August 17, 2023

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Antiviral Therapeutics and Vaccines

Safety Profile and Clinical and Virological Outcomes of Nirmatrelvir-Ritonavir Treatment in Patients With Advanced Chronic Kidney Disease and Coronavirus Disease 2019 (COVID-19)
To determine the safety profile and clinical and virological outcomes of nirmatrelvir-ritonavir use at a modified dosage in adults with chronic kidney disease (CKD), a prospective, single-arm, interventional trial recruited patients with eGFR <30 mL/minute/1.73 m2 and on dialysis. Primary outcomes included safety profile, adverse/serious adverse events, and events leading to drug discontinuation. Disease symptoms, virological outcomes by serial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral polymerase chain reaction (PCR) tests, rapid antigen tests, and virological and symptomatic rebound were also recorded. Fifty-nine (69.4%) of the 85 participants had stage 5 CKD and were on dialysis. Eighty (94.1%) completed the full treatment course; 9.4% and 5.9% had adverse and serious adverse events, and these were comparable between those with eGFR < or >30 mL/minute/1.73 m2. The viral load significantly decreased on days 5, 15, and 30 (P < .001 for all), and the reduction was consistent in the subgroup with eGFR <30 mL/minute/1.73 m2. Ten patients had virological rebound, which was transient and asymptomatic. Among patients with CKD, a modified dose of nirmatrelvir-ritonavir is a well-tolerated therapy in mild COVID-19 as it can effectively suppress the SARS-CoV-2 viral load with a favorable safety profile. Virological and symptomatic rebound, although transient with low infectivity, may occur after treatment. Nirmatrelvir-ritonavir should be considered for use in patients with CKD, including stage 5 CKD on dialysis.
The STOP COVID 2 study: Fluvoxamine vs placebo for outpatients with symptomatic COVID-19, a fully-remote randomized controlled trial
This randomized, double-blind, placebo-controlled, fully-remote multi-site clinical trial evaluated whether fluvoxamine prevents clinical deterioration in higher-risk outpatients with acute COVID-19. Between December 2020 and May 2021, non-hospitalized US and Canadian participants with confirmed symptomatic infection received fluvoxamine (50 mg on Day 1, 100 mg twice daily thereafter) or placebo for 15 days. The primary modified intent-to-treat (mITT) population included participants who started the intervention within 7 days of symptom onset with a baseline oxygen saturation ≥ 92%. The primary outcome was clinical deterioration within 15 days of randomization defined as having both (1) shortness of breath (severity ≥ 4 on 0-10 scale or requiring hospitalization), and (2) oxygen saturation <92% on room air or need for supplemental oxygen. A total of 547 participants were randomized and met mITT criteria (n = 272 fluvoxamine, n = 275 placebo). The Data Safety Monitoring Board recommended stopping early for futility related to lower than predicted event rate and declining accrual concurrent with vaccine availability in the U.S. and Canada. Clinical deterioration occurred in 13 (4.8%) participants in the fluvoxamine group and 15 (5.5%) participants in the placebo group (absolute difference at day 15, 0.68% [95% CI, -3.0% to 4.4%]; log rank P = 0.91). This trial did not find fluvoxamine efficacious in preventing clinical deterioration in unvaccinated outpatients with symptomatic COVID-19. It was stopped early and underpowered due to low primary outcome rates.
The effect of corticosteroids, antibiotics, and anticoagulants on the development of post-COVID-19 syndrome in COVID-19 hospitalized patients 6 months after discharge: a retrospective follow up study
To assess the effect of pharmacotherapeutic interventions commonly employed in the management of COVID-19 hospitalized patients on the development of post-COVID-19 syndrome. This study employed two distinct databases, the Medisch Spectrum Twente (MST) clinical database comprising electronic health records of COVID-19 patients hospitalized at MST, and the Post-COVID cohort database which contains follow-up information on the same patients. These databases were integrated to establish the potential relationship between the administration of corticosteroids, antibiotics, or anticoagulants during hospitalization and the occurrence of post-COVID-19 syndrome after a 6-month interval following discharge. A total of 123 patients who were hospitalized due to COVID-19 infection were included in this study. Among these patients, 33 (26.8%) developed post-COVID-19 syndrome which persisted even 6 months after hospital discharge. Multivariate analysis revealed that patients who received treatment with corticosteroids had a significantly lower likelihood (OR 0.32, 95% CI 0.11–0.90) of developing post-COVID-19 syndrome, while no significant association was observed for treatment with antibiotics (OR 1.26, 95% CI 0.47–3.39) or anticoagulants (OR 0.55, 95% CI 0.18–1.71). The findings of this study indicate that corticosteroids exert a significant protective effect against the development of post-COVID-19 syndrome in patients who were hospitalized due to COVID-19 infection. Although a trend towards a protective effect of anticoagulants was observed, it did not reach statistical significance. On the contrary, patients treated with antibiotics were shown to have increased chances of developing post-COVID-19 syndrome, although this effect was also not statistically significant.

