesion resolution challenged current infection prevention and control guidance. There is an urgent need for prospective studies of antivirals for this disease. FUNDING: None.

Family cluster of three cases of monkeypox imported from Nigeria to the United Kingdom, May 2021.

Most reported cases of human monkeypox occur in Central and West Africa, where the causing virus is endemic. We describe the identification and public health response to an imported case of West African monkeypox from Nigeria to the United Kingdom (UK) in May 2021. Secondary transmission from the index case occurred within the family to another adult and a toddler. Concurrent COVID-19-related control measures upon arrival and at the hospital, facilitated detection and limited the number of potential contacts.

What do people hospitalised with COVID-19 think about their care? Results of a satisfaction survey during the first wave of COVID-19 in Liverpool.

Despite huge advances in vaccines, testing and treatments for COVID-19, there is negligible evidence on the perceptions of people hospitalised with COVID-19 about the care they received. To address this, we developed a satisfaction survey for people with COVID-19 admitted to our hospital during the first COVID-19 wave in Liverpool. Of those invited, 98/160 (61%) responded, of whom 94/98 (96%) completed the survey. Respondents rated overall care highly (mean 4.7/5) and 89/94 (95%) reported that they would recommend the hospital to friends and/or family. Most respondents felt safe on the ward (94%), with privacy maintained (93%) and pain well managed (90%). Fewer than two-thirds (63%) of respondents considered themselves adequately consulted regarding medications and side effects. Sleep and food/drink quality were also highlighted as areas for improvement. To overcome the issues raised, we generated a 'COVID-19 practice pointers' poster within an integrated educational bundle on COVID-19 wards. The impact of the bundle on perceptions of people hospitalised with COVID-19 will be evaluated in people hospitalised with COVID-19 in Liverpool in 2021. Whether hospitalised for COVID-19 or other conditions, our survey results are a timely reminder of the importance of involving patients in shaping the care that they receive.

A patient satisfaction survey and educational package to improve the care of people hospitalised with COVID-19: a quality improvement project, Liverpool, UK.

Background: The perspectives and experiences of people hospitalised with COVID-19 have been under-reported during the coronavirus pandemic. We developed and conducted a COVID-19 patient satisfaction survey in a large university-affiliated secondary healthcare centre in Liverpool, UK, during Europe's first coronavirus wave (April-June 2020). The survey found that care was rated highly, including among people of Black Asian and Minority Ethnic (BAME) background. However, sleep-quality and communication about medications and discharge-planning were identified as areas for improvement.   Methods: To improve care for people with COVID-19 admitted to our centre, we designed an educational package for healthcare professionals working on COVID-19 wards. The package, implemented in August 2020, included healthcare worker training sessions on providing holistic care and placement of "Practice Pointers" posters. Patient satisfaction was re-evaluated during the second/third COVID-19 waves in Liverpool (September 2020 - February 2021). Results: Across waves, most (95%) respondents reported that they would recommend our hospital to friends and/or family and rated overall care highly. Comparison of the responses of second/third-wave respondents (n=101) with first-wave respondents (n=94) suggested improved patient satisfaction across most care domains but especially those related to having worries and fears addressed and being consulted about medications and their side-effects. Conclusions: People admitted with COVID-19 to our centre in Liverpool, including those from BAME background, rated the care they received highly. A simple education package improved the feedback on care received by respondents between the first and second/third waves. These UK-first findings are informing regional strategies to improve person-centred care of hospitalised people with COVID-19.

Hyperinflammation with COVID-19: The key to patient deterioration?

BACKGROUND: The potential risk of cytokine storm in patients with coronavirus disease 2019 (COVID-19) has been described [1]; we write to share our experience treating a 17-year-old male with haemophagocytic lymphohistiocytosis (HLH) secondary to COVID-19 infection. CASE REPORT: This patient presented with cough, sore throat, anorexia and pyrexia. On examination, he had gross cervical lymphadenopathy and palpable splenomegaly. Nose and throat swab for SARS-CoV-2 was positive and blood tests revealed pancytopaenia with very high ferritin, triglyceride and d-dimer levels. The patient's H-Score [2] was calculated at 220, suggesting probability of HLH of 93-96%. Considering Russell and colleagues' [3] comments about potential harm of corticosteroid use in patients with COVID-19 infection, the patient was commenced on treatment with the selective IL-1 receptor antagonist drug, Anakinra, and a two-day course of intravenous immunoglobulin. RESULTS: The patient responded rapidly to treatment, becoming apyrexial after 24 h. His lymph nodes and spleen began to normalise after the first 48 h, at which time point the ferritin also started to decrease. He was discharged after 11 days feeling fit and well. CONCLUSION: This case certainly illustrates the importance of hyperinflammation syndromes in COVID-19. It also raises the question - is the severe pneumonitis seen in patients with COVID-19 an immunological phenomenon? We know that the viral load of patients with COVID-19 seems to peak in the early stages of illness [4,5]; however, patients deteriorate later in the disease course, at around days 10-14. This patient, who had risk factors for deterioration (male, pancytopaenic), did not develop an oxygen requirement and clinically and biochemically improved rapidly on Anakinra with no adverse events. We might suggest Anakinra to the scientific community as a treatment option in COVID-19 infection.

