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1.
Ann Vasc Surg ; 2021 Nov 11.
Article in English | MEDLINE | ID: covidwho-1596282

ABSTRACT

OBJECTIVE: The aim of this study was to examine the COVID-19 pandemic and its associated impact on the provision of vascular services, and the pattern of presentation and practice in a tertiary referral vascular unit. METHODS: This is a retrospective observational study from a prospectively maintained data-base comparing two time frames, Period 1(15th March-30th May 2019-P1) and Period 2(15th March-30th May 2020-P2)All the patients who presented for a vascular review in the 2 timeframes were included. Metrics of service and patient care episodes were collected and compared including, the number of emergency referrals, patient encounters, consultations, emergency admissions and interventions. Impact on key hospital resources such as critical care and imaging facilities during the two time periods were also examined. RESULTS: There was an absolute reduction of 44% in the number of patients who required urgent or emergency treatment from P1 to P2 (141 vs 79). We noted a non-significant trend towards an increase in the proportion of patients presenting with Chronic Limb Threatening Ischaemia (CLTI) Rutherford 5&6 (P=0.09) as well as a reduction in the proportion of admissions related to Aortic Aneurysm (P=0.21). There was a significant absolute reduction of 77% in all vascular interventions from P1 to P2 with the greatest reductions noted in Carotid (P=0.02), Deep Venous (P=0.003) and Aortic interventions (P=0.016). The number of lower limb interventions also decreased though there was a significant increase as a relative proportion of all vascular interventions in P2 (P=0.001). There was an absolute reduction in the number of scans performed for vascular pathology; Duplex scans reduced by 86%(P<0.002), CT scans by 68%(P<0.003) and MRIs by 74%(P<0.009). CONCLUSIONS AND RELEVANCE: We report a decrease in urgent and emergency vascular presentations, admissions and interventions. The reduction in patients presenting with lower limb pathology was not as significant as other vascular conditions, resulting in a significant rise in interventions for CLTI and DFI as a proportion of all vascular interventions. These observations will help guide the provision of vascular services during future pandemics.

2.
Vaccine ; 2021.
Article in English | ScienceDirect | ID: covidwho-1586269

ABSTRACT

Introduction Individuals with an underlying malignancy have high risk of poor COVID-19 outcomes. In clinical trials, COVID-19 vaccines were safe and efficacious against infection, hospitalization, and death, but most trials excluded participants with cancer. We report results from participants with a history of past or active neoplasm (malignant or benign/unknown) and up to 6 months’ follow-up post-dose 2 from the placebo-controlled, observer-blinded trial of the 2-dose BNT162b2 mRNA COVID-19 vaccine. Patients and methods Between July 2020–January 2021, 46,429 participants aged ≥12 years were randomized at 152 sites in 6 countries. Healthy participants with pre-existing stable neoplasm could participate;those receiving immunosuppressive therapy were excluded. Data are reported for participants, aged ≥16 years for safety and ≥12 years for efficacy, who had any history of neoplasm at baseline (data cut-off: March 13, 2021). Adverse-event (AE) data are controlled for follow-up time before unblinding and reported as incidence rates (IRs) per 100 person-years follow-up. Results At baseline, 3813 participants had a history of neoplasm;most common malignancies were breast (n = 460), prostate (n = 362), and melanoma (n = 223). Four BNT162b2 and 71 placebo recipients developed COVID-19 from 7 days post-dose 2;vaccine efficacy was 94.4% (95% CI: 85.2, 98.5) after up to 6 months’ follow-up post-dose 2. This compares favorably with vaccine efficacy of 91.1% in the overall trial population after the same follow-up. AEs were reported at IRs of 95.4(BNT162b2) and 48.3 (placebo) per 100 person-years. Most common AEs were reactogenicity events (injection-site pain, fatigue, pyrexia). Three BNT162b2 and 1 placebo recipients withdrew because of vaccine-related AEs. No vaccine-related deaths were reported. Conclusion In participants with past or active neoplasms, BNT162b2 vaccine has a similar efficacy and safety profile as in the overall trial population. These results can inform BNT162b2 use during the COVID-19 pandemic and future trials in participants with cancer. Clinical trial number: NCT04368728

3.
Preprint | EuropePMC | ID: ppcovidwho-296874

ABSTRACT

Conventional methods for quantifying and phenotyping antigen-specific lymphocytes can rapidly deplete irreplaceable specimens. This is due to the fact that antigen-specific T and B cells have historically been analyzed in independent assays each requiring millions of cells. A technique that facilitates the simultaneous detection of antigen-specific T and B cells would allow for more thorough immune profiling with significantly reduced sample requirements. To this end, we developed the B And T cell Tandem Lymphocyte Evaluation (BATTLE) assay, which allows for the simultaneous identification of SARS-CoV-2 Spike reactive T and B cells using an optimized Activation Induced Marker (AIM) T cell assay and dual-color B cell antigen probes. Using this assay, we demonstrate that antigen-specific B and T cell subsets can be identified simultaneously using conventional flow cytometry platforms and provide insight into the differential effects of mRNA vaccination on B and T cell populations following natural SARS-CoV-2 infection.

4.
Qatar Med J ; 2021(3): 44, 2021.
Article in English | MEDLINE | ID: covidwho-1572869

ABSTRACT

Despite protective measures such as personal protective equipment (PPE) and a COVID airway management program (CAMP), some emergency physicians will inevitably test positive for COVID. We aim to develop a model predicting weekly numbers of emergency physician COVID converters to aid operations planning. The data were obtained from the electronic medical record (EMR) used throughout the national healthcare system. Hamad Medical Corporation's internal emergency medicine workforce data were used as a source of information on emergency physician COVID conversion and numbers of emergency physicians completing CAMP training. The study period included the spring and summer months of 2020 and started on March 7 and ran for 21 whole weeks through July 31. Data were extracted from the system's EMR database into a spreadsheet (Excel, Microsoft, Redmond, USA). The statistical software used for all analyses and plots was Stata (version 16.1 MP, StataCorp, College Station, USA). All data definitions were made a priori. A total of 35 of 250 emergency physicians (14.0%, 95% CI 9.9%-19.9%) converted to a positive real-time reverse transcriptase-polymerase chain reaction (PCR) during the study's 21-week period. Of these. only two were hospitalized for having respiratory-only disease, and none required respiratory support. Both were discharged within a week of admission. The weekly number of newly COVID-positive emergency physicians was zero and was seen in eight of 21 (38.1%) weeks. The peak weekly counts of six emergency physicians with new COVID-positive were seen in week 14. The mean weekly number of newly COVID-positive emergency physicians was 1.7 ± 1.9, and the median was 1 (IQR, 0 to 3). This study demonstrates that in the State of Qatar's Emergency Department (ED) system, knowing only four parameters allows the reliable prediction of the number of emergency physicians likely to convert COVID PCR tests within the next week. The results also suggest that attention to the details of minimizing endotracheal intubation (ETI) risk can eliminate the expected finding of the association between ETI numbers and emergency physician COVID numbers.

5.
Lancet Diabetes Endocrinol ; 9(10): 671-680, 2021 10.
Article in English | MEDLINE | ID: covidwho-1531932

ABSTRACT

BACKGROUND: Diabetic ketoacidosis (DKA) has been reported to be increasing in frequency during the COVID-19 pandemic. We aimed to examine the rates of DKA hospital admissions and the patient demographics associated with DKA during the pandemic compared with in prepandemic years. METHODS: Using a comprehensive, multiethnic, national dataset, the Secondary Uses Service repository, we extracted all emergency hospital admissions in England coded with DKA from March 1 to June 30, 2020 (first wave of the pandemic), July 1 to Oct 31, 2020 (post-first wave), and Nov 1, 2020, to Feb 28, 2021 (second wave), and compared these with DKA admissions in the equivalent periods in 2017-20. We also examined baseline characteristics, mortality, and trends in patients who were admitted with DKA. FINDINGS: There were 8553 admissions coded with DKA during the first wave, 8729 during the post-first wave, and 10 235 during the second wave. Compared with preceding years, DKA admissions were 6% (95% CI 4-9; p<0·0001) higher in the first wave of the pandemic (from n=8048), 6% (3-8; p<0·0001) higher in the post-first wave (from n=8260), and 7% (4-9; p<0·0001) higher in the second wave (from n=9610). In the first wave, DKA admissions reduced by 19% (95% CI 16-21) in those with pre-existing type 1 diabetes (from n=4965 to n=4041), increased by 41% (35-47) in those with pre-existing type 2 diabetes (from n=2010 to n=2831), and increased by 57% (48-66) in those with newly diagnosed diabetes (from n=1072 to n=1681). Compared with prepandemic, type 2 diabetes DKA admissions were similarly common in older individuals and men but were higher in those of non-White ethnicities during the first wave. The increase in newly diagnosed DKA admissions occurred across all age groups and these were significantly increased in men and people of non-White ethnicities. In the post-first wave, DKA admissions did not return to the baseline level of previous years; DKA admissions were 14% (11-17) lower in patients with type 1 diabetes (from n=5208 prepandemic to n=4491), 30% (24-36) higher in patients with type 2 diabetes (from n=2011 to n=2613), and 56% (47-66) higher in patients with newly diagnosed diabetes (from n=1041 to n=1625). During the second wave, DKA admissions were 25% (22-27) lower in patients with type 1 diabetes (from n=5769 prepandemic to n=4337), 50% (44-56) higher in patients with type 2 diabetes (from n=2608 to n=3912), and 61% (52-70) higher in patients with newly diagnosed diabetes (from n=1234 to n=1986). INTERPRETATION: Our results provide evidence for differences in the numbers and characteristics of people presenting with DKA during the COVID-19 pandemic compared with in the preceding 3 years. Greater awareness of risk factors for DKA in type 2 diabetes and vigilance for newly diagnosed diabetes presenting with DKA during the COVID-19 pandemic might help mitigate the increased impact of DKA. FUNDING: None.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Diabetic Ketoacidosis/epidemiology , Emergency Service, Hospital/trends , Patient Admission/trends , Population Surveillance , Adolescent , Adult , Aged , COVID-19/prevention & control , Databases, Factual/trends , Diabetes Mellitus, Type 2/therapy , Diabetic Ketoacidosis/therapy , England/epidemiology , Female , Humans , Male , Middle Aged , Population Surveillance/methods , Time Factors , Young Adult
6.
Clin Infect Dis ; 73(10): 1776-1783, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1522132

ABSTRACT

BACKGROUND: As a priority group, healthcare personnel (HCP) will be key to the success of coronavirus disease 2019 (COVID-19) vaccination programs. This study assessed HCP willingness to get vaccinated and identified specific concerns that would undermine vaccination efforts. METHODS: We conducted a cross-sectional survey of HCP, including clinical and nonclinical staff, researchers, and trainees, between 23 November and 5 December 2020. The survey evaluated attitudes, beliefs, and willingness to get vaccinated. RESULTS: There were 5287 respondents with a mean (SD) age of 42.5 (13.56) years; 72.8% were female (n = 3842). Overall, 57.5 % of individuals expressed intent to receive COVID-19 vaccine; 80.4% were physicians and scientists representing the largest group. 33.6% of registered nurses, 31.6% of allied health professionals, and 32% of master's level clinicians were unsure they would take the vaccine (P < .001). Respondents who were older, male, White, or Asian were more likely to get vaccinated than other groups. Vaccine safety, potential adverse events, efficacy, and speed of vaccine development dominated concerns listed by participants. Fewer (54.0%) providers of direct care versus non-care providers (62.4%) and 52.0% of those who had provided care for COVID-19 patients (vs 60.6% of those who had not) indicated they would take the vaccine if offered (P < .001). CONCLUSIONS: We observed that self-reported willingness to receive vaccination against COVID-19 differs by hospital roles, with physicians and research scientists showing the highest acceptance. These findings highlight important heterogeneity in personal attitudes among HCPs around COVID-19 vaccines and highlight a need for tailored communication strategies.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Attitude , Cross-Sectional Studies , Delivery of Health Care , Female , Humans , Male , SARS-CoV-2 , Universities , Vaccination
7.
BMJ Open Respir Res ; 8(1)2021 11.
Article in English | MEDLINE | ID: covidwho-1504009

ABSTRACT

Delayed presentation of COVID-19 pneumonia increases the risk of mortality and need for high-intensity healthcare. Conversely, early identification of COVID-19 pneumonia grants an opportunity to intervene early and thus prevent more complicated, protracted and less successful hospital admissions. To improve the earlier detection of COVID-19 pneumonia in the community we provide a narrative review of current evidence examining the clinical parameters associated with early disease progression. Through an evolving literature review, we examined: the symptoms that may suggest COVID-19 progression; the timing of deterioration; the utility of basic observations, clinical examination and chest X-ray; the value of postexertion oxygen saturations; and the use of CRP to monitor disease progression. We go on to discuss the challenges in monitoring the COVID-19 patient in the community and discuss thresholds for further assessment. Confusion, persistent fever and shortness of breath were identified as worrying symptoms suggestive of COVID-19 disease progression necessitating urgent clinical contact. Importantly, a significant proportion of COVID-19 pneumonia patients appear not to suffer dyspnoea despite severe disease. Patients with this asymptomatic hypoxia seem to have a poorer prognosis. Such patients may present with other signs of hypoxia: severe fatigue, exertional fatigue and/or altered mental status. We found duration of symptoms to be largely unhelpful in determining risk, with evidence of deterioration at any point in the disease. Basic clinical parameters (pulse, respiratory rate, blood pressure, temperature and oxygen saturations (SpO2)) are likely of high value in detecting the deteriorating community COVID-19 patient and/or COVID-19 mimickers/complications (eg, sepsis, bacterial pneumonia and pulmonary embolism). Of these, SpO2 carried the greatest utility in detecting COVID-19 progression. CRP is an early biochemical parameter predictive of disease progression and used appropriately is likely to contribute to the early identification of COVID-19 pneumonia. Identifying progressive COVID-19 in the community is feasible using basic clinical questions and measurements. As such, if we are to limit the mortality, morbidity and the need for complicated, protracted admissions, monitoring community COVID-19 cases for signs of deterioration to facilitate early intervention is a viable strategy.


Subject(s)
COVID-19 , Humans , Hypoxia , Risk Assessment , SARS-CoV-2 , Treatment Outcome
8.
Qatar Med J ; 2021(3): 56, 2021.
Article in English | MEDLINE | ID: covidwho-1502710

ABSTRACT

In this short communication, we summarized the analyses, models, and interpretations of the corporate department of emergency medicine's (CDEM) COVID-19 numbers and their relationship to predict the national COVID-19 trends and numbers in Qatar. Data included in this analysis were obtained between March 1, 2020 and July 31, 2021. It included the number of COVID-19 cases that presented to four major EDs under the Hamad Medical Corporation CDEM umbrella and published data from the Qatar Ministry of public health (MoPH). On plotting weighted scatterplot smoothing (lowess) trend lines, there were striking similarities between CDEM and national COVID-19 n curves for overall trends and peaks. In conclusion, CDEM COVID-19 spike may be useful to predict national COVID-19 spike in 2-3 weeks.

