Categories
Commentary COVID-19

Debunked: RFK Jr. Claims COVID is ‘Ethnically Targeted’

Recent statements from 2024 Democratic presidential candidate Robert F. Kennedy Jr. have drawn great public attention. Speaking at a press event in New York City, he claimed that COVID-19 “disproportionately attacks certain races,” particularly Caucasians and Black people, with Ashkenazi Jews and Chinese being seemingly more immune. Kennedy attributed these disparities to genetic variations of the host cell receptor, ACE2, a key player in the virus’s infectious cycle. He insinuated that this is proof that SARS-CoV-2, the virus that causes COVID-19, was a biological weapon designed to target certain ethnicities. But how sound are these alarming claims?

First, let’s look at the specific study Kennedy linked to on Twitter to validate his claim. The paper investigated the correlation between allele frequencies of certain ACE2 variants and their predicted effects on its ability to bind the SARS-CoV-2 spike protein, a crucial step in the infectious cycle of the virus. For instance, the p.Met383Thr and p.Asp427Tyr variants, which the article alleges are linked to worse COVID outcomes, have frequencies of just 0.003% and 0.01%, respectively. Their rarity suggests that they are unlikely to meaningfully affect large population groups. Not only are these variants incredibly rare, but they are also based on alleles associated with adverse outcomes for SARS-CoV-1, not SARS-CoV-2, the virus causing the COVID-19 pandemic. Hence, the information from this study should not be directly applied to the current pandemic and certainly cannot prove an ethnic targeting of the virus.

Another critical study that disproves Kennedy’s claim revolves around ACE2 variants but examines them in relation to SARS-CoV-2 susceptibility, unlike the former study. Even in this research, the ACE2 variants that could affect susceptibility to SARS-CoV-2 are extremely rare, with maximum prevalence values ranging from 0.00003 to 0.006. For example, an ACE2 variant that was found to increase spike protein binding was found at a frequency of only 3 in 10,000 Latino/Admixed American samples. Consequently, the low occurrence rates of these variants indicates that their impact on broad racial or ethnic groups is statistically insignificant when it comes to widespread racial or ethnic susceptibility.

Upon close examination, it’s clear that Kennedy’s claims lack robust scientific backing. While it’s true that COVID-19 has impacted different communities in different ways, it’s not due to any supposed “genetic targeting” inherent in the virus. Instead, this disparity arises from a multitude of factors, including access to healthcare, occupation types, living conditions, systemic racial disparities in healthcare, and perhaps biological variations unrelated to host cell receptor ACE2.

The assertion that COVID-19 is “ethnically targeted” is not only scientifically unsound but also has the potential to sow confusion and fear among the public. As we continue to grapple with this global health crisis, let’s keep the discourse grounded in verifiable science and promote unity rather than divisive misinformation.

References
  • Hou, Y., Zhao, J., Martin, W., Kallianpur, A., Chung, M. K., Jehi, L., Sharifi, N., Erzurum, S., Eng, C., & Cheng, F. (2020). New insights into genetic susceptibility of COVID-19: An ACE2 and TMPRSS2 polymorphism analysis. BMC Medicine, 18(1), 216. https://doi.org/10.1186/s12916-020-01673-z
  • Levine, J. (2023, July 15). RFK Jr. Says COVID was “ethnically targeted” to spare Jews. New York Post. https://nypost.com/2023/07/15/rfk-jr-says-covid-was-ethnically-targeted-to-spare-jews/
  • MacGowan, S. A., Barton, M. I., Kutuzov, M., Dushek, O., Van Der Merwe, P. A., & Barton, G. J. (2022). Missense variants in human ACE2 strongly affect binding to SARS-CoV-2 Spike providing a mechanism for ACE2 mediated genetic risk in Covid-19: A case study in affinity predictions of interface variants. PLOS Computational Biology, 18(3), e1009922. https://doi.org/10.1371/journal.pcbi.1009922
Categories
COVID-19 Public Health

COVID Disease Severity Lower Than Ever, Most People Infected Unaware of Status

As the omicron BA.5 subvariant has become dominant, many countries are heading into their third wave of Omicron cases. Japan reports its largest-ever surge in cases, recording over 200,000 new cases in one day.

