Paxlovid in patients who are immunocompromised and hospitalised with SARS-CoV-2 infection.
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ABSTRACT:
SUBMITTER: Sun F
PROVIDER: S-EPMC9282758 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
Publications
Paxlovid in patients who are immunocompromised and hospitalised with SARS-CoV-2 infection.
Sun Fangfang F Lin Yanwei Y Wang Xiaodong X Gao Yuan Y Ye Shuang S
The Lancet. Infectious diseases 20220714 9
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Project description:BackgroundNirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities.MethodsWe conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated.Findings264 patients (mean age, 70.35 years; 122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27; 95% CI -2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group; ARD, -0.62; 95% CI -2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39; serious adverse events, 4.55% vs. 3.788%, P = 0.76).InterpretationPaxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS-CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities.FundingNational Natural Science Foundation of China (grant number: 82172152, 81873944).
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Project description:BackgroundMost patients with SARS-CoV-2 are non-infectious within 2 weeks, though viral RNA may remain detectable for weeks. However there are reports of persistent SARS-CoV-2 infection, with viable virus and ongoing infectivity months after initial detection. Beyond individuals, viral evolution during persistent infections may be accelerated, driving emergence of mutations associated with viral variants of concern. These patients often do not meet inclusion criteria for clinical trials, meaning clinical and virologic characteristics, and optimal management strategies are poorly evidence-based.MethodsWe analysed cases of SARS-CoV-2 infection from a regional testing laboratory in South-West England between March 2020 and December 2021, with at least two SARS-CoV-2 positive samples separated by ≥ 56 days were identified. Excluding those with confirmed or likely re-infection, we identified patients with persistent infection, characterised by an ongoing clinical syndrome consistent with COVID-19 alongside monophyletic viral lineage of SARS-CoV-2. We examined clinical and virologic characteristics, treatment, and outcome. We further performed a literature review investigating cases of persistent SARS-CoV-2 infection, reviewing patient characteristics and treatment.ResultsWe identified six patients with persistent SARS-CoV-2 infection. All were hypogammaglobulinaemic and had underlying haematological malignancy, with four having received B-cell depleting therapy. Evidence of viral evolution, including accrual of mutations associated with variants of concern, was demonstrated in five cases. Four patients ultimately cleared SARS-CoV-2. In two patients, clearance followed treatment with casirivimab/imdevimab. Both survived beyond thirty days following viral clearance, having experienced infections of 305- and 269-days duration respectively, after failed attempts at clearance with alternative therapies. We found 60 cases of confirmed persistent infection in the literature, with a further 31 probable cases. Of those, 80% of patients treated with monoclonal antibodies cleared SARS-CoV-2, and none died.ConclusionHaematological malignancy and patients receiving B-cell depleting therapies represent key groups at risk of persistent SARS-CoV-2 infection. Throughout persistent infection, SARS-CoV-2 can evolve rapidly, giving rise to significant mutations, including those implicated in variants of concern. Monoclonal antibodies appear to be a promising therapeutic option, potentially in combination with antivirals, crucial for individuals, and for public health.
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