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1.
Lancet ; 398(10303): 843-855, 2021 09 04.
Article in English | MEDLINE | ID: covidwho-2106189

ABSTRACT

BACKGROUND: A previous efficacy trial found benefit from inhaled budesonide for COVID-19 in patients not admitted to hospital, but effectiveness in high-risk individuals is unknown. We aimed to establish whether inhaled budesonide reduces time to recovery and COVID-19-related hospital admissions or deaths among people at high risk of complications in the community. METHODS: PRINCIPLE is a multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial done remotely from a central trial site and at primary care centres in the UK. Eligible participants were aged 65 years or older or 50 years or older with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to hospital. Participants were randomly assigned to usual care, usual care plus inhaled budesonide (800 µg twice daily for 14 days), or usual care plus other interventions, and followed up for 28 days. Participants were aware of group assignment. The coprimary endpoints are time to first self-reported recovery and hospital admission or death related to COVID-19, within 28 days, analysed using Bayesian models. The primary analysis population included all eligible SARS-CoV-2-positive participants randomly assigned to budesonide, usual care, and other interventions, from the start of the platform trial until the budesonide group was closed. This trial is registered at the ISRCTN registry (ISRCTN86534580) and is ongoing. FINDINGS: The trial began enrolment on April 2, 2020, with randomisation to budesonide from Nov 27, 2020, until March 31, 2021, when the prespecified time to recovery superiority criterion was met. 4700 participants were randomly assigned to budesonide (n=1073), usual care alone (n=1988), or other treatments (n=1639). The primary analysis model includes 2530 SARS-CoV-2-positive participants, with 787 in the budesonide group, 1069 in the usual care group, and 974 receiving other treatments. There was a benefit in time to first self-reported recovery of an estimated 2·94 days (95% Bayesian credible interval [BCI] 1·19 to 5·12) in the budesonide group versus the usual care group (11·8 days [95% BCI 10·0 to 14·1] vs 14·7 days [12·3 to 18·0]; hazard ratio 1·21 [95% BCI 1·08 to 1·36]), with a probability of superiority greater than 0·999, meeting the prespecified superiority threshold of 0·99. For the hospital admission or death outcome, the estimated rate was 6·8% (95% BCI 4·1 to 10·2) in the budesonide group versus 8·8% (5·5 to 12·7) in the usual care group (estimated absolute difference 2·0% [95% BCI -0·2 to 4·5]; odds ratio 0·75 [95% BCI 0·55 to 1·03]), with a probability of superiority 0·963, below the prespecified superiority threshold of 0·975. Two participants in the budesonide group and four in the usual care group had serious adverse events (hospital admissions unrelated to COVID-19). INTERPRETATION: Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications. FUNDING: National Institute of Health Research and United Kingdom Research Innovation.


Subject(s)
Budesonide/administration & dosage , COVID-19/drug therapy , Glucocorticoids/administration & dosage , Administration, Inhalation , Aged , Bayes Theorem , COVID-19/mortality , Female , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , SARS-CoV-2 , Treatment Outcome
2.
EBioMedicine ; 86: 104341, 2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2104818

ABSTRACT

BACKGROUND: The COVID-19 pandemic continues to cause morbidity and mortality worldwide. Most approved COVID-19 vaccines generate a neutralizing antibody response that primarily targets the highly variable receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. SARS-CoV-2 "variants of concern" have acquired mutations in this domain allowing them to evade vaccine-induced humoral immunity. Recent approaches to improve the breadth of protection beyond SARS-CoV-2 have required the use of mixtures of RBD antigens from different sarbecoviruses. It may therefore be beneficial to develop a vaccine in which the protective immune response targets a more conserved region of the S protein. METHODS: Here we have developed a vaccine based on the conserved S2 subunit of the S protein and optimized the adjuvant and immunization regimen in Syrian hamsters and BALB/c mice. We have characterized the efficacy of the vaccine against SARS-CoV-2 variants and other coronaviruses. FINDINGS: Immunization with S2-based constructs elicited a broadly cross-reactive IgG antibody response that recognized the spike proteins of not only SARS-CoV-2 variants, but also SARS-CoV-1, and the four endemic human coronaviruses. Importantly, immunization reduced virus titers in respiratory tissues in vaccinated animals challenged with SARS-CoV-2 variants B.1.351 (beta), B.1.617.2 (delta), and BA.1 (omicron) as well as a pangolin coronavirus. INTERPRETATION: These results suggest that S2-based constructs can elicit a broadly cross-reactive antibody response resulting in limited virus replication, thus providing a framework for designing vaccines that elicit broad protection against coronaviruses. FUNDING: NIH, Japan Agency for Medical Research and Development, Garry Betty/ V Foundation Chair Fund, and NSF.