Though omicron BA.5 has become the most dominant subvariant of COVID (accounting for 88% of new cases in the US) and is highly contagious, CDC data shows disease severity at its lowest point ever.

Intensive Care Unit (ICU) admission among hospitalized COVID-19 patients. (cdc.gov)

Among hospitalized COVID patients, about 1 in 10 are admitted to the ICU as of July 2022. This figure was as high as 1 in 3 in March 2020, and 1 in 5 as recently as December 2021.

Mortality among hospitalized COVID-19 patients. (cdc.gov)

Similarly, mortality among hospitalized COVID patients has decreased appreciably from 1 in 5 in March 2020 to 1 in 40 in July 2022.

These decreases in COVID disease severity follow the emergence of the omicron variant in November 2021 and its ever-growing share of new infections. The omicron variant, while of high concern and contagion, does not appear to be of proportionally high consequence compared to earlier variants.

The most common symptoms of COVID include cough, fever, and chills. Many report symptoms resembling a common cold with symptoms like upper respiratory congestion. Most people (56%) who are infected with the omicron variant are not aware of their positive status according to a recent Cedars-Sinai study.

Multiple factors could explain omicron’s lower severity, including widespread vaccination or immunity gained from prior exposure and infection. It is also possible that omicron has mutations that decrease severity while favoring infectivity.

Categories
COVID-19

CRISPR Test Detects All Variants of COVID-19, Could Run on Mobile Phones

During the pandemic, laboratories across the world worked hard to improve current diagnostic testing methods. The main method, quantitative polymerase chain reaction (qPCR) turns a small quantity of DNA into a larger amount and uses fluorescent dyes to indicate the presence or absence of viral genetic material. However, this method falls short in the following ways:

  1. It requires expensive equipment and reagents, along with trained personnel.
  2. It requires temperature cycles, so it cannot be performed at a single temperature.
  3. It takes time. Depending on the initial amount of target present, a qPCR test can take as long as 90 minutes.

At the University of Florida, PhD student Long T. Nguyen, working under Dr. Piyush Jain, has developed a rapid, single temperature COVID-19 diagnostic test that provides results in under 30 minutes. Amazingly, the test distinguishes between five COVID variants, achieves amplification, and RNA to DNA conversion all in one “pot.” Finally, the results can be read on a mobile phone.

The system they used is based on a detection system found in bacteria. Bacteria contain natural immune systems called CRISPR Cas, which function to create both a memory of past viral infections, along with a defense system once these viruses come back. Cas is a protein which is sometimes described as “a pair of molecular scissors,” capable of cutting DNA or RNA fragments, while CRISPR contains complementary sequences to attacking viruses and acts as a “molecular GPS,” helping Cas find a certain target. For this reason, it is also called a Guide RNA.

DNA sequence matching the guide RNA and being cut by a Cas protein into two slices. / Javier Zarracina via vox.com

Some Cas proteins locate their target and only make cuts around the target DNA/RNA; this is called cis cleavage. Others go on a “cutting frenzy.” After finding the target and cutting, the Cas protein starts cutting up other DNA or RNA fragments surrounding it, termed trans cleavage. Cas9 proteins, famous for genetic engineering, employ cis cleavage and only cut DNA. Cas12 and Cas13 proteins utilize trans cleavage, cutting DNA and RNA respectively. All bacteria have adapted their own systems, with slight variations, allowing scientists to harness each’s individual powers.

Cas12 and Cas13 proteins are at the forefront of diagnostic research. Their cutting frenzy may not be great for gene editing, but recent innovation has found that FQ reporters, or fluorescent quenchers, can be used to detect a signal with light. These reporters are dampened by a piece of RNA or DNA located between the fluorescent and quencher. Once cut, they glow and show a light on a fluorescent reader. If a Cas12 or Cas13 protein detects its target, it will cut the target then rapidly start cutting the FQ reporters nearby.