9.
N Engl J Med ; 385(19): 1761-1773, 2021 11 04.
Article in English | MEDLINE | ID: covidwho-1410390

ABSTRACT

BACKGROUND: BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) full-length spike protein. BNT162b2 is highly efficacious against coronavirus disease 2019 (Covid-19) and is currently approved, conditionally approved, or authorized for emergency use worldwide. At the time of initial authorization, data beyond 2 months after vaccination were unavailable. METHODS: In an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy trial, we randomly assigned 44,165 participants 16 years of age or older and 2264 participants 12 to 15 years of age to receive two 30-µg doses, at 21 days apart, of BNT162b2 or placebo. The trial end points were vaccine efficacy against laboratory-confirmed Covid-19 and safety, which were both evaluated through 6 months after vaccination. RESULTS: BNT162b2 continued to be safe and have an acceptable adverse-event profile. Few participants had adverse events leading to withdrawal from the trial. Vaccine efficacy against Covid-19 was 91.3% (95% confidence interval [CI], 89.0 to 93.2) through 6 months of follow-up among the participants without evidence of previous SARS-CoV-2 infection who could be evaluated. There was a gradual decline in vaccine efficacy. Vaccine efficacy of 86 to 100% was seen across countries and in populations with diverse ages, sexes, race or ethnic groups, and risk factors for Covid-19 among participants without evidence of previous infection with SARS-CoV-2. Vaccine efficacy against severe disease was 96.7% (95% CI, 80.3 to 99.9). In South Africa, where the SARS-CoV-2 variant of concern B.1.351 (or beta) was predominant, a vaccine efficacy of 100% (95% CI, 53.5 to 100) was observed. CONCLUSIONS: Through 6 months of follow-up and despite a gradual decline in vaccine efficacy, BNT162b2 had a favorable safety profile and was highly efficacious in preventing Covid-19. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.).


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Immunogenicity, Vaccine , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral/analysis , COVID-19/epidemiology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Child , Female , Follow-Up Studies , Humans , Immunization, Secondary , Incidence , Male , Middle Aged , SARS-CoV-2/immunology , Single-Blind Method , Treatment Outcome , Young Adult
10.
Clin Infect Dis ; 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1381000

ABSTRACT

BACKGROUND: We previously reported on COVID-19 vaccination intent among HCP before emergency use authorization. We found widespread hesitancy and a substantial proportion of HCP did not intend to vaccinate. METHODS: We conducted a cross-sectional survey of HCP, including clinical and non-clinical staff, researchers, and trainees between February 21 and March 19, 2021. The survey evaluated vaccine attitudes, beliefs, intent and acceptance. RESULTS: Overall, 3,981 (87.7%) of respondents had already received a COVID-19 vaccine or planned to get vaccinated. There were significant differences in vaccine acceptance by gender, age, race, and hospital role. Males (93.7%) were more likely than females (89.8%) to report vaccine acceptance (p<0.001). Mean age was higher among those reporting vaccine acceptance (p<0.001). Physicians and scientists showed the highest acceptance rate (97.3%), while staff in ancillary services showed the lowest acceptance rate (79.9%). Unvaccinated respondents were more likely to be females, to have refused vaccines in the past due to reasons other than illness or allergy, to care for COVID-19 patients, or to rely on themselves when making vaccination decision. Vaccine acceptance was more than twice previous intent among Black respondents, an increase from 30.8% to 73.8%, and across all hospital roles with all >80% vaccine acceptance. CONCLUSIONS: The majority of HCP were vaccinated, much higher than reporting intent before vaccine was available. However, many HCP-particularly ancillary services-are still hesitant. Feasible and effective interventions to address the hesitant, including individually-tailored education strategies are needed, or vaccine can be mandated.

