December 5, 2024

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Flu

Estimated Effectiveness of Influenza Vaccines in Preventing Secondary Infections in Households
In this prospective case-ascertained cohort study of 699 primary cases and 1,581 household contacts, the secondary infection risk of influenza infection among household contacts was 18.8% (95% CI, 15.9% to 22.0%). The estimated effectiveness of influenza vaccines for preventing secondary infections among household contacts was 21.0% (95% CI, 1.4% to 36.7%). A case-ascertained household study is where the households are recruited after an 'index case' is identified, and household cohort studies, are where a household is enrolled before.
Benefit of Early Oseltamivir Therapy for Adults Hospitalized with Influenza A: An Observational Study
These are the results of a multicenter US observational study that prospectively enrolled adults (aged ≥18 years) hospitalized with laboratory-confirmed influenza at 24 hospitals during October 1, 2022–July 21, 2023. A multivariable proportional odds model was used to compare peak pulmonary disease severity (no oxygen support, standard supplemental oxygen, high-flow oxygen/non-invasive ventilation, invasive mechanical ventilation, or death) after the day of hospital admission among patients starting oseltamivir treatment on the day of admission (early) versus those who did not (late or not treated), adjusting for baseline (admission day) severity, age, sex, site, and vaccination status. Multivariable logistic regression models were used to evaluate the odds of intensive care unit (ICU) admission, acute kidney replacement therapy or vasopressor use, and in-hospital death. A total of 840 influenza-positive patients were analyzed, including 415 (49%) who started oseltamivir treatment on the day of admission, and 425 (51%) who did not. Compared with late or not treated patients, those treated early had lower peak pulmonary disease severity (proportional aOR: 0.60, 95% CI: 0.49–0.72), and lower odds of intensive care unit admission (aOR: 0.24, 95% CI: 0.13–0.47), acute kidney replacement therapy or vasopressor use (aOR: 0.40, 95% CI: 0.22–0.67), and in-hospital death (aOR: 0.36, 95% CI: 0.18–0.72).

COVID: Children, Pregnant Individuals, other Vulnerable Populations

Maternal Infection of SARS-CoV-2 During the First and Second Trimesters Leads to Newborn Telomere Shortening
Telomere shortening is associated with aging, mortality, and aging-related diseases in experimental animals. Longer telomeres may be associated with lifespan in humans. Shorter telomeres maybe a shortened lifespan and from some other studies, maybe an increased risk of cancer. Here investigators recruited 413 normally delivered newborns whose mothers were either non-infected or infected with SARS-CoV-2 during different trimesters of pregnancy (otherwise healthy) and measured the Telomere length (TL) fo the babies using cord blood (CB). Control (non-infected maternal) newborn TL was significantly longer than that from maternal infection (1.568 ± 0.340 vs 1.390 ± 0.350, P = 0.005). Such shorter TL was observed only if maternal infection of SARS-CoV-2 occurred in the first and second trimesters of pregnancy (1.261 ± 0.340 and 1.346 ± 0.353, P < 0.0001 and 0.001, respectively). There were no differences in TL between controls and infection at the third trimester (1.568 ± 0.340 vs 1.565 ± 0.329, P > 0.05). Across the first trimester, there was a positive correlation between newborn TL and gestational weeks with maternal infection, suggesting that the earlier maternal infection occurs, the worse effect is taken on fetal telomere homeostasis. Placental senescence coupled with the downregulated expression of telomerase reverse transcriptase was significantly more frequent from the maternal infection at the first trimester. There were no differences in IL-6, C reactive protein and other cytokine levels in CB and maternal serum or placentas. Conclusions: Maternal SARS-CoV-2 infection at the first and second trimesters leads to significantly shorter TL and earlier infection causes much more severe TL damage. The infection-mediated cell senescence and other histopathological abnormalities result in defective placental function through which fetal telomere homeostasis is impaired. Thus, vaccination against COVID-19 should be done in advance for women who plan pregnancy.