CRISPR RNA, shortened as crRNA, can be “programmed” to target any part of a target sequence. Specifically for the virus that causes COVID-19, there is a highly conserved region called the N gene. Since this same sequence is found across all variants, it can indicate the presence of the virus, but does not distinguish between mutated strains. The Jain lab identified mutated regions on each of the five variants: Alpha, Beta, Gamma, Delta, and Omicron, and created crRNAs which were complementary to each of these mutated regions. 

The N gene encodes for the nucleocapsid region on the COVID-19 virus. It is found in all variants of COVID-19.(Kubina & Dziedzic, 2020)

They then had to choose the optimal Cas protein, which could withstand higher temperatures. This was necessary because amplification occurs at high temperatures, ranging from 55-70°C. BrCas12b comes from a thermophilic bacterium found in hot springs and was the optimal choice.

They combined this Cas protein, along with a crRNA and finally, a master mix of RT-LAMP (Reverse Transcription Loop Mediated Isothermal Amplification). This is a very complex sounding term, but it can be broken down fairly easily. Reverse transcription is the process of converting RNA into DNA. Isothermal means it works at a single temperature and amplification implies the amount of DNA increases greatly. This amplification also provides a checkpoint. Researchers were able to first see if the patient sample was amplified; if so, COVID must be present. Then, using the CRISPR Cas system, they can determine exactly what variant is present. 

Image showing all of the components used in the Jain lab’s one-pot detection. (Nguyen et al., 2022)

Detection is completed in under 30 minutes and patient samples with a higher viral load (i.e., they had more SARS-CoV-2 virions present in their sample), exhibited 100% accuracy with about 95% sensitivity in distinguishing variants. The figure below, from Long et. al shows the incredible accuracy which comes from this detection. The colored titles, “Alpha, Beta, etc.” are the variant present in the patient sample, while the x-axis shows the crRNA used. For instance, it was expected that if a patient contained the Beta strain, only the Beta crRNA would show high signal.

Detection results for variants, showing high sensitivity. (Nguyen et al., 2022)

Most studies combining RT-LAMP with a CRISPR reaction have extremely low sensitivity and difficulty distinguishing a positive sample. The use of specifically BrCas12b, a less studied Cas protein, allowed the Jain lab to circumvent many of the problems others have had combining the two. The applicability of this research extends far beyond COVID-19 detection. Any RNA or DNA detection could be done utilizing this research, simply by changing the sequence located on the crRNA.

Moreover, the Jain lab aims to create portable and cheap methods for testing. They proposed an inexpensive lens which can be attached to any mobile phone camera. In a dark setting, the lens, which costs less than $5 can shine light of a specific wavelength on a sample with the added CRISPR Cas reagent and glow in the presence of COVID-19.

Potential for at-home testing using a specialized lens. Positive samples will glow in the dark once subjected to the light. (Nguyen et al., 2022)
References
  • Kubina, R., & Dziedzic, A. (2020, June 26). Molecular and serological tests for COVID-19. A comparative review of SARS-Cov-2 coronavirus laboratory and point-of-care diagnostics. MDPI. https://doi.org/10.3390/diagnostics10060434
  • Nguyen, L. T., et al. (2022, March 1). A Thermostable Cas12b from Brevibacillus Leverages One-pot Detection of SARS-CoV-2 Variants of Concern. eBioMedicine, The Lancet Discovery Science. https://doi.org/10.1016/j.ebiom.2022.103926
Categories
COVID-19 Immunology

As Antibodies Wane in Quantity and Efficacy, T Cells Remain Effective Against Omicron

Background

As the Omicron variant of COVID-19 becomes increasingly dominant among skyrocketing cases, including in vaccinated individuals, concerns of the variant’s immune escape abilities have grown.

Vaccines provoke important responses in the immune system to prevent disease, including creation of T cells and antibodies specific to the pathogen they introduce. In the case of mRNA vaccines for COVID-19, genetic code (mRNA) for the spike protein enters our cells, causing them to manufacture spike proteins. Our immune system then recognizes these proteins as foreign to our bodies, promptly destroying them while creating T cells and antibodies that can work against them in the future.

