Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 358
Filter
Add filters

Document Type
Year range
1.
N Engl J Med ; 385(16): 1474-1484, 2021 10 14.
Article in English | MEDLINE | ID: covidwho-1612234

ABSTRACT

BACKGROUND: Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity. METHODS: At the largest medical center in Israel, we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case-control analysis. We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity. RESULTS: Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented. CONCLUSIONS: Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.


Subject(s)
COVID-19 Vaccines , COVID-19/epidemiology , Health Personnel/statistics & numerical data , Adult , Asymptomatic Diseases , COVID-19/diagnosis , COVID-19/prevention & control , COVID-19 Nucleic Acid Testing , Case-Control Studies , Female , Humans , Israel/epidemiology , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Treatment Failure
3.
Ann Intern Med ; 174(2): 283-284, 2021 02.
Article in English | MEDLINE | ID: covidwho-1553980
4.
Ann Intern Med ; 174(2): 286-287, 2021 02.
Article in English | MEDLINE | ID: covidwho-1534506
5.
Ann Intern Med ; 174(2): 284-285, 2021 02.
Article in English | MEDLINE | ID: covidwho-1518754
6.
Ann Intern Med ; 174(2): 284, 2021 02.
Article in English | MEDLINE | ID: covidwho-1518753
7.
PLoS One ; 16(11): e0259908, 2021.
Article in English | MEDLINE | ID: covidwho-1511834

ABSTRACT

INTRODUCTION: The incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections in the Belgian community is mainly estimated based on test results of patients with coronavirus disease (COVID-19)-like symptoms. The aim of this study was to investigate the evolution of the SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) positivity ratio and distribution of viral loads within a cohort of asymptomatic patients screened prior hospitalization or surgery, stratified by age category. MATERIALS/METHODS: We retrospectively studied data on SARS-CoV-2 real-time RT-PCR detection in respiratory tract samples of asymptomatic patients screened pre-hospitalization or pre-surgery in nine Belgian hospitals located in Flanders over a 12-month period (1 April 2020-31 March 2021). RESULTS: In total, 255925 SARS-CoV-2 RT-PCR test results and 2421 positive results for which a viral load was reported, were included in this study. An unweighted overall SARS-CoV-2 real-time RT-PCR positivity ratio of 1.27% was observed with strong spatiotemporal differences. SARS-CoV-2 circulated predominantly in 80+ year old individuals across all time periods except between the first and second COVID-19 wave and in 20-30 year old individuals before the second COVID-19 wave. In contrast to the first wave, a significantly higher positivity ratio was observed for the 20-40 age group in addition to the 80+ age group compared to the other age groups during the second wave. The median viral load follows a similar temporal evolution as the positivity rate with an increase ahead of the second wave and highest viral loads observed for 80+ year old individuals. CONCLUSION: There was a high SARS-CoV-2 circulation among asymptomatic patients with a predominance and highest viral loads observed in the elderly. Moreover, ahead of the second COVID-19 wave an increase in median viral load was noted with the highest overall positivity ratio observed in 20-30 year old individuals, indicating they could have been the hidden drivers of this wave.


Subject(s)
Asymptomatic Diseases/epidemiology , COVID-19/diagnosis , Respiratory Tract Infections/epidemiology , SARS-CoV-2/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Belgium/epidemiology , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , Female , Hospitalization , Humans , Male , Middle Aged , Respiratory Tract Infections/pathology , Respiratory Tract Infections/surgery , Respiratory Tract Infections/virology , SARS-CoV-2/pathogenicity , Young Adult
8.
Front Immunol ; 12: 750229, 2021.
Article in English | MEDLINE | ID: covidwho-1506957

ABSTRACT

Improving COVID-19 intervention strategies partly relies on animal models to study SARS-CoV-2 disease and immunity. In our pursuit to establish a model for severe COVID-19, we inoculated young and adult male ferrets intranasally or intratracheally with SARS-CoV-2. Intranasal inoculation established an infection in all ferrets, with viral dissemination into the brain and gut. Upon intratracheal inoculation only adult ferrets became infected. However, neither inoculation route induced observable COVID-19 symptoms. Despite this, a persistent inflammation in the nasal turbinates was prominent in especially young ferrets and follicular hyperplasia in the bronchi developed 21 days post infection. These effects -if sustained- might resemble long-COVID. Respiratory and systemic cellular responses and antibody responses were induced only in animals with an established infection. We conclude that intranasally-infected ferrets resemble asymptomatic COVID-19 and possibly aspects of long-COVID. Combined with the increasing portfolio to measure adaptive immunity, ferrets are a relevant model for SARS-CoV-2 vaccine research.


Subject(s)
Bronchi/pathology , COVID-19/complications , COVID-19/immunology , Ferrets/immunology , SARS-CoV-2/physiology , Administration, Intranasal , Age Factors , Animals , Asymptomatic Diseases , Disease Models, Animal , Ferrets/virology , Humans , Hyperplasia , Immunity, Cellular , Immunity, Humoral , Injection, Intratympanic , Male , Virus Internalization
9.
Front Immunol ; 12: 730404, 2021.
Article in English | MEDLINE | ID: covidwho-1459289

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes a spectrum of clinical manifestations, ranging from asymptomatic to mild, moderate, or severe illness with multi-organ failure and death. Using a new machine learning algorithm developed by us, we have reported a significantly higher number of predicted COVID-19 cases than the documented counts across the world. The sole reliance on confirmed symptomatic cases overlooking the symptomless COVID-19 infections and the dynamics of waning immunity may not provide 'true' spectrum of infection proportion, a key element for an effective planning and implementation of protection and prevention strategies. We and others have previously shown that strategic orthogonal testing and leveraging systematic data-driven modeling approach to account for asymptomatics and waning cases may situationally have a compelling role in informing efficient vaccination strategies beyond prevalence reporting. However, currently Centers for Disease Control and Prevention (CDC) does not recommend serological testing either before or after vaccination to assess immune status. Given the 27% occurrence of breakthrough infections in fully vaccinated (FV) group with many being asymptomatics and still a larger fraction of the general mass remaining unvaccinated, the relaxed mask mandate and distancing by CDC can drive resurgence. Thus, we believe it is a key time to focus on asymptomatics (no symptoms) and oligosymptomatics (so mild that the symptoms remain unrecognized) as they can be silent reservoirs to propagate the infection. This perspective thus highlights the need for proactive efforts to reevaluate the current variables/strategies in accounting for symptomless and waning fractions.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/physiology , Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , Asymptomatic Diseases , COVID-19/transmission , COVID-19 Serological Testing , Centers for Disease Control and Prevention, U.S. , Humans , Immunity , United States , Vaccination
10.
Sci Rep ; 11(1): 19744, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1454810

ABSTRACT

Infections produced by non-symptomatic (pre-symptomatic and asymptomatic) individuals have been identified as major drivers of COVID-19 transmission. Non-symptomatic individuals, unaware of the infection risk they pose to others, may perceive themselves-and be perceived by others-as not presenting a risk of infection. Yet, many epidemiological models currently in use do not include a behavioral component, and do not address the potential consequences of risk misperception. To study the impact of behavioral adaptations to the perceived infection risk, we use a mathematical model that incorporates the behavioral decisions of individuals, based on a projection of the system's future state over a finite planning horizon. We found that individuals' risk misperception in the presence of non-symptomatic individuals may increase or reduce the final epidemic size. Moreover, under behavioral response the impact of non-symptomatic infections is modulated by symptomatic individuals' behavior. Finally, we found that there is an optimal planning horizon that minimizes the final epidemic size.


Subject(s)
Asymptomatic Diseases/psychology , Behavior , COVID-19/epidemiology , Asymptomatic Diseases/epidemiology , COVID-19/pathology , COVID-19/virology , Humans , Models, Theoretical , Perception , SARS-CoV-2/isolation & purification
11.
J Pediatr ; 239: 74-80.e1, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1433570

ABSTRACT

OBJECTIVES: To assess rates of asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positivity in K-8 schools with risk mitigation procedures in place, and to evaluate SARS-CoV-2 transmission in school and household contacts of these positive individuals. STUDY DESIGN: In this prospective observational study, screening testing for SARS-CoV-2 was performed by oropharyngeal swabbing and polymerase chain reaction (PCR) analysis in students and staff at K-8 private schools in high-risk Chicago ZIP codes. New coronavirus disease 2019 (COVID-19) diagnoses or symptoms among participants, household contacts, and nonparticipants in each school were queried. RESULTS: Among 11 K-8 private schools across 8 Chicago ZIP codes, 468 participants (346 students, 122 staff members) underwent screening testing. At the first school, 17 participants (36%) tested positive, but epidemiologic investigation suggested against in-school transmission. Only 5 participants in the subsequent 10 schools tested positive for an overall 4.7% positivity rate (1.2% excluding school 1). All but 1 positive test among in-person students had high PCR cycle threshold values, suggesting very low SARS-CoV-2 viral loads. In all schools, no additional students, staff, or household contacts reported new diagnoses or symptoms of COVID-19 during the 2 weeks following screening testing. CONCLUSIONS: We identified infrequent asymptomatic COVID-19 in schools in high-risk Chicago communities and did not identify transmission among school staff, students, or their household contacts. These data suggest that COVID-19 mitigation procedures, including masking and physical distancing, are effective in preventing transmission of COVID-19 in schools. These results may inform future strategies for screening testing in K-8 schools.


Subject(s)
Asymptomatic Diseases/epidemiology , COVID-19/diagnosis , Mass Screening , Schools , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Testing , Chicago/epidemiology , Faculty , Humans , Prospective Studies , Students
13.
Rev Bras Ginecol Obstet ; 43(8): 595-599, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1428974

ABSTRACT

OBJECTIVE: To describe the hematological changes, the platelet indices in particular, in pregnant women with coronavirus disease 2019 (COVID-19) compared to healthy pregnant women. METHODS: A retrospective case-control study conducted at the Al Yarmouk Teaching Hospital, in Baghdad, Iraq, involving 100 pregnant women, 50 with positive viral DNA for COVID-19 (case group), and 50 with negative results (control group); both groups were subjected to a thorough hematological evaluation. RESULTS: Among the main hematological variables analyzed, the platelet indices, namely the mean platelet volume (MPV) and the platelet distribution width (PDW), showed statistically significant differences (MPV: 10.87 ± 66.92 fL for the case group versus 9.84 ± 1.2 fL for the control group; PDW: 14.82 ± 3.18 fL for the case group versus 13.3 ± 2.16 fL for the controls). The criterion value of the receiver operating characteristic (ROC) curve for PDW at a cutoff point of > 11.8 fL showed a weak diagnostic marker, while the MPV at a cutoff value of > 10.17 fL showed a good diagnostic marker. CONCLUSION: The MPV and PDW are significantly affected by the this viral infection, even in asymptomatic confirmed cases, and we recommend that both parameters be included in the diagnostic panel of this infection.


Descrever as alterações hematológicas, em particular os índices plaquetários em gestantes com doença coronavírus 2019 (COVID-19) em comparação com gestantes saudáveis. MéTODOS: Estudo caso-controle retrospectivo realizado no Hospital Universitário Al Yarmouk, em Bagdá, Iraque envolvendo 100 gestantes, 50 com DNA viral positivo para COVID-19 (grupo caso) e 50 com resultados negativos (grupo controle); ambos os grupos foram submetidos a uma avaliação hematológica completa. Entre as principais variáveis hematológicas analisadas, os índices plaquetários, nomeadamente o volume plaquetário médio (VPM) e a largura de distribuição plaquetária (PDW), apresentaram diferenças estatisticamente significativas (VPM: 10,87 ± 66,92 fL para o grupo caso versus 9,84 ± 1.2 fL para o o grupo controle; PDW: 14,82 ± 3,18 fL para o grupo caso versus 13,3 ± 2,16 fL para os controles). O valor de critério da curva de característica de operação do receptor (ROC) para PDW em um ponto de corte de> 11,8 fL mostrou um marcador diagnóstico fraco, enquanto o do VPM em um valor de corte de> 10,17 fL mostrou um bom marcador de diagnóstico. CONCLUSãO: O MPV e PDW são significativamente afetados por esta infecção viral, mesmo em casos confirmados assintomáticos, e recomendamos que ambos os parâmetros sejam incluídos no painel de diagnóstico desta infecção.


Subject(s)
Blood Platelets/virology , COVID-19/blood , Pregnancy Complications, Infectious/blood , Adult , Asymptomatic Diseases , Biomarkers/blood , Blood Platelets/physiology , COVID-19/diagnosis , COVID-19 Testing , Case-Control Studies , Female , Humans , Mean Platelet Volume , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Retrospective Studies
15.
Ann Rheum Dis ; 80(10): 1286-1298, 2021 10.
Article in English | MEDLINE | ID: covidwho-1406632

ABSTRACT

BACKGROUND: Despite growing interest, there is no guidance or consensus on how to conduct clinical trials and observational studies in populations at risk of rheumatoid arthritis (RA). METHODS: An European League Against Rheumatism (EULAR) task force formulated four research questions to be addressed by systematic literature review (SLR). The SLR results informed consensus statements. One overarching principle, 10 points to consider (PTC) and a research agenda were proposed. Task force members rated their level of agreement (1-10) for each PTC. RESULTS: Epidemiological and demographic characteristics should be measured in all clinical trials and studies in at-risk individuals. Different at-risk populations, identified according to clinical presentation, were defined: asymptomatic, musculoskeletal symptoms without arthritis and early clinical arthritis. Study end-points should include the development of subclinical inflammation on imaging, clinical arthritis, RA and subsequent achievement of arthritis remission. Risk factors should be assessed at baseline and re-evaluated where appropriate; they include genetic markers and autoantibody profiling and additionally clinical symptoms and subclinical inflammation on imaging in those with symptoms and/or clinical arthritis. Trials should address the effect of the intervention on risk factors, as well as progression to clinical arthritis or RA. In patients with early clinical arthritis, pharmacological intervention has the potential to prevent RA development. Participants' knowledge of their RA risk may inform their decision to participate; information should be provided using an individually tailored approach. CONCLUSION: These consensus statements provide data-driven guidance for rheumatologists, health professionals and investigators conducting clinical trials and observational studies in individuals at risk of RA.


Subject(s)
Arthritis, Rheumatoid/prevention & control , Asymptomatic Diseases , Clinical Trials as Topic/methods , Observational Studies as Topic/methods , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/therapy , Europe , Humans , Rheumatology , Risk Factors , Severity of Illness Index , Societies, Medical
17.
Infect Genet Evol ; 95: 105075, 2021 11.
Article in English | MEDLINE | ID: covidwho-1401708

ABSTRACT

T-cell-mediated immunity to SARS-CoV-2-derived peptides in individuals unexposed to SARS-CoV-2 has been previously reported. This pre-existing immunity was suggested to largely derive from prior exposure to 'common cold' endemic human coronaviruses (HCoVs). To test this, we characterised the sequence homology of SARS-CoV-2-derived T-cell epitopes reported in the literature across the full proteome of the Coronaviridae family. 54.8% of these epitopes had no homology to any of the HCoVs. Further, the proportion of SARS-CoV-2-derived epitopes with any level of sequence homology to the proteins encoded by any of the coronaviruses tested is well-predicted by their alignment-free phylogenetic distance to SARS-CoV-2 (Pearson's r = -0.958). No coronavirus in our dataset showed a significant excess of T-cell epitope homology relative to the proportion of expected random matches, given their genetic similarity to SARS-CoV-2. Our findings suggest that prior exposure to human or animal-associated coronaviruses cannot completely explain the T-cell repertoire in unexposed individuals that recognise SARS-CoV-2 cross-reactive epitopes.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Coronaviridae/immunology , Disease Resistance , Immunologic Memory , SARS-CoV-2/immunology , Animals , Antibodies, Viral/genetics , Antibodies, Viral/immunology , Antigens, Viral/genetics , Antigens, Viral/immunology , Asymptomatic Diseases , COVID-19/genetics , COVID-19/pathology , COVID-19/virology , Chiroptera/virology , Coronaviridae/classification , Coronaviridae/genetics , Coronaviridae/pathogenicity , Cross Reactions , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/immunology , Eutheria/virology , Humans , Immunity, Cellular , Phylogeny , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Severity of Illness Index , T-Lymphocytes/immunology , T-Lymphocytes/virology
19.
J Clin Neurosci ; 89: 65-67, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1386091

ABSTRACT

The neuro-ophthalmological complications of SARS-CoV-2 infection are emerging but the spectrum of presentations and pathophysiological mechanism underpinning the association remains to be fully determined. We describe the case of a 44-year-old female who presented with a 12-hour history of diplopia preceded by a mild headache and found to have an isolated right abducens nerve palsy. Initial vital signs were normal but she developed a fever and nasopharyngeal swab confirmed SARS-CoV-2 infection by RT-PCR. All other investigations returned normal including blood tests, chest X-ray, MRI brain and cerebrospinal fluid analysis. She remained systemically well, and there was complete resolution of the abducens palsy and diplopia at two week follow up. In the absence of an alternative underlying cause or risk factors identified, the aetiology was presumed to be microvascular and potentially related to the viral infection. We add to the evolving literature of neuro-ophthalmological associations of SARS-CoV-2, discuss possible causal mechanisms and suggest considering asymptomatic SARS-CoV-2 infection in cases of isolated abducens palsy without clear risk factors.


Subject(s)
Abducens Nerve Diseases/diagnostic imaging , Abducens Nerve Diseases/etiology , Asymptomatic Diseases , COVID-19/complications , COVID-19/diagnostic imaging , SARS-CoV-2/isolation & purification , Adult , Diplopia/diagnostic imaging , Diplopia/etiology , Female , Humans , Magnetic Resonance Imaging
SELECTION OF CITATIONS
SEARCH DETAIL
...