Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
1.
N Engl J Med ; 2022 Jul 21.
Article in English | MEDLINE | ID: covidwho-2016969

ABSTRACT

BACKGROUND: Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined. METHODS: We formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction-confirmed monkeypox virus infections. RESULTS: We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having <10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported. CONCLUSIONS: In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.

2.
Med (N Y) ; 3(6): 422-432.e3, 2022 06 10.
Article in English | MEDLINE | ID: covidwho-1926778

ABSTRACT

Background: SARS-CoV-2 Omicron variant of concern (VOC) has evolved multiple mutations within the spike protein, raising concerns of increased antibody evasion. In this study, we assessed the neutralization potential of COVID-19 convalescent sera and sera from vaccinated individuals against ancestral SARS-CoV-2 and VOCs. Methods: The neutralizing activity of sera from 65 coronavirus disease (COVID-19) vaccine recipients and convalescent individuals against clinical isolates of ancestral SARS-CoV-2 and Beta, Delta, and Omicron VOCs was assessed using a micro-neutralization assay. Findings: Convalescent sera from unvaccinated individuals infected by the ancestral virus demonstrated reduced neutralization against Beta and Omicron VOCs. Sera from individuals that received three doses of the Pfizer or Moderna vaccines demonstrated reduced neutralization of the Omicron variant relative to ancestral SARS-CoV-2. Sera from individuals that were naturally infected with ancestral SARS-CoV-2 and subsequently received two doses of the Pfizer vaccine induced significantly higher neutralizing antibody levels against ancestral virus and all VOCs. Infection alone, either with ancestral SARS-CoV-2 or the Delta variant, was not sufficient to induce high neutralizing antibody titers against Omicron. Conclusions: In summary, we demonstrate that convalescent and vaccinated sera display varying levels of SARS-CoV-2 VOC neutralization. Data from this study will inform booster vaccination strategies against SARS-CoV-2 VOCs. Funding: This research was funded by the Canadian Institutes of Health Research (CIHR). VIDO receives operational funding from the Government of Saskatchewan through Innovation Saskatchewan and the Ministry of Agriculture and from the Canada Foundation for Innovation through the Major Science Initiatives for its CL3 facility.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19/therapy , Humans , Immunization, Passive , Membrane Glycoproteins/genetics , Neutralization Tests , SARS-CoV-2/genetics , Saskatchewan , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins/genetics
3.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327589

ABSTRACT

Background To partially immunize more persons against COVID-19 during a time of limited vaccine availability, Canadian public health officials recommended extending the vaccine dose interval and brand mixing. Impact on the antibody response among the older ambulatory population was unclear. Methods Decentralized prospective cohort study with self-report of adverse events and collection of dried blood spots. Data is presented for 1193 (93%) of the 911 older (aged >70 years) and 375 younger (30-50 years) recruits. Findings Local and systemic reactivity rates were high but short-lived, particularly in the younger cohort and with mRNA-1273 vaccine. After a single COVID-19 vaccine, 84% younger but only 46% older participants had positive IgG antibodies to both spike protein and receptor binding domain (RBD) antigens, increasing to 100/98% with the second dose respectively. In multivariable linear regression model, lower normalized IgG RBD antibody ratios two weeks after the second dose were statistically associated with older age, male gender, cancer diagnosis, lower body weight, BNT162b2 relative to mRNA-1273 and longer dose intervals. Antibody ratios in both cohorts declined 12 weeks post second vaccine dose. Interpretation We report success of a decentralized serology study. Antibody responses were higher in the younger than older cohort and were greater for those with at least one mRNA-1273 dose. The immunity threshold is unknown but correlations between binding and neutralizing antibodies are strongly positive. Trends with time and at breakthrough infection will inform vaccine booster strategies. Funding Supported by the Public Health Agency of Canada and the University Health Network Foundation.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322458