3.
Nature ; 2022 Nov 02.
Article in English | MEDLINE | ID: covidwho-2096734

ABSTRACT

The BA.2 sublineage of the SARS-CoV-2 Omicron variant has become dominant in most countries around the world; however, the prevalence of BA.4 and BA.5 is increasing rapidly in several regions. BA.2 is less pathogenic in animal models than previously circulating variants of concern (VOC)1-4. Compared with BA.2, however, BA.4 and BA.5 possess additional substitutions in the spike protein, which play a key role in viral entry, raising concerns that the replication capacity and pathogenicity of BA.4 and BA.5 are higher than those of BA.2. Here, we evaluated the replicative ability and pathogenicity of BA.4 and BA.5 isolates in wild-type Syrian hamsters, human ACE2 (hACE2) transgenic hamsters, and hACE2 transgenic mice. we observed no obvious differences among BA.2, BA.4, and BA.5 isolates in growth ability or pathogenicity in rodent models, and less pathogenicity compared to a previously circulating Delta (B.1.617.2 lineage) isolate. In addition, in vivo competition experiments revealed that BA.5 outcompeted BA.2 in hamsters, whereas BA.4 and BA.2 exhibited similar fitness. These findings suggest that BA.4 and BA.5 clinical isolates have similar pathogenicity to BA.2 in rodents and that BA.5 possesses viral fitness superior to that of BA.2.

4.
Nat Rev Microbiol ; 2022 Nov 02.
Article in English | MEDLINE | ID: covidwho-2096725
5.
Lancet ; 2022 Nov 04.
Article in English | MEDLINE | ID: covidwho-2096175

ABSTRACT

BACKGROUND: For patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric carboxymaltose administration improves quality of life and exercise capacity in the short-term and reduces hospital admissions for heart failure up to 1 year. We aimed to evaluate the longer-term effects of intravenous ferric derisomaltose on cardiovascular events in patients with heart failure. METHODS: IRONMAN was a prospective, randomised, open-label, blinded-endpoint trial done at 70 hospitals in the UK. Patients aged 18 years or older with heart failure (left ventricular ejection fraction ≤45%) and transferrin saturation less than 20% or serum ferritin less than 100 µg/L were eligible. Participants were randomly assigned (1:1) using a web-based system to intravenous ferric derisomaltose or usual care, stratified by recruitment context and trial site. The trial was open label, with masked adjudication of the outcomes. Intravenous ferric derisomaltose dose was determined by patient bodyweight and haemoglobin concentration. The primary outcome was recurrent hospital admissions for heart failure and cardiovascular death, assessed in all validly randomly assigned patients. Safety was assessed in all patients assigned to ferric derisomaltose who received at least one infusion and all patients assigned to usual care. A COVID-19 sensitivity analysis censoring follow-up on Sept 30, 2020, was prespecified. IRONMAN is registered with ClinicalTrials.gov, NCT02642562. FINDINGS: Between Aug 25, 2016, and Oct 15, 2021, 1869 patients were screened for eligibility, of whom 1137 were randomly assigned to receive intravenous ferric derisomaltose (n=569) or usual care (n=568). Median follow-up was 2·7 years (IQR 1·8-3·6). 336 primary endpoints (22·4 per 100 patient-years) occurred in the ferric derisomaltose group and 411 (27·5 per 100 patient-years) occurred in the usual care group (rate ratio [RR] 0·82 [95% CI 0·66 to 1·02]; p=0·070). In the COVID-19 analysis, 210 primary endpoints (22·3 per 100 patient-years) occurred in the ferric derisomaltose group compared with 280 (29·3 per 100 patient-years) in the usual care group (RR 0·76 [95% CI 0·58 to 1·00]; p=0·047). No between-group differences in deaths or hospitalisations due to infections were observed. Fewer patients in the ferric derisomaltose group had cardiac serious adverse events (200 [36%]) than in the usual care group (243 [43%]; difference -7·00% [95% CI -12·69 to -1·32]; p=0·016). INTERPRETATION: For a broad range of patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric derisomaltose administration was associated with a lower risk of hospital admissions for heart failure and cardiovascular death, further supporting the benefit of iron repletion in this population. FUNDING: British Heart Foundation and Pharmacosmos.