Long-term antifungal treatment improves health status in patients with chronic pulmonary aspergillosis: a longitudinal analysis.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is an infectious disease that progressively destroys lung tissue. To date, no longitudinal data on the efficacy of antifungal treatment on health status in CPA patients exist. METHODS: Using the standardized St George's Respiratory Questionnaire, the health status of 122 patients with was assessed at baseline and quarterly over 12 months. The score range was 0-100, where higher score indicates worse heath status, and a change of ≥4 was deemed the minimal clinically important difference. Lung function, body mass index, Medical Research Council dyspnea scale, disease severity, and demographic data were reported. RESULTS: Mean age of patients was 59 years, and 45% were female. Overall, patients with CPA had substantial health status impairment at baseline. After treatment, 47%-50% gained substantial health improvement with a mean reduction of score of 14 at both 6 and 12 months, whereas 32% deteriorated with a mean rise of score of 11 and 14 after 6 and 12 months of treatment and observation, respectively, and 21% were not much different (stable). Patients gained therapeutic benefit irrespective of their illness severity where >50% of those who had "poor" and "very poor" status at baseline improved with score reduction of ≥4 after 6 months of treatment. Replicating this analysis using a health status category, we found that at least 50% of patients with a "poor/very poor" health status category at baseline improved significantly to "fair" or "good/very good" categories. Side effects burdened health status considerably. In multivariate analysis, dyspnea and disease severity significantly defined health status impairment. CONCLUSIONS: Antifungal therapy improved health status and prevented CPA progression in most patients.

Managing hepatitis B/HIV co-infected: adding entecavir to truvada (tenofovir disoproxil/emtricitabine) experienced patients.

BACKGROUND: Combination emtricitabine (FTC) or lamivudine (LAM) with tenofovir disoproxil (TDF) is the recommended first-line regime for treatment in chronic hepatitis B virus (HBV)/HIV co-infection. However, in those failing to suppress, few data exist regarding further management. In HBV/HIV co-infection, there are no published data describing outcomes when entecavir (ETV) is then added to TDF-based regimes in patients no longer suppressing their HBV. We report the first series of patients using ETV with truvada-based HAART in HBV/HIV co-infected patients with previous HBV therapy failure, including inadequate suppression. METHODS: A prospective observational study. RESULTS: Thirteen HIV/HBV co-infected patients (all male, hepatitis B e antigen positive and hepatitis B e antibody negative) were commenced on ETV in addition to background truvada. All patients were previously exposed to LAM or FTC and TDF (median 53 months, range 6−123). Seven patients had LAM monotherapy prior to TDF/LAM or FTC combination; the remaining six patients were exposed to FTC or LAM and TDF combination. Median time of follow-up was 74 weeks (range 16−159) and median HBV decline was 2.53 log(10) IU/ml (range 1.28−7.36). Thirty-eight percent of patients achieved undetectable HBV DNA level by the end of the study and eight of 13 (62%) achieved normal alanine aminotransferase (ALT) levels with median reduction −28 U/l (range −152 to 37). TDF was stopped in one patient because of renal toxicity. ETV was well tolerated with no change of estimated glomerular filtration rate during the study. CONCLUSION: Entecavir can be considered in addition to TDF/FTC in HBV/HIV co-infected treatment-experienced patients failing to fully suppress their HBV viral load.

Audit of the management of antiretroviral treatment-naïve HIV patients in Greater Manchester, UK.

We evaluated the management of antiretroviral treatment (ART)-naïve HIV-positive patients in Greater Manchester against the 2005 British HIV association (BHIVA) guidelines. Fifty-seven HIV patients (median age 36 years, 61% males, 53% black Africans) commenced their first ART regimen between 1 October and 31 December 2005. Most of them presented with advanced HIV disease (74% had CD4 lymphocytes <200 and 33% were Centers for Disease Control and Prevention stage C) and 51% commenced ART within three months of their HIV diagnosis. Ninety-six percent had baseline laboratory investigations performed but only 53% had baseline blood pressure estimation. Only 25% had urinalysis performed. A combination of two nucleoside reverse transcriptase inhibitors (NRTI) and one non-NRTI was chosen in 76% of patients. Eighty-two percent of patients had a clinical review and blood tests within five weeks of starting treatment.