Effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system.

BACKGROUND: In the USA, oral nirmatrelvir-ritonavir is authorised for use in patients aged 12 years or older with mild-to-moderate COVID-19 who are at risk of progression to severe disease and hospitalisation. We aimed to establish the effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and death in people with COVID-19 in an outpatient prescribing context in the USA. METHODS: In this matched observational outpatient cohort study in the Kaiser Permanente Southern California (CA, USA) health-care system, data were extracted from electronic health records of non-hospitalised patients aged 12 years or older who received a positive SARS-CoV-2 PCR test result (their index test) between April 8 and Oct 7, 2022, and had not received another positive test result within the preceding 90 days. We compared outcomes between people who received nirmatrelvir-ritonavir and those who did not receive nirmatrelvir-ritonavir by matching cases by date, age, sex, clinical status (including care received, the presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), vaccination history, comorbidities, health-care seeking during the previous year, and BMI. Our primary endpoint was the estimated effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions or death within 30 days of a positive test for SARS-CoV-2. FINDINGS: 7274 nirmatrelvir-ritonavir recipients and 126 152 non-recipients with positive SARS-CoV-2 tests were included in our study. 5472 (75·2%) treatment recipients and 84 657 (67·1%) non-recipients were tested within 5 days of symptom onset. Nirmatrelvir-ritonavir had an overall estimated effectiveness of 53·6% (95% CI 6·6-77·0) in preventing hospital admission or death within 30 days of a positive test for SARS-CoV-2, which increased to 79·6% (33·9-93·8) when nirmatrelvir-ritonavir was dispensed within 5 days of symptom onset. Within the subgroup of patients tested within 5 days of symptom onset and whose treatment was dispensed on the day of their test, the estimated effectiveness of nirmatrelvir-ritonavir was 89·6% (50·2-97·8). INTERPRETATION: In a setting with high levels of COVID-19 vaccine uptake, nirmatrelvir-ritonavir effectively reduced the risk of hospital admission or death within 30 days of a positive outpatient SARS-CoV-2 test. FUNDING: US Centers for Disease Control and Prevention and US National Institutes of Health.

Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome.

Expansion of the SARS-CoV-2 BA.4 and BA.5 Omicron subvariants in populations with prevalent immunity from prior infection and vaccination, and associated burden of severe COVID-19, has raised concerns about epidemiologic characteristics of these lineages including their association with immune escape or severe clinical outcomes. Here we show that BA.4/BA.5 cases in a large US healthcare system had at least 55% (95% confidence interval: 43-69%) higher adjusted odds of prior documented infection than time-matched BA.2 cases, as well as 15% (9-21%) and 38% (27-49%) higher adjusted odds of having received 3 and ≥4 COVID-19 vaccine doses, respectively. However, after adjusting for differences in epidemiologic characteristics among cases with each lineage, BA.4/BA.5 infection was not associated with differential risk of emergency department presentation, hospital admission, or intensive care unit admission following an initial outpatient diagnosis. This finding held in sensitivity analyses correcting for potential exposure misclassification resulting from unascertained prior infections. Our results demonstrate that the reduced severity associated with prior (BA.1 and BA.2) Omicron lineages, relative to the Delta variant, has persisted with BA.4/BA.5, despite the association of BA.4/BA.5 with increased risk of breakthrough infection among previously vaccinated or infected individuals.

Retrospective cohort study to assess the association between treatment with tocilizumab and mortality among mechanically ventilated patients with COVID-19.

OBJECTIVES: Assess the association between tocilizumab administration and clinical outcomes among mechanically ventilated patients with COVID-19 pneumonia. DESIGN: Retrospective cohort study. SETTING: Large integrated health system with 9 million members in California, USA. PARTICIPANTS: 4185 Kaiser Permanente members hospitalised with COVID-19 pneumonia requiring invasive mechanical ventilation (IMV). INTERVENTIONS: Receipt of tocilizumab within 10 days of initiation of IMV. OUTCOME MEASURES: Using a retrospective cohort of consecutive patients hospitalised with COVID-19 pneumonia who required IMV in a large integrated health system in California, USA, we assessed the association between tocilizumab administration and 28-day mortality, time to extubation from IMV and time to hospital discharge. RESULTS: Among 4185 patients, 184 received tocilizumab and 4001 patients did not receive tocilizumab within 10 days of initiation of IMV. After inverse probability weighting, baseline characteristics were well balanced between groups. Patients treated with tocilizumab had a similar risk of death in the 28 days after intubation compared with patients not treated with tocilizumab (adjusted HR (aHR), 1.21, 95% CI 0.98 to 1.50), but did have a significantly longer time-to-extubation (aHR 0.71; 95% CI 0.57 to 0.88) and time-to-hospital-discharge (aHR 0.66; 95% CI 0.50 to 0.88). However, patients treated with tocilizumab ≤2 days after initiation of IMV had a similar risk of mortality (aHR 1.47; 95% CI 0.96 to 2.26), but significantly shorter time-to-extubation (aHR 0.37; 95% CI 0.23 to 0.58) and time-to-hospital-discharge (aHR 0.31; 95% CI CI 0.17 to 0.56) compared with patients treated with tocilizumab 3-10 days after initiation of IMV. CONCLUSIONS: Among mechanically ventilated patients with COVID-19, the risk of death in the 28-day follow-up period was similar, but time-to-extubation and time-to-hospital-discharge were longer in patients who received tocilizumab within 10 days of initiation of IMV compared with patients who did not receive tocilizumab.

Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization.

BACKGROUND: Obesity, race/ethnicity, and other correlated characteristics have emerged as high-profile risk factors for adverse coronavirus disease 2019 (COVID-19)-associated outcomes, yet studies have not adequately disentangled their effects. OBJECTIVE: To determine the adjusted effect of body mass index (BMI), associated comorbidities, time, neighborhood-level sociodemographic factors, and other factors on risk for death due to COVID-19. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Southern California, a large integrated health care organization. PATIENTS: Kaiser Permanente Southern California members diagnosed with COVID-19 from 13 February to 2 May 2020. MEASUREMENTS: Multivariable Poisson regression estimated the adjusted effect of BMI and other factors on risk for death at 21 days; models were also stratified by age and sex. RESULTS: Among 6916 patients with COVID-19, there was a J-shaped association between BMI and risk for death, even after adjustment for obesity-related comorbidities. Compared with patients with a BMI of 18.5 to 24 kg/m2, those with BMIs of 40 to 44 kg/m2 and greater than 45 kg/m2 had relative risks of 2.68 (95% CI, 1.43 to 5.04) and 4.18 (CI, 2.12 to 8.26), respectively. This risk was most striking among those aged 60 years or younger and men. Increased risk for death associated with Black or Latino race/ethnicity or other sociodemographic characteristics was not detected. LIMITATION: Deaths occurring outside a health care setting and not captured in membership files may have been missed. CONCLUSION: Obesity plays a profound role in risk for death from COVID-19, particularly in male patients and younger populations. Our capitated system with more equalized health care access may explain the absence of effect of racial/ethnic and socioeconomic disparities on death. Our data highlight the leading role of severe obesity over correlated risk factors, providing a target for early intervention. PRIMARY FUNDING SOURCE: Roche-Genentech.