Antibodies and T cells play different roles in the event of an infection. Antibodies work by creating sites that bind to certain parts of a pathogen. As they pertain to mRNA COVID-19 vaccines, the antibodies will bind strongly to the spike protein. Since the spike protein is what enables SARS-CoV-2 to enter cells, binding antibodies to them will prevent infection.

On the other hand, T cells help fight infection by injecting poison into cells that are already infected, killing both the cell and the pathogen. mRNA vaccines help T cells recognize when a cell is infected with SARS-CoV-2. This means that antibodies are more useful for preventing infection via neutralization while T cells are better at stopping an infection that has already infected some cells.

These figures model T cell and antibody responses to viral infection. In an average SARS-CoV-2 infection, T cells have a greater response than antibodies, and this response effectively decreases viral load. In a severe infection, antibodies are far more prominent than T cells, and this response is ineffective at decreasing the viral load. T cells are more effective at managing instead of preventing an infection, so they would be more useful than antibodies in an already severe infection. (Sette, Crotty 2021)

Much of the focus surrounding COVID-19 vaccines and their efficacy has related to antibody quantity and binding affinity to the changed spike proteins of new variants in order to prevent infection instead of the role of T cells in managing infection. Researchers sought to quantify both antibody and T cell counts and efficacy in unvaccinated, twice vaccinated, and three-times vaccinated patients.

Results

A preprint study from Erasmus University Medical Center in the Netherlands detected high antibody levels against the original SARS-CoV-2 spike protein following receipt of the Pfizer or Moderna mRNA vaccines. Lower (but still significant) antibody levels were detected from the Johnson & Johnson viral vector vaccine. However, antibody levels from the mRNA vaccines decreased significantly within 6 months, while those from the viral vector vaccine did not. Though, even if neutralizing antibody levels remained high, researchers from Beijing’s Peking University found that Omicron escapes most SARS-CoV-2 neutralizing antibodies.

Studies from the Icahn School of Medicine at Mount Sinai in New York supported earlier reports that convalescent (unvaccinated, previously infected) and twice-vaccinated individuals had nonexistent protection against symptomatic infection from the Omicron variant. Boosted (three-times vaccinated) individuals had about 75% protection against symptomatic disease from Omicron, though it is unknown how long this protection will last.

Importantly, the Erasmus study found that unlike neutralizing antibodies, SARS-CoV-2-specific T cells were still detected in the blood 6 months after mRNA and viral vector vaccination as well as natural infection.

In contrast to findings that most neutralizing antibodies are largely ineffective against Omicron, data from Pfizer and BioNTech showed that 80% of spike-specific T cells in vaccinated individuals retained function. The Erasmus researchers corroborate this, finding that vaccinated individuals retain T cell immunity to the Omicron variant.

Discussion

Results from multiple studies now support a consensus that naturally infected and twice-vaccinated individuals have nonexistent protection against symptomatic infection due to depleted and ineffective neutralizing antibodies.

However, both populations can reattain significant protection against symptomatic infection by receiving initial vaccinations or a booster–though it is still unknown how long this protection will last.

These data indicate that convalescent individuals greatly benefit from vaccination, an observation that is of significant public health importance.

Carreño et al., 2021

Even though it has become significantly more difficult to prevent symptomatic infection due to the waning quantity and efficacy of neutralizing antibodies in convalescent and vaccinated individuals, T cells have been shown to remain active and are expected to still help prevent severe infection.

This is supported by new data that has shown that SARS-CoV-2-specific T cells remain present in the long-term and are still mostly effective against the Omicron variant in convalescent and vaccinated individuals.

Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa.

