Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has spread globally in a few short months. Substantial evidence now supports ...preliminary conclusions about transmission that can inform rational, evidence-based policies and reduce misinformation on this critical topic. This article presents a comprehensive review of the evidence on transmission of this virus. Although several experimental studies have cultured live virus from aerosols and surfaces hours after inoculation, the real-world studies that detect viral RNA in the environment report very low levels, and few have isolated viable virus. Strong evidence from case and cluster reports indicates that respiratory transmission is dominant, with proximity and ventilation being key determinants of transmission risk. In the few cases where direct contact or fomite transmission is presumed, respiratory transmission has not been completely excluded. Infectiousness peaks around a day before symptom onset and declines within a week of symptom onset, and no late linked transmissions (after a patient has had symptoms for about a week) have been documented. The virus has heterogeneous transmission dynamics: Most persons do not transmit virus, whereas some cause many secondary cases in transmission clusters called "superspreading events." Evidence-based policies and practices should incorporate the accumulating knowledge about transmission of SARS-CoV-2 to help educate the public and slow the spread of this virus.
Mild or Moderate Covid-19 Gandhi, Rajesh T; Lynch, John B; del Rio, Carlos
The New England journal of medicine,
10/2020, Letnik:
383, Številka:
18
Journal Article
Recenzirano
The diagnosis of Covid-19 is usually based on SARS-CoV-2 PCR testing of a nasopharyngeal swab or other specimen. Remdesivir and dexamethasone have benefits in hospitalized patients with severe ...Covid-19, but in patients with moderate disease, dexamethasone is not efficacious and data are insufficient to recommend for or against routine use of remdesivir.
Nirmatrelvir–ritonavir (Paxlovid Pfizer) is used as first-line therapy for nonhospitalized persons with Covid-19
1
on the basis of the results of the Evaluation of Protease Inhibition for Covid-19 in ...High-Risk Patients (EPIC-HR) trial, which showed that this medication reduced the risk of hospitalization or death by 88%.
2
The EPIC-HR trial enrolled adults who had not received a SARS-CoV-2 vaccine and who were at high risk for progression to severe Covid-19. Given those results, the question arose as to whether nirmatrelvir–ritonavir conferred a benefit in persons who had been vaccinated or who did not have risk factors for severe disease. The manufacturer-sponsored . . .
COVID-19 Therapeutics for Nonhospitalized Patients Gandhi, Rajesh T; Malani, Preeti N; del Rio, Carlos
JAMA : the journal of the American Medical Association,
02/2022, Letnik:
327, Številka:
7
Journal Article
Recenzirano
This Viewpoint provides a summary of currently available therapeutics for nonhospitalized patients with COVID-19 in the setting of the Omicron variant including principles for equitable allocation.
A 52-year-old man with a history of HIV-1 infection and poor medication adherence presents for evaluation. A single-pill regimen is considered. For some patients with HIV-1 infection, combination ...regimens consisting of one pill to be taken daily can improve adherence.
Foreword
This
Journal
feature begins with a case vignette that includes a therapeutic recommendation. A discussion of the clinical problem and the mechanism of benefit of this form of therapy follows. Major clinical studies, the clinical use of this therapy, and potential adverse effects are reviewed. Relevant formal guidelines, if they exist, are presented. The article ends with the authors' clinical recommendations.
A 52-year-old man with a history of homelessness, depression, and polysubstance use received a diagnosis of human immunodeficiency virus type 1 (HIV-1) infection in 2005 but has declined antiretroviral therapy (ART) in the past. His CD4+ T-cell count is now 257 per cubic millimeter, and his plasma HIV-1 RNA level is 17,000 copies per milliliter. The patient was prescribed a multipill antiretroviral regimen 2 months ago but has not followed this regimen regularly because “taking out lots of pills in the shelter just announces to the world that I have AIDS the acquired immunodeficiency syndrome.” The patient desires to keep his HIV status private and states that he would take medications regularly if he could take just “one pill once a day.” The patient is not taking any other medications; his renal function is normal. How should he be evaluated and treated?
The Clinical Problem
Effective HIV treatment requires lifelong and daily consumption of multiple antiretroviral medications. With the advent and refinement of combination ART, the life expectancy of HIV-infected patients has risen dramatically.
1
,
2
In addition to benefiting infected persons, ART almost completely blocks HIV-1 transmission to uninfected sexual partners.
3
If we were able to treat most or all HIV-infected patients and thereby prevent new infections, “the beginning of the end of AIDS” would be in sight.
4
,
5
For the benefits of ART to be realized at the individual and population levels, patients must maintain high levels of adherence to all . . .
Antiretroviral therapy (ART) reduces levels of HIV-1 and immune activation but both can persist despite clinically effective ART. The relationships among pre-ART and on-ART levels of HIV-1 and ...activation are incompletely understood, in part because prior studies have been small or cross-sectional. To address these limitations, we evaluated measures of HIV-1 persistence, inflammation, T cell activation and T cell cycling in a longitudinal cohort of 101 participants who initiated ART and had well-documented sustained suppression of plasma viremia for a median of 7 years. During the first 4 years following ART initiation, HIV-1 DNA declined by 15-fold (93%) whereas cell-associated HIV-1 RNA (CA-RNA) fell 525-fold (>99%). Thereafter, HIV-1 DNA levels continued to decline slowly (5% per year) with a half-life of 13 years. Participants who had higher HIV-1 DNA and CA-RNA before starting treatment had higher levels while on ART, despite suppression of plasma viremia for many years. Markers of inflammation and T cell activation were associated with plasma HIV-1 RNA levels before ART was initiated but there were no consistent associations between these markers and HIV-1 DNA or CA-RNA during long-term ART, suggesting that HIV-1 persistence is not driving or driven by inflammation or activation. Higher levels of inflammation, T cell activation and cycling before ART were associated with higher levels during ART, indicating that immunologic events that occurred well before ART initiation had long-lasting effects despite sustained virologic suppression. These findings should stimulate studies of viral and host factors that affect virologic, inflammatory and immunologic set points prior to ART initiation and should inform the design of strategies to reduce HIV-1 reservoirs and dampen immune activation that persists despite ART.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the EPIC-HR (Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients) trial, nirmatrelvir plus ritonavir led to an 89% reduction in hospitalization or death among unvaccinated ...outpatients with early COVID-19. The clinical impact of nirmatrelvir plus ritonavir among vaccinated populations is uncertain.
To assess whether nirmatrelvir plus ritonavir reduces risk for hospitalization or death among outpatients with early COVID-19 in the setting of prevalent SARS-CoV-2 immunity and immune-evasive SARS-CoV-2 lineages.
Population-based cohort study analyzed to emulate a clinical trial using inverse probability-weighted models to account for anticipated bias in treatment.
A large health care system providing care for 1.5 million patients in Massachusetts and New Hampshire during the Omicron wave (1 January to 17 July 2022).
44 551 nonhospitalized adults (90.3% with ≥3 vaccine doses) aged 50 years or older with COVID-19 and no contraindications for nirmatrelvir plus ritonavir.
The primary outcome was a composite of hospitalization within 14 days or death within 28 days of a COVID-19 diagnosis.
During the study period, 12 541 (28.1%) patients were prescribed nirmatrelvir plus ritonavir, and 32 010 (71.9%) were not. Patients prescribed nirmatrelvir plus ritonavir were more likely to be older, have more comorbidities, and be vaccinated. The composite outcome of hospitalization or death occurred in 69 (0.55%) patients who were prescribed nirmatrelvir plus ritonavir and 310 (0.97%) who were not (adjusted risk ratio, 0.56 95% CI, 0.42 to 0.75). Recipients of nirmatrelvir plus ritonavir had lower risk for hospitalization (adjusted risk ratio, 0.60 CI, 0.44 to 0.81) and death (adjusted risk ratio, 0.29 CI, 0.12 to 0.71).
Potential residual confounding due to differential access to COVID-19 vaccines, diagnostic tests, and treatment.
The overall risk for hospitalization or death was already low (1%) after an outpatient diagnosis of COVID-19, but nirmatrelvir plus ritonavir reduced this risk further.
National Institutes of Health.
The phases of SARS-CoV-2 infection may be viewed along a spectrum.1 Following exposure, patients may have asymptomatic infection in which they test positive for the virus by reverse ...transcriptase-polymerase chain reaction (RT-PCR) but have no clinical evidence of disease. A subgroup of patients progress to developing symptomatic infection, usually within 12 days. Patients with symptomatic COVID-19 range from having mild or moderate disease, typically managed in the outpatient setting, to severe or critical COVID-19, which requires hospitalization. Those with mild or moderate COVID-19 often have high nasopharyngeal SARS-CoV-2 levels, and it is in this phase that antiviral therapy, such as anti-SARS-CoV-2 monoclonal antibodies, appears to be most beneficial. Monoclonal antibodies are currently used for postexposure prophylaxis and for treatment of symptomatic SARS-CoV-2 infection. In this issue of JAMA, an analysis of individuals with asymptomatic infection by O'Brien et al2 provides insights into this phase of SARS-CoV-2 infection and the potential role of monoclonal antibodies in its management.
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