Evaluating the performance characteristics of five lateral flow assays for the detection of the SARS-CoV-2 nucleocapsid antigen.

In response to the COVID-19 pandemic, lateral flow assays (LFAs) for the detection of SARS-CoV-2 antigen have been proposed as a complementary option to the more costly and time consuming reverse-transcriptase polymerase chain reaction (RT-PCR). We assessed five commercially available SARS-CoV-2 antigen detecting LFAs (ASSUT EUROPE (Rome, Italy), Besthree (Taizhou, China), Encode (Zhuhai, China), Fortress (Antrim UK), and Hughes Medical (Buckinghamshire, UK), using samples collected from hospitalised individuals with COVID-19 and compared these results against established RT-PCR assays with the aim of estimating test performance characteristics. We performed a diagnostic accuracy study of the five LFAs on 110 inpatients with confirmed COVID-19 and 75 COVID-19 negative control participants. Assay evaluation was performed using a modified version of each manufacturer's protocol allowing for parallel testing of a single sample on multiple assays. Additional variables were studied including infection acquisition, oxygenation requirements at time of swabbing, and patient outcomes. The 110 patients were 48% (53) female, with mean age 67 years (range 26-100 years), and 77% (85) cases were community onset SARS-CoV-2. Across the five assays, sensitivity ranged from 64 (95% CI 53-73) to 76% (95% CI 65-85); Fortress performed best with sensitivity of 76% (95% CI 65-85). Specificity was high across all assays with 4/5 LFAs achieving 100%. LFA sensitivity was not dependant on RT-PCR cycle thresholds. SARS-CoV-2 antigen detecting LFAs may complement RT-PCR testing to facilitate early diagnosis and provide community testing strategies for identification of patients with COVID-19, however we find suboptimal test performance characteristics across a range of commercially available manufacturers, below WHO and MHRA pre-set sensitivity performance thresholds. With such variation in sensitivity between LFAs and PCR testing and between assay brands, we advise caution in the deployment of LFAs outside of environments with clinical oversight.

"It's always hard being a mom, but the pandemic has made everything harder": A qualitative exploration of the experiences of perinatal women during the COVID-19 pandemic.

BACKGROUND: Understanding the psychosocial impacts of the COVID-19 pandemic in vulnerable groups, such as pregnant and parenting women, is a critical research and clinical imperative. Although many survey-based perinatal health studies have contributed important information about mental health, few have given full voice about the experiences of pregnant and postpartum women during the prolonged worldwide pandemic using a qualitative approach. OBJECTIVE: The purpose of this study is to explore the lived experience of pregnant and postpartum women in the United States during the ongoing COVID-19 pandemic. DESIGN: Qualitative phenomenological study. SETTING: This study was conducted in the community, by recruiting women throughout the U.S. PARTICIPANTS: Fifty-four pregnant and postpartum women participated in qualitative interviews. METHODS: Data from one-on-one semi-structured interviews were analyzed using a team-based phenomenological qualitative approach. RESULTS: Two key themes were apparent: the pandemic has shined a light on the many typical struggles of motherhood; and, there is a lack of consistent, community-based or healthcare system resources available to address the complex needs of pregnant and postpartum women, both in general and during the pandemic. CONCLUSIONS: Going forward, as the world continues to deal with the current pandemic and possible future global health crises, health care systems and providers are encouraged to consider the suggestions provided by these participants: talk early and often to women about mental health; help pregnant and postpartum women create and institute a personal plan for early support of their mental health needs and create an easily accessible mental health network; conceptualize practice methods that enhance coping and resilience; practice in community-based and interdisciplinary teams (e.g., midwives, doulas, perinatal social workers/ psychotherapists) to ensure continuity of care and to foster relationships between providers and pregnant/ postpartum women; and consider learning from other countries' successful perinatal healthcare practices. REGISTRATION: Number (& date of first recruitment): not applicable. TWEETABLE ABSTRACT: Pregnant and postpartum women insist that mental health care must be overhauled, stating the pandemic has highlighted inherent cracks in the system.

Point-of-care SARS-CoV-2 serological assays for enhanced case finding in a UK inpatient population.

