{"id":30812,"date":"2026-07-23T04:18:00","date_gmt":"2026-07-22T20:18:00","guid":{"rendered":"https:\/\/csccm.org.cn\/?p=30812"},"modified":"2026-07-23T07:04:35","modified_gmt":"2026-07-22T23:04:35","slug":"nejm%e5%8f%91%e8%a1%a8%e8%bf%b0%e8%af%84%ef%bc%9a%e5%90%8c%e8%8d%af%e4%b8%8d%e5%90%8c%e6%95%88-%e9%87%8d%e6%96%b0%e8%af%84%e4%bc%b0%e5%a5%88%e7%8e%9b%e7%89%b9%e9%9f%a6-%e5%88%a9%e6%89%98","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=30812","title":{"rendered":"[NEJM\u53d1\u8868\u8ff0\u8bc4]\uff1a\u540c\u836f\u4e0d\u540c\u6548\u2014\u91cd\u65b0\u8bc4\u4f30\u5948\u739b\u7279\u97e6-\u5229\u6258\u90a3\u97e6\u7684\u7597\u6548"},"content":{"rendered":"\n

EDITORIAL<\/a><\/p>\n\n\n\n

Same Pill, Different Impact \u2014 Reassessing the Efficacy of Nirmatrelvir\u2013Ritonavir<\/h1>\n\n\n\n

H. Clifford\u00a0Lane,\u00a0Anthony S.\u00a0Fauci<\/h3>\n\n\n\n

N Engl J Med\u00a02026;394:1649-1650<\/h3>\n\n\n\n

DOI: 10.1056\/NEJMe2603127<\/h3>\n\n\n\n

The first cases of Covid-19 were reported at the end of 2019, and from January 20, 2020, to May 5, 2023, Covid-19 was considered to be a public health emergency of international concern. The total number of cases worldwide exceeded 1 million by early April 2020. In the United States, entire floors of hospitals were converted to Covid-19 units. In New York City, at the peak of the pandemic, a person was dying every 2 minutes (four times the normal death rate) and the bodies of persons who had died from Covid-19 were being placed in refrigerated trailers because of the lack of capacity in morgues and funeral homes.1<\/a><\/sup> A massive research effort was launched globally, and with the help of Operation Warp Speed and partnerships among the National Institutes of Health (NIH), the Food and Drug Administration, and private industry,2<\/a><\/sup> a series of double-blind, randomized, placebo-controlled trials were quickly implemented. The trials showed the safety and efficacy of a number of vaccines and antiviral therapies. These countermeasures were then rapidly deployed in the United States by the end of 2020 through emergency-use authorizations.<\/p>\n\n\n\n

Given the availability of a number of repurposed agents being proposed as potential treatments and the introduction of a number of new agents, a great need was identified early in the pandemic to provide guidance to the treating clinicians who were facing an overwhelming caseload of critically ill patients. Panels of experts provided such guidance \u2014 which rapidly changed as the body of evidence evolved. In the final release of the NIH Covid-19 treatment guidelines (in February 2024), the preferred antivirals were nirmatrelvir\u2013ritonavir and remdesivir.3<\/a><\/sup> According to the current Pfizer package insert, nirmatrelvir\u2013ritonavir is indicated for the treatment of mild-to-moderate Covid-19 in adults who are at high risk for progression to severe Covid-19, including hospitalization or death.4<\/a><\/sup> It is suggested by Pfizer that three out of four adults with Covid-19 are at high risk.5<\/a><\/sup><\/p>\n\n\n\n

In the 4 years since the Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients (EPIC-HR) trial showed the efficacy of nirmatrelvir\u2013ritonavir in an unvaccinated population at high risk for progression,6<\/a><\/sup> much has changed regarding the prognosis in persons with Covid-19. Owing to increases in the level of preexisting host immunity resulting from previous infection, vaccination, or both, as well as viral evolution from the delta variant to the less pathogenic omicron variants,7<\/a><\/sup> Covid-19 is a less serious condition today than it was in 2021.8<\/a><\/sup>Thus, there is a great need for more recent data on the safety and efficacy of the treatments that are currently available. In this regard, the open-label, randomized, controlled trials of nirmatrelvir\u2013ritonavir in vaccinated, higher-risk adults with Covid-19 reported by Butler et al. in this issue of the Journal<\/em>9<\/a><\/sup> represent a welcome addition to the medical literature.<\/p>\n\n\n\n

The authors report on the current analyses of the comparison of nirmatrelvir\u2013ritonavir with usual care in two separate but closely related community-based adaptive platform trials \u2014 one in the United Kingdom (PANORAMIC) and one in Canada (CanTreatCOVID). The primary end point for these trials was hospitalization or death. An earlier report from the PANORAMIC trial compared molnupiravir with usual care among 25,054 participants and showed an overall incidence of events of 0.8%. The authors concluded that molnupiravir did not affect the incidence of hospitalization or death from Covid-19; however, they noted that participant-reported recovery (a secondary end point) was faster by at least 4 days.10<\/a><\/sup> A similar set of conclusions was drawn from the current analyses in these trials in which 4232 participants were randomly assigned to receive nirmatrelvir\u2013ritonavir plus usual care or usual care alone. It is important to note that the CanTreatCOVID trial was stopped early owing to slow recruitment and because the supply of nirmatrelvir\u2013ritonavir was discontinued. The overall incidence of events (0.7%) was similar to that in the analysis of molnupiravir in the PANORAMIC trial (0.8%); however, the low number of total events in the current analysis (31) makes it difficult to know whether one might have drawn a different conclusion regarding the primary end point with a larger sample size. Although secondary end points are not usually highlighted when the primary end point has not been able to be adequately addressed, it is worth noting that the nirmatrelvir\u2013ritonavir group had a shorter median time to early sustained recovery than the usual-care group (14 vs. 21 days in the United Kingdom and 6 vs. 9 days in Canada) and a more rapid reduction in viral load in a subgroup of participants in the United Kingdom.<\/p>\n\n\n\n

Taken together, these new data indicate that the 89% relative risk reduction seen in the analysis of hospitalizations or death associated with the use of nirmatrelvir\u2013ritonavir in the EPIC-HR trial does not apply to the current circumstances, in which most adults have varying degrees of preexisting immunity and the circulating variants are different. However, one should be cautious not to overinterpret the new data and conclude that nirmatrelvir\u2013ritonavir is not of current value. The enhanced recovery and more-rapid reduction in viral load indicate a degree of clinical efficacy and antiviral activity. Clinicians may become more selective regarding which patients to refer for treatment, but it still would seem prudent to consider antivirals on a case-by-case basis, particularly in older adults, persons with a compromised immune system, and persons for whom more-rapid recovery is a priority.<\/p>\n","protected":false},"excerpt":{"rendered":"

EDITORIAL Same Pill, Different Impact \u2014 Reassessing the […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[24,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/30812"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=30812"}],"version-history":[{"count":1,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/30812\/revisions"}],"predecessor-version":[{"id":30813,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/30812\/revisions\/30813"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=30812"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=30812"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=30812"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}