Annals of Internal Medicine最新文献

Background: Clinicians and patients need updated information on antiviral treatments for COVID-19.

Purpose: To provide a final update on the benefits and harms of COVID-19 antiviral treatments in adult outpatients.

Data sources: Ovid/MEDLINE, Epistemonikos COVID-19 L·OVE platform, and iSearch COVID-19 portfolio (22 January 2025); Ovid/MEDLINE (24 September 2025).

Study selection: Two reviewers screened 20% of abstracts and full texts, then single screening. Randomized controlled trials were included for benefits and harms, and cohort studies were included for harms.

Data extraction: One reviewer extracted data and assessed risk of bias and certainty of evidence (CoE); a second reviewer verified.

Data synthesis: Seven studies from the Omicron period were included. 125 mg of ensitrelvir may not reduce time to recovery and may result in no difference in serious adverse events (both low CoE) but may increase adverse events (44.2% vs. 24.8%; low CoE). Molnupiravir probably improves recovery (31.8% vs. 22.6%) and reduces time to recovery (9 vs. 15 median days) and persistent symptoms from 3 to 6 months (8.5% vs. 11.0%), with no effect on mortality, hospitalization, serious adverse events, and adverse events (all moderate CoE). Nirmatrelvir-ritonavir may increase recovery (70.7% vs. 53.6%; low CoE) and reduce time to recovery (no data, P = 0.011; low CoE) but probably increases adverse events (1.3% vs. 1.0%; moderate CoE). Simnotrelvir-ritonavir reduces time to recovery (-35.8 median hours; high CoE) and probably increases adverse events (28.9% vs. 21.6%; moderate CoE). There was no difference in recovery between molnupiravir and favipiravir (high CoE) and nirmatrelvir-ritonavir and molnupiravir (low CoE).

Limitation: Evidence for many outcomes is limited.

Conclusion: Three COVID-19 antivirals improved or accelerated recovery, with varying adverse event profiles. Molnupiravir probably offers long-term benefits.

Primary funding source: American College of Physicians. (PROSPERO: CRD420251029146; OSF: https://osf.io/ywp6u).

Description: The American College of Physicians (ACP) maintains living, rapid practice points on antiviral treatment in the outpatient setting for COVID-19.

Methods: The Population Health and Medical Science Committee (PHMSC) developed this version 3 based on evidence from a focused update of a living, rapid review conducted by the ACP Center for Evidence Reviews at Cochrane Austria. This version addresses the SARS-CoV-2 Omicron variant and reaffirms previous practice points on the use of antiviral treatments of confirmed COVID-19 in unvaccinated or vaccinated and symptomatic patients in the outpatient setting.

Practice point 1: Consider nirmatrelvir-ritonavir combination therapy to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease.

Practice point 2: Consider molnupiravir to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease.

Practice point 3: Do not use ivermectin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting.

Practice point 4: Do not use sotrovimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting.

Retirement from living status: The PHMSC is retiring this topic from living status considering that this update and previous surveillance have not yielded important changes to the practice points.

Background: Anemia affects up to 50% of pregnancies. The relation between early pregnancy maternal hemoglobin concentration and important perinatal outcomes in high-income countries is largely unknown.

Objective: To assess early pregnancy hemoglobin concentration and associated severe neonatal morbidity and mortality (SNM-M) in a high-income setting.

Design: Population-based, retrospective cohort study.

Setting: Ontario, Canada, where health care is publicly funded.

Participants: Women aged 18 to 50 years with a singleton birth between 2007 and 2023 and hemoglobin measurement at 2 to 12 weeks' gestation.

Measurements: The nonlinear relation between early pregnancy hemoglobin concentration and SNM-M was analyzed in 1-g/L increments using restricted cubic splines, with 125 g/L as the referent. The primary outcome was a validated composite measure of SNM-M (major neonatal conditions and critical interventions) up to 27 days after birth. Relative risks (RRs) were adjusted (aRR) for maternal demographic characteristics and chronic conditions.

Results: A total of 1 100 341 births were included. A U-shaped relation was observed between early pregnancy hemoglobin concentration and SNM-M. For example, relative to a hemoglobin value of 125 g/L and a corresponding SNM-M rate of 6.7%, the aRR for SNM-M was 1.08 (95% CI, 1.04 to 1.11) at a hemoglobin concentration of 105 g/L and 1.17 (CI, 1.10 to 1.25) at 90 g/L. The aRR for SNM-M was 1.05 (CI, 1.03 to 1.07) at a hemoglobin concentration of 135 g/L and 1.20 (CI, 1.16 to 1.24) at 150 g/L.

Limitation: Iron replacement status before and during pregnancy was unknown, and residual confounding may influence observed associations.

Conclusion: Maternal anemia and relative erythrocytosis were each associated with neonatal morbidity and mortality in a high-income setting. Randomized clinical trials should evaluate the effect of iron therapy on maternal and perinatal outcomes by degree of hemoglobin correction.

Primary funding source: University of Toronto Alexandra Yeo Hematology Grant.