Epidemiology

Florida local transmission of dengue cases now 10, New cases reported in Broward and Miami-Dade counties
Florida state health officials reported four additional cases of locally acquired dengue were in the past week from Broward (2) and Miami-Dade (2) counties. This brings the total to 10 so far in 2023–in Miami-Dade (8) and Broward (2) counties, with onsets in January, March, June (3), and July (5). Seven of the cases were identified as dengue virus type 3 (DENV-3) and three were identified as dengue virus type 2 (DENV-2).
Infants Admitted to US Intensive Care Units for RSV Infection During the 2022 Seasonal Peak
The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonincubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days. In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness.
Long term risk of death and readmission after hospital admission with covid-19 among older adults: retrospective cohort study
The covid-19 cohort compared with the influenza cohort was younger (77.9 v 78.9 years, standardized mean difference −0.12) and had a lower proportion of women (51.7% v 57.3%, −0.11). Both groups had a similar proportion of black beneficiaries (10.3% v 8.1%, 0.07) and beneficiaries with dual Medicaid-Medicare eligibility status (20.1% v 19.2%; 0.02). The covid-19 cohort had a lower comorbidity burden, including atrial fibrillation (24.3% v 29.5%, −0.12), heart failure (43.4% v 49.9%, −0.13), and chronic obstructive pulmonary disease (39.2% v 52.9%, −0.27). After weighting, the covid-19 cohort had a higher risk (ie, cumulative incidence) of all cause death at 30 days (10.9% v 3.9%; standardized risk difference 7.0%, 95% confidence interval 6.8% to 7.2%), 90 days (15.5% v 7.1%; 8.4%, 8.2% to 8.7%), and 180 days (19.1% v 10.5%; 8.6%, 8.3% to 8.9%) compared with the influenza cohort. The covid-19 cohort also experienced a higher risk of hospital readmission at 30 days (16.0% v 11.2%; 4.9%, 4.6% to 5.1%) and 90 days (24.1% v 21.3%; 2.8%, 2.5% to 3.2%) but a similar risk at 180 days (30.6% v 30.6%;–0.1%, −0.5% to 0.3%). Over the study period, the 30 day risk of death for patients discharged after a covid-19 admission decreased from 17.9% to 7.2%. Medicare beneficiaries who were discharged alive after a covid-19 hospital admission had a higher post-discharge risk of death compared with historical influenza controls; this difference, however, was concentrated in the early post-discharge period. The risk of death for patients discharged after a covid-19 related hospital admission substantially declined over the course of the pandemic.
Long COVID and Significant Activity Limitation Among Adults, by Age — United States, June 1–13, 2022, to June 7–19, 2023
Long COVID includes a wide range of ongoing symptoms that can last for weeks, months, or years following SARS-CoV-2 infection. Prevalence of long COVID among noninstitutionalized U.S. adults aged ≥18 years decreased from 7.5% (95% CI = 7.1–7.9) during June 1–13, 2022 to 6.0% (95% CI = 5.7–6.3) during June 7–19, 2023 and from 18.9% (95% CI = 17.9–19.8) to 11.0% (95% CI = 10.4–11.6) among adults reporting previous COVID-19. After an initial decline, prevalence remained unchanged beginning January 4–16, 2023. Approximately one quarter of adults with long COVID report significant activity limitations. COVID-19 prevention efforts, including staying up to date with recommended COVID-19 vaccination and planning for long COVID symptom management and health care service needs, remain important.
Incidence of diabetes following COVID-19 vaccination and SARS-CoV-2 infection in Hong Kong: A population-based cohort study
The risk of incident diabetes following Coronavirus Disease 2019 (COVID-19) vaccination remains to be elucidated. Also, it is unclear whether the risk of incident diabetes after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is modified by vaccination status or differs by SARS-CoV-2 variants. Researchers evaluated the incidence of diabetes following mRNA (BNT162b2), inactivated (CoronaVac) COVID-19 vaccines, and after SARS-CoV-2 infection. In this population-based cohort study, individuals without known diabetes were identified from an electronic health database in Hong Kong. The first cohort included people who received ≥1 dose of COVID-19 vaccine and those who did not receive any COVID-19 vaccines up to September 2021. The second cohort consisted of confirmed COVID-19 patients and people who were never infected up to March 2022. Both cohorts were followed until August 15, 2022. A total of 325,715 COVID-19 vaccine recipients (CoronaVac: 167,337; BNT162b2: 158,378) and 145,199 COVID-19 patients were 1:1 matched to their respective controls using propensity score for various baseline characteristics. We also adjusted for previous SARS-CoV-2 infection when estimating the conditional probability of receiving vaccinations, and vaccination status when estimating the conditional probability of contracting SARS-CoV-2 infection. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident diabetes were estimated using Cox regression models. In the first cohort, researchers identified 5,760 and 4,411 diabetes cases after receiving CoronaVac and BNT162b2 vaccines, respectively. Upon a median follow-up of 384 to 386 days, there was no evidence of increased risks of incident diabetes following CoronaVac or BNT162b2 vaccination (CoronaVac: 9.08 versus 9.10 per 100,000 person-days, HR = 0.998 [95% CI 0.962 to 1.035]; BNT162b2: 7.41 versus 8.58, HR = 0.862 [0.828 to 0.897]), regardless of diabetes type. In the second cohort, we observed 2,109 cases of diabetes following SARS-CoV-2 infection. Upon a median follow-up of 164 days, SARS-CoV-2 infection was associated with significantly higher risk of incident diabetes (9.04 versus 7.38, HR = 1.225 [1.150 to 1.305])—mainly type 2 diabetes—regardless of predominant circulating variants, albeit lower with Omicron variants (p for interaction = 0.009). The number needed to harm at 6 months was 406 for 1 additional diabetes case. Subgroup analysis revealed no evidence of increased risk of incident diabetes among fully vaccinated COVID-19 survivors. Main limitations of our study included possible misclassification bias as type 1 diabetes was identified through diagnostic coding and possible residual confounders due to its observational nature. There was no evidence of increased risks of incident diabetes following COVID-19 vaccination. The risk of incident diabetes increased following SARS-CoV-2 infection, mainly type 2 diabetes. The excess risk was lower, but still statistically significant, for Omicron variants. Fully vaccinated individuals might be protected from risks of incident diabetes following SARS-CoV-2 infection.
Diabetes following SARS-CoV-2 infection: Incidence, persistence, and implications of COVID-19 vaccination. A cohort study of fifteen million people
In the pre-vaccination cohort, aHRS for T2DM incidence after COVID-19 (compared to before or without diagnosis) declined from 3.01 (95% CI: 2.76,3.28) in weeks 1-4 to 1.24 (1.12,1.38) in weeks 53-102. aHRS were higher in unvaccinated than vaccinated people (4.86 (3.69,6.41)) versus 1.42 (1.24,1.62) in weeks 1-4) and for hospitalized COVID-19 (pre-vaccination cohort 21.1 (18.8,23.7) in weeks 1-4 declining to 2.04 (1.65,2.51) in weeks 52-102), than non-hospitalized COVID-19 (1.45 (1.27,1.64) in weeks 1-4, 1.10 (0.98,1.23) in weeks 52-102). T2DM persisted for 4 months after COVID-19 for ∼73% of those diagnosed. Patterns were similar for Type 1 diabetes, though excess incidence did not persist beyond a year post-COVID-19. Elevated T2DM incidence after COVID-19 is greater, and persists longer, in hospitalized than non-hospitalized people. It is markedly less apparent post-vaccination. Testing for T2DM after severe COVID-19 and promotion of vaccination are important tools in addressing this public health problem. There is a 30-50% elevated T2DM incidence post-COVID-19, but researchers report the novel finding that there is elevated incidence beyond one-year post-diagnosis. Elevated T1DM incidence did not appear to persist beyond a year, which may explain why previous studies disagree. For the first time in a general-population dataset, researchers demonstrate that COVID-19 vaccination reduces, but does not entirely ameliorate, excess diabetes incidence after COVID-19. This supports a policy of universal vaccination and suggests that other public health activities, such as enhanced diabetes screening after severe COVID-19, may be warranted, particularly in unvaccinated people.