6.
Drug Safety ; JOUR:1171-1172, 45(10).
Article in English | EMBASE | ID: covidwho-2085698

ABSTRACT

Introduction: The South African Health Products Regulatory Authority (SAHPRA) utilises various AEFI reporting tools to monitor vaccine safety in the country. In 2020, SAHPRA in collaboration with the National Department of Health's (NDoH) Expanded Programme on Immunisation (EPI), joined the African Union Smart Safety Surveillance programme, as one of four pilot countries, to introduce an electronic adverse event following immunisation (AEFI) reporting system (Med Safety App) for healthcare professionals and consumers [1]. On 17/05/2021, the NDoH introduced its national COVID-19 vaccination programme. SAHPRA launched a microsite during 2021, to provide feedback to the public on AEFI with the COVID-19 vaccines. Objective(s): To provide an overview of COVID-19 vaccine safety surveillance and describe causality assessment outcomes for serious AEFI reported during the first year of COVID-19 vaccine administration. Method(s): All severe and/or serious AEFI are investigated by provincial EPI surveillance teams, followed by causality assessment conducted by the National Immunisation Safety Expert Committee (NISEC), using the World Health Organization (WHO) methodology [2]. Causality assessment outcomes are classified based on the final diagnoses determined during the assessment by NISEC according to WHO categories, seriousness, Medical Dictionary for Regulatory Activities (MedDRA) system organ class and patient demographics. Data were collected retrospectively from the SAHPRA COVID-19 AEFI microsite and the EPI national AEFI database. Result(s): By 01/04/2022, 33,063,221 COVID-19 vaccine doses had been administered, with 5 815 spontaneous AEFI reports (0.0173%) submitted. Of these, 2,571 (0.008%) were reported as serious. Spontaneous reporting of AEFI increased significantly compared to pre-COVID-19 vaccine introduction. The most frequently reported AEFIs were side effects already listed in the product information. No safety concerns were raised based on causality assessment outcomes for 273 serious cases analysed by 01/04/2022. Over two thirds of these cases were classified as coincidental (70.7%) as cardiac-, respiratory- or vascular disorders (MedDRA system organ class), with 12.1% classified as vaccine product related (see table below). The presentation will include all causality assessments conducted up to 31/08/2022, and more detailed information about causality assessed cases will be available in the public domain at the time of the conference and will be included in the presentation. Conclusion(s): Vaccine safety surveillance and monitoring trends of reported AEFI are vital measures to ensure that the benefits of immunisation are maintained in the interest of public health and efficient vaccination programmes. Transparent communication with the public is important to maintain public confidence in vaccines and prevent all AEFI being misinterpreted as caused by the vaccine.

9.
Affective science ; JOUR: 1-17,
Article in English | EuropePMC | ID: covidwho-2083582

ABSTRACT

Meta-analyses indicate that positive psychological interventions are effective at increasing positive affect, as well as reducing anxiety and depression;however, it is unclear how well these effects generalize during periods of high stress. Therefore, the current study tested whether a 2-week online positive psychological intervention delivered during the COVID-19 pandemic, a naturalistic stressor, (1) increased positive affect;(2) improved psychological well-being, optimism, life satisfaction, perceived social support, and loneliness;(3) and reduced negative affect in college students, a group known to have high pandemic distress. Participants (N = 250;76.9% female) ages 18–45 were recruited from the University of Pittsburgh undergraduate subject pool between September and November of 2020. Participants were randomized to the online positive psychological intervention or active control condition and stratified by trait positive affect, sex, and year in college. Participants in both conditions completed one writing activity every other day for two consecutive weeks. Control participants documented their activities for that day (e.g., meals, going to gym). Intervention participants chose from six positive psychology activities. All outcome variables were assessed pre- and post-intervention by validated questionnaires. Across both conditions, positive and negative affect decreased from pre- to post-intervention. No other psychological factor differed by condition, time, or their interaction. The current null findings are in line with a more recent meta-analysis indicating that positive psychological interventions may have smaller effects on psychological well-being and depressive symptoms than was reported pre-pandemic. Study findings may suggest reduced efficacy of virtual positive psychological interventions under highly stressful circumstances. Supplementary Information The online version contains supplementary material available at 10.1007/s42761-022-00148-z.