11.
Qatar Med J ; 2021(2): 18, 2021.
Article in English | MEDLINE | ID: covidwho-1369880

ABSTRACT

INTRODUCTION: The presence of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and its associated disease, COVID-19 has had an enormous impact on the operations of the emergency department (ED), particularly the triage area. The aim of the study was to derive and validate a prediction rule that would be applicable to Qatar's adult ED population to predict COVID-19-positive patients. METHODS: This is a retrospective study including adult patients. The data were obtained from the electronic medical records (EMR) of the Hamad Medical Corporation (HMC) for three EDs. Data from the Hamad General Hospital ED were used to derive and internally validate a prediction rule (Q-PREDICT). The Al Wakra Hospital ED and Al Khor Hospital ED data formed an external validation set consisting of the same time frame. The variables in the model included the weekly ED COVID-19-positivity rate and the following patient characteristics: region (nationality), age, acuity, cough, fever, tachypnea, hypoxemia, and hypotension. All statistical analyses were executed with Stata 16.1 (Stata Corp). The study team obtained appropriate institutional approval. RESULTS: The study included 45,663 adult patients who were tested for COVID-19. Out of these, 47% (n = 21461) were COVID-19 positive. The derivation-set model had very good discrimination (c = 0.855, 95% Confidence intervals (CI) 0.847-0.861). Cross-validation of the model demonstrated that the validation-set model (c = 0.857, 95% CI 0.849-0.863) retained high discrimination. A high Q-PREDICT score ( ≥ 13) is associated with a nearly 6-fold increase in the likelihood of being COVID-19 positive (likelihood ratio 5.9, 95% CI 5.6-6.2), with a sensitivity of 84.7% (95% CI, 84.0%-85.4%). A low Q-PREDICT ( ≤ 6) is associated with a nearly 20-fold increase in the likelihood of being COVID-19 negative (likelihood ratio 19.3, 95% CI 16.7-22.1), with a specificity of 98.7% (95% CI 98.5%-98.9%). CONCLUSION: The Q-PREDICT is a simple scoring system based on information readily collected from patients at the front desk of the ED and helps to predict COVID-19 status at triage. The scoring system performed well in the internal and external validation on datasets obtained from the state of Qatar.

13.
Commun Biol ; 4(1): 915, 2021 07 26.
Article in English | MEDLINE | ID: covidwho-1327224

ABSTRACT

Vaccines against SARS-CoV-2 are urgently required, but early development of vaccines against SARS-CoV-1 resulted in enhanced disease after vaccination. Careful assessment of this phenomena is warranted for vaccine development against SARS CoV-2. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent high dose challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titre were boosted by a second dose. Data from these challenge models on the absence of enhanced disease and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.


Subject(s)
COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/immunology , Ferrets , Macaca mulatta
14.
N Engl J Med ; 385(3): 239-250, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1246454

ABSTRACT

BACKGROUND: Until very recently, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had not been authorized for emergency use in persons younger than 16 years of age. Safe, effective vaccines are needed to protect this population, facilitate in-person learning and socialization, and contribute to herd immunity. METHODS: In this ongoing multinational, placebo-controlled, observer-blinded trial, we randomly assigned participants in a 1:1 ratio to receive two injections, 21 days apart, of 30 µg of BNT162b2 or placebo. Noninferiority of the immune response to BNT162b2 in 12-to-15-year-old participants as compared with that in 16-to-25-year-old participants was an immunogenicity objective. Safety (reactogenicity and adverse events) and efficacy against confirmed coronavirus disease 2019 (Covid-19; onset, ≥7 days after dose 2) in the 12-to-15-year-old cohort were assessed. RESULTS: Overall, 2260 adolescents 12 to 15 years of age received injections; 1131 received BNT162b2, and 1129 received placebo. As has been found in other age groups, BNT162b2 had a favorable safety and side-effect profile, with mainly transient mild-to-moderate reactogenicity (predominantly injection-site pain [in 79 to 86% of participants], fatigue [in 60 to 66%], and headache [in 55 to 65%]); there were no vaccine-related serious adverse events and few overall severe adverse events. The geometric mean ratio of SARS-CoV-2 50% neutralizing titers after dose 2 in 12-to-15-year-old participants relative to 16-to-25-year-old participants was 1.76 (95% confidence interval [CI], 1.47 to 2.10), which met the noninferiority criterion of a lower boundary of the two-sided 95% confidence interval greater than 0.67 and indicated a greater response in the 12-to-15-year-old cohort. Among participants without evidence of previous SARS-CoV-2 infection, no Covid-19 cases with an onset of 7 or more days after dose 2 were noted among BNT162b2 recipients, and 16 cases occurred among placebo recipients. The observed vaccine efficacy was 100% (95% CI, 75.3 to 100). CONCLUSIONS: The BNT162b2 vaccine in 12-to-15-year-old recipients had a favorable safety profile, produced a greater immune response than in young adults, and was highly effective against Covid-19. (Funded by BioNTech and Pfizer; C4591001 ClinicalTrials.gov number, NCT04368728.).


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , Adolescent , Adult , Age Factors , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Child , Female , Humans , Immunoglobulin G/blood , Injections, Intramuscular/adverse effects , Male , Pain/etiology , Treatment Outcome , Young Adult
15.
BMJ Case Rep ; 14(5)2021 May 24.
Article in English | MEDLINE | ID: covidwho-1242195

ABSTRACT

We report a case of severe hypercalcaemia secondary to rhabdomyolysis in a woman with COVID-19 (SARS CoV-2) infection. The patient presented with myalgia and anuria with an acute kidney injury requiring haemodialysis. Creatine kinase peaked at 760 000 IU/L. A biphasic calcaemic response was observed with initial severe hypocalcaemia followed by severe, symptomatic hypercalcaemia, persistent despite haemodialysis. Control of the calcium levels was achieved by continuous haemofiltration.


Subject(s)
Acute Kidney Injury , COVID-19 , Rhabdomyolysis , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Calcium , Female , Homeostasis , Humans , Rhabdomyolysis/etiology , SARS-CoV-2
16.
Viruses ; 13(5)2021 05 15.
Article in English | MEDLINE | ID: covidwho-1234827

ABSTRACT

SARS-CoV-2 represents an unprecedented public health challenge. While the majority of SARS-CoV-2-infected individuals with mild-to-moderate COVID-19 resolve their infection with few complications, some individuals experience prolonged symptoms lasting for weeks after initial diagnosis. Persistent viral infections are commonly accompanied by immunologic dysregulation, but it is unclear if persistent COVID-19 impacts the development of virus-specific cellular immunity. To this end, we analyzed SARS-CoV-2-specific cellular immunity in convalescent COVID-19 patients who experienced eight days or fewer of COVID-19 symptoms or symptoms persisting for 18 days or more. We observed that persistent COVID-19 symptoms were not associated with the development of an overtly dysregulated cellular immune response. Furthermore, we observed that reactivity against the N protein from SARS-CoV-2 correlates with the amount of reactivity against the seasonal human coronaviruses 229E and NL63. These results provide insight into the processes that regulate the development of cellular immunity against SARS-CoV-2 and related human coronaviruses.


Subject(s)
COVID-19/complications , Immunity, Cellular/immunology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/metabolism , Coronavirus 229E, Human/immunology , Cross Reactions , Epitopes, T-Lymphocyte/immunology , Female , Humans , Male , Middle Aged , New York/epidemiology , SARS-CoV-2/pathogenicity , T-Lymphocytes/immunology
17.
Nat Commun ; 12(1): 1260, 2021 02 24.
Article in English | MEDLINE | ID: covidwho-1101645

ABSTRACT

A novel coronavirus, SARS-CoV-2, has been identified as the causative agent of the current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to assess the safety and efficacy of novel vaccines and therapeutics. Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques. Immune responses against SARS-CoV-2 are also similar in both species and equivalent to those reported in milder infections and convalescent human patients. This finding is reiterated by our transcriptional analysis of respiratory samples revealing the global response to infection. We describe a new method for lung histopathology scoring that will provide a metric to enable clearer decision making for this key endpoint. In contrast to prior publications, in which rhesus are accepted to be the preferred study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of interventions against SARS-CoV-2. Importantly, accessing cynomolgus macaques will greatly alleviate the pressures on current rhesus stocks.