ABSTRACT

Background: Post-exposure prophylaxis (PEP) is a well-established strategy for the prevention of infectious diseases, in which recently exposed people take a short course of medication to prevent infection. The primary objective of the COVID-19 Ring-based Prevention Trial with lopinavir/ritonavir (CORIPREV-LR) is to evaluate the efficacy of a 14-day course of oral lopinavir/ritonavir as PEP against COVID-19 among individuals with a high-risk exposure to a confirmed case. Methods: : This is an open-label, multicenter, 1:1 cluster-randomized trial of LPV/r versus no intervention, using an adaptive approach to sample size calculation. Participants will be individuals aged >6 months with a high-risk exposure to a confirmed COVID-19 case within the past 7 days. A combination of remote and in-person study visits at days 1, 7, 14, 35 and 90 include comprehensive epidemiological, clinical, microbiologic and serologic sampling. The primary outcome is microbiologically confirmed COVID-19 infection within 14 days after exposure, defined as a positive respiratory tract specimen for SARS-CoV-2 by polymerase chain reaction. Secondary outcomes include safety, symptomatic COVID-19, seropositivity, hospitalization, respiratory failure requiring ventilator support, mortality, psychological impact, and health-related quality of life. Additional analyses will examine the impact of LPV/r on these outcomes in the subset of participants who test positive for SARS-CoV-2 at baseline. To detect a relative risk reduction of 40% with 80% power at α=0.05, assuming p 0 =15%, 5 contacts per case and intra-class correlation coefficient (ICC)=0.05, we require 110 clusters per arm, or 220 clusters overall and approximately 1220 enrollees after accounting for 10% loss-to-follow-up. We will modify the sample size target after 60 clusters, based on preliminary estimates of p0, ICC and cluster size and consider switching to an alternative drug after interim analyses and as new data emerges. The primary analysis will be a generalized linear mixed model with logit link to estimate the effect of LPV/r on the probability of infection. Discussion: Harnessing safe, existing drugs such as LPV/r as PEP could provide an important tool for control of the COVID-19 pandemic. Novel aspects of our design include the ring-based prevention approach, and the incorporation of remote strategies for conducting study visits and biospecimen collection. Trial registration: This trial was registered at www.clinicaltrials.gov (NCT04321174) on March 25, 2020. https://clinicaltrials.gov/ct2/show/NCT04321174

5.
BMJ Open ; 11(12): e054208, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1623564

ABSTRACT

INTRODUCTION: Most existing vaccines require higher or additional doses or adjuvants to provide similar protection for people living with HIV (PLWH) compared with HIV-uninfected individuals. Additional research is necessary to inform COVID-19 vaccine use in PLWH. METHODS AND ANALYSIS: This multicentred observational Canadian cohort study will enrol 400 PLWH aged >16 years from Montreal, Ottawa, Toronto and Vancouver. Subpopulations of PLWH of interest will include individuals: (1) >55 years of age; (2) with CD4 counts <350 cells/mm3; (3) with multimorbidity (>2 comorbidities) and (4) 'stable' or 'reference' PLWH (CD4 T cells >350 cells/mm3, suppressed viral load for >6 months and <1 comorbidity). Data for 1000 HIV-negative controls will be obtained via a parallel cohort study (Stop the Spread Ottawa), using similar time points and methods. Participants receiving >1 COVID-19 vaccine will attend five visits: prevaccination; 1 month following the first vaccine dose; and at 3, 6 and 12 months following the second vaccine dose. The primary end point will be the percentage of PLWH with COVID-19-specific antibodies at 6 months following the second vaccine dose. Humoral and cell-mediated immune responses, and the interplay between T cell phenotypes and inflammatory markers, will be described. Regression techniques will be used to compare COVID-19-specific immune responses to determine whether there are differences between the 'unstable' PLWH group (CD4 <350 cells/mm3), the stable PLWH cohort and the HIV-negative controls, adjusting for factors believed to be associated with immune response. Unadjusted analyses will reveal whether there are differences in driving factors associated with group membership. ETHICS AND DISSEMINATION: Research ethics boards at all participating institutions have granted ethics approval for this study. Written informed consent will be obtained from all study participants prior to enrolment. The findings will inform the design of future COVID-19 clinical trials, dosing strategies aimed to improve immune responses and guideline development for PLWH. TRIAL REGISTRATION NUMBER: NCT04894448.


