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1.
Open forum infectious diseases ; 9(1), 2021.
Article in English | EuropePMC | ID: covidwho-1619398

ABSTRACT

We developed a simple, noninvasive mask sampling method to quantify and sequence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from exhaled breath. We found substantial variation between individuals in SARS-CoV-2 copies exhaled over a 15-minute period, which moderately correlated with nasal swab viral load. Talking was associated with a median of 2 log10 greater exhaled viral copies. Exposure varies substantially between individuals but may be risk stratified by nasal swab viral load and whether the exposure involved conversation.

2.
Clin Infect Dis ; 73(9): e3130-e3132, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1532491

ABSTRACT

We investigated feasibility and accuracy of an interferon-γ release assay (IGRA) for detection of T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whole blood IGRA accurately distinguished between convalescent and uninfected healthy blood donors with a predominantly CD4+ T-cell response. SARS-CoV-2 IGRA may serve as a useful diagnostic tool in managing the coronavirus disease 2019 pandemic.


Subject(s)
COVID-19 , Interferon-gamma Release Tests , Antibodies, Viral , Humans , SARS-CoV-2 , T-Lymphocytes
3.
Nat Commun ; 12(1): 6220, 2021 10 28.
Article in English | MEDLINE | ID: covidwho-1493098

ABSTRACT

A two-dose regimen of the Oxford-AstraZeneca (ChAdOx1) Covid-19 vaccine with an inter-dose interval of three months has been implemented in many countries with restricted vaccine supply. However, there is limited evidence for the effectiveness of ChAdOx1 by dose in elderly populations in countries with high prevalence of the Gamma variant of SARS-CoV-2. Here, we estimate ChAdOx1 effectiveness by dose against the primary endpoint of RT-PCR-confirmed Covid-19, and secondary endpoints of Covid-19 hospitalization and Covid-19-related death, in adults aged ≥60 years during an epidemic with high Gamma variant prevalence in São Paulo state, Brazil using a matched, test-negative case-control study. Starting 28 days after the first dose, effectiveness of a single dose of ChAdOx1 is 33.4% (95% CI, 26.4-39.7) against Covid-19, 55.1% (95% CI, 46.6-62.2) against hospitalization, and 61.8% (95% CI, 48.9-71.4) against death. Starting 14 days after the second dose, effectiveness of the two-dose schedule is 77.9% (95% CI, 69.2-84.2) against Covid-19, 87.6% (95% CI, 78.2-92.9) against hospitalization, and 93.6% (95% CI, 81.9-97.7) against death. Completion of the ChAdOx1 vaccine schedule affords significantly increased protection over a single dose against mild and severe Covid-19 outcomes in elderly individuals during widespread Gamma variant circulation.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Aged , Brazil , COVID-19/epidemiology , COVID-19/immunology , COVID-19/prevention & control , Case-Control Studies , Female , Humans , Male , Middle Aged , SARS-CoV-2/metabolism
4.
MDM Policy Pract ; 6(2): 23814683211049249, 2021.
Article in English | MEDLINE | ID: covidwho-1477249

ABSTRACT

Background. Mexico City Metropolitan Area (MCMA) has the largest number of COVID-19 (coronavirus disease 2019) cases in Mexico and is at risk of exceeding its hospital capacity in early 2021. Methods. We used the Stanford-CIDE Coronavirus Simulation Model (SC-COSMO), a dynamic transmission model of COVID-19, to evaluate the effect of policies considering increased contacts during the end-of-year holidays, intensification of physical distancing, and school reopening on projected confirmed cases and deaths, hospital demand, and hospital capacity exceedance. Model parameters were derived from primary data, literature, and calibrated. Results. Following high levels of holiday contacts even with no in-person schooling, MCMA will have 0.9 million (95% prediction interval 0.3-1.6) additional COVID-19 cases between December 7, 2020, and March 7, 2021, and hospitalizations will peak at 26,000 (8,300-54,500) on January 25, 2021, with a 97% chance of exceeding COVID-19-specific capacity (9,667 beds). If MCMA were to control holiday contacts, the city could reopen in-person schools, provided they increase physical distancing with 0.5 million (0.2-0.9) additional cases and hospitalizations peaking at 12,000 (3,700-27,000) on January 19, 2021 (60% chance of exceedance). Conclusion. MCMA must increase COVID-19 hospital capacity under all scenarios considered. MCMA's ability to reopen schools in early 2021 depends on sustaining physical distancing and on controlling contacts during the end-of-year holiday.