Subject(s)
COVID-19/immunology , COVID-19/virology , Lung/pathology , Lung/virology , Animals , Disease Models, Animal , Female , Immunity, Cellular/physiology , Interferon-gamma/metabolism , Macaca fascicularis , Macaca mulatta , Male , Pandemics , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity
18.
Clin Infect Dis ; 73(10): 1776-1783, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1045875

ABSTRACT

BACKGROUND: As a priority group, healthcare personnel (HCP) will be key to the success of coronavirus disease 2019 (COVID-19) vaccination programs. This study assessed HCP willingness to get vaccinated and identified specific concerns that would undermine vaccination efforts. METHODS: We conducted a cross-sectional survey of HCP, including clinical and nonclinical staff, researchers, and trainees, between 23 November and 5 December 2020. The survey evaluated attitudes, beliefs, and willingness to get vaccinated. RESULTS: There were 5287 respondents with a mean (SD) age of 42.5 (13.56) years; 72.8% were female (n = 3842). Overall, 57.5 % of individuals expressed intent to receive COVID-19 vaccine; 80.4% were physicians and scientists representing the largest group. 33.6% of registered nurses, 31.6% of allied health professionals, and 32% of master's level clinicians were unsure they would take the vaccine (P < .001). Respondents who were older, male, White, or Asian were more likely to get vaccinated than other groups. Vaccine safety, potential adverse events, efficacy, and speed of vaccine development dominated concerns listed by participants. Fewer (54.0%) providers of direct care versus non-care providers (62.4%) and 52.0% of those who had provided care for COVID-19 patients (vs 60.6% of those who had not) indicated they would take the vaccine if offered (P < .001). CONCLUSIONS: We observed that self-reported willingness to receive vaccination against COVID-19 differs by hospital roles, with physicians and research scientists showing the highest acceptance. These findings highlight important heterogeneity in personal attitudes among HCPs around COVID-19 vaccines and highlight a need for tailored communication strategies.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Attitude , Cross-Sectional Studies , Delivery of Health Care , Female , Humans , Male , SARS-CoV-2 , Universities , Vaccination
19.
Nat Commun ; 12(1): 81, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1007628

ABSTRACT

There is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report a dose titration study of SARS-CoV-2 in the ferret model. After a high (5 × 106 pfu) and medium (5 × 104 pfu) dose of virus is delivered, intranasally, viral RNA shedding in the upper respiratory tract (URT) is observed in 6/6 animals, however, only 1/6 ferrets show similar signs after low dose (5 × 102 pfu) challenge. Following sequential culls pathological signs of mild multifocal bronchopneumonia in approximately 5-15% of the lung is seen on day 3, in high and medium dosed groups. Ferrets re-challenged, after virus shedding ceased, are fully protected from acute lung pathology. The endpoints of URT viral RNA replication & distinct lung pathology are observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease.


Subject(s)
COVID-19/immunology , Disease Models, Animal , Ferrets/immunology , SARS-CoV-2/immunology , Animals , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/pharmacology , Dose-Response Relationship, Drug , Female , Lung/immunology , Lung/pathology , RNA, Viral/isolation & purification , SARS-CoV-2/genetics , Virus Replication/drug effects , Virus Replication/immunology , Virus Shedding/drug effects , Virus Shedding/immunology
20.
N Engl J Med ; 383(27): 2603-2615, 2020 12 31.
Article in English | MEDLINE | ID: covidwho-968768

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. METHODS: In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 µg per dose). BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. RESULTS: A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. CONCLUSIONS: A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.).


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2 , Adolescent , Adult , Aged , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Fatigue/etiology , Female , Headache/etiology , Humans , Immunization, Secondary , Male , Middle Aged , SARS-CoV-2/genetics , Single-Blind Method , Treatment Outcome , Vaccines, Synthetic , Young Adult
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