Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

Cell June 2020

A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become

the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal.

The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RTPCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.

PDF

https://www.cell.com/action/showPdf?pii=S0092-8674%2820%2930820-5

July 10, 2020 at 8:32 pm

Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy: A Cohort Study

Ann Intern Med. June 26, 2020     

Background

The incidence and severity of coronavirus disease 2019 (COVID-19) among HIV-positive persons receiving antiretroviral therapy (ART) have not been characterized in large populations.

Objective

To describe the incidence and severity of COVID-19 by nucleos(t)ide reverse transcriptase inhibitor (NRTI) use among HIV-positive persons receiving ART.

Design

Cohort study.

Setting

HIV clinics in 60 Spanish hospitals between 1 February and 15 April 2020.

Participants

77 590 HIV-positive persons receiving ART.

Measurements

Estimated risks (cumulative incidences) per 10 000 persons and 95% CIs for polymerase chain reaction-confirmed COVID-19 diagnosis, hospitalization, intensive care unit (ICU) admission, and death. Risk and 95% CIs for COVID-19 diagnosis and hospital admission by use of the NRTIs tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC), and others were estimated through Poisson regression models.

Results

Of 77 590 HIV-positive persons receiving ART, 236 were diagnosed with COVID-19, 151 were hospitalized, 15 were admitted to the ICU, and 20 died. The risks for COVID-19 diagnosis and hospitalization were greater in men and persons older than 70 years. The risk for COVID-19 hospitalization was 20.3 (95% CI, 15.2 to 26.7) among patients receiving TAF/FTC, 10.5 (CI, 5.6 to 17.9) among those receiving TDF/FTC, 23.4 (CI, 17.2 to 31.1) among those receiving ABC/3TC, and 20.0 (CI, 14.2 to 27.3) for those receiving other regimens. The corresponding risks for COVID-19 diagnosis were 39.1 (CI, 31.8 to 47.6), 16.9 (CI, 10.5 to 25.9), 28.3 (CI, 21.5 to 36.7), and 29.7 (CI, 22.6 to 38.4), respectively. No patient receiving TDF/FTC was admitted to the ICU or died.

Limitation

Residual confounding by comorbid conditions cannot be completely excluded.

Conclusion

HIV-positive patients receiving TDF/FTC have a lower risk for COVID-19 and related hospitalization than those receiving other therapies. These findings warrant further investigation in HIV preexposure prophylaxis studies and randomized trials in persons without HIV.

Primary funding source

Instituto de Salud Carlos III and National Institutes of Health.

FULL TEXT

https://www.acpjournals.org/doi/full/10.7326/M20-3689?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed&

July 6, 2020 at 7:24 pm

Treatment of advanced AIDS-associated Kaposi sarcoma in resource-limited settings: a three-arm, open-label, randomised, non-inferiority trial.

Lancet April 11, 2020 V.395 N.10231 P.1195-1207.

Background

Optimal treatment regimens for AIDS-associated Kaposi sarcoma, a frequent contributor to morbidity and mortality among people with HIV, have not been systematically evaluated in low-income and middle-income countries, where the disease is most common. In this study, we aimed to investigate optimal treatment strategies for advanced stage disease in areas of high prevalence and limited resources.

Methods

In this open-label, non-inferiority trial, we enrolled people with HIV and advanced stage AIDS-associated Kaposi sarcoma attending 11 AIDS Clinical Trials Group sites in Brazil, Kenya, Malawi, South Africa, Uganda, and Zimbabwe. Eligible participants were randomly assigned (1:1:1) with a centralised computer system to receive either intravenous bleomycin and vincristine or oral etoposide (the investigational arms), or intravenous paclitaxel (the control arm), together with antiretroviral therapy (ART; combined efavirenz, tenofovir disoproxil fumarate, and emtricitabine). The primary outcome was progression-free survival (PFS) at week 48, using a 15% non-inferiority margin to compare the investigational groups against the active control group. Safety was assessed in all eligible treated study participants. The study was registered with ClinicalTrials.gov, NCT01435018.