6.
Clin Infect Dis ; 73(Suppl 2): S138-S145, 2021 07 30.
Article in English | MEDLINE | ID: covidwho-1373634

ABSTRACT

BACKGROUND: Although much of the public health effort to combat coronavirus disease 2019 (COVID-19) has focused on disease control strategies in public settings, transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within households remains an important problem. The nature and determinants of household transmission are poorly understood. METHODS: To address this gap, we gathered and analyzed data from 22 published and prepublished studies from 10 countries (20 291 household contacts) that were available through 2 September 2020. Our goal was to combine estimates of the SARS-CoV-2 household secondary attack rate (SAR) and to explore variation in estimates of the household SAR. RESULTS: The overall pooled random-effects estimate of the household SAR was 17.1% (95% confidence interval [CI], 13.7-21.2%). In study-level, random-effects meta-regressions stratified by testing frequency (1 test, 2 tests, >2 tests), SAR estimates were 9.2% (95% CI, 6.7-12.3%), 17.5% (95% CI, 13.9-21.8%), and 21.3% (95% CI, 13.8-31.3%), respectively. Household SARs tended to be higher among older adult contacts and among contacts of symptomatic cases. CONCLUSIONS: These findings suggest that SARs reported using a single follow-up test may be underestimated, and that testing household contacts of COVID-19 cases on multiple occasions may increase the yield for identifying secondary cases.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Family Characteristics , Humans , Incidence , Motivation
7.
BMJ ; 374: n2015, 2021 08 20.
Article in English | MEDLINE | ID: covidwho-1367428

ABSTRACT

OBJECTIVE: To estimate the effectiveness of the inactivated whole virus vaccine, CoronaVac (Sinovac Biotech), against symptomatic covid-19 in the elderly population of São Paulo state, Brazil during widespread circulation of the gamma variant. DESIGN: Test negative case-control study. SETTING: Community testing for covid-19 in São Paulo state, Brazil. PARTICIPANTS: 43 774 adults aged ≥70 years who were residents of São Paulo state and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 29 April 2021. 26 433 cases with symptomatic covid-19 and 17 622 test negative controls with covid-19 symptoms were formed into 13 283 matched sets, one case with to up to five controls, according to age, sex, self-reported race, municipality of residence, previous covid-19 status, and date of RT-PCR test (±3 days). INTERVENTION: Vaccination with a two dose regimen of CoronaVac. MAIN OUTCOME MEASURES: RT-PCR confirmed symptomatic covid-19 and associated hospital admissions and deaths. RESULTS: Adjusted vaccine effectiveness against symptomatic covid-19 was 24.7% (95% confidence interval 14.7% to 33.4%) at 0-13 days and 46.8% (38.7% to 53.8%) at ≥14 days after the second dose. Adjusted vaccine effectiveness against hospital admissions was 55.5% (46.5% to 62.9%) and against deaths was 61.2% (48.9% to 70.5%) at ≥14 days after the second dose. Vaccine effectiveness ≥14 days after the second dose was highest for the youngest age group (70-74 years)-59.0% (43.7% to 70.2%) against symptomatic disease, 77.6% (62.5% to 86.7%) against hospital admissions, and 83.9% (59.2% to 93.7%) against deaths-and declined with increasing age. CONCLUSIONS: Vaccination with CoronaVac was associated with a reduction in symptomatic covid-19, hospital admissions, and deaths in adults aged ≥70 years in a setting with extensive transmission of the gamma variant. Vaccine protection was, however, low until completion of the two dose regimen, and vaccine effectiveness was observe to decline with increasing age among this elderly population.


Subject(s)
COVID-19 Nucleic Acid Testing/statistics & numerical data , COVID-19 Vaccines/therapeutic use , COVID-19/mortality , COVID-19/virology , SARS-CoV-2 , Aged , Aged, 80 and over , Brazil/epidemiology , COVID-19/prevention & control , Case-Control Studies , Female , Humans , Male , Treatment Outcome
8.
Lancet Reg Health Am ; 1: 100025, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1356347

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Gamma, emerged in the city of Manaus in late 2020 during a large resurgence of coronavirus disease (COVID-19), and has spread throughout Brazil. The effectiveness of vaccines in settings with widespread Gamma variant transmission has not been reported. Methods: We performed a matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, in healthcare workers (HCWs) in Manaus, where the Gamma variant accounted for 86% of genotyped SARS-CoV-2 samples at the peak of its epidemic. We performed an early analysis of effectiveness following administration of at least one vaccine dose and an analysis of effectiveness of the two-dose schedule. The primary outcome was symptomatic SARS-CoV-2 infection. Findings: For the early at-least-one-dose and two-dose analyses the study population was, respectively, 53,176 and 53,153 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. Among 53,153 HCWs eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from 19 January, 2021 to 13 April, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive. 393 and 418 case-control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. Among those who had received both vaccine doses before the RT-PCR sample collection date, the average time from second dose to sample collection date was 14 days (IQR 7-24). In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness (VE), 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first dose (aOR 2.11, 95% CI 1.36-3.27) suggests that unmeasured confounding led to downward bias in the vaccine effectiveness estimate. Interpretation: Evidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic Gamma variant transmission. However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented. Funding: Fundação Oswaldo Cruz (Fiocruz); Municipal Health Secretary of Manaus; Fundação de Vigilância em Saúde do Amazonas.

9.
Lancet Public Health ; 6(10): e760-e770, 2021 10.
Article in English | MEDLINE | ID: covidwho-1345513

ABSTRACT

BACKGROUND: Residents of prisons have experienced disproportionate COVID-19-related health harms. To control outbreaks, many prisons in the USA restricted in-person activities, which are now resuming even as viral variants proliferate. This study aims to use mathematical modelling to assess the risks and harms of COVID-19 outbreaks in prisons under a range of policies, including resumption of activities. METHODS: We obtained daily resident-level data for all California state prisons from Jan 1, 2020, to May 15, 2021, describing prison layouts, housing status, sociodemographic and health characteristics, participation in activities, and COVID-19 testing, infection, and vaccination status. We developed a transmission-dynamic stochastic microsimulation parameterised by the California data and published literature. After an initial infection is introduced to a prison, the model evaluates the effect of various policy scenarios on infections and hospitalisations over 200 days. Scenarios vary by vaccine coverage, baseline immunity (0%, 25%, or 50%), resumption of activities, and use of non-pharmaceutical interventions (NPIs) that reduce transmission by 75%. We simulated five prison types that differ by residential layout and demographics, and estimated outcomes with and without repeated infection introductions over the 200 days. FINDINGS: If a viral variant is introduced into a prison that has resumed pre-2020 contact levels, has moderate vaccine coverage (ranging from 36% to 76% among residents, dependent on age, with 40% coverage for staff), and has no baseline immunity, 23-74% of residents are expected to be infected over 200 days. High vaccination coverage (90%) coupled with NPIs reduces cumulative infections to 2-54%. Even in prisons with low room occupancies (ie, no more than two occupants) and low levels of cumulative infections (ie, <10%), hospitalisation risks are substantial when these prisons house medically vulnerable populations. Risks of large outbreaks (>20% of residents infected) are substantially higher if infections are repeatedly introduced. INTERPRETATION: Balancing benefits of resuming activities against risks of outbreaks presents challenging trade-offs. After achieving high vaccine coverage, prisons with mostly one-to-two-person cells that have higher baseline immunity from previous outbreaks can resume in-person activities with low risk of a widespread new outbreak, provided they maintain widespread NPIs, continue testing, and take measures to protect the medically vulnerable. FUNDING: Horowitz Family Foundation, National Institute on Drug Abuse, Centers for Disease Control and Prevention, National Science Foundation, Open Society Foundation, Advanced Micro Devices.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Disease Outbreaks , Prisons , SARS-CoV-2/isolation & purification , Adolescent , Adult , Aged , COVID-19/prevention & control , COVID-19/transmission , COVID-19 Vaccines/administration & dosage , California/epidemiology , Female , Humans , Male , Middle Aged , Models, Theoretical , Organizational Policy , Prisons/organization & administration , Risk Assessment , Vaccination/statistics & numerical data , Young Adult
10.
Open Forum Infect Dis ; 8(7): ofab310, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1322651

ABSTRACT

Background: Given the persistence of viral RNA in clinically recovered coronavirus disease 2019 (COVID-19) patients, subgenomic RNAs (sgRNAs) have been reported as potential molecular viability markers for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, few data are available on their longitudinal kinetics, compared with genomic RNA (gRNA), in clinical samples. Methods: We analyzed 536 samples from 205 patients with COVID-19 from placebo-controlled, outpatient trials of peginterferon Lambda-1a (Lambda; n = 177) and favipiravir (n = 359). Nasal swabs were collected at 3 time points in the Lambda (days 1, 4, and 6) and favipiravir (days 1, 5, and 10) trials. N-gene gRNA and sgRNA were quantified by quantitative reverse transcription polymerase chain reaction. To investigate the decay kinetics in vitro, we measured gRNA and sgRNA in A549ACE2+ cells infected with SARS-CoV-2, following treatment with remdesivir or dimethylsulfoxide control. Results: At 6 days in the Lambda trial and 10 days in the favipiravir trial, sgRNA remained detectable in 51.6% (32/62) and 49.5% (51/106) of the samples, respectively. Cycle threshold (Ct) values for gRNA and sgRNA were highly linearly correlated (marginal R 2 = 0.83), and the rate of increase did not differ significantly in the Lambda trial (1.36 cycles/d vs 1.36 cycles/d; P = .97) or the favipiravir trial (1.03 cycles/d vs 0.94 cycles/d; P = .26). From samples collected 15-21 days after symptom onset, sgRNA was detectable in 48.1% (40/83) of participants. In SARS-CoV-2-infected A549ACE2+ cells treated with remdesivir, the rate of Ct increase did not differ between gRNA and sgRNA. Conclusions: In clinical samples and in vitro, sgRNA was highly correlated with gRNA and did not demonstrate different decay patterns to support its application as a viability marker.

11.
J Gen Intern Med ; 36(10): 3096-3102, 2021 10.
Article in English | MEDLINE | ID: covidwho-1320128

ABSTRACT

BACKGROUND: Correctional institutions nationwide are seeking to mitigate COVID-19-related risks. OBJECTIVE: To quantify changes to California's prison population since the pandemic began and identify risk factors for COVID-19 infection. DESIGN: For California state prisons (March 1-October 10, 2020), we described residents' demographic characteristics, health status, COVID-19 risk scores, room occupancy, and labor participation. We used Cox proportional hazard models to estimate the association between rates of COVID-19 infection and room occupancy and out-of-room labor, respectively. PARTICIPANTS: Residents of California state prisons. MAIN MEASURES: Changes in the incarcerated population's size, composition, housing, and activities. For the risk factor analysis, the exposure variables were room type (cells vs. dormitories) and labor participation (any room occupant participating in the prior 2 weeks) and the outcome variable was incident COVID-19 case rates. KEY RESULTS: The incarcerated population decreased 19.1% (119,401 to 96,623) during the study period. On October 10, 2020, 11.5% of residents were aged ≥60, 18.3% had high COVID-19 risk scores, 31.0% participated in out-of-room labor, and 14.8% lived in rooms with ≥10 occupants. Nearly 40% of residents with high COVID-19 risk scores lived in dormitories. In 9 prisons with major outbreaks (6,928 rooms; 21,750 residents), dormitory residents had higher infection rates than cell residents (adjusted hazard ratio [AHR], 2.51 95% CI, 2.25-2.80) and residents of rooms with labor participation had higher rates than residents of other rooms (AHR, 1.56; 95% CI, 1.39-1.74). CONCLUSION: Despite reductions in room occupancy and mixing, California prisons still house many medically vulnerable residents in risky settings. Reducing risks further requires a combination of strategies, including rehousing, decarceration, and vaccination.


