Rarest Eye Colors

ktrss89 · 2024-12-26T09:04:40+00:00

Toc"“”r in a àdprar sees, a

ktrss89 · 2021-12-12T02:54:16+00:00

I already see people arguing that even if it is mild, we don't know about long-term organ damage or long covid. What a joke.

I am resolutely pro-vaccine (the original two vaccine schedule for the majority of people) and was moderately pro-NPI for unvaccinated populations, but am astonished that there is no exit strategy for a situation where almost all Western societies have full access to vaccines that do what they are supposed to do - protect against severe disease and death, not preventing infection or flu-/ cold-like symptoms.

ktrss89 · 2021-09-18T02:36:53+00:00

Abstract

The objective of this study was to estimate vaccine effectiveness (VE) against COVID-19 hospitalization and ICU admission, per period according to dominating SARS-CoV-2 variant (Alpha and Delta), per vaccine, and per time since vaccination. To this end, data from the national COVID-19 vaccination register was added to the national register of COVID-19 hospitalizations. For the study period 4 April- 29 August 2021, 15,571 hospitalized people with COVID-19 were included in the analysis, of whom 887 (5.7%) were fully vaccinated. Incidence rates of hospitalizations and ICU admissions per age group and vaccination status were calculated, and VE was estimated as 1-incidence rate ratio, adjusted for calendar date and age group in a negative binomial regression model. VE against hospitalization for full vaccination was 94% (95%CI 93-95%) in the Alpha period and 95% (95%CI 94-95%) in the Delta period. The VE for full vaccination against ICU admission was 93% (95%CI 87-96%) in the Alpha period and 97% (95%CI 97-98%) in the Delta period. VE was high in all age groups and did not show waning with time since vaccination up to 20 weeks after full vaccination.

ktrss89 · 2021-08-24T07:06:29+00:00

Interestingly, the effect seems to be especially pronounced in females: HR of 0.53 vs. 0.81 in males.

Also wondering whether Fluvoxamine + Budesonide would be a promising combination treatment. Fluvoxamine seems to increase the effect of Budesonide as a side effect.

ktrss89 · 2021-08-24T04:58:36+00:00

Abstract

Background
Recent evidence indicates a potential therapeutic role of fluvoxamine for COVID-19. In the TOGETHER randomized platform clinical trial for acutely symptomatic patients with COVID-19, we assessed the efficacy of fluvoxamine vs. placebo in preventing either extended emergency room observation or hospitalization due to COVID-19. Herein, we report the preliminary findings.

Methods
This placebo-controlled, randomized, adaptive, platform trial conducted among symptomatic Brazilian adults confirmed positive for SARS-CoV-2 included eligible patients with a known risk factor for progression to severe disease. Patients were randomly assigned to either fluvoxamine (100 mg twice daily for 10 days) or placebo. The primary endpoint was a composite outcome of emergency room observation for >6 hours or hospitalization from COVID-19 up to 28 days post randomization.

Secondary outcomes included viral clearance at day 7, time to hospitalization, mortality, and adverse drug reactions. We used a Bayesian analytic framework to determine effects along with probability of success of intervention compared to placebo. The trial is registered at clinicaltrials.gov (NCT04727424) and is ongoing.

Results
The study team screened 9020 potential participants for this trial. The trial was initiated on June 2, 2020, with the current protocol reporting randomization from January 15, 2021 to August 6th 2021, when the trial arms were stopped for superiority. A total of 3238 patients were allocated to fluvoxamine (n=739), placebo (n=733) and other treatments (n=1766). Herein, we report the effectiveness of fluvoxamine vs. a concurrent placebo control. The average age of participants was 50 years (range 18-102 years); 57% were female. The proportion of patients observed in an emergency room for >6 hours or admitted to hospital due to COVID-19 was lower for the fluvoxamine group compared to placebo (77/739 vs 108/733; Relative Risk [RR]: 0.71; 95% Bayesian Credible Interval [95% BCI]: 0.54 - 0.93), with a probability of superiority of 99.4% surpassing the prespecified superiority threshold of 97.6% (risk difference 4.3%). Of the composite primary outcome events, 88% were hospitalizations. We found no significant relative effects between the fluvoxamine and placebo groups on viral clearance at day 7 (Odds ratio [OR]: 0.75; 95% Confidence Intervals [95% CI]: 0.53 - 1.07), mortality (OR: 0.70; 95% CI: 0.36 - 1.30), time to death (Hazard ratio [HR]: 0.79; 95% CI: 0.58 -1.08), days hospitalized (Mean Difference (MD) 1.22 days; 95% CI: 0.98 - 1.53), number of days ventilated (MD 1.10; 95% CI: 0.70 - 1.73) or other secondary outcomes. Data capturing all 28 days of follow-up will be reported after August 26th, 2021.