Findings

334 participants were enrolled between Oct 1, 2013, and March 8, 2018, when the study was closed early due to inferiority of the bleomycin and vincristine plus ART arm, as per the recommendations of the Data and Safety Monitoring Board (DSMB). The etoposide plus ART arm also closed due to inferiority in March, 2016, following a DSMB recommendation. Week-48 PFS rates were higher in the paclitaxel plus ART arm than in both investigational arms. The absolute differences in PFS were -30% (95% CI -52 to -8) for the comparison of paclitaxel plus ART (week 48 PFS 50%, 32 to 67; n=59) and etoposide plus ART (20%, 6 to 33; n=59), and -20% (-33% to -7%) for the comparison of paclitaxel plus ART (64%, 55 to 73; n=138) and bleomycin and vincristine plus ART (44%, 35 to 53; n=132). Both CIs overlapped the non-inferiority margin. The most common adverse events, in 329 eligible participants who began treatment, were neutropenia (48 [15%]), low serum albumin (33 [10%]), weight loss (29 [9%]), and anaemia (28 [9%]), occurring at similar frequency across treatment arms.

Interpretation

Non-inferiority of either investigational intervention was not shown, with paclitaxel plus ART showing superiority to both oral etoposide plus ART and bleomycin and vincristine plus ART, supporting its use in treating advanced AIDS-associated Kaposi sarcoma in resource-limited settings.

Funding

US National Institute of Allergy and Infectious Diseases and National Cancer Institute, National Institutes of Health.

PDF

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(19)33222-2.pdf

July 1, 2020 at 6:38 pm

Treatment of Staphylococcal Device Infections: Synergistic Daptomycin With Ceftaroline Versus Rifampin-Adjunct Therapy

Open Forum Infectious Diseases March 2020

Las infecciones de dispositivos médicos son un problema de salud grave con una mayor morbilidad, mortalidad de hasta el 25% y costos que van desde $ 1000 a $ 50 000 asociados con cada caso.

El organismo causal más común en estas infecciones es el estafilococo, que es un organismo comensal frecuente que puede colonizar dispositivos durante la implantación.

La extracción física del dispositivo y la terapia con antibióticos son los principales métodos utilizados para tratar las infecciones del dispositivo, aunque es más probable que se logre el éxito clínico si se implementa una combinación de ambos enfoques.

Ciertos pacientes no son candidatos para la intervención quirúrgica debido al riesgo sustancial de complicaciones; por lo tanto, en estos casos, se usa terapia antibiótica sola, que a menudo requiere supresión indefinida. Las tasas crecientes de resistencia a los antibióticos y la aparición de infecciones refractarias son consideraciones de tratamiento comunes con todas las infecciones; sin embargo, las infecciones del dispositivo plantean desafíos terapéuticos adicionales si no se logra el control de la fuente.

FULL TEXT

https://academic.oup.com/ofid/article/7/3/ofaa072/5763092

PDF (CLIC en PDF)

June 29, 2020 at 5:52 pm

High-Dose Intravenous Immunoglobulin as a Therapeutic Option for Deteriorating Patients With Coronavirus Disease 2019

Open Forum Infectious Diseases March 2020

COVID-19 se ha extendido rápidamente en China. Hasta ahora, no se ha identificado un tratamiento efectivo definitivo. Informamos sobre 3 pacientes con COVID-19 grave que recibieron inmunoglobulina intravenosa (IGIV) en dosis altas con recuperación satisfactoria.

En base a estas observaciones, se deben considerar estudios aleatorios de dosis altas de IgIV en pacientes deteriorados infectados con COVID-19.

FULL TEXT

https://academic.oup.com/ofid/article/7/3/ofaa102/5810740

PDF (CLIC en PDF)

June 29, 2020 at 5:50 pm

Dosificación de cefazolina prequirúrgica en pacientes obesos y no obesos. Importa el peso

Revista Española de Quimioterapia Junio 2020

PDF

https://seq.es/wp-content/uploads/2020/04/rodriguez15apr2020.pdf

June 29, 2020 at 5:48 pm

REVISION – Remdesivir, la esperanza antiviral frente al SARS-CoV-2

Revista Española de Quimioterapia Junio 2020

PDF

https://seq.es/wp-content/uploads/2020/04/reina01apr2020.pdf

June 29, 2020 at 5:42 pm

Efficacy of Early Oral Switch (EOS) with β-Lactams for Low-Risk (LR) Staphylococcus aureus Bacteremia (SAB)

Antimicrob. Agents Chemother. July 2020 V.64 N.7

El objetivo de este estudio fue evaluar la seguridad del cambio oral temprano (EOS) antes de 14 días para la bacteriemia por Staphylococcus aureus de bajo riesgo (LR-SAB), que es la estrategia de tratamiento primario utilizada en nuestra institución. La terapia recomendada habitual es 14 días de ATB IV.

Todos los pacientes con SAB en nuestro hospital fueron identificados entre el 1/01/14 y 31/12/18.

Aquellos que cumplen con los criterios de bajo riesgo (asociados con la atención médica, sin evidencia de infección profunda o implicación demostrada de material protésico, y no más hemocultivos positivos después de 72 h) fueron incluidos en el estudio.

abstract

https://aac.asm.org/content/64/7/e02345-19.abstract?etoc

PDF

https://aac.asm.org/content/aac/64/7/e02345-19.full.pdf

June 25, 2020 at 1:12 pm

Commentary – Early Oral Antibiotic Switch for Staphylococcus aureus Bacteremia – Many Are Called, but Few Are Chosen

Antimicrob. Agents Chemother. July 2020  V.64 N.7

La bacteriemia por Staphylococcus aureus (SAB) es una enfermedad complicada y de alto riesgo.

Para SAB de bajo riesgo seleccionado, se desconoce el papel de la terapia de reducción antibiótica oral.

Bupha-Intr y col. informan una cohorte retrospectiva de pacientes con SAB de bajo riesgo que obtuvieron buenos resultados con una corta duración de los ATB IV, seguidos de 10 días adicionales de ATB VO, principalmente con betalactámicos.

Los ensayos prospectivos ayudarán a definir aún más la eficacia de este enfoque.

https://aac.asm.org/content/64/7/e00317-20.abstract?etoc

PDF (CLIC en PDF)

June 25, 2020 at 1:11 pm

REVIEW – Perioperative Considerations in Urgent Surgical Care of Suspected and Confirmed COVID-19 Orthopaedic Patients: Operating Room Protocols and Recommendations in the Current COVID-19 Pandemic

J Am Acad Orthop Surg. June 2020 V.28 N.11 P.451-463

Mohamed E. Awad, MD

Jacob C.L. Rumley, DO

Jose A. Vazquez, MD, FACP, FIDSA

John G. Devine, MD, FAOA

From the Hull College of Business, Augusta University (Dr. Awad), the Department of Orthopedic Surgery,

Medical College of Georgia, Augusta University (Dr. Awad, Dr. Rumley, and Dr. Devine), the Division of Infectious Diseases, Department of Medicine, Medical College of Georgia, Augusta University (Dr. Vazquez), and Antimicrobial Stewardship Service, Augusta University (Dr. Vazquez), Augusta, GA.

By April 7, 2020, severe acute respiratory syndrome coronavirus 2 was responsible for 1,383,436 confirmed cases of Coronavirus disease 2019 (COVID-19), involving 209 countries around the world; 378,881 cases have been confirmed in the United States. During this pandemic, the urgent surgical requirements will not stop. As an example, the most recent Centers of Disease Control and Prevention reports estimate that there are 2.8 million trauma patients hospitalized in the United States. These data illustrate an increase in the likelihood of encountering urgent surgical patients with either clinically suspected or confirmed COVID-19 in the near future. Preparation for a pandemic involves considering the different levels in the hierarchy of controls and the different phases of the pandemic. Apart from the fact that this pandemic certainly involves many important health, economic, and community ramifications, it also requires several initiatives to mandate what measures are most appropriate to prepare for mitigating the occupational risks. This article provides evidence-based recommendations and measures for the appropriate personal protective equipment for different clinical and surgical activities in various settings. To reduce the occupational risk in treating suspected or confirmed COVID-19 urgent orthopaedic patients, recommended precautions and preventive actions (triage area, emergency department consultation room, induction room, operating room, and recovery room) are reviewed….

FULL TEXT

https://pubmed.ncbi.nlm.nih.gov/32282441/

June 24, 2020 at 3:18 pm

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