Keeton et al., 2021
References
  • BioNTech. “Update – Omicron Variant (B.1.1.529).” BioNTech Investors & Media, 8 Dec. 2021, https://investors.biontech.de/static-files/47b4131a-0545-4a0b-a353-49b3a1d01789.
  • Cao, Yunlong, et al. “Omicron Escapes the Majority of Existing SARS-COV-2 Neutralizing Antibodies.” Nature, 23 Dec. 2021, https://doi.org/10.1038/d41586-021-03796-6.
  • Carreño, Juan Manuel, et al. “Activity of Convalescent and Vaccine Serum against SARS-COV-2 Omicron.” Nature, 31 Dec. 2021, https://doi.org/10.1038/d41586-021-03846-z.
  • Geurts van Kessel, Corine H., et al. “Divergent Sars Cov-2 Omicron-Specific T- and B-Cell Responses in COVID-19 Vaccine Recipients.” MedRxiv, 29 Dec. 2021, https://doi.org/10.1101/2021.12.27.21268416.
  • Keeton, Roanne, et al. “SARS-COV-2 Spike T Cell Responses Induced upon Vaccination or Infection Remain Robust against Omicron.” MedRxiv, 28 Dec. 2021, https://doi.org/10.1101/2021.12.26.21268380.
  • Sette, Alessandro, and Shane Crotty. “Adaptive Immunity to SARS-COV-2 and COVID-19.” Cell, 18 Feb. 2021, https://doi.org/10.1016/j.cell.2021.01.007.
  • Wu, Katherine J. “T Cells Might Be Our Bodies’ Best Shot against Omicron.” The Atlantic, 14 Dec. 2021, https://www.theatlantic.com/science/archive/2021/12/t-cells-omicron-vaccine-immunity/620995/.
Categories
COVID-19

Researchers Reveal Portable COVID Testing Method, Gives Results Within One Second

Researchers from the University of Florida, along with collaborators from the National Chiao Tung University, recently created the world’s fastest COVID detection test to date using a new method with antibody-infused test strips and a small circuit board.

Since the beginning of the COVID-19 pandemic, RT-PCR tests, commonly referred to as PCR, have been regarded as the gold standard for COVID-19 testing.

Reverse Transcription Polymerase Chain Reaction (RT-PCR) works by first converting RNA into DNA, followed by copying small segments of this DNA over and over, primarily using temperature to denature and bind DNA, along with “primers” to make new copies. The process takes about two hours and uses expensive machinery. Such amplification of DNA makes it easy for machines to detect the small amounts of viral particles present in infected patient samples, but difficult to apply to large populations during a pandemic.

One of the defining features of the coronavirus is the spike proteins, which enable the virus to penetrate host cells due to their geometry and location. Rather than having to convert RNA to DNA, copy the DNA, and read a signal as is done with RT-PCR tests, a new study described a system which uses the spike protein-antibody bond and circuitry for detection.

Antibodies are Y-shaped proteins our immune system produces to fight and prevent future infection. They work by creating sites to which infectious particles bind, effectively blocking those particles from infecting cells. These sites can include binding locations for viruses such as SARS-CoV-2, which researchers have found to be quite useful for detection.


As our need for fast, cheap, and portable detection grows, researchers have been searching for new methods. The researchers from the University of Florida ingeniously combined knowledge of antibodies and circuitry to detect presence of COVID in one second.

First, they modeled commercially available glucose testing strips commonly used for testing blood sugar levels in diabetic patients. If you were to dissect a glucose test strip, you would find several electrodes, coated and made of different materials.

Most commonly, glucose test strips are coated with an enzyme that reacts with glucose to steal its available electrons. These electrons are then transported to the electrode which can detect and quantify their presence, indicating how much glucose was in the blood sample.

In the study, researchers worked to transform the electrodes using different biological and chemical materials. One of the electrodes was plated with gold then “biofunctionalized” with coronavirus antibodies.  An electrode in the middle was connected to an electronic component called a metal-oxide-semiconductor field-effect transistor (MOSFET), which is used to control and amplify electrical signals.

When spike proteins from a sample interact with the surface, the antibody-antigen complex will spring up and down, causing an electrical signal to be sent to the gate of the MOSFET. The device’s circuit board can then quickly convert and read the signal. 

The MOSFET is especially important as it can convert electrical activity from the interaction of a very small amount of coronavirus with the antibodies into a very large signal, similar to how RT-PCR tests amplify the small amount of genetic material into a much larger and easier-to-detect sample.

The accuracy and acute sensitivity of this method are a direct result of combining electrical and biological tools of detection. Not only does this allow for the detection of extremely low quantities of virus particles, but it can be accomplished in merely 1 second. Furthermore, the device is inexpensive and portable, paving the way for fast, economical, and highly sensitive at-home diagnostic kits.

Notably, Minghan Xian, first author of the study, remarked that by simply altering the type of antibody used, this detection kit could be reapplied to a multitude of other infectious diseases. The electronic components can also be reused with new electrodes.

References
Categories
COVID-19 Public Health

Recovered Patients of Severe COVID-19 Infection 233% More Likely To Die Within Year Than Negative Counterparts

Research published by University of Florida scientists in Frontiers in Medicine reported that patients (aged 18-65) who recovered from severe COVID-19 infection were 233% more likely to die within 12 months than COVID-19-negative counterparts.

Methodology

The study analyzed 13,638 patients in the University of Florida Health system over a 12-month period, including positive (mild, severe) and negative cases. A severe case was defined as one requiring hospitalization within 30 days of a positive COVID-19 test. The 12-month risk of mortality was adjusted for age, sex, race, and comorbidities–meaning these factors did not affect the data.

Results

Survival curve showing probability of survival over time following mild, severe, and lack of COVID-19 illness. / Mainous 2021

Patients aged 18 to 65 who recovered from an initial episode of severe COVID-19 had a 233% increased incidence of mortality in a 12-month period compared to negative counterparts. Recovered patients aged over 65 also had increased mortality compared to negative counterparts, but to a lesser extent.

The difference in 12-month mortality between COVID-negative and mild COVID patients was not statistically significant.

Only 20% of the deaths in the 12-month period were attributed to cardiovascular or respiratory conditions.

Discussion

These results show that those who recover from severe COVID-19 infections are much more likely to die within 12 months of recovery compared to those with mild or no infection. This reveals that the increased risk of death from COVID-19 is not limited to the initial episode of infection, indicating that the biological and physiological insult from severe infection is significant. This is further demonstrated by the unexpectedly low portion of deaths caused by cardiovascular or respiratory conditions.

Arch G. Mainous III, Ph.D., first author of the study and University of Florida College of Medicine faculty member, said in a statement to the University of Florida Health Newsroom that “patients may feel that if they are hospitalized and recover from COVID-19 then they have beaten COVID-19. Unfortunately, having a substantially increased [risk] of death in the next year after recovery from a severe episode of COVID-19 shows that this is not the case. Preventing severe COVID-19 should be our primary focus.”

The study mentions that nearly all hospitalizations and severe infections are preventable. Pfizer and Moderna’s COVID-19 vaccines prevent severe infection in more than 95% of cases.

Mainous hopes that the data, which he described as devastating, will “make everyone rethink the impact of COVID-19.”

References
Categories
COVID-19 Pharmacology

Combining a Protein Found in Milk with Benadryl Reduces SARS-CoV-2 Replication in Lung Cells by 99%

Researchers looking for prevention and treatment strategies for COVID-19 that are not impacted by SARS-CoV-2 mutations published findings in Pathogens that showed that a combination of diphenhydramine (the active ingredient antihistamine in Benadryl) with lactoferrin (an immunologically active protein found in human and cow milk) reduced SARS-CoV-2 replication by 99% in human cells.

Background

The key to the researchers’ findings related to proteins called the sigma receptors. These receptor proteins are located in the endoplasmic reticulum (ER), an organelle responsible for protein folding and transportation. Sigma receptors have multiple functions, including regulation of the ER stress response.

The ER stress response occurs when the ER is overwhelmed with unfolded or misfolded proteins. This triggers the unfolded protein response (UPR), which seeks to return the cell to a normal state by increasing protein folding, autophagy (destruction of damaged proteins), and in the case of prolonged UPR, apoptosis (cell suicide).