Subject(s)
COVID-19 , Prisoners , California/epidemiology , Humans , Prisons , Risk Factors , SARS-CoV-2
13.
Nat Commun ; 12(1): 1967, 2021 03 30.
Article in English | MEDLINE | ID: covidwho-1159789

ABSTRACT

Type III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized, single-blind, placebo-controlled trial (NCT04331899) in 120 outpatients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) within 72 hours of diagnosis could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively, and symptom duration did not differ significantly between groups (HR 0.94; 95% CI 0.64 to 1.39). Both Lambda and placebo were well-tolerated, though liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/drug therapy , Interleukins/administration & dosage , Polyethylene Glycols/administration & dosage , Adult , Aged , COVID-19/virology , Female , Humans , Injections, Subcutaneous , Male , Middle Aged , Outpatients , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Single-Blind Method , Treatment Failure , Virus Shedding/drug effects , Young Adult
14.
Nat Immunol ; 22(1): 67-73, 2021 01.
Article in English | MEDLINE | ID: covidwho-1065904

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 infections can cause coronavirus disease 2019 (COVID-19), which manifests with a range of severities from mild illness to life-threatening pneumonia and multi-organ failure. Severe COVID-19 is characterized by an inflammatory signature, including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi. Here we show that patients with severe COVID-19 produced a unique serologic signature, including an increased likelihood of IgG1 with afucosylated Fc glycans. This Fc modification on severe acute respiratory syndrome coronavirus 2 IgGs enhanced interactions with the activating Fcγ receptor FcγRIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including interleukin-6 and tumor necrosis factor. These results show that disease severity in COVID-19 correlates with the presence of proinflammatory IgG Fc structures, including afucosylated IgG1.


Subject(s)
COVID-19/immunology , Cytokines/immunology , Immunoglobulin G/immunology , Receptors, IgG/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , COVID-19/metabolism , COVID-19/virology , Child , Cytokines/metabolism , Female , Glycosylation , Humans , Immunoglobulin G/metabolism , Interleukin-6 , Male , Middle Aged , Receptors, IgG/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Severity of Illness Index , Tumor Necrosis Factor-alpha/immunology , Tumor Necrosis Factor-alpha/metabolism
15.
J Clin Med ; 9(6)2020 Jun 24.
Article in English | MEDLINE | ID: covidwho-613339

ABSTRACT

Early identification of pneumonia is essential in patients with acute febrile respiratory illness (FRI). We evaluated the performance and added value of a commercial deep learning (DL) algorithm in detecting pneumonia on chest radiographs (CRs) of patients visiting the emergency department (ED) with acute FRI. This single-centre, retrospective study included 377 consecutive patients who visited the ED and the resulting 387 CRs in August 2018-January 2019. The performance of a DL algorithm in detection of pneumonia on CRs was evaluated based on area under the receiver operating characteristics (AUROC) curves, sensitivity, specificity, negative predictive values (NPVs), and positive predictive values (PPVs). Three ED physicians independently reviewed CRs with observer performance test to detect pneumonia, which was re-evaluated with the algorithm eight weeks later. AUROC, sensitivity, and specificity measurements were compared between "DL algorithm" vs. "physicians-only" and between "physicians-only" vs. "physicians aided with the algorithm". Among 377 patients, 83 (22.0%) had pneumonia. AUROC, sensitivity, specificity, PPV, and NPV of the algorithm for detection of pneumonia on CRs were 0.861, 58.3%, 94.4%, 74.2%, and 89.1%, respectively. For the detection of 'visible pneumonia on CR' (60 CRs from 59 patients), AUROC, sensitivity, specificity, PPV, and NPV were 0.940, 81.7%, 94.4%, 74.2%, and 96.3%, respectively. In the observer performance test, the algorithm performed better than the physicians for pneumonia (AUROC, 0.861 vs. 0.788, p = 0.017; specificity, 94.4% vs. 88.7%, p < 0.0001) and visible pneumonia (AUROC, 0.940 vs. 0.871, p = 0.007; sensitivity, 81.7% vs. 73.9%, p = 0.034; specificity, 94.4% vs. 88.7%, p < 0.0001). Detection of pneumonia (sensitivity, 82.2% vs. 53.2%, p = 0.008; specificity, 98.1% vs. 88.7%; p < 0.0001) and 'visible pneumonia' (sensitivity, 82.2% vs. 73.9%, p = 0.014; specificity, 98.1% vs. 88.7%, p < 0.0001) significantly improved when the algorithm was used by the physicians. Mean reading time for the physicians decreased from 165 to 101 min with the assistance of the algorithm. Thus, the DL algorithm showed a better diagnosis of pneumonia, particularly visible pneumonia on CR, and improved diagnosis by ED physicians in patients with acute FRI.

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