Subject(s)
COVID-19 , HIV Infections , COVID-19 Vaccines , Canada , Cohort Studies , Diterpenes , Humans , Multicenter Studies as Topic , Observational Studies as Topic , SARS-CoV-2 , Vaccination
6.
Curr HIV/AIDS Rep ; 18(4): 280-288, 2021 08.
Article in English | MEDLINE | ID: covidwho-1258268

ABSTRACT

PURPOSE OF REVIEW: To highlight recent trends in the epidemiology of HIV and syphilis, the impact of the COVID epidemic, our approach to care of co-infected patients, and our views on important next steps in advancing the field. RECENT FINDINGS: HIV and syphilis co-infection has been on the rise in recent years although since the COVID pandemic there is a decrease in new diagnoses-it remains unclear if this represents a true decline or inadequate testing or under-reporting. Standard HIV care should include regular syphilis serology .Treatment and serological follow-up of syphilis in HIV positive and negative patients can be conducted similarly. Challenges remain in the diagnosis and management of neurosyphilis. New models for testing and prevention will be crucial next steps in controlling co-infection. The intersection of HIV and syphilis infections continues to pose new and unique challenges in diagnosis, treatment, and prevention.


Subject(s)
COVID-19 , HIV Infections , Syphilis , HIV Infections/complications , HIV Infections/diagnosis , HIV Infections/drug therapy , Humans , SARS-CoV-2 , Syphilis/diagnosis , Syphilis/drug therapy , Syphilis/epidemiology , Syphilis Serodiagnosis
7.
Trials ; 22(1): 224, 2021 Mar 22.
Article in English | MEDLINE | ID: covidwho-1147039

ABSTRACT

BACKGROUND: Post-exposure prophylaxis (PEP) is a well-established strategy for the prevention of infectious diseases, in which recently exposed people take a short course of medication to prevent infection. The primary objective of the COVID-19 Ring-based Prevention Trial with lopinavir/ritonavir (CORIPREV-LR) is to evaluate the efficacy of a 14-day course of oral lopinavir/ritonavir as PEP against COVID-19 among individuals with a high-risk exposure to a confirmed case. METHODS: This is an open-label, multicenter, 1:1 cluster-randomized trial of LPV/r 800/200 mg twice daily for 14 days (intervention arm) versus no intervention (control arm), using an adaptive approach to sample size calculation. Participants will be individuals aged > 6 months with a high-risk exposure to a confirmed COVID-19 case within the past 7 days. A combination of remote and in-person study visits at days 1, 7, 14, 35, and 90 includes comprehensive epidemiological, clinical, microbiologic, and serologic sampling. The primary outcome is microbiologically confirmed COVID-19 infection within 14 days after exposure, defined as a positive respiratory tract specimen for SARS-CoV-2 by polymerase chain reaction. Secondary outcomes include safety, symptomatic COVID-19, seropositivity, hospitalization, respiratory failure requiring ventilator support, mortality, psychological impact, and health-related quality of life. Additional analyses will examine the impact of LPV/r on these outcomes in the subset of participants who test positive for SARS-CoV-2 at baseline. To detect a relative risk reduction of 40% with 80% power at α = 0.05, assuming the secondary attack rate in ring members (p0) = 15%, 5 contacts per case and intra-class correlation coefficient (ICC) = 0.05, we require 110 clusters per arm, or 220 clusters overall and approximately 1220 enrollees after accounting for 10% loss-to-follow-up. We will modify the sample size target after 60 clusters, based on preliminary estimates of p0, ICC, and cluster size and consider switching to an alternative drug after interim analyses and as new data emerges. The primary analysis will be a generalized linear mixed model with logit link to estimate the effect of LPV/r on the probability of infection. Participants who test positive at baseline will be excluded from the primary analysis but will be maintained for additional analyses to examine the impact of LPV/r on early treatment. DISCUSSION: Harnessing safe, existing drugs such as LPV/r as PEP could provide an important tool for control of the COVID-19 pandemic. Novel aspects of our design include the ring-based prevention approach, and the incorporation of remote strategies for conducting study visits and biospecimen collection. TRIAL REGISTRATION: This trial was registered at www.ClinicalTrials.gov ( NCT04321174 ) on March 25, 2020.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/prevention & control , Lopinavir/therapeutic use , Post-Exposure Prophylaxis/methods , Ritonavir/therapeutic use , Drug Combinations , Hospitalization , Humans , Randomized Controlled Trials as Topic , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome
8.
Trials ; 21(1): 647, 2020 Jul 14.
Article in English | MEDLINE | ID: covidwho-647104

