Administration of the TNF-alpha inhibitor, infliximab, reduces mortality in hospitalized patients with COVID pneumonia. Results of a randomized controlled trial

Background. Severe COVID-19 infection is characterized by a dysregulated hyperinflammatory state that contributes to morbidity and mortality. Immunomodulatory therapy has been shown to improve outcomes. We investigated if the TNF-alpha inhibitor, infliximab (IFX), provides additional benefit over standard of care. Methods. We conducted a double-blind, randomized, placebo-controlled trial of IFX (single infusion of 5 mg/kg) compared to standard of care (including remdesivir and dexamethasone) in patients hospitalized with COVID-19 pneumonia. The primary outcome was time to recovery by day 29. Key secondary endpoints included 14-day clinical status and 28-day mortality. Results. A total of 1033 patients received study agent (517 assigned to IFX, 516 to common placebo), constituting the analyzed modified intention-to-treat cohort. Mean age 54.8 years, 60.3% were male, 48.6% Hispanic/Latino and 14% Black. Randomization was balanced for severity of illness and comorbidities. Participants randomized to IFX did not show a statistically significant difference in the primary endpoint with a recovery rate ratio of 1.13 (95% CI 0.99-1.27, p=0.0631) compared to placebo. The median (IQR) time to recovery was 8 days (7, 9) for IFX and 9 days (8, 10) for placebo. Patients assigned to IFX were more likely to have an improved clinical status at day 14 (OR 1.32;95% CI 1.05, 1.66). The 28-day mortality was 10.1% in the IFX arm and 14.5% in the placebo (OR 0.59 (95% CI 0.39, 0.90)), with a 40.7% lower odds of dying in patients receiving IFX. The improvement in mortality was demonstrated in patients requiring low- or high-flow O2 at baseline but not in those requiring mechanical ventilation or ECMO. Subgroup analysis identified the strongest effect in those with baseline CRP >75mg/ml. There was no imbalances in serious adverse events. Secondary infections were similar between groups (IFX 18.0%, placebo 16.5%). Conclusion. Although single-dose IV IFX did not demonstrate statistically significant improvement in time to recovery, it was associated with improvement in clinical status at day 14 and showed a substantial reduction in 28 day mortality compared to standard of care.

Administration of abatacept, reduces mortality in hospitalized patients with COVID pneumonia. Results of a randomized controlled trial

Background. Severe COVID-19 infection is characterized by a dysregulated hyperinflammatory state that contributes to morbidity and mortality. Immunomodulatory therapy has been shown to improve outcomes. We investigated if abatacept, CTLA-4-Ig, a selective costimulation modulator, provides additional benefit when added to standard of care. Methods. We conducted a double-blind, randomized, placebo-controlled trial evaluating abatacept (given as a single infusion of 10mg/kg, to a maximum of 1000 mg) compared to standard of care (including remdesivir and dexamethasone) in patients hospitalized with COVID-19 pneumonia. The primary outcome was median time to recovery by day 29. Key secondary endpoints included 28-day mortality. Results. A total of 1019 patients received an infusion (509 assigned to abatacept and 510 to placebo), constituting the analyzed modified intention-to-treat cohort. The mean age 54.9 years (SD 14.65), 60.5% were male, 44.2% Hispanic or Latino and 13.7% black. Patients were evenly matched in terms of severity of illness, and comorbidities. Participants randomized to abatacept did not show a statistically significant difference in the primary endpoint with a recovery rate ratio of 1.135 (95% CI 0.996-1.294, p=0.057) compared to placebo. The median (IQR) time to recovery was 9 days (8, 10) for both groups. The 28-day mortality in the abatacept arm was 11.0% and in control arm 15.0% (OR 0.62 (95% CI 0.41, 0.94)), with a 37.8% lower odds of dying in patients receiving abatacept. The improvement in mortality was demonstrated for patients requiring low or high flow O2 at baseline but was not seen in patients who required mechanical ventilation or ECMO at time of randomization. Subgroup analysis identified the strongest effect in those with baseline CRP >75mg/L, age >65 and diabetics. Safety data demonstrated slightly lower risk of adverse events. Rates of secondary infections were similar (abatacept 16.1% and placebo 14.3%). Conclusion. Although single-dose IV abatacept did not demonstrate statistically significant improvement in time to recovery, it did show a substantial reduction in 28-day mortality compared to standard of care.