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Case identification is currently made by real-time polymerase chain reaction (PCR) during the acute phase and largely restricted to healthcare laboratories. Serological assays are emerging but independent validation is urgently required to assess their utility. We evaluated five different point-of-care (POC) SARS-CoV-2 antibody test kits against PCR, finding concordance across the assays (n = 15). We subsequently tested 200 patients using the OrientGene COVID-19 IgG/IgM Rapid Test Cassette and find a sensitivity of 74% in the early infection period (day 5-9 post symptom onset), with 100% sensitivity not seen until day 13, demonstrating inferiority to PCR testing in the infectious period. Negative rate was 96%, but in validating the serological tests uncovered potential false-negatives from PCR testing late-presenting cases. A positive predictive value (PPV) of 37% in the general population precludes any use for general screening. Where a case definition is applied however, the PPV is substantially improved (95.4%), supporting use of serology testing in carefully targeted, high-risk populations. Larger studies in specific patient cohorts, including those with mild infection are urgently required to inform on the applicability of POC serological assays to help control the spread of SARS-CoV-2 and improve case finding of patients that may experience late complications.

Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting.

OBJECTIVES: To investigate the incidence of bacterial and fungal coinfection of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this retrospective observational study across two London hospitals during the first UK wave of coronavirus disease 2019 (COVID-19). METHODS: A retrospective case series of hospitalized patients with confirmed SARS-CoV-2 by PCR was analysed across two acute NHS hospitals (20 February-20 April 2020; each isolate reviewed independently in parallel). This was contrasted to a control group of influenza-positive patients admitted during the 2019-2020 flu season. Patient demographics, microbiology and clinical outcomes were analysed. RESULTS: A total of 836 patients with confirmed SARS-CoV-2 were included; 27 (3.2%) of 836 had early confirmed bacterial isolates identified (0-5 days after admission), rising to 51 (6.1%) of 836 throughout admission. Blood cultures, respiratory samples, pneumococcal or Legionella urinary antigens and respiratory viral PCR panels were obtained from 643 (77%), 110 (13%), 249 (30%), 246 (29%) and 250 (30%) COVID-19 patients, respectively. A positive blood culture was identified in 60 patients (7.1%), of which 39 were classified as contaminants. Bacteraemia resulting from respiratory infection was confirmed in two cases (one each community-acquired Klebsiella pneumoniae and ventilator-associated Enterobacter cloacae). Line-related bacteraemia was identified in six patients (three Candida, two Enterococcus spp. and one Pseudomonas aeruginosa). All other community-acquired bacteraemias (n = 16) were attributed to nonrespiratory infection. Zero concomitant pneumococcal, Legionella or influenza infection was detected. A low yield of positive respiratory cultures was identified; Staphylococcus aureus was the most common respiratory pathogen isolated in community-acquired coinfection (4/24; 16.7%), with pseudomonas and yeast identified in late-onset infection. Invasive fungal infections (n = 3) were attributed to line-related infections. Comparable rates of positive coinfection were identified in the control group of confirmed influenza infection; clinically relevant bacteraemias (2/141; 1.4%), respiratory cultures (10/38; 26.3%) and pneumococcal-positive antigens (1/19; 5.3%) were low. CONCLUSIONS: We found a low frequency of bacterial coinfection in early COVID-19 hospital presentation, and no evidence of concomitant fungal infection, at least in the early phase of COVID-19.

New-onset anosmia and ageusia in adult patients diagnosed with SARS-CoV-2 infection.