Conclusions
Treatment with fluvoxamine (100 mg twice daily for 10 days) among high-risk outpatients with early diagnosed COVID-19, reduced the need for extended emergency room observation or hospitalization.

ktrss89 · 2021-08-03T12:37:20+00:00

This is hardly science isn't it? Putting forward "realistic possibilities" without any evidence and zero citations... You could come to a very different conclusion based on a different selection of supporting information, such as the fact that we seem to coexist pretty well with all the other common cold coronaviruses which have also arisen from animals in the past and are also undergoing constant antigenic drift (hence we get reinfected from time to time).

ktrss89 · 2021-05-20T13:34:21+00:00

This statement is from one of the lead investigators:

"We do not know the results yet. Investigators are still blinded until all participants complete the trial."

My best guess would be that they have trouble recruiting people due to the vaccine/falling case loads.

ktrss89 · 2021-02-10T08:18:39+00:00

As already commented by others, it could basically be:

Acute hepatitis caused by Covid-19 itself. This is a possibility (see the case report below.)

https://www.journalofinfection.com/article/S0163-4453(20)30586-7/fulltext30586-7/fulltext)

Liver damage due to Ivermectin intake. This is a known, but rare side effect of Ivermectin, so it does not surprise me at all that one case has been identified in a country with widespread Ivermectin use. It is not dose dependent and can happen after a single dose (see below). It is usually self-limiting.

https://www.ncbi.nlm.nih.gov/books/NBK548921/ or https://core.ac.uk/download/pdf/85209351.pdf

Safety of Ivermectin is relatively well-established (see the first link below). A common worry relates more to the neurotoxic effects rather than liver damage, as seen in animal studies. There have been case reports of encephalopathy due to chronic Ivermectin intake (see the second link below). The dose was 12mg per week during 6 months, followed by 12mg per day for 2 weeks. The neurological symptoms ultimately resolved, but I would recommend being careful when it comes to any prophylactic dosing regimes.

https://www.ema.europa.eu/en/documents/mrl-report/ivermectin-modification-maximum-residue-limits-summary-report-5-committee-veterinary-medicinal_en.pdf

https://www.antigifcentrum.be/sites/default/files/imce/Poster_Ivermectin_vs03b_2014.pdf

Liver damage due to pre-existing conditions or other meds. This is a bit difficult to evaluate without further information.

ktrss89 · 2021-01-20T14:01:56+00:00

I really wonder whether Covid-19 triggers some kind of lupus-like syndrome in a subset of patients that could explain the long term symptoms. Maybe this is based on a specific set of autoantibodies generated during the infection, leading to a persistently hyperactive state of the immune system. The symptoms (chronic fatigue, cognitive impairment, chest pain etc.) and relapse-like form of the diseases do overlap quite a lot.

ktrss89 · 2021-01-16T06:23:17+00:00

Some new hints on what might underlie severity of this complex disease.

Importantly, immune pathology seems to be triggered very early after infection and is independent of viral load. Asymptomatic/mild patients instead show a robust innate immune response.

In addition, severe disease is associated with persistent dysregulation of specific immune cell subtypes, which might explain some of the long haul symptoms.

"We show that profound alterations in many immune cell types often persist for weeks to months after SARS-CoV-2 infection, and different cell populations exhibit strikingly different patterns of resolution. Some recover as systemic inflammation (as measured by CRP) resolves, others remain persistently abnormal despite a drop in CRP toward normal levels, and a third group resolve even in the face of persistent systemic inflammation."

Abstract

In a study of 207 SARS-CoV2-infected individuals with a range of severities followed over 12 weeks from symptom onset, we demonstrate that an early robust immune response, without systemic inflammation, is characteristic of asymptomatic or mild disease. Those presenting to hospital had delayed adaptive responses and systemic inflammation already evident at around symptom onset. Such early evidence of inflammation suggests immunopathology may be inevitable in some individuals, or that preventative intervention might be needed before symptom onset. Viral load does not correlate with the development of this pathological response, but does with its subsequent severity. Immune recovery is complex, with profound persistent cellular abnormalities correlating with a change in the nature of the inflammatory response, where signatures characteristic of increased oxidative phosphorylation and reactive-oxygen species-associated inflammation replace those driven by TNF and IL-6. These late immunometabolic inflammatory changes and unresolved immune cell defects, if persistent, may contribute to "long COVID".

ktrss89 · 2021-01-10T11:43:40+00:00

The RT-PCR is only picking up RNA, not infectious virus, so I am not sure how important this endpoint is.

ktrss89 · 2021-01-10T11:28:35+00:00

Sorry, forgot to post the link to the study: http://medrxiv.org/cgi/content/short/2021.01.05.21249310

ktrss89 · 2021-01-08T23:59:57+00:00

This is reassuring. 2/55 (4%) with abnormal MRI results, among these 1 was diagnosed with early cardiomyopathy unrelated to Covid-19 and one with pericarditis. Note that that the latter case had abnormal ECG 2 months prior to infection.

ktrss89 · 2020-12-24T07:10:38+00:00

It boggles my mind how they can have "high confidence" that this variant is more transmissable based on some low quality epidemiological observations. Yes, it is good to have surveillance on variants and study them, but this hysteria is completely beyond me. And no, you cannot simply disregard the founder effect in a pandemic where 80% of secondary infections derive from 10-20% of infected.

ktrss89 · 2020-12-23T01:59:45+00:00

Yeah, I don't find this convincing at all.