ABSTRACT

OBJECTIVES: Primary Objective: To determine if pre-exposure prophylaxis (PrEP) with 400mg hydroxychloroquine (HCQ), taken orally once daily reduces microbiologically confirmed COVID-19 among front line health care workers at high risk for SARS-CoV-2 exposure. Secondary Objectives: To compare the following between study arms: adverse events; symptomatic COVID-19; duration of symptomatic COVID-19; days hospitalized attributed to COVID-19; respiratory failure attributable to COVID-19 requiring i) non-invasive ventilation or ii) intubation/mechanical ventilation; mortality attributed to COVID-19, number of days unable to work attributed to COVID-19, seroconversion (COVID-19 negative to COVID-19 positive over the study period); ability of participant plasma to neutralize SARS-CoV-2 virus in vitro; To describe short-term psychological distress associated with risk of COVID-19 exposure at 1, 60, 120 days of the study. To explore laboratory markers within participants with confirmed COVID-19: including circulating markers of host immune and endothelial activation in participant plasma and their correlation with disease severity and outcome TRIAL DESIGN: The HEROS study is a two-arm, parallel-group, individually randomized (1:1 allocation ratio), placebo controlled, participant and investigator-blinded, multi-site superiority trial of oral HCQ 400 mg taken once daily for 90 days as PrEP to prevent COVID-19 in health care workers at high risk of SARS-CoV-2 exposure. At 90 days, there is an open label extension wherein all participants are offered a one-month course of HCQ 400mg once daily for PrEP of COVID-19. PARTICIPANTS: Frontline HCWs aged 18 years of age or older, at high risk of SARS-CoV-2 exposure (including staff of emergency departments, intensive care units, intubation teams, COVID-wards, and staff deployed to Long Term Care facilities) of five academic hospitals in downtown Toronto, Canada. Exclusion criteria include: currently pregnant, planning to become pregnant during the study period, and/or breast feeding; known hypersensitivity/allergy to hydroxychloroquine or to 4-aminoquinoline compounds; current use of hydroxychloroquine; known prolonged QT syndrome and/or baseline resting ECG with QTc>450 ms and/or concomitant medications which simultaneously may prolong the QTc that cannot be temporarily suspended/replaced; known pre-existing retinopathy, G6PD deficiency, porphyria, liver disease including cirrhosis, encephalopathy, hepatitis or alcoholism, diabetes on oral hypoglycemics or insulin, or renal insufficiency/failure; disclosure of self-administered use of hydroxychloroquine or chloroquine within 12 weeks prior to study; confirmed symptomatic COVID-19 at time of enrollment. INTERVENTION AND COMPARATOR: Intervention: hydroxychloroquine, 400mg (2 tablets) orally per day. Comparator: placebo, two tablets visually identical to the intervention, orally per day MAIN OUTCOMES: The primary outcome is microbiologically confirmed COVID-19 (i.e. SARS-CoV-2 infection). This is a composite endpoint which includes positive results from any validated SARS-CoV-2 diagnostic assay including detection of viral RNA, and/or seroconversion. Participants will be assessed at baseline, and then undergo monthly follow-up at day 30, 60, and 90, 120. At each visit, participants will provide an oropharyngeal sample, blood sample, and will undergo electrocardiogram monitoring of the QTc interval. Secondary outcome measures include: adverse events; symptom duration of COVID-19; days of hospitalization attributed to COVID-19; respiratory failure requiring ventilator support attributed to COVID-19; mortality attributed to COVID-19; total days off work attributed to COVID-19; seropositivity (reactive serology by day 120); and short term psychological impact of exposure to SARS-CoV-2 at day 1, 60, 120 days using the K10, a validated measure of non-specific psychological distress. RANDOMISATION: Within each site, participants will be individually randomized to either the intervention arm with HCQ or the placebo arm using a fixed 1:1 allocation ratio using an interactive web-based response system to ensure concealment of allocation. Randomization schedules will be computer-generated and blocked using variable block sizes. BLINDING (MASKING): All participants, research coordinators, technicians, clinicians and investigators will be blinded to the participant allocation group. Numbers to be randomised (sample size) N=988, randomised into two groups of 494 patients. TRIAL STATUS: This summary describes protocol version No. 1.6, May 15, 2020. Recruitment is ongoing - started April 20, 2020 and anticipated end date is July 30, 2021 TRIAL REGISTRATION: ISRCTN.com Identifier: ISRCTN14326006, registered April 14, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Subject(s)
Betacoronavirus , Coronavirus Infections/prevention & control , Health Personnel , Hydroxychloroquine/therapeutic use , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pre-Exposure Prophylaxis , Randomized Controlled Trials as Topic , Adolescent , Adult , COVID-19 , Humans , Outcome Assessment, Health Care , SARS-CoV-2 , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL