The impact of the COVID-19 pandemic on the provision & utilisation of primary health care services in Goma, Democratic Republic of the Congo, Kambia district, Sierra Leone & Masaka district, Uganda.

INTRODUCTION: This study aimed to determine whether the COVID-19 pandemic had an impact on essential primary healthcare services at public primary healthcare facilities. METHODS: The number of weekly consultations for antenatal care (ANC), outpatient (OPD), immunisations (EPI), family planning (FP) and HIV services, between January 2018 and December 2020, were collected from 25 facilities in Masaka district, Uganda, 21 in Goma, and 29 in Kambia district, Sierra Leone. Negative binomial regression models accounting for clustering and season were used to analyse changes in activity levels between 2018, 2019 and 2020. RESULTS: In Goma, we found no change in OPD, EPI or ANC consultations, FP was 17% lower in March-July 2020 compared to 2019, but this recovered by December 2020. New diagnoses of HIV were 34% lower throughout 2020 compared to 2019. In Sierra Leone, compared to the same periods in 2019, facilities had 18-29% fewer OPD consultations throughout 2020, and 27% fewer DTP3 doses in March-July 2020. There was no evidence of differences in other services. In Uganda there were 20-35% fewer under-5 OPD consultations, 21-66% fewer MCV1 doses, and 48-51% fewer new diagnoses of HIV throughout 2020, compared to 2019. There was no difference in the number of HPV doses delivered. CONCLUSIONS: The level of disruption varied across the different settings and qualitatively appeared to correlate with the strength of lockdown measures and reported attitudes towards the risk posed by COVID-19. Mitigation strategies such as health communications campaigns and outreach services may be important to limit the impact of lockdowns on primary healthcare services.

Clinical presentations and management of COVID-19 infected children seen in a district health facility in Kambia, northern Sierra Leone

Studies reporting the clinical presentations of COVID-19 in children in sub-Saharan Africa are few, especially from resource-constrained countries. This case series reports the demographic and clinical characteristics and laboratory findings of confirmed cases of COVID-19 in children seen at a district hospital in Sierra Leone. This is a report of nine COVID-19 paediatric cases managed at a secondary level hospital in Kambia District, Northern Sierra Leone. Each child was detected by contact tracing after an infected adult was identified by the COVID-19 response team. The clinical symptoms at presentation, clinical courses, and treatments instituted and patient outcomes are discussed in the context of the facilities available at a typical West African district hospital. Nine out of 30 individuals with confirmed COVID-19 infection who presented to the hospital from 24 April to 20 September 2020 and who were admitted to the isolation center of the hospital were in the paediatric age group. The mean age (SD) and median (IQR) of the children were 69.0 +/- 51.7months and 84.0 (10.5, 108.0) months, respectively;five (55.6%) were males. The children were asymptomatic or only had mild illnesses and none required intranasal oxygen or ventilatory support. In the five symptomatic children, the most common symptoms were fever (40%) and cough (40%). All children had normal haemoglobin, platelet and white blood cell (WBC) count. Four children had a positive malaria test and were treated with a complete course of anti-malaria medications. No child received steroid or had specific anti-COVID-19 treatment. All children stayed in the isolation center for 14 days and were re-tested for COVID-19 two weeks after initial diagnosis. No complications have been reported in any of them since discharge. The proportion of children among COVID-19 infected cases seen in a rural community in Sierra Leone was 30%. Fever was the most common symptom and malaria was confirmed in 40% of the infected children. This has significant implication on the diagnosis of COVID-19 in malaria-endemic settings and on how best to manage children who present with fever during the COVID-19 pandemic. Copyright © Hammed Hassan Adetola et al.

Prevalence and Mechanisms of Mucus Accumulation in COVID-19 Lung Disease.

Rationale: The incidence and sites of mucus accumulation and molecular regulation of mucin gene expression in coronavirus (COVID-19) lung disease have not been reported. Objectives: To characterize the incidence of mucus accumulation and the mechanisms mediating mucin hypersecretion in COVID-19 lung disease. Methods: Airway mucus and mucins were evaluated in COVID-19 autopsy lungs by Alcian blue and periodic acid-Schiff staining, immunohistochemical staining, RNA in situ hybridization, and spatial transcriptional profiling. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected human bronchial epithelial (HBE) cultures were used to investigate mechanisms of SARS-CoV-2-induced mucin expression and synthesis and test candidate countermeasures. Measurements and Main Results: MUC5B and variably MUC5AC RNA concentrations were increased throughout all airway regions of COVID-19 autopsy lungs, notably in the subacute/chronic disease phase after SARS-CoV-2 clearance. In the distal lung, MUC5B-dominated mucus plugging was observed in 90% of subjects with COVID-19 in both morphologically identified bronchioles and microcysts, and MUC5B accumulated in damaged alveolar spaces. SARS-CoV-2-infected HBE cultures exhibited peak titers 3 days after inoculation, whereas induction of MUC5B/MUC5AC peaked 7-14 days after inoculation. SARS-CoV-2 infection of HBE cultures induced expression of epidermal growth factor receptor (EGFR) ligands and inflammatory cytokines (e.g., IL-1α/ß) associated with mucin gene regulation. Inhibiting EGFR/IL-1R pathways or administration of dexamethasone reduced SARS-CoV-2-induced mucin expression. Conclusions: SARS-CoV-2 infection is associated with a high prevalence of distal airspace mucus accumulation and increased MUC5B expression in COVID-19 autopsy lungs. HBE culture studies identified roles for EGFR and IL-1R signaling in mucin gene regulation after SARS-CoV-2 infection. These data suggest that time-sensitive mucolytic agents, specific pathway inhibitors, or corticosteroid administration may be therapeutic for COVID-19 lung disease.

Healthcare providers' attitudes towards delay in cancer treatment during COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has created unprecedented obstacles leading to delays in treatment for older adults with cancer. Due to limited resources at the height of the pandemic, healthcare providers were constantly faced with ethical dilemmas regarding postponing or rescheduling care for their patients. MATERIALS AND METHODS: Two survey-based studies were conducted at different time-points during the pandemic looking at factors affecting oncology care providers' attitudes towards delay in treatment for older adults with cancer. Eligible participants were recruited by email sent through professional organizations' listservs, email blasts, and social media. Change in provider attitude over time was analyzed by comparing responses from the 2020 and 2021 surveys. Data analysis included descriptive statistics and chi-squares. RESULTS: In 2020, 17.5% of respondents were strongly considering/considering postponing cancer treatment for younger patients (age 30 and below), while 46.2% were considering delaying treatment for patients aged >85. These responses were in stark contrast to the results of the 2021 survey, where only 1.4% of respondents strongly considered postponing treatment for younger patients, and 13.5% for patients aged >85. DISCUSSION: All recommendations to postpone treatment for older adults with cancer must be made after mutual discussion with the patient. Throughout the COVID-19 pandemic, oncology care providers had to consider multiple factors while treating patients, frequently making most decisions without appropriate institutional support.

SARS-CoV-2 infection produces chronic pulmonary epithelial and immune cell dysfunction with fibrosis in mice.

A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal tissue samples. The mouse-adapted SARS-CoV-2 strain MA10 produces an acute respiratory distress syndrome in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute to clinical recovery phases. At 15 to 120 days after virus clearance, pulmonary histologic findings included subpleural lesions composed of collagen, proliferative fibroblasts, and chronic inflammation, including tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal up-regulation of profibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early antifibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC.

SARS-CoV-2 infection produces chronic pulmonary epithelial and immune cell dysfunction with fibrosis in mice

A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal tissue samples. The mouse-adapted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute to clinical recovery phases. At 15 to 120 days post-virus clearance, pulmonary histologic findings included subpleural lesions composed of collagen, proliferative fibroblasts, and chronic inflammation, including tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal up-regulation of pro-fibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early anti-fibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC. After recovery from acute SARS-CoV-2 infection, mice exhibit chronic lung disease similar to some humans, allowing for testing of therapeutics. Description

Protease-anti-protease compartmentalization in SARS-CoV-2 ARDS: Therapeutic implications.

BACKGROUND: Interleukin-6 (IL-6) is elevated in SARS-CoV-2 infection. IL-6 regulates acute-phase proteins, such as alpha-1 antitrypsin (AAT), a key lung anti-protease. We investigated the protease-anti-protease balance in the circulation and pulmonary compartments in SARS-CoV-2 acute respiratory distress syndrome (ARDS) compared to non-SARS-CoV-2 ARDS (nsARDS) and the effects of tocilizumab (IL-6 receptor antagonist) on anti-protease defence in SARS-CoV-2 infection. METHODS: Levels and activity of AAT and neutrophil elastase (NE) were measured in plasma, airway tissue and tracheal secretions (TA) of people with SARS-CoV-2 ARDS or nsARDS. AAT and IL-6 levels were evaluated in people with moderate SARS-CoV-2 infection who received standard of care +/- tocilizumab. FINDINGS: AAT plasma levels doubled in SARS-CoV-2 ARDS. In lung parenchyma AAT levels were increased, as was the percentage of neutrophils involved in NET formation. A protease-anti-protease imbalance was detected in TA with active NE and no active AAT. The airway anti-protease, secretory leukoprotease inhibitor was decreased in SARS-CoV-2-infected lungs and cleaved in TA. In nsARDS, plasma AAT levels were elevated but TA samples had less AAT cleavage, with no detectable active NE in most samples. Induction of AAT in ARDS occurred mainly through IL-6. Tocilizumab down-regulated AAT during SARS-CoV-2 infection. INTERPRETATION: There is a protease-anti-protease imbalance in the airways of SARS-CoV-2-ARDS patients. This imbalance is a target for anti-protease therapy. FUNDING: NIH Serological Sciences Network, National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases.

A model of persistent post SARS-CoV-2 induced lung disease for target identification and testing of therapeutic strategies (preprint)

COVID-19 survivors develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal samples. Mouse-adapted SARS-CoV-2 MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute disease through clinical recovery. At 15-120 days post-virus clearance, histologic evaluation identified subpleural lesions containing collagen, proliferative fibroblasts, and chronic inflammation with tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal upregulation of pro-fibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early anti-fibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC.

Modified Insulin Infusion Protocol for COVID-19 Patients Is Safe and Effective for Controlling Hyperglycemia

During the first phase of the COVID-19 pandemic, we modified our insulin infusion protocol (IIP) for use in COVID-19 patients with severe hyperglycemia, in order to reduce entry into patient rooms and minimize viral exposure for healthcare workers (HCW), and preserve personal protective equipment (PPE). Blood glucose (BG) monitoring was less frequent (Q2h vs. Q1h in our standard IIP) and the BG target higher (150-199 mg/dl vs. 120-160 mg/dl). We sought to validate the safety and effectiveness of the COVID-19 IIP. We reviewed the medical records of 40 adult patients admitted with COVID-19 from 3/2020-5/2020 who were treated with either standard IIP (n=20) or COVID-19 IIP (n=20) to compare safety (hypoglycemia) and effectiveness (achievement of BG target, mean BG.) All results (Table) are reported as mean ± SD. Four patients in the standard IIP group and 2 in the COVID-19 IIP did not achieve target BG before IIP discontinuation. Preliminary results using our modified COVID-19 IIP show that it is safe and effective in controlling severe hyperglycemia, achieving its distinct BG target in a similar timeframe and without any increased risk of hypoglycemia despite reduced BG monitoring frequency. We conclude that our COVID-19 IIP can be used to safely manage hyperglycemia while protecting patients and HCWs as the pandemic continues.

Rapid Transition to Online Learning for Baccalaureate Students: Teamwork During a Pandemic.

BACKGROUND: This article describes how a college of nursing (CON) converted its traditional undergraduate academic program to a 100% online program within 2 weeks of being informed of the need for curricular modifications due to the COVID-19 pandemic. METHOD: The college faculty met online prior to implementation to discuss student needs and special considerations. Clinical simulation experiences were developed based on International Association for Clinical Simulation and Learning (INACSL) standards and delivered through virtual simulation. RESULTS: Students evaluated the clinical simulation experiences in each course using Likert-style measures and reported positive experiences overall. Each cohort of students, including the May 2020 graduating seniors, successfully completed all of their classes for progression to the next semester or graduation. CONCLUSION: The successful conversion of traditional academic programs into a virtual environment requires leadership, collaboration, and teamwork. This CON had positive outcomes and offers lessons learned for future implementation. [J Nurs Educ. 2021;60(7): 397-399.].