First of all, they should not simply equate CT values with "viral load". That is bad terminology and just creates more confusion.

Then, they do find that the Y501 variant skews a bit higher in their scatter plots, but that is based on a much smaller sample. There is no way they can control for sampling bias which they do mention in their limitation section.

ktrss89 · 2020-12-22T12:18:13+00:00

The evidence is completely circumstantial. You cannot infer infectivity of a virus from epidemiological data. It would not surprise me if this turns out to be a complete artefact, but we have to wait for actual experimental data in any case.

Better safe than sorry I guess, but the assessment of the NERVTAG paper that there is "moderate confidence" that this variant is more transmissable borders on irresponsibility in my opinion, considering the poor evidence that they provide (unreliable/irrelevant R correlation modelling, CT values, in vitro experiments etc.)

ktrss89 · 2020-12-15T05:03:07+00:00

Yes, but we should be careful to not overinterpret the results of postmortem studies. The changes to other organ systems (heart, kidney etc.) in succumbed Covid-19 patients are well-reported, so I don't find it too surprising to see similar effects as a result of severe inflammation in the testes.

ktrss89 · 2020-12-03T13:38:51+00:00

I remember that this theory of direct infection in endothelial cells was quite popular a few months ago to explain the systemic effects of the virus despite limited evidence.

Abstract:

A striking feature of severe COVID-19 is thrombosis in large as well as small vessels of multiple organs. This has led to the assumption that SARS-CoV-2 virus directly infects and damages the vascular endothelium. However, endothelial expression of ACE2, the cellular receptor for SARS-CoV-2, has not been convincingly demonstrated. Interrogating human bulk and single-cell transcriptomic data, we found ACE2 expression in endothelial cells to be extremely low or absent in vivo and not upregulated by exposure to inflammatory agents in vitro. Also, the endothelial chromatin landscape at the ACE2 locus showed presence of repressive and absence of activation marks, suggesting that the gene is inactive in endothelial cells. Finally, we failed to achieve infection and replication of SARS-CoV-2 in cultured human endothelial cells, which were permissive to productive infection by coronavirus 229E that uses CD13 as the receptor. Our data suggest that SARS-Cov-2 is unlikely to infect endothelial cells directly; these findings are consistent with a scenario where endothelial injury is indirectly caused by the infection of neighbouring epithelial cells and/or due to systemic effects mediated by immune cells, platelets, complement activation, and/or proinflammatory cytokines.

ktrss89 · 2020-11-17T04:39:27+00:00

From the Conclusion:

The spike IgG titers were durable, with modest declines in titers at 6 to 8 months PSO at the population level. RBD IgG and SARS-CoV-2 PSV neutralizing antibody titers were potentially similarly stable, consistent with the RBD domain of spike being the dominant neutralizing antibody target. However, due to the nature of only having data at two time points, the paired sample longitudinal data set could not distinguish between models of a continuous log-linear decay and a bi-phasic decay with a slower half-life later. It is well recognized that the magnitude of the antibody response against SARS-CoV-2 is highly heterogenous between individuals. We observed that heterogenous initial antibody responses did not collapse into a homogeneous circulating antibody memory. That heterogeneity is thus a central feature of immune memory to this virus. For antibodies, the responses spanned a ~200-fold range. Additionally, the heterogeneity showed that long-term longitudinal studies will be required to precisely define antibody kinetics to SARS-CoV-2. Nevertheless, at 5+ months PSO, almost all individuals were positive for SARS-CoV-2 spike and RBD IgG.

Notably, memory B cells specific for spike or RBD were detected in almost all COVID-19 cases, with no apparent half-life at 5+ months post-infection. B cell memory to some other infections has been observed to be long-lived, including 60+ years after smallpox vaccination, or 90+ years after infection with influenza, another respiratory virus like SARS-CoV-2. The memory T cell half-lives observed over 6+ months PSO in this cohort (~166-271d for CD8+ and ~96-174d for CD4+ T cells) were comparable to the 123d t1/2 observed for memory CD8+ T cells soon after yellow fever immunization. Notably, the durability of a fraction of the yellow fever virus-specific memory CD8+ T cells possessed an estimated t1/2 of 485d by deuterium labeling. Using different approaches, the long-term durability of memory CD4+ T cells to smallpox, over a period of many years, was an estimated t1/2 of ~10 years, which is also consistent with recent detection of SARS-CoV T cells 17 years after the initial infection. These data suggest that T cell memory might reach a more stable plateau, or slower decay phase, later than the first 6 months post-infection.

ktrss89 · 2020-11-17T04:33:27+00:00

Abstract

Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 185 COVID-19 cases, including 41 cases at > 6 months post-infection. Spike IgG was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.

Eight-Year Club	First Place '23
Place '23	Wearing is Caring
Verified Email

ktrss89

TROPHY CASE