PROVIDING PHARMACY SUPPORT TO HOUSEBOUND PATIENTS: LEARNING FROM THE COVID-19 PANDEMIC

Introduction: Housebound patients may face challenges to their medicines management due to reduced household mobility and potential lack of access to healthcare services. Previous literature has explored the medication-related needs of housebound patients from pharmacists' perspectives (1-2). However little work has focussed on the patient/family perspective. In this study, we used data obtained from those staying at home as much as possible during the COVID-19 pandemic to fill this gap. Aim: To explore home medicine practices and safety for people who were housebound during the COVID19 pandemic and to create guidance, from the patient/family perspective, for enabling pharmacists to facilitate safe medicine practices for this population. Methods: Interviews were carried out with people who were taking at least one long term medication and met the criteria for ?shielding' and/or were over 70 years of age during the first wave of the COVID-19 pandemic in the UK and/or their family carers. Respondents were recruited through patient and public involvement representatives, the research team's networks, and support groups. Potential participants were approached via personal contact and social media. Interviews were conducted by telephone or video conferencing and participants asked about their medicines management while staying at home. Inductive thematic analysis was carried out. Patient and public involvement representatives were involved in the data analysis alongside the researchers. Results: Fifty people were interviewed (16 males, 34 females;mean age 68 years, range 26-93 years). Interview data suggested diversity of experiences of medicines management while staying at home. Some respondents reported no or little change, others an initial crisis followed by re-stabilisation, and others that the pandemic was a tipping point, exacerbating underlying challenges and having negative effects on their health and wellbeing. Medicine safety issues reported included omitted doses and less-effective formulations being used. Participants also described experiencing high levels of anxiety related to obtaining medicines, monitoring medicines and feeling at risk of contracting COVID-19 while accessing medicine-related healthcare services. Key factors identified as facilitating a smooth transition included patients' own agency, support from family, friends and community, good communication with pharmacy staff, continuity of pharmacy services and synchronisation of medicines supply so that a maximum of one collection/delivery was required each month. Conclusion: The study findings that we have presented relate to the UK only;this may limit the generalisability of our findings to other countries. Findings from Ireland are in the process of being analysed and will provide a basis of comparison. In addition, more females took part than males, despite efforts to address this. However, our findings suggest pharmacy staff can support medicines management for people who are housebound by synchronisation of medicines supply, delivering medicines where possible, developing/raising awareness of alternative means of communication, providing continuity of pharmacy services and signposting any community support available.

Computing the Original eBWT Faster, Simpler, and with Less Memory

Mantaci et al. [TCS 2007] defined the eBWT to extend the definition of the BWT to a collection of strings. However, since this introduction, it has been used more generally to describe any BWT of a collection of strings, and the fundamental property of the original definition (i.e., the independence from the input order) is frequently disregarded. In this paper, we propose a simple linear-time algorithm for the construction of the original eBWT, which does not require the preprocessing of Bannai et al. [CPM 2021]. As a byproduct, we obtain the first linear-time algorithm for computing the BWT of a single string that uses neither an end-of-string symbol nor Lyndon rotations. We combine our new eBWT construction with a variation of prefix-free parsing to allow for scalable construction of the eBWT. We evaluate our algorithm (pfpebwt) on sets of human chromosomes 19, Salmonella, and SARS-CoV2 genomes, and demonstrate that it is the fastest method for all collections, with a maximum speedup of 7.6 × on the second best method. The peak memory is at most 2 × larger than the second best method. Comparing with methods that are also, as our algorithm, able to report suffix array samples, we obtain a 57.1 × improvement in peak memory. The source code is publicly available at https://github.com/davidecenzato/PFP-eBWT. © 2021, Springer Nature Switzerland AG.

Significant impact of covid-19 on the first pillars of the hiv care continuum

Background: After SARS-CoV-2 reached the Netherlands in February 2020, rapid interventions were taken to mitigate viral spread and optimise care for COVID-19 patients. Lockdowns and downscaling of regular healthcare practices were necessary to scale up COVID-19-related care. The effect of these interventions on HIV care are uncertain. We assessed the impact of the nationwide lockdown in March and May during the first COVID-19 wave on HIV diagnosis and linkage to care. Methods: An observational study was conducted at the Erasmus MC, a regional reference tertiary hospital in the Netherlands. All patients ≥ 18 years presenting with HIV indicator conditions (ICs) were identified in electronic patient records, using an automated identification system for ICD-10 and health insurance codes. Primary outcomes measured were the number of HIV tests performed, number of HIV ICs and corresponding HIV testing rates, and new HIV diagnoses before, during and after lockdown. Results: From January to April, all newly registered diagnoses decreased by 35%, and in patients referred for HIV ICs by 69% (figure 1). The proportion of patients presenting with HIV ICs that were adequately tested for HIV remained relatively stable, especially where HIV testing is standardised, even during lockdown in March, April and May when a cumulative 328 proven or suspected COVID-19 patients were admitted. The absolute number of HIV tests performed during the first half year of 2020 was 13% lower than the same period in 2019, and new HIV patient referrals dropped 67%. The number of HIV IC, HIV testing rates and HIV referrals showed recovery after the lockdown. Conclusion: The first two pillars of the HIV care continuum were affected by the lockdown during the COVID-19 pandemic. Standardisation of HIV testing could prevent diagnostic delays to a certain extent. With an eye on subsequent COVID-19 waves, these data indicate that maintaining focus on adequate identification and testing of patients with undiagnosed HIV is essential to prevent unwanted declines affecting the 95-95-95 goals.

Integrated Single-Cell Atlases Reveal an Oral SARS-CoV-2 Infection and Transmission Axis (preprint)

Despite signs of infection, the involvement of the oral cavity in COVID-19 is poorly understood. To address this, single-cell RNA sequencing datasets were integrated from human minor salivary glands and gingiva to identify 11 epithelial, 7 mesenchymal, and 15 immune cell clusters. Analysis of SARS-CoV-2 viral entry factor expression showed enrichment in epithelia including the ducts and acini of the salivary glands and the suprabasal cells of the mucosae. COVID-19 autopsy tissues confirmed in vivo SARS CoV-2 infection in the salivary glands and mucosa. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 expression and SARS-CoV-2 RNA. Matched nasopharyngeal and saliva samples found distinct viral shedding dynamics and viral burden in saliva correlated with COVID-19 symptoms including taste loss. Upon recovery, this cohort exhibited salivary antibodies against SARS-CoV-2 proteins. Collectively, the oral cavity represents a robust site for COVID-19 infection andimplicates saliva in viral transmission.