Browsing by Subject "SARS-CoV-2"

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    AGILE: a seamless phase I/IIa platform for the rapid evaluation of candidates for COVID-19 treatment: an update to the structured summary of a study protocol for a randomised platform trial letter
    (2021-07-26) Griffiths, Gareth O; FitzGerald, Richard; Jaki, Thomas; Corkhill, Andrea; Reynolds, Helen; Ewings, Sean; Condie, Susannah; Tilt, Emma; Johnson, Lucy; Radford, Mike; Simpson, Catherine; Saunders, Geoffrey; Yeats, Sara; Mozgunov, Pavel; Tansley-Hancock, Olana; Martin, Karen; Downs, Nichola; Eberhart, Izabela; Martin, Jonathan W B; Goncalves, Cristiana; Song, Anna; Fletcher, Tom; Byrne, Kelly; Lalloo, David G; Owen, Andrew; Jacobs, Michael; Walker, Lauren; Lyon, Rebecca; Woods, Christie; Gibney, Jennifer; Chiong, Justin; Chandiwana, Nomathemba; Jacob, Shevin; Lamorde, Mohammed; Orrell, Catherine; Pirmohamed, Munir; Khoo, Saye
    Background There is an urgent unmet clinical need for the identification of novel therapeutics for the treatment of COVID-19. A number of COVID-19 late phase trial platforms have been developed to investigate (often repurposed) drugs both in the UK and globally (e.g. RECOVERY led by the University of Oxford and SOLIDARITY led by WHO). There is a pressing need to investigate novel candidates within early phase trial platforms, from which promising candidates can feed into established later phase platforms. AGILE grew from a UK-wide collaboration to undertake early stage clinical evaluation of candidates for SARS-CoV-2 infection to accelerate national and global healthcare interventions. Methods/design AGILE is a seamless phase I/IIa platform study to establish the optimum dose, determine the activity and safety of each candidate and recommend whether it should be evaluated further. Each candidate is evaluated in its own trial, either as an open label single arm healthy volunteer study or in patients, randomising between candidate and control usually in a 2:1 allocation in favour of the candidate. Each dose is assessed sequentially for safety usually in cohorts of 6 patients. Once a phase II dose has been identified, efficacy is assessed by seamlessly expanding into a larger cohort. AGILE is completely flexible in that the core design in the master protocol can be adapted for each candidate based on prior knowledge of the candidate (i.e. population, primary endpoint and sample size can be amended). This information is detailed in each candidate specific trial protocol of the master protocol. Discussion Few approved treatments for COVID-19 are available such as dexamethasone, remdesivir and tocilizumab in hospitalised patients. The AGILE platform aims to rapidly identify new efficacious and safe treatments to help end the current global COVID-19 pandemic. We currently have three candidate specific trials within this platform study that are open to recruitment. Trial registration EudraCT Number: 2020-001860-27 14 March 2020 ClinicalTrials.gov Identifier: NCT04746183  19 February 2021 ISRCTN reference: 27106947
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    The clinical features and estimated incidence of MIS-C in Cape Town, South Africa
    (2022-05-02) Butters, Claire; Abraham, Deepthi R; Stander, Raphaella; Facey-Thomas, Heidi; Abrahams, Debbie; Faleye, Ayodele; Allie, Nazneen; Soni, Khushbu; Rabie, Helena; Scott, Christiaan; Zühlke, Liesl; Webb, Kate
    Background Multisystem inflammatory syndrome is a severe manifestation of SARS-CoV-2 in children. The incidence of MIS-C after infection is poorly understood. There are very few cohorts describing MIS-C in Africa despite MIS-C being more common in Black children worldwide. Methods A cohort of children with MIS-C and healthy children was recruited from May 2020 until May 2021 from the two main paediatric hospitals in Cape Town, South Africa. Clinical and demographic data were collected, and serum was tested for SARS-CoV-2 antibodies. The incidence of MIS-C was calculated using an estimation of population exposure from seroprevalence in the healthy group. Summary data, non-parametric comparisons and logistic