OBJECTIVES: We investigated the prevalence of anosmia and ageusia in adult patients with a laboratory-confirmed diagnosis of infection with severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2). METHODS: This was a retrospective observational analysis of patients infected with SARS-CoV-2 admitted to hospital or managed in the community and their household contacts across a London population during the period March 1st to April 1st, 2020. Symptomatology and duration were extracted from routinely collected clinical data and follow-up telephone consultations. Descriptive statistics were used. RESULTS: Of 386 patients, 141 (92 community patients, 49 discharged inpatients) were included for analysis; 77/141 (55%) reported anosmia and ageusia, nine reported only ageusia and three only anosmia. The median onset of anosmia in relation to onset of SARS-CoV-2 disease (COVID-19) symptoms (as defined by the Public Health England case definition) was 4 days (interquartile range (IQR) 5). Median duration of anosmia was 8 days (IQR 16). Median duration of COVID-19 symptoms in community patients was 10 days (IQR 8) versus 18 days (IQR 13.5) in admitted patients. As of April 1, 45 patients had ongoing COVID-19 symptoms and/or anosmia; 107/141 (76%) patients had household contacts, and of 185 non-tested household contacts 79 (43%) had COVID-19 symptoms with 46/79 (58%) reporting anosmia. Six household contacts had anosmia only. CONCLUSIONS: Over half of the positive patients reported anosmia and ageusia, suggesting that these should be added to the case definition and used to guide self-isolation protocols. This adaptation may be integral to case findings in the absence of population-level testing. Until we have successful population-level vaccination coverage, these steps remain critical in the current and future waves of this pandemic.

Evaluating the risk of hyperkalaemia and acute kidney injury with cotrimoxazole: a retrospective observational study.

OBJECTIVES: Increasing antimicrobial resistance has renewed interest in older, less used antimicrobials. Cotrimoxazole shows promise; however, hyperkalaemia and acute kidney injury (AKI) are potential complications. Identifying risk factors for and quantification of these events is required for safe use. This study aimed to evaluate predictors of cotrimoxazole-associated AKI and hyperkalaemia in a clinical setting. METHODS: Patients prescribed cotrimoxazole were identified using electronic healthcare records over 3 years (1 April 2016 to 31 March 2019). Individual risk factors were recognized. Serum creatinine and potassium trends were analysed over the subsequent 21 days. AKI and patients with hyperkalaemia were classified using Kidney Disease Improving Global Outcomes (KDIGO) and laboratory criteria. Univariate and multiple logistic regression analyses were performed. RESULTS: Among 214 patients prescribed cotrimoxazole, 42 (19.6%, 95% confidence interval (CI) 14.6-25.7) met AKI criteria and 33 (15.4%, 95% CI 11.0-21.1) developed hyperkalaemia. Low baseline estimated glomerular filtration rate (<60 mL/min/1.73 m2, odds ratio (OR) 7.78, 95% CI 3.57-16.13, p < 0.0001) and cardiac disorders (OR 2.40, 95% CI 1.17-4.82, p 0.011) predicted AKI, while low baseline estimated glomerular filtration rate (<60 mL/min/1.73 m2, OR 6.80, 95% CI 3.09-15.06, p < 0.0001) and higher baseline serum potassium (p 0.001) predicted hyperkalaemia. Low-dose cotrimoxazole (<1920 mg/d) was associated with lower AKI and hyperkalaemia risk (p 0.007 and 0.019 respectively). Early (within the first 2-4 days of therapy) serum creatinine changes predicted AKI (OR 3.65, 95% CI 1.73-7.41, p 0.001), and early serum potassium changes predicted hyperkalaemia (>0.6 mmol/L, OR 2.47, 95% CI 1.14-5.27, p 0.0236). CONCLUSIONS: Cotrimoxazole-associated AKI and hyperkalaemia is frequent and dose dependent. Renal function, serum potassium and preexisting cardiac disorders should be evaluated before prescribing cotrimoxazole. Serum creatinine and potassium monitoring within first 2 to 4 days of treatment to identify susceptible patients is recommended, and the lowest effective dose ought to be prescribed.

Late presentation of a deep sternal wound infection and left breast abscess.

In this paper, we present a case review of a 58-year-old female who presented to our emergency department with pyrexia, dyspnoea, dehydration and pain in her left breast six months following coronary artery bypass grafting (CABG). Although her sternotomy wound had healed well, examination revealed fluctuance of the whole precordium and left breast. She underwent antibiotic treatment and subsequent surgical debridement, followed by the application of vacuum-assisted dressings. Surgical reconstruction was deemed unsuitable and therefore the patient continued to be managed with vacuum dressings followed by routine dressings to allow the wound to heal by secondary intention. The patient was discharged three months after initial presentation in a good condition. The wound had completely healed four months later.

Gene therapy in the treatment of peripheral arterial disease.

BACKGROUND: Peripheral arterial disease remains a significant global health burden despite revolutionary improvements in endovascular techniques over the past decade. The durability of intervention for critical limb ischaemia is poor, and the condition is associated with high morbidity and mortality rates. To address this deficiency, alternative therapeutic options are being explored. Advances in the fields of gene therapy and therapeutic angiogenesis have led to these being advocated as potential future treatments. METHODS: Relevant medical literature from PubMed, Embase, the Cochrane Library and Google Scholar from the inception of these databases to June 2011 was reviewed. RESULTS: Encouraging outcomes in preclinical trials using a variety of proangiogenic growth factors have led to numerous efficacy and safety studies. However, no clinical study has shown significant benefit for gene therapy over placebo. CONCLUSION: Identifying the optimal site for gene delivery, choice of vector and duration of treatment is needed if gene therapy is to become a credible therapeutic option for peripheral arterial disease.

Cycling related common femoral artery disease: an unusual case in an otherwise healthy male.

A cyclist reported gradual onset, bilateral leg claudication without any atherosclerotic risk factors and with a normal vascular examination. Duplex ultrasound and magnetic resonance angiography revealed bilateral focal stenoses due to coralline plaques of the common femoral arteries (CFAs) but normal proximal and distal vasculature. A surgical endarterectomy with vein patch angioplasty resolved all symptoms. Cyclist's iliac syndrome (whereby mechanical and anatomical factors in competitive cyclists and runners lead to arterial kinking and subsequent intimal hyperplasia, endofibrosis and, ultimately, stenoses of the external iliac arteries) is well documented. This is the first report to our knowledge of a similar process isolated to the CFA.

Self-reported eye disease in elderly South Asian subjects from an inner city cluster in Bradford: a small-scale study to investigate knowledge and awareness of ocular disease.

PURPOSE: To investigate various issues relating to eye diseases in a sample of 200 South Asian residents living in an inner city regional cluster in Bradford. METHODS: Door to door interviews were carried out by one investigator who spoke English, Punjabi and Urdu. Visual acuity and pinhole acuity were measured using a portable LogMAR acuity chart. A structured questionnaire investigated various issues including self-reported eye disease, knowledge of eye disease, the effectiveness of various sources for eye-related information, the importance of early detection of eye diseases and the need for adequate control of systemic diseases linked to eye diseases such as diabetes. RESULTS: Data revealed poor knowledge of self-reported eye diseases and of the importance of early detection and inadequate knowledge of the link between the control of systemic disease such as diabetes and ocular complications. Language barrier problems and poor utilisation of available ocular health care services were also evident. CONCLUSIONS: These data, although not exhaustive, give an insight into various factors that affect the ocular health of the South Asian community in Bradford.

Dexamethasone and bacterial meningitis in Pakistan.

The objective of this study was to assess, in a developing country setting, the effect of dexamethasone therapy on bacterial meningitis outcomes. A prospective double blind placebo controlled trial was conducted in 89 children aged from 2 months to 12 years suffering from bacterial meningitis. Neurological, developmental, and hearing assessments were conducted at one, four, and 12 months after discharge. Forty eight patients received dexamethasone and 41 placebo. Initial antimicrobial drugs used were ampicillin and chloramphenicol. For all patients at the time of admission the mean duration of illness was 5.7 days; 47% had had seizures and 56% had impaired consciousness. Seventeen of 89 (19%) patients died. The mortality for the dexamethasone group was 25% as compared with 12% in the group receiving placebo. Presentation to the hospital after four days of symptoms and with impaired conscious state were independent predictors of death. Of the dexamethasone group survivors, 26.5% had neurological sequelae and 42.3% had hearing impairment, whereas in the placebo group it was 24% and 30% respectively. Altered state of consciousness was a predictor of neurological sequelae. The presence of neurological sequelae and high cerebrospinal fluid protein independently predicted hearing loss. No beneficial effect of dexamethasone was observed on morbidity or mortality of this group of patients with bacterial meningitis. Dexamethasone is therefore not useful in developing countries as adjunctive treatment in patients seriously ill with bacterial meningitis, who present late for treatment and have been partially treated.