April 11, 2024

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COVID

Rural-urban Differences in Long-term Mortality and Readmission Following COVID-19 Hospitalization, 2020 to 2023
Investigators compared long-term mortality and readmission rates after COVID-19 hospitalization based on rural-urban status and assessed the impact of COVID-19 vaccination introduction on clinical outcomes by rurality. The main analysis involved 9,325 COVID-19 hospitalized patients: 31% were from 187 rural counties in 31 states; 69% from 234 urban counties in 44 states; There were 1,738 deaths and 2,729 readmissions. During a median follow-up of 602 days, rural residence was associated with a 22% higher all-cause mortality (Log-rank, P<0.001; hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.10-1.34, P<0.001), and a trend toward a higher readmission rate (Log-rank, P=0.038; HR 1.06; 95% CI 0.98-1.15, P=0.130). The results remained consistent in the sensitivity analysis and in both pre- and post-vaccination time periods.

COVID: Early Viral phase

Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with COVID-19
These are the results of a phase 2–3 trial, with randomly assigned adults who had confirmed COVID-19 with symptom onset within the past five days in a 1:1 ratio to receive nirmatrelvir–ritonavir or placebo every 12 hours for five days. Patients who were fully vaccinated against COVID-19 and who had at least one risk factor for severe disease, as well as patients without such risk factors who had never been vaccinated against COVID-19 or had not been vaccinated within the previous year, were eligible for participation. Participants logged the presence and severity of prespecified COVID-19 signs and symptoms daily from day one through day 28. The primary end point was the time to sustained alleviation of all targeted COVID-19 signs and symptoms. COVID-19–related hospitalization and death from any cause were also assessed through day 28. There were 1296 participants who underwent randomization and 1288 received at least one dose of nirmatrelvir–ritonavir (654 participants) or placebo (634 participants) and had at least one postbaseline visit. The median time to sustained alleviation of all targeted signs and symptoms of COVID-19 was 12 days in the nirmatrelvir–ritonavir group and 13 days in the placebo group (P=0.60). There was a 50% reduction in the composite end-point of hospitalization or all-cause mortality associated with receipt of paxlovid, (0.8%) in the nirmatrelvir–ritonavir group and (1.6%) in the placebo group (95% CI, −2.0 to 0.4). The percentages of participants with adverse events were similar in the two groups.

COVID: The Late Phase/PASC/Long COVID

Brain and Cognitive Changes in Patients with Long COVID Compared with Infection-recovered Control Subjects
This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in Long COVID and the potential association between them. In this study, 83 patients with persistent neurological symptoms after COVID-19 were recruited, and 22 now healthy controls chosen because they had suffered COVID-19 but did not experience persistent neurological symptoms. Patients and controls were matched for age, sex and educational level. All participants were assessed by clinical interview, comprehensive standardized neuropsychological tests and structural MRI. The mean global cognitive function of patients with Long COVID assessed by using the Addenbrooke’s cognitive examination III (ACE III) screening test. Think of this as an open access alternative to the mini-mental status test of MMSE. (Overall Cognitive level - OCLz= -0.39± 0.12) was significantly below the infection recovered-controls (OCLz= +0.32± 0.16, p< 0.01). They observed that 48% of patients with Long COVID had episodic memory deficit, with 27% also impaired overall cognitive function, especially attention, working memory, processing speed and verbal fluency. The MRI examination included grey matter morphometry and whole brain structural connectivity analysis. Compared to infection recovered controls, patients had thinner cortex in a specific cluster centered on the left posterior superior temporal gyrus. In addition, lower fractional anisotropy (FA) and higher radial diffusivity (RD) were observed in widespread areas of the patients’ cerebral white matter relative to these controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency. “Our data indicate a specific profile of cognitive dysfunction in neurological Long COVID characterized by impairment in episodic memory, attention, processing speed, and verbal fluency,” Víctor M. Serrano del Pueblo, University of Castilla-La Mancha, Albacete, Spain, and colleagues. “This altered cognitive performance is associated with reduced integrity of specific white matter regions involved in the interconnection of distal regions responsible for these cognitive functions.”
Incident Allergic Diseases in Post-COVID-19 Condition: Multinational Cohort Studies from South Korea, Japan and the UK
The investigators used nationwide claims-based cohorts in South Korea (K-CoV-N; n = 836,164; main cohort) and Japan (JMDC; n = 2,541,021; replication cohort A) and the UK Biobank cohort (UKB; n = 325,843; replication cohort B) and used 1:5 propensity score matching. Among the 836,164 individuals in the main cohort (mean age, 50.25 years [SD, 13.86]; 372,914 [44.6%] women), 147,824 were infected with SARS-CoV-2 during the follow-up period (2020−2021). The risk of developing allergic diseases, beyond the first 30 days of diagnosis of COVID-19, significantly increased (HR, 1.20; 95% CI, 1.13−1.27), notably in asthma (HR, 2.25; 95% CI, 1.80−2.83) and allergic rhinitis (HR, 1.23; 95% CI, 1.15−1.32). This risk gradually decreased over time, but it persisted throughout the follow-up period (≥6 months). In addition, the risk increased with increasing severity of COVID-19. Notably, COVID-19 vaccination of at least two doses had a protective effect against subsequent allergic diseases (HR, 0.81; 95% CI, 0.68−0.96). Similar findings were reported in the replication cohorts.
Functional Limitations and Exercise Intolerance in Patients with Post-COVID Condition - A Randomized Crossover Clinical Trial
These are the results of a small randomized crossover clinical trial of 31 patients with PCC and 31 matched control participants. Nonhospitalized patients without concomitant diseases and with persistent (≥3 months) symptoms, including postexertional malaise, after SARS-CoV-2 infection were recruited in Sweden from September 2022 to July 2023. Age- and sex-matched control participants were also recruited. After comprehensive physiologic characterization, participants completed three exercise trials (high-intensity interval training [HIIT], moderate-intensity continuous training [MICT], and strength training [ST]) in a randomized order. Symptoms were reported at baseline, immediately after exercise, and 48 hours after exercise. The primary outcome was between-group differences in changes in fatigue symptoms from baseline to 48 hours after exercise, assessed via the visual analog scale (VAS). Questionnaires, cardiopulmonary exercise testing, inflammatory markers, and physiologic characterization provided information on the physiologic function of patients with PCC. They reported that patients with PCC reported more symptoms than controls at all time points. However, there was no difference between the groups in the worsening of fatigue in response to the different exercises. They noted that four patients with PCC (13%) had postural orthostatic tachycardia, and 18 of 29 (62%) showed signs of myopathy as determined by neurophysiologic testing. The authors conclude by saying: “The findings suggest cautious exercise adoption could be recommended to prevent further skeletal muscle deconditioning and health impairment in patients with PCC.” The context for this study is that international guidelines from public health organizations, including the World Health Organization, caution against graded exercise for treating patients with post-exertional symptom exacerbation (PESE), a commonly reported feature of post–COVID-19 condition (PCC). These recommendations are provided despite the well-documented deleterious effects of physical inactivity and its close association with secondary health conditions and deterioration in quality of life.