regression analyses were performed. Results Sixty eight children with MIS-C were recruited with a median age of 7 years (3.6, 9.9). Ninety seven healthy children were recruited with a 30% seroprevalence. The estimated incidence of MIS-C was 22/100 000 exposures in the city in this time. Black children were over-represented in the MIS-C group (62% vs 37%, p = 0.002). The most common clinical features in MIS-C were fever (100%), tachycardia (98.5%), rash (85.3%), conjunctivitis (77.9%), abdominal pain (60.3%) and hypotension (60.3%). The median haemoglobin, sodium, neutrophil count, white cell count, CRP, ferritin, cardiac (pro-BNP, trop-T) and coagulation markers (D-dimer and fibrinogen) were markedly deranged in MIS-C. Cardiac, pulmonary, central nervous and renal organ systems were involved in 71%, 29.4%, 27.9% and 27.9% respectively. Ninety four percent received intravenous immune globulin, 64.7% received methylprednisolone and 61.7% received both. Forty percent required ICU admission, 38.2% required inotropic support, 38.2% required oxygen therapy, 11.8% required invasive ventilation and 6% required peritoneal dialysis. Older age was an independent predictor for the requirement for ionotropic support (OR = 1.523, CI 1.074, 2.16, p = 0.018). The median hospital stay duration was 7 days with no deaths. Conclusion The lack of reports from Southern Africa does not reflect a lack of cases of MIS-C. MIS-C poses a significant burden to children in the region as long as the pandemic continues. MIS-C disproportionately affects black children. The clinical manifestations and outcomes of MIS-C in this region highlight the need for improved surveillance, reporting and data to inform diagnosis and treatment.
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    Clinical features and predictors of mortality among hospitalized patients with COVID-19 in Niger
    (2021-12-14) Katoto, Patrick D M C; Aboubacar, Issoufou; Oumarou, Batouré; Adehossi, Eric; Anya, Blanche-Philomene M; Mounkaila, Aida; Moustapha, Adamou; Ishagh, El k; Diawara, Gbaguidi A; Nsiari-Muzeyi, Biey J; Didier, Tambwe; Wiysonge, Charles S
    Introduction COVID-19 has spread across the African continent, including Niger. Yet very little is known about the phenotype of people who tested positive for COVID-19. In this humanitarian crises region, we aimed at characterizing variation in clinical features among hospitalized patients with COVID-19-like syndrome and to determine predictors associated with COVID-19 mortality among those with confirmed COVID-19. Methods The study was a retrospective nationwide cohort of hospitalized patients isolated for COVID-19 infection, using the health data of the National Health Information System from 19 March 2020 (onset of the pandemic) to 17 November 2020. All hospitalized patients with COVID-19-like syndrome at admission were included. A Cox-proportional regression model was built to identify predictors of in-hospital death among patients with confirmed COVID-19. Results Sixty-five percent (472/729) of patients hospitalized with COVID-19 like syndrome tested positive for SARS-CoV-2 among which, 70 (15%) died. Among the patients with confirmed COVID-19 infection, age was significantly associated with increased odds of reporting cough (adjusted odds ratio [aOR] 1.02; 95% confidence interval [CI] 1.01–1.03) and fever/chills (aOR 1.02; 95% CI 1.02–1.04). Comorbidity was associated with increased odds of presenting with cough (aOR 1.59; 95% CI 1.03–2.45) and shortness of breath (aOR 2.03; 95% CI 1.27–3.26) at admission. In addition, comorbidity (adjusted hazards ratio [aHR] 2.04; 95% CI 2.38–6.35), shortness of breath at baseline (aHR 2.04; 95% CI 2.38–6.35) and being 60 years or older (aHR 5.34; 95% CI 3.25–8.75) increased the risk of COVID-19 mortality two to five folds. Conclusion Comorbidity, shortness of breath on admission, and being aged 60 years or older are associated with a higher risk of death among patients hospitalized with COVID-19 in a humanitarian crisis setting. While robust prospective data are needed to guide evidence, our data might aid intensive care resource allocation in Niger.
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    Cost‐effectiveness of intensive care for hospitalized COVID-19 patients: experience from South Africa
    (2021-01-22) Cleary, S M; Wilkinson, T; Tamandjou Tchuem, C R; Docrat, S; Solanki, G C
    Background Given projected shortages of critical care capacity in public hospitals during the COVID-19 pandemic, the South African government embarked on an initiative to purchase this capacity from private hospitals. In order to inform purchasing decisions, we assessed the cost-effectiveness of intensive care management for admitted COVID-19 patients across the public and private health systems in South Africa. Methods Using a modelling framework and health system perspective, costs and health outcomes of inpatient management of severe and critical COVID-19 patients in (1) general ward and intensive care (GW + ICU) versus (2) general ward only (GW) were assessed. Disability adjusted life years (DALYs) were evaluated and the cost per admission in public and private sectors was determined. The model made use of four variables: mortality rates, utilisation of inpatient days for each management approach, disability weights associated with severity of disease, and the unit cost per general ward day and per ICU day in public and private hospitals. Unit costs were multiplied by utilisation estimates to determine the cost per admission. DALYs were calculated as the sum of years of life lost (YLL) and years lived with disability (YLD). An incremental cost-effectiveness ratio (ICER) - representing difference in costs and health outcomes of the two management strategies - was compared to a cost-effectiveness threshold to determine the value for money of expansion in ICU services during COVID-19 surges. Results A cost per admission of ZAR 75,127 was estimated for inpatient management of severe and critical COVID-19 patients in GW as opposed to ZAR 103,030 in GW + ICU. DALYs were 1.48 and 1.10 in GW versus GW + ICU, respectively. The ratio of difference in costs and health outcomes between the two management strategies produced an ICER of ZAR 73,091 per DALY averted, a value above the cost-effectiveness threshold of ZAR 38,465. Conclusions Results indicated that purchasing ICU capacity from the private sector during COVID-19 surges may not be a cost-effective investment. The ‘real time’, rapid, pragmatic, and transparent nature of this analysis demonstrates an approach for evidence generation for decision making relating to the COVID-19 pandemic response and South Africa’s wider priority setting agenda.
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    COVID-19 Diagnosis: A Review of Rapid Antigen, RT-PCR and Artificial Intelligence Methods
    (Multidisciplinary Digital Publishing Institute, 2022-04-03) Aruleba, Raphael Taiwo; Adekiya, Tayo Alex; Ayawei, Nimibofa; Obaido, George; Aruleba, Kehinde; Mienye, Ibomoiye Domor; Aruleba, Idowu; Ogbuokiri, Blessing
    As of 27 December 2021, SARS-CoV-2 has infected over 278 million persons and caused 5.3 million deaths. Since the outbreak of COVID-19, different methods, from medical to artificial intelligence, have been used for its detection, diagnosis, and surveillance. Meanwhile, fast and efficient point-of-care (POC) testing and self-testing kits have become necessary in the fight against COVID-19 and to assist healthcare personnel and governments curb the spread of the virus. This paper presents a review of the various types of COVID-19 detection methods, diagnostic technologies, and surveillance approaches that have been used or proposed. The review provided in this article should be beneficial to researchers in this field and health policymakers at large.
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    Investigating expressed RNA variants that are related to disease severity in SARS-CoV-2-infected patients with mild-to-severe disease
    (2022-04-28) Okendo, Javan; Okanda, David
    Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a significant public health challenge globally. SARS-CoV-2 is a novel virus, and the understanding of what constitutes expressed RNAseq variants in healthy, convalescent, severe, moderate, and those admitted to the intensive care unit (ICU) is yet to be presented. We characterize the different expressed RNAseq variants in healthy, severe, moderate, ICU, and convalescent individuals. Materials and methods: The bulk RNA sequencing data with identifier PRJNA639275 were downloaded from Sequence Reads Archive (SRA). The individuals were divided into: (1) healthy, n = 34, moderate, n = 8, convalescent, n = 2, severe, n = 16, and ICU, n = 8. Fastqc version 0.11.9 and Cutadapt version 3.7 were used to assess the read quality and perform adapter trimming, respectively. STAR was used to align reads to the reference genome, and GATK best practice was followed to call variants using the rnavar pipeline, part of the nf-core pipelines. Results: Our analysis demonstrated that different sets of unique RNAseq variants characterize convalescent, moderate, severe, and those admitted to the ICU. The data show that the individuals who recover from SARS-CoV-2 infection have the same set of expressed variants as the healthy controls. We showed that the healthy and SARS-CoV-2-infected individuals display different sets of expressed variants characteristic of the patient phenotype. Conclusion: The individuals with severe, moderate, those admitted to the ICU, and convalescent display a unique set of variants. The findings in this study will inform the test kit development and SARS-CoV-2 patients classification to enhance the management and control of SARS-CoV-2 infection in our population.
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    LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters
    (2023-06-21) de Moor, Warren R. J.; Williamson, Anna-Lise; Schäfer, Georgia; Douglass, Nicola; Gers, Sophette; Sutherland, Andrew D.; Blumenthal, Melissa J.; Margolin, Emmanuel; Shaw, Megan L.; Preiser, Wolfgang; Chapman, Rosamund
    The SARS-CoV-2 pandemic demonstrated the need for potent and broad-spectrum vaccines. This study reports the development and testing of a lumpy skin disease virus (LSDV)-vectored vaccine against SARS-CoV-2, utilizing stabilized spike and conserved nucleocapsid proteins as antigens to develop robust immunogenicity. Construction of the vaccine (LSDV-SARS2-S,N) was confirmed by polymerase chain reaction (PCR) amplification and sequencing. In vitro characterization confirmed that cells infected with LSDV-SARS2-S,N expressed SARS-CoV-2 spike and nucleocapsid protein. In BALB/c mice, the vaccine elicited high magnitude IFN-γ ELISpot responses (spike: 2808 SFU/106 splenocytes) and neutralizing antibodies (ID50 = 6552). Testing in hamsters, which emulate human COVID-19 disease progression, showed the development of high titers of neutralizing antibodies against the Wuhan and Delta SARS-CoV-2 variants (Wuhan ID50 = 2905; Delta ID50 = 4648). Additionally, hamsters vaccinated with LSDV-SARS2-S,N displayed significantly less weight loss, lung damage, and reduced viral RNA copies following SARS-CoV-2 infection with the Delta variant as compared to controls, demonstrating protection against disease. These data demonstrate that LSDV-vectored vaccines display promise as an effective SARS-CoV-2 vaccine and as a potential vaccine platform for communicable diseases in humans and animals. Further efficacy testing and immune response analysis, particularly in non-human primates, are warranted.
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    Predictors of COVID-19 Vaccine Hesitancy in South African Local Communities: The VaxScenes Study
    (Multidisciplinary Digital Publishing Institute, 2022-02-25) Katoto, Patrick D M C; Parker, Saahier; Coulson, Nancy; Pillay, Nirvana; Cooper, Sara; Jaca, Anelisa; Mavundza, Edison; Houston, Gregory; Groenewald, Candice; Essack, Zaynab; Simmonds, Jane; Shandu, Londiwe Deborah; Couch, Marilyn; Khuzwayo, Nonkululeko; Ncube, Nobukhosi; Bhengu, Phelele; Rooyen, Heidi van; Wiysonge, Charles Shey
    South Africa launched a mass COVID-19 vaccination campaign in May 2021, targeting 40 million adults. Understanding predictors of COVID-19 vaccine intentions was required to achieve this goal. We conducted a population-based survey in June–July 2021 using the WHO Behavioral and Social Drivers (BeSD) of COVID-19 Vaccination tool to determine predictors of vaccine hesitancy, defined as intention to refuse or uncertainty whether to accept COVID-19 vaccination. There were 1193 participants, mean age 39 (standard deviation 15) years, and 53% women, of whom 58% trusted information provided by healthcare workers and 32% were vaccine hesitant. Independent predictors of vaccine hesitancy included concerns about side effects (odds ratio (OR) 11.41; 95% confidence interval (CI) 3.5–50.80), lack of access to the online vaccine registration platform (OR 4.75; CI 2.15–10.37), distrust of government (OR 3.0; CI 1.33–6.77), belief in conspiracy theories (OR 3.01; CI 1.32–6.77), having no monthly income (OR 1.84; CI 1.12–3.07), and depending on someone else to make vaccination decision (OR 2.47; CI 1.06–5.77). We identified modifiable predictors of vaccine hesitancy at the start of South Africa’s COVID-19 vaccination rollout. These factors should be addressed by different stakeholders involved in the national immunization program through tailored communication and other effective strategies that increase vaccine literacy, reach low-income households, and engender confidence in government.
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    SARS-CoV-2 cases reported from long-term residential facilities (care homes) in South Africa: a retrospective cohort study
    (2022-05-24) Arendse, Tracy; Cowper, Beverley; Cohen, Cheryl; Masha, Maureen; Tempia, Stefano; Legodu, Civil; Singh, Sandhya; Ratau, Tebogo; Geffen, Leon; Heymans, Ansie; Coetzer, Dane; Blumberg, Lucille; Jassat, Waasila
    Background Globally, long-term care facilities (LTCFs) experienced a large burden of deaths during the COVID-19 pandemic. The study aimed to describe the temporal trends as well as the characteristics and risk factors for mortality among residents and staff who tested positive for SARS-CoV-2 in selected LTCFs across South Africa. Method We analysed data reported to the DATCOV sentinel surveillance system by 45 LTCFs. Outbreaks in LTCFs were defined as large if more than one-third of residents and staff had been infected or there were more than 20 epidemiologically linked cases. Multivariable logistic regression was used to assess risk factors for mortality amongst LTCF residents. Results A total of 2324 SARS-CoV-2 cases were reported from 5 March 2020 through 31 July 2021; 1504 (65%) were residents and 820 (35%) staff. Among LTCFs, 6 reported sporadic cases and 39 experienced outbreaks. Of those reporting outbreaks, 10 (26%) reported one and 29 (74%) reported more than one outbreak. There were 48 (66.7%) small outbreaks and 24 (33.3%) large outbreaks reported. There were 30 outbreaks reported in the first wave, 21 in the second wave and 15 in the third wave, with 6 outbreaks reporting between waves. There were 1259 cases during the first COVID-19 wave, 362 during the second wave, and 299 during the current third wave. The case fatality ratio was 9% (138/1504) among residents and 0.5% (4/820) among staff. On multivariable analysis, factors associated with SARS-CoV-2 mortality among LTCF residents were age 40–59 years, 60–79 years and ≥ 80 years compared to < 40 years and being a resident in a LTCF in Free State or Northern Cape compared to Western Cape. Compared to pre-wave 1, there was a decreased risk of mortality in wave 1, post-wave 1, wave 2, post-wave 2 and wave 3. Conclusion The analysis of SARS-CoV-2 cases in sentinel LTCFs in South Africa points to an encouraging trend of decreasing numbers of outbreaks, cases and risk for mortality since the first wave. LTCFs are likely to have learnt from international experience and adopted national protocols, which include improved measures to limit transmission and administer early and appropriate clinical care.
