February 29, 2024

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COVID: Early Viral phase

Effectiveness of Nirmatrelvir-ritonavir on Severe Outcomes of COVID-19 in the Era of Vaccination and Omicron: An Updated Meta-analysis
A total of 32 studies were included in the meta-analysis. Pooled risk ratio (RR) for the effect of NR on mortality was 0.36 (95% confidence interval [CI]: 0.25−0.52), hospitalization , 0.43 (CI: 0.37−0.51), hospitalization and/or mortality 0.52 (CI: 0.45−0.61), and progression to severe disease was 0.54 (CI: 0.41−0.73). A subgroup analysis on vaccinated patients indicated lower effectiveness of NR on mortality (RR: 0.55, CI: 0.45−0.68), but similar effectiveness for hospitalization, hospitalization and/or mortality, or progression to severe disease (RR: 0.52, 0.58, and 0.66, respectively). The authors comment that “This updated meta-analysis robustly confirms the protective effects of NR on severe COVID-19 outcomes.”
Randomized Controlled Trial of Molnupiravir SARS-CoV-2 Viral and Antibody Response in At-risk Adult Outpatients
In this study non-hospitalized participants within five days of SARS-CoV-2 symptoms were randomized to receive molnupiravir (n = 253) or not (n = 324). Here, they studied viral and antibody dynamics and the effect of molnupiravir on viral whole genome sequence from 1,437 viral genomes. Not just PCR as they collected swabs in viral transport medium which were cultured with Calu-3 cells. Using a high throughput culture method with screening over seven days for evidence of cytopathic effect and the presence of SARS CoV-2 by lateral flow immunochromatography and PCR, they were able to recover viable virus. The positive culture rate for samples collected during treatment (Days 2-5) was 10.4% with molnupiravir versus 15.2% for Usual Care. Post-treatment viability (Days 6-20) dropped to 5.1% for molnupiravir and 2.5% for Usual Care. They reported that molnupiravir is associated with lower anti-SARS-CoV-2 spike antibody titers compared to Usual Care. Serial sequencing reveals increased mutagenesis with molnupiravir treatment.

PASC/Long COVID

Spontaneous, Persistent, T cell–dependent IFN-γ Release in Patients Who Progress to Long Covid
Unexposed donor samples (n = 54) were recruited by the National Institute for Health Research (NIHR) BioResource Cambridge through the ARIA (Anti-viral Responses in Ageing, CBR53). This cohort was recruited before October 2019, and so no participants were exposed to SARS-CoV-2 infections. The COVID-confirmed hospitalized patients [day 28 (n = 51), day 90 (n = 20), and day 180 (n = 40)], were enrolled following admission to Addenbrooke’s Hospital, Royal Papworth, and Cambridge and Peterborough Foundation Trust with a confirmed diagnosis of COVID-19 via a positive RT-qPCR test for SARS-CoV-2. Then, they enrolled Long Covid study patients (n = 55). This cohort had symptoms that had persisted for at least 5 months after acute COVID-19 that could not be explained by an alternative diagnosis. As some patients were infected before routine testing began, a positive RT-qPCR result, antibody seropositivity to N, or a positive IL-2 response to M and N peptides was required as proof of SARS-CoV-2 infection. Investigators detected persistently high levels of interferon-γ (IFN-γ) from peripheral blood mononuclear cells of patients with Long Covid using highly sensitive FluoroSpot assays. This IFN-γ release was seen in the absence of ex vivo peptide stimulation and remained persistently elevated in patients with Long Covid, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. The IFN-γ release was CD8+ T cell–mediated and dependent on antigen presentation by CD14+ cells. They followed the Long Covid cohort for up to 31 months after acute infection. During this follow-up period, a considerable number of patients experienced resolution of some, if not all, of their symptoms either spontaneously or after SARS-CoV-2 vaccination. They measured unstimulated IFN-γ release in patients with Long Covid before and after vaccination and found a significant decrease in IFN-γ after vaccination that correlated with symptom resolution. The investigators point out in their discussion that “At this stage, it is not clear whether IFN-γ is a mediator or a biomarker of Long Covid symptoms.”
Blood–brain Barrier Disruption and Sustained Systemic Inflammation in Individuals with Long COVID-associated Cognitive Impairment
Participants included patients who had recovered from COVID-19, male or female aged 18 and above with and without neurological symptoms. Participants with Long COVID, with symptom persistence over 12 weeks from infection, were also recruited. They used dynamic contrast-enhanced magnetic resonance imaging to assess BBB disruption. They then did transcriptomic analysis of peripheral blood mononuclear cells to look for dysregulation of the coagulation system and the adaptive immune response in individuals with brain fog.
Prevalence of Persistent SARS-CoV-2 in a Large Community Surveillance Study
Investigators identified 381 individuals with SARS-CoV-2 RNA detected by PCR at low Ct values persisting for at least 30 days, of which 54 had viral RNA persisting for at least 60 days. In some individuals, they identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. All PCR data, so no viral culture, plaque assays, or any ability to distinguish remnant RNA from replicating virus.
Long Term Outcomes of Hyperbaric Oxygen Therapy in Post Covid Condition: Longitudinal Follow-up of a Randomized Controlled Trial
In July 2022 this group published the article “Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial,” where they reported improvements in a number of symptoms with HBOT, which they attributed to increased brain perfusions and neuroplasticity. Here the authors performed follow up on this cohort. The protocol involved 40 daily sessions, five sessions per week within a two-month period. The HBOT protocol included breathing 100% oxygen by mask at 2ATA for 90 min with five-minute air breaks every 20 min. Compression/decompression rates were 1.0 m/min. 79 patients were randomized to either HBOT or control/SHAM in the original study. Out of the 40 patients allocated to the HBOT arm, 37 patients completed the intervention and performed the short term evaluation. Of those, six declined their participation in long term evaluation. Accordingly, a total of 31 patients received HBOT, had both short term and long-term post treatment evaluations and were included in the current study analysis. The sample size was relatively small with 31 patients in total. The primary endpoint in the original study, cognitive function, as well as brain imaging were not evaluated in the current longitudinal evaluation. Since the original sham group, after completing the study protocol, were offered to be treated with HBOT, and most of them received it (27/39, 69%) they could not serve as a proper control group for the current study. They did, however, report that based on response to a short survey, there appeared to be encouraging long-term improvements in quality of life, quality of sleep, psychiatry, and pain symptoms.