COVID: Active Vaccination/Immunity

The Effect of Pre-COVID and Post-COVID Vaccination on Long COVID: A Systematic Review and Meta-analysis
Certain characteristics such as being hospitalized, female sex, higher body mass index, smoking, preexisting comorbidities, not receiving early antiviral therapy, and not being vaccinated are associated with an increased risk of Long COVID. Certain genetic factors have also been identified. Here is meta-analysis involving more than 14 million people that COVID-19 vaccination is associated with a lower risk of developing Long COVID, with two doses reducing the odds by 24%. After reviewing the literature these investigators obtained 6,717 studies and after sorting through these they systematically reviewed 25 studies. They included data from 19 studies that reported pre-COVID vaccination, and six studies reported post-COVID vaccination.
Delayed Induction of Noninflammatory SARS-CoV-2 Spike-Specific IgG4 Antibodies Detected One Year After BNT162b2 Vaccination in Children
Humoral immune responses after BNT162b2 vaccination are predominantly composed of immunoglobulin (Ig) G1 and IgG3 subclass antibodies. Previously described in adults, S1-specific and receptor-binding domain–specific IgG4 levels increase significantly one year after the second BNT162b2 vaccination, and now these investigators are reporting this in children 5-11 years of age. This may be mRNA vaccine specific as it has not been observed after other vaccinations such as with homologous vaccination with adenovirus-based and Modified Vaccinia virus Ankara (MVA)–based SARS-CoV-2 vaccines. In general, the protective humoral response, so the protective antibodies after vaccination or infection we think is predominantly due to IgG1 and IgG3 antibodies, both capable of mediating effector functions such as antibody-dependent cytotoxicity, phagocytosis and complement activation via their fragment crystallizable (Fc) region. Real-life data and passive and active immunization studies in mice suggest that the engagement of the Fc region with Fc gamma receptors is required for vaccine-induced antibody-mediated protection. IgG4, as the least abundant IgG subclass in humans, has some unique structural and functional features resulting in them being described as “blocking” and “anti-inflammatory” antibodies.
Relative effectiveness of homologous NVX-CoV2373 and BNT162b2 COVID-19 vaccinations in South Korea
To estimate the relative effectiveness of NVX-CoV2373 versus BNT162b2 (Pfizer-BioNTech) in preventing SARS-CoV-2 infection and severe COVID-19 disease during the Omicron variant dominance in South Korea, investigators conducted a retrospective cohort-study among ≥12-year-olds. Among homologous primary-series NVX-CoV2373 versus BNT162b2 recipients at Day 180 post-vaccination, the aHR was 0.90 (95% CI: 0.87-0.93) for all laboratory-confirmed and 0.65 (95% CI: 0.48-0.88) for severe infections. Among homologous first-booster recipients, it was 1.15 (95% CI: 1.01-1.30) for all laboratory-confirmed and 0.39 (95% CI: 0.20-0.75) for severe infections.
Remdesivir Effectiveness in Reducing the Risk of 30-day Readmission in Vulnerable Patients Hospitalized for COVID-19: A Retrospective US Cohort Study Using Propensity Scores
These are results from a retrospective study that utilized the US PINC AI Healthcare Database to identify adult patients discharged alive from an index COVID-19 hospitalization between December 1, 2021 and February 29, 2024. Odds of 30-day COVID-19-related readmission to the same hospital were compared between patients who received remdesivir vs those not, after balancing characteristics of two groups. Of 326,033 patients hospitalized for COVID-19 during study period, 210,586 patients met the eligibility criteria. Of these, 109,551 (52%) patients were treated with remdesivir. They reported a lower odds of 30-day COVID-19-related readmission in patients who received remdesivir vs those who did not, in the overall population (3.3% vs 4.2%, respectively; odds ratio [95% confidence interval]: 0.78 [0.75–0.80]), elderly population (3.7% vs 4.7%, respectively; 0.78 [0.75–0.81]), and those with underlying immunocompromising conditions (5.3% vs 6.2%, respectively; 0.86 [0.80–0.92]). These results were consistent irrespective of supplemental oxygen requirements.

COVID: The Late Phase/PASC/Long COVID

Transcutaneous Electrical Nerve Stimulation for Fibromyalgia-like Syndrome in Patients with Long-COVID: A Pilot Randomized Clinical Trial
Authors investigated the effect of Transcutaneous Electrical Nerve Stimulation (TENS) for fibromyalgia-like symptoms including chronic widespread musculoskeletal pain, fatigue, and/or gait impairment in twenty-five individuals with long-COVID. Participants were randomized to a high dose (intervention group, IG) or low dose (placebo group, PG) TENS device. Both groups received daily 3–5 h of TENS therapy for four weeks. They used the Brief Pain Inventory to assess functional interference from pain (BPI-I), and pain severity (BPI-S). They used the global fatigue index (GFI) to assess functional interference from fatigue. Wearable technology measured gait parameters during three 30-feet consecutive walking tasks. At four-weeks, the IG (that is the intervention group) exhibited a greater decrease in BPI-I (functional interference from pain) compared to the PG (placebo group) (mean difference = 2.61, p = 0.008), and improved in gait parameters including stride time (4-8%, test condition dependent), cadence (4-10%, depending on condition), and double-support phase (12% in dual-task) when compared to baseline. A sub-group meeting the 2010 American College of Rheumatology Fibromyalgia diagnostic criteria undergoing high-dose TENS showed GFI improvement at 4-weeks from baseline (mean change = 6.08, p = 0.005). They conclude that daily TENS therapy showed potential in reducing functional interference from pain, fatigue, and gait alterations in long-COVID individuals. Limitations: This study encountered limitations, including a small sample size and substantial missing data (n = 11 patients) in the second/unblinded phase (weeks four to eight) due to challenges such as patients managing in-person clinic visits and coordinating appointments with specialists in pulmonology, cardiology, and rheumatology. The prevalent ‘brain fog’ hindered participants from remembering study-related tasks, impacting questionnaire completion and appointment tracking. The short TENS therapy duration and unanalyzed adjuvant medications effects for pain and fatigue added complexity. While five patients (PG, n = 4; IG, n = 1) received concurrent physical therapy, detailed session information was not collected. Unblinding at the four-week visit may have increased loss to follow-up and decreased therapy adherence.
Mitigating the Risks of Post-acute Sequelae of SARS-CoV-2 Infection (PASC) with Intranasal Chlorpheniramine: Perspectives from the ACCROS Studies
This prospective survey study included 259 participants in ACROSS I and III RCTs. They compared the effect of Intranasal chlorpheniramine (iCPM) versus placebo on the reduction of PASC symptoms. A PASC questionnaire containing 17 questions regarding the most common PASC symptoms was used in this study. The iCPM cohort had a lower proportion of patients with fatigue or tiredness vs. placebo (0 Vs 17, 21, p < 0.001). iCPM cohort had a lower proportion of patients with difficulty concentrating or mental confusion (0 vs. 22, 27, p < 0.001). iCPM cohort had also a lower number of patients with difficulty in the ability to perform daily activities or work vs. placebo (1 Vs 38, 48, p < 0.001). A smaller number of patients in the iCPM cohort sought medical attention for PACS symptoms compared to placebo (0 vs. 48, 68, p < 0.001).
Measurement of Circulating Viral Antigens Post-SARS-CoV-2 Infection in a Multicohort Study
Plasma and serum samples were collected from adults participating in four independent studies at different time points, ranging from several days up to 14 months post-SARS-CoV-2 infection. The primary outcome measure was to quantify SARS-CoV-2 antigens, including the S1 subunit of spike, full-length spike, and nucleocapsid, in participant samples. The presence of 34 commonly reported PASC symptoms during the post-acute period was determined from participant surveys or chart reviews of electronic health records. Of the 1,569 samples analyzed from 706 individuals infected with SARS-CoV-2, 21% (95% CI, 18-24%) were positive for either S1, spike, or nucleocapsid. Spike was predominantly detected, and the highest proportion of samples was spike positive (20%; 95% CI, 18-22%) between four and seven months postinfection. In total, 578 participants (82%) reported at least one of the 34 PASC symptoms included in our analysis ≥1 month postinfection. Cardiopulmonary, musculoskeletal, and neurologic symptoms had the highest reported prevalence in over half of all participants, and among those participants, 43% (95% CI, 40-45%) on average were antigen-positive. Contrast this to the finding here that among the participants who reported no ongoing symptoms, antigen was ‘only ‘ detected in 28 participants (21%). The presence of antigen was associated with the presence of one or more PASC symptoms, adjusting for sex, age, time postinfection, and cohort (OR, 1.8; 95% CI, 1.4-2.2).