10.
MMWR Morb Mortal Wkly Rep ; 71(42): 1335-1342, 2022 Oct 21.
Article in English | MEDLINE | ID: covidwho-2081113

ABSTRACT

Persons with moderate-to-severe immunocompromising conditions might have reduced protection after COVID-19 vaccination, compared with persons without immunocompromising conditions (1-3). On August 13, 2021, the Advisory Committee on Immunization Practices (ACIP) recommended that adults with immunocompromising conditions receive an expanded primary series of 3 doses of an mRNA COVID-19 vaccine. ACIP followed with recommendations on September 23, 2021, for a fourth (booster) dose and on September 1, 2022, for a new bivalent mRNA COVID-19 vaccine booster dose, containing components of the BA.4 and BA.5 sublineages of the Omicron (B.1.1.529) variant (4). Data on vaccine effectiveness (VE) of monovalent COVID-19 vaccines among persons with immunocompromising conditions since the emergence of the Omicron variant in December 2021 are limited. In the multistate VISION Network,§ monovalent 2-, 3-, and 4-dose mRNA VE against COVID-19-related hospitalization were estimated among adults with immunocompromising conditions¶ hospitalized with COVID-19-like illness,** using a test-negative design comparing odds of previous vaccination among persons with a positive or negative molecular test result (case-patients and control-patients) for SARS-CoV-2 (the virus that causes COVID-19). During December 16, 2021-August 20, 2022, among SARS-CoV-2 test-positive case-patients, 1,815 (36.3%), 1,387 (27.7%), 1,552 (31.0%), and 251 (5.0%) received 0, 2, 3, and 4 mRNA COVID-19 vaccine doses, respectively. Among test-negative control-patients during this period, 6,928 (23.7%), 7,411 (25.4%), 12,734 (43.6%), and 2,142 (7.3%) received these respective doses. Overall, VE against COVID-19-related hospitalization among adults with immunocompromising conditions hospitalized for COVID-like illness during Omicron predominance was 36% ≥14 days after dose 2, 69% 7-89 days after dose 3, and 44% ≥90 days after dose 3. Restricting the analysis to later periods when Omicron sublineages BA.2/BA.2.12.1 and BA.4/BA.5 were predominant and 3-dose recipients were eligible to receive a fourth dose, VE was 32% ≥90 days after dose 3 and 43% ≥7 days after dose 4. Protection offered by vaccination among persons with immunocompromising conditions during Omicron predominance was moderate even after a 3-dose monovalent primary series or booster dose. Given the incomplete protection against hospitalization afforded by monovalent COVID-19 vaccines, persons with immunocompromising conditions might benefit from updated bivalent vaccine booster doses that target recently circulating Omicron sublineages, in line with ACIP recommendations. Further, additional protective recommendations for persons with immunocompromising conditions, including the use of prophylactic antibody therapy, early access to and use of antivirals, and enhanced nonpharmaceutical interventions such as well-fitting masks or respirators, should also be considered.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Humans , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , Antiviral Agents , Hospitalization , Vaccines, Combined , RNA, Messenger
11.
J Mol Cell Biol ; 2022 Oct 14.
Article in English | MEDLINE | ID: covidwho-2077797

ABSTRACT

Accumulating evidence indicates a potential role for bacterial lipopolysaccharide (LPS) in the overactivation of the immune response during SARS-CoV-2 infection. LPS is recognised by Toll-like receptor 4 (TLR4), mediating proinflammatory effects. We previously reported that LPS directly interacts with SARS-CoV-2 spike (S) protein and enhances proinflammatory activities. Using native gel electrophoresis and hydrogen-deuterium exchange mass spectrometry, we showed that LPS binds to multiple hydrophobic pockets spanning both the S1 and S2 subunits of the S protein. Molecular simulations validated by a microscale thermophoresis binding assay revealed that LPS binds to the S2 pocket with a lower affinity compared to S1, suggesting a role as an intermediate in LPS transfer. ໿Congruently, nuclear factor-kappa B (NF-κB) activation in monocytic THP-1 cells is strongly boosted by S2. Using NF-κB reporter mice followed by bioimaging, a boosting effect was observed for both S1 and S2, with the former potentially facilitated by proteolysis. The Omicron S variant binds to LPS, but with reduced affinity and LPS boosting in vitro and in vivo. Taken together, the data provide a molecular mechanism by which S protein augments LPS-mediated hyperinflammation.

12.
Ann Neurol ; 2022 Oct 19.
Article in English | MEDLINE | ID: covidwho-2074911

ABSTRACT

OBJECTIVE: The objective of this study was to assess the impact of treatment with dexamethasone, remdesivir or both on neurological complications in acute coronavirus diease 2019 (COVID-19). METHODS: We used observational data from the International Severe Acute and emerging Respiratory Infection Consortium World Health Organization (WHO) Clinical Characterization Protocol, United Kingdom. Hospital inpatients aged ≥18 years with laboratory-confirmed severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection admitted between January 31, 2020, and June 29, 2021, were included. Treatment allocation was non-blinded and performed by reporting clinicians. A propensity scoring methodology was used to minimize confounding. Treatment with remdesivir, dexamethasone, or both was assessed against the standard of care. The primary outcome was a neurological complication occurring at the point of death, discharge, or resolution of the COVID-19 clinical episode. RESULTS: Out of 89,297 hospital inpatients, 64,088 had severe COVID-19 and 25,209 had non-hypoxic COVID-19. Neurological complications developed in 4.8% and 4.5%, respectively. In both groups, neurological complications were associated with increased mortality, intensive care unit (ICU) admission, worse self-care on discharge, and time to recovery. In patients with severe COVID-19, treatment with dexamethasone (n = 21,129), remdesivir (n = 1,428), and both combined (n = 10,846) were associated with a lower frequency of neurological complications: OR = 0.76 (95% confidence interval [CI] = 0.69-0.83), OR = 0.69 (95% CI = 0.51-0.90), and OR = 0.54 (95% CI = 0.47-0.61), respectively. In patients with non-hypoxic COVID-19, dexamethasone (n = 2,580) was associated with less neurological complications (OR = 0.78, 95% CI = 0.62-0.97), whereas the dexamethasone/remdesivir combination (n = 460) showed a similar trend (OR = 0.63, 95% CI = 0.31-1.15). INTERPRETATION: Treatment with dexamethasone, remdesivir, or both in patients hospitalized with COVID-19 was associated with a lower frequency of neurological complications in an additive manner, such that the greatest benefit was observed in patients who received both drugs together. ANN NEUROL 2022.

13.
JAMA Netw Open ; 5(10): e2236524, 2022 10 03.
Article in English | MEDLINE | ID: covidwho-2074852

ABSTRACT

Importance: Although telemedicine expanded rapidly during the COVID-19 pandemic and is widely available for primary care, required broadband internet speeds may limit access. Objective: To identify disparities in primary care access in the Veterans Health Administration based on the association between broadband availability and primary care visit modality. Design, Setting, and Participants: This cohort study used administrative data on veterans enrolled in Veterans Health Administration primary care to identify visits at 937 primary care clinics providing telemedicine and in-person clinical visits before the COVID-19 pandemic (October 1, 2016, to February 28, 2020) and after the onset of the pandemic (March 1, 2020, to June 30, 2021). Exposures: Federal Communications Commission-reported broadband availability was classified as inadequate (download speed, ≤25 MB/s; upload speed, ≤3 MB/s), adequate (download speed, ≥25 <100 MB/s; upload speed, ≥5 and <100 MB/s), or optimal (download and upload speeds, ≥100 MB/s) based on data reported at the census block by internet providers and was spatially merged to the latitude and longitude of each veteran's home address using US Census Bureau shapefiles. Main Outcomes and Measures: All visits were coded as in-person or virtual (ie, telephone or video) and counted for each patient, quarterly by visit modality. Poisson models with Huber-White robust errors clustered at the census block estimated the association between a patient's broadband availability category and the quarterly primary care visit count by visit type, adjusted for covariates. Results: In primary care, 6 995 545 veterans (91.8% men; mean [SD] age, 63.9 [17.2] years; 71.9% White; and 63.0% residing in an urban area) were seen. Adjusted regression analyses estimated the change after the onset of the pandemic vs before the pandemic in patients' quarterly primary care visit count; patients living in census blocks with optimal vs inadequate broadband had increased video visit use (incidence rate ratio [IRR], 1.33; 95% CI, 1.21-1.46; P < .001) and decreased in-person visits (IRR, 0.84; 95% CI, 0.84-0.84; P < .001). The increase in the rate of video visits before vs after the onset of the pandemic was greatest among patients in the lowest Area Deprivation Index category (indicating least social disadvantage) with availability of optimal vs inadequate broadband (IRR, 1.73; 95% CI, 1.42-2.09). Conclusions and Relevance: This cohort study found that patients with optimal vs inadequate broadband availability had more video-based primary care visits and fewer in-person primary care visits after the onset of the COVID-19 pandemic, suggesting that broadband availability was associated with video-based telemedicine use. Future work should assess the association of telemedicine access with clinical outcomes.


Subject(s)
COVID-19 , COVID-19/epidemiology , Cohort Studies , Female , Humans , Internet , Male , Middle Aged , Pandemics , Primary Health Care , Veterans Health
14.
Int J Environ Res Public Health ; 19(20)2022 Oct 17.
Article in English | MEDLINE | ID: covidwho-2071481

ABSTRACT

OBJECTIVE: In this evaluation of COVID-19 preventative response programs in South Kivu, Democratic Republic of the Congo (DRC), we aimed to explore community understandings of COVID-19, assess operational successes and challenges of COVID response activities, and identify barriers to practicing COVID-19 preventative behaviors. METHODS: Thirty-one semi-structured interviews were conducted from April to September 2021 in South Kivu, DRC, with community members (n = 16) and programmatic stakeholders (n = 15) (healthcare providers, government officials, and developmental and NGO staff engaged in COVID-19 response). FINDINGS: Most community members were aware of COVID-19 and its global burden, but few were aware of local transmission in their area. Some community members attributed COVID-19 to actions of malevolent neighbors, miasma ("bad air"), or spirits. Awareness of COVID-19 preventative measures was widespread, largely because of radio and TV health promotion programs. Community members and programmatic stakeholders both said community-level non-compliance to COVID-19 preventative measures was high despite high awareness of preventative methods. Community members expressed concern that face masks distributed as part of preventative programs contained the COVID-19 virus. Programmatic stakeholders emphasized the need for broader health system strengthening with improved coordination, provision of resources to health facilities at the provincial level, and prioritization of research. Lessons learned from addressing Ebola were leveraged for COVID-19 health promotion, rapid training of healthcare personnel, and surveillance. CONCLUSIONS: Community-informed approaches are needed for effective COVID-19 preventative response programs in South Kivu, DRC. Our study identified successes and challenges in COVID-19 response activities. Future research should assess the effectiveness of integrating preventive programs with COVID-19 vaccination efforts.


Subject(s)
COVID-19 , Hemorrhagic Fever, Ebola , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Democratic Republic of the Congo/epidemiology , COVID-19 Vaccines , Hemorrhagic Fever, Ebola/epidemiology , SARS-CoV-2
16.
Preprint in English | bioRxiv | ID: ppbiorxiv-514592

ABSTRACT

The rapid evolution of SARS-CoV-2 Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identify S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) and derived from an individual previously infected with SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrates broad cross-neutralization of all dominant variants including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1). Furthermore, it protected hamsters against in vivo challenges with wildtype, Delta, and BA.1 viruses. Structural analysis reveals that this antibody targets a class 1 epitope via multiple hydrophobic and polar interactions with its CDR-H3, in addition to common class 1 motifs in CDR-H1/CDR-H2. Importantly, this epitope is more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared to diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential, and may inform target-driven vaccine design against future SARS-CoV-2 variants.

17.
J Cardiothorac Surg ; 17(1): 263, 2022 Oct 08.
Article in English | MEDLINE | ID: covidwho-2064825

ABSTRACT

BACKGROUND: Crescent cannula adhesion in the setting of COVID-19 respiratory failure requiring extracorporeal membrane oxygenation (ECMO) support is a novel complication. The objective of this case presentation is to highlight this rare complication and to explore potential predisposing factors and our management strategies. CASE PRESENTATION: We present the case of a 25 y.o. patient with COVID-19 respiratory failure requiring ECMO support for 16-days in which a 32 Fr crescent cannula became adherent to the SVC and proximal jugular vein. Attempts to remove the cannula at the bedside failed due to immobility of the cannula. Ultrasound of the right neck was unremarkable, so he was taken to the hybrid OR where both TEE and fluoroscopy were unrevealing. An upper sternotomy was performed, and the superior vena cava and proximal jugular vein were dissected revealing a 2 cm segment of the distal SVC and proximal jugular vein that was densely sclerosed and adherent to the cannula. The vessel was opened across the adherent area at the level of the innominate vein and the cannula was then able to be withdrawn. The patient suffered no ill effects and had an unremarkable recovery to discharge. CONCLUSIONS: To date, there have been no reports of crescent cannula adhesion related complications. In patients with COVID-19 respiratory failure requiring ECMO, clinicians should be aware of widespread hypercoagulability and the potential of unprovoked, localized venous sclerosis and cannula adhesion. We report our technique of decannulation in the setting of cannula adhesion and hope that presentation will shed further light on this complication allowing clinicians to optimize patient care.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome , Respiratory Insufficiency , COVID-19/therapy , Cannula , Extracorporeal Membrane Oxygenation/methods , Humans , Male , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Vena Cava, Superior
19.
Atmospheric Pollution Research ; : 101570, 2022.
Article in English | ScienceDirect | ID: covidwho-2060408

ABSTRACT

Air pollution associated health issues are increasing globally. This is due to both anthropogenic sources, such as traffic, and natural sources, such as bushfires. Natural disasters, such as bushfires, impact air quality by releasing large concentrations of pollutants affecting respiratory health. However, another recent global event has also had severe impacts on the environment and health, the global COVID-19 pandemic. Global pandemics, such as COVID-19, can also influence air quality by altering human activity, resulting in its own associated health impacts. This study aimed to investigate the impact of a natural disaster and global pandemic on outdoor ambient air pollution by quantifying and comparing the spatial distribution of two air pollutants, nitrogen dioxide (NO2) and particulate matter (PM10), during the different periods across the Greater Sydney region, Australia, while correcting for anthropogenic sources and meteorological influences such as temperature and rain. COVID-19 and bushfire affected periods were compared to a control period when both of these influences were absent. We found that NO2 was significantly higher during the COVID-19 pandemic than during the control period and the recent 2019 bushfires. Conversely, PM10 was significantly lower during the COVID-19 pandemic than the bushfire and control periods. The spatial distribution of both pollutants and influencers also varied across the study site. These results suggest that both events markedly impacted air quality, although they impacted the air pollutants differently. These findings further demonstrate a greater need to understand the impact of natural disasters and anthropocentric events on air pollution as multifaceted, spatially relevant policies are required to address these events, particularly if they increase in frequency or severity in the future.

20.
Appl Plant Sci ; 10(5): e11495, 2022.
Article in English | MEDLINE | ID: covidwho-2059283

ABSTRACT

Premise: The effective ex situ conservation of exceptional plants, whether in living collections or cryo-collections, requires more resources than the conservation of other species. Because of their expertise with rare plants, botanical gardens are well positioned to lead this effort, but a well-developed strategy requires a clear understanding of the resources needed. Methods: Grant funding was obtained from the Institute of Museum and Library Services to support a three-year project on cryobanking, and to provide smaller grants to 10 other botanical gardens for one-year projects on either (1) seed behavior studies or (2) the development of protocols for in vitro propagation or cryopreservation. Results: Nine of the partner gardens worked on 19 species (one was unable to continue due to the COVID-19 pandemic), while the larger project focused on 14 species. A point system was developed for tasks accomplished, and the average costs per point of the larger and smaller projects were similar. Labor accounted for half the costs. Projects focused on species in the Asteraceae and Orchidaceae had lower costs per point than other species. Discussion: Both large and small projects can contribute to a strategy for exceptional plant conservation for similar costs. Prioritizing species with lower costs could help advance the field while allowing time for work on more difficult species to develop.

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