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    SARS-CoV-2 Infection Is Associated with Uncontrolled HIV Viral Load in Non-Hospitalized HIV-Infected Patients from Gugulethu, South Africa
    (2022-06-03) Lambarey, Humaira; Blumenthal, Melissa J; Chetram, Abeen; Joyimbana, Wendy; Jennings, Lauren; Tincho, Marius B; Burgers, Wendy A; Orrell, Catherine; Schäfer, Georgia
    In South Africa, high exposure to SARS-CoV-2 occurs primarily in densely populated, low-income communities, which are additionally burdened by highly prevalent Human Immunodeficiency Virus (HIV). With the aim to assess SARS-CoV-2 seroprevalence and its association with HIV-related clinical parameters in non-hospitalized patients likely to be highly exposed to SARS-CoV-2, this observational cross-sectional study was conducted at the Gugulethu Community Health Centre Antiretroviral clinic between October 2020 and June 2021, after the first COVID-19 wave in South Africa and during the second and beginning of the third wave. A total of 150 adult (median age 39 years [range 20–65 years]) HIV-infected patients (69% female; 31% male) were recruited. 95.3% of the cohort was on antiretroviral therapy (ART), had a median CD4 count of 220 cells/µL (range 17–604 cells/µL) and a median HIV viral load (VL) of 49 copies/mL (range 1–1,050,867 copies/mL). Furthermore, 106 patients (70.7%) were SARS-CoV-2 seropositive, and 0% were vaccinated. When stratified for HIV VL, patients with uncontrolled HIV viremia (HIV VL > 1000 copies/mL) had significantly higher odds of SARS-CoV-2 seropositivity than patients with HIV VL < 1000 copies/mL, after adjusting for age, sex and ART status (p = 0.035, adjusted OR 2.961 [95% CI: 1.078–8.133]). Although the cause–effect relationship could not be determined due to the cross-sectional study design, these results point towards a higher risk of SARS-CoV-2 susceptibility among viremic HIV patients, or impaired HIV viral control due to previous co-infection with SARS-CoV-2.
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    Survival among people hospitalized with COVID-19 in Switzerland: a nationwide population-based analysis
    (2022-04-26) Anderegg, Nanina; Panczak, Radoslaw; Egger, Matthias; Low, Nicola; Riou, Julien
    Background: Increasing age, male sex, and pre-existing comorbidities are associated with lower survival from SARS-CoV-2 infection. The interplay between different comorbidities, age, and sex is not fully understood, and it remains unclear if survival decreases linearly with higher ICU occupancy or if there is a threshold beyond which survival falls. Method: This national population-based study included 22,648 people who tested positive for SARS-CoV-2 infection and were hospitalized in Switzerland between February 24, 2020, and March 01, 2021. Bayesian survival models were used to estimate survival after positive SARS-CoV-2 test among people hospitalized with COVID-19 by epidemic wave, age, sex, comorbidities, and ICU occupancy. Two-way interactions between age, sex, and comorbidities were included to assess the differential risk of death across strata. ICU occupancy was modeled using restricted cubic splines to allow for a non-linear association with survival. Results: Of 22,648 people hospitalized with COVID-19, 4785 (21.1%) died. The survival was lower during the first epidemic wave than in the second (predicted survival at 40 days after positive test 76.1 versus 80.5%). During the second epidemic wave, occupancy among all available ICU beds in Switzerland varied between 51.7 and 78.8%. The estimated survival was stable at approximately 81.5% when ICU occupancy was below 70%, but worse when ICU occupancy exceeded this threshold (survival at 80% ICU occupancy: 78.2%; 95% credible interval [CrI] 76.1 to 80.1%). Periods with higher ICU occupancy (>70 vs 70%) were associated with an estimated number of 137 (95% CrI 27 to 242) excess deaths. Comorbid conditions reduced survival more in younger people than in older people. Among comorbid conditions, hypertension and obesity were not associated with poorer survival. Hypertension appeared to decrease survival in combination with cardiovascular disease. Conclusions: Survival after hospitalization with COVID-19 has improved over time, consistent with improved management of severe COVID-19. The decreased survival above 70% national ICU occupancy supports the need to introduce measures for prevention and control of SARS-CoV-2 transmission in the population well before ICUs are full.