Monday, June 19, 2023

COVID-Vaccinated MORE Likely to Be Hospitalized: CDC Data

There are some problems with inferences here but a complete reversal of the expected result is extreme and seems unlikely to be explained by confounds etc. We may have to allow that the vaccines are more harmful than helpful in the medium term

COVID-19 vaccine effectiveness against hospitalization turned negative over time, according to U.S. Centers for Disease Control and Prevention (CDC) data presented on June 15.

The effectiveness against hospitalization plummeted to negative 8 percent for people who received one of the old COVID-19 vaccines, according to data from a CDC-run hospital network.

A dose of one of the updated bivalent vaccines moved the protection above zero, to 29 percent, but the protection fell back to negative 8 percent beyond 89 days, the data show.

The protection estimates were for adults without a compromised immune system from Jan. 23 to May 24, when the XBB strain was dominant in the United States. The data came from people hospitalized at one of 25 hospitals across 20 states that are part of the Investigating Respiratory Viruses in the Acutely Ill network. Both cases and controls were hospitalized with COVID-like illness but the cases tested positive for COVID-19 and the controls tested negative for COVID-19.

“We see a pattern of waning against hospitalization,” Dr. Ruth Link-Gelles of the CDC said while presenting the data to a U.S. Food and Drug Administration (FDA) panel as they consider updating the composition of the vaccines.

Link-Gelles didn’t specifically comment on how the effectiveness turned negative but noted the wide confidence intervals for some of the effectiveness estimates.

The bivalent vaccines, made by Moderna and Pfizer, were introduced in the fall of 2022 with the hopes of improving protection against hospitalization and death after the old vaccines proved increasingly incapable of providing sustained shielding.

Dr. Robert Malone, who helped invent the messenger RNA technology utilized by the vaccine companies in their vaccines, said that the negative effectiveness is consistent with prior data such as a study from the Cleveland Clinic that found each successive vaccine dose increased the risk of infection.

Other papers have also estimated that protection against infection turns negative over time. Some datasets have indicated that vaccinated people were at higher risk of hospitalization, long seen as a surrogate for severe disease.

Researchers in one recent paper said that repeated vaccination—some Americans have received a half-dozen COVID-19 shots in under three years—weakens immune systems, potentially making people susceptible to life-threatening conditions such as cancer.

The estimates were negative even after CDC officials made adjustments for factors such as age, sex, and ethnicity. The median time since the last dose for the people who only received one or more doses of an old vaccine was 464 days. For the group who received a bivalent vaccine but saw effectiveness turn negative, the median time was 137 days.

Other Data

Data from another network found that protection neared zero over time.

Among adults deemed immunocompetent after XBB became dominant, the protection from the old vaccines against hospitalization was measured at 9 percent in the CDC’s VISION network. A shot of a bivalent vaccine increased protection to 51 percent, but the shielding plunged to 20 percent 90 to 179 days after the shot.

From September 2022 to May 2023, immunocompromised adults in the same network who only received an old vaccine had just 3 percent protection against hospitalization.

A bivalent shot increased the protection to 39 percent, although the shielding was reduced to 11 percent beyond 119 days.

VISION includes sites across 11 states, including Kaiser Permanente Northern California and Columbia University in New York.

Under half of each age group in the United States has received a bivalent dose, including 43 percent of those age 65 and older and 0.6 percent of 2- to 4-year-olds.

The CDC didn’t present data on the effectiveness against infection.

XBB became dominant in the United States in January, displacing BA.5 and its subvariants. The bivalents contain a BA.4/BA.5 component in addition to the Wuhan component. The FDA plans to update the vaccines to target XBB and its sublineages for a renewed vaccine campaign in late 2023 and early 2024.

“We’re concerned that we may have another wave of COVID-19 during the time when the virus has further evolved, immunity of the population has waned further, and we move indoors for wintertime,” Dr. Peter Marks, an FDA official, said during the meeting.

Turn to ‘Critical Illness’

Officials have increasingly been focusing on protection against so-called critical illness, or intensive care unit admission or death, as protection against hospitalization drops lower and lower.

Protection against critical illness from a bivalent was 58 percent initially and only dropped to 48 percent, according to data from VISION during XBB’s predominance.

There weren’t enough critical cases in the Investigating Respiratory Viruses in the Acutely Ill network to provide estimates of protection against critical illness, Link-Gelles said.

She said that patterns of waning with the bivalent vaccines “have been very similar to what we knew from the monovalent vaccine” and that U.S. officials don’t make vaccine policy decisions “based solely on vaccine effectiveness data.”

Limitations of the data include the high levels of prior infection, or natural immunity, and potential differences between unvaccinated and vaccinated people, officials said.


Chinese Researchers Demonstrate in Lab D-glucosamine Inhibits SARS-CoV-2 and other Coronaviruses

Researchers from the Beijing Institute of Microbiology and Epidemiology, China report in the peer-reviewed journal Nature on the urgent need for the development of broad-spectrum antiviral therapies targeting not only SARS-CoV-2 but also all other coronaviruses, which may either reemerge or emerge for the first time, not to mention mutant variants that can cause so much trouble as humanity discovered during the COVID-19 pandemic.

For example, in China, directed by top-down command and control ethos, this led to extremely costly (both in terms of human health and economy) societal lockdowns, finally changing the so-called “zero tolerance COVID policy” toward the end of the pandemic. In this study involving both infected cells and mice, a dietary supplement with 50 years of use as a regimen against osteoarthritis could possibly, as a supplement administered at daily doses help reduce the impacts of SARS-CoV-2. Of course, more research, including human trials, is needed to investigate the potential of D-glucosamine (GlcN) as a regimen against COVID-19, but the output from this study demonstrates promise.

This research, represented by corresponding authors Chengfeng Qin and Xiaotao Daun, both employed at the Beijing Institute of Microbiology and Epidemiology identified a possible target for broad-spectrum antiviral therapy centering on O-GlcNAcylation, a posttranslational modification derived from hexosamine biosynthetic pathway (HBP), and essential for virus-induced MAVS activation and IFN signaling.

In the lab, the team from the People’s Republic of China identified that a common dietary supplement known as D-glucosamine (GlcN), “enhanced MAVS-mediated IFN signaling, meaning that this low-cost accessible supplement exhibits a broad-spectrum antiviral activity.”

What about applied coronaviruses, however? Before answering that question, a brief overview of D-glucosamine.

What is D-glucosamine?

A naturally occurring amino sugar, D-glucosamine is a building block for various important molecules in the body. It’s a derivative of glucose and is commonly found in the exoskeletons of shellfish, as well as in the tissues of some fungi and microorganisms.

It’s often used as a dietary supplement in support of joint health.

Any studies in humans to date?

Yes. These authors point to a recent clinical study ( NCT04706416) reporting that orally administrated N-acetyl glucosamine (NAG), a downstream metabolite of GlcN, decreases the mortality rate and improves clinical outcomes of SARS-CoV-2 infected patients. That was a phase 1 study sponsored by LLC. See the link.

A total of five studies involving D-glucosamine are registered in They include three complete studies and two active studies. The two active studies include the use of a drug sulodexide which is a mixture of glycosaminoglycans (GAGs) composed of dermatan sulfate (DS) and fast-moving heparin.

The study

The investigational team set up a model for infection based on human lung epithelial cells like Calu-3 and human liver cancer cell line Huh7. The study team used GlcN ultimately at 20mM for 3 h on the Calu-3 or Huh7 cells infected with SARS-CoV-2 at a multiplicity of infection (MOI) of 1.

At 24 hours of infection, the team “observed that SARS-CoV-2 infected cells showed a significantly enhanced intensity of cellular O-GlcNAcylation compared to the non-infected group.”

According to Qin, Duan and their colleagues as conveyed in Nature this observation indicated that SARS-CoV-2 does promote HBP metabolism and protein O-GlcNAcylation in host cells.

Similar to other observations in RSV virus-based infections (e.g., IAV and VSV) they report, “As expected, we found that GlcN significantly increased the cellular level of O-GlcNAcylation and substantially suppressed SARS-CoV-2 replication in infected lung epithelial cells as measured by SARS-CoV-2 spike protein expression.”

The authors further report, “Virus titers in the supernatant were significantly reduced (P < 0.01) in GlcN treatment group.” Additionally, Qin, Duan and colleagues write in their study, “Time course measurements (6 to 24 h post-infection) further confirmed our observation, GlcN treatment significantly inhibited replication of SARS-CoV-2, consistent with titer reduction.”

Moving on, the authors further report the median effective concentration (EC50) value of GlcN against SARS-CoV-2: “GlcN inhibited SARS-CoV-2 infection in Calu-3 cells with a EC50 value of 11.82 mM.”

The authors also conducted an investigation to better understand the viral mechanism of GlcN against the novel coronavirus showcasing intriguing observations that the supplement led to “a considerable increase of both phosphorylated IRF3 and phosphorylated TBK1 and thereby promoted IFN signaling in response to SARS-CoV-2. This in turn decreased the expression of SARS-CoV-2 spike protein in the GlcN treatment group.”

What about the antiviral effect of GlcN against SARS-CoV-2 in vivo? The authors used mice that were infected and treated with the targeted regimen. While the body weight of the orally GlcN-based treatment of mice remained normal, a review of the impact of GlcN against samples of the mice lungs, spleens and livers showed no inducement of systemic IFN response.

The regimen demonstrated potential against at least a couple of other coronaviruses suggesting the potential for application against a broad spectrum of coronaviruses as well.

Overall, the authors report:

“Taken together, this study demonstrated that GlcN enhances SARS-CoV-2 induced IFNs signaling and restricts SARS-CoV-2 replication in multiple human cell lines. In the SARS-CoV-2 infected mouse model, prophylactic administration of GlcN at a clinical-relevant dose significantly reduces the viral load in lung and trachea, and considerably alleviates lung inflammation.”


This lab study in China demonstrates that GlcN shows potential efficacy against multiple coronaviruses including SARS-CoV-2 in both cell-based and mouse infection models.

The authors remind us:

“GlcN has been clinically applied for the treatment of osteoarthritis for more than 50 years. As a nutrient supplement, orally administered GlcN at daily doses ranging from 750 to 3500 mg is well tolerated in human subjects. Given the safety profile and its broad-spectrum anti-HCoVs activity, GlcN may serve as a promising drug for preventing the spread of SARS-CoV-2 and its emerging variants in healthy populations.”




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