ER stress usually occurs when the ER is overwhelmed with unfolded or misfolded proteins. Cells mitigate ER stress by provoking the unfolded protein response (UPR), which includes increased protein folding, autophagy (destruction of damaged proteins) and, in prolonged cases, apoptosis (cell suicide).

When the UPR causes autophagy, it does so by forming sites near the ER called autophagosomes. Coronaviruses (CoV) have been found to bind directly to the sigma-2 receptor to cause ER stress, enabling them to hijack autophagosomes for use as virus replication sites.

Implication

Researchers found that by binding a drug molecule to the sigma-2 receptor, SARS-CoV-2 would no longer be able to bind to it to cause ER stress (and ultimately virus replication). This is made even more effective by also binding to and activating the function of the sigma-1 receptor.

Results

The team identified a ligand called AZ66 as being able to bind to both sigma-1 and sigma-2 receptors. In experiments with human lung cells infected with SARS-CoV-2, AZ66 completely blocked virus production. However, the safety of AZ66 is unknown, as the drug candidate has not been tested in clinical trials.

Molecular docking model of human sigma-2 receptor (orange) bound to AZ66 (yellow).

Searching for common compounds with proven records of safety, the researchers analyzed electronic medical records to identify diphenhydramine (DPH), the active ingredient antihistamine in Benadryl, as being associated with higher survival rates for COVID-19 patients. This is due to DPH having effects on the sigma-1 receptor. DPH was found to reduce replication of SARS-CoV-2 in the infected human lung cells by about 30%.

Lactoferrin is an antimicrobial and immunostimulatory iron-sequestering protein found in human and cow milk that was brought to a researcher’s attention by the Global Virus Network’s COVID-19 task force due to its antiviral effects on SARS-CoV-2. When tested, it was also found to reduce virus replication by about 30%. The milk protein has a proven safety record as a supplement widely used to treat stomach ulcers.

When a diphenhydramine/lactoferrin combination was tested in human and monkey epithelial lung cells, they found that a synergistic effect occurred, reducing virus replication by 99%.

Commentary

The study’s first author, David A. Ostrov, Ph.D. of the University of Florida, hailed diphenhydramine and lactoferrin as “effective, economical,” and unlike AZ66, “[having] a long history of safety.” The combination could be used to prevent infection as well as decrease recovery time from COVID-19.

While the researchers await potential interest from pharmaceutical companies, Ostrov told the University of Florida Health Newsroom that he cautions against self-medicating with diphenhydramine or lactoferrin as a COVID-19 prevention or treatment. He said that any off-label use of medication should follow a consultation with a physician. Further, commercially available lactoferrin used for treatment of stomach ulcers is not exactly the same as the lactoferrin used in the study.


Lactovid™ is a combination of diphenhydramine and lactoferrin

Would you be interested in purchasing Lactovid™ as a non-FDA approved over-the-counter product?(required)


Warning against off-label self-medication

This article does not offer medical advice. University of Florida researcher, David A. Ostrov, Ph.D., said that any off-label use of medication should follow a consultation with a physician. Off-label use is when a medication is used for anything other than its approved purpose.

This article is based on the following sources

– Bennett, D. (2020, December 3). Existing antihistamine drugs show effectiveness against COVID-19 virus in cell testing. University of Florida Health Newsroom. https://ufhealth.org/news/2020/existing-antihistamine-drugs-show-effectiveness-against-covid-19-virus-cell-testing
– Bennett, D. (2021, November 22). Two common compounds show effectiveness against COVID-19 virus in early testing. University of Florida Health Newsroom. https://ufhealth.org/news/2021/two-common-compounds-show-effectiveness-against-covid-19-virus-early-testing
– Ostrov, D. A., Bluhm, A. P., Li, D., Norris, M. H., et al. (2021, November 20). Highly specific sigma receptor ligands exhibit anti-viral properties in SARS-Cov-2 infected cells. Pathogens. https://doi.org/10.3390/pathogens10111514
– Vela, J. M. (2020). Repurposing sigma-1 receptor ligands for COVID-19 therapy? Frontiers in Pharmacology. https://doi.org/10.3389/fphar.2020.582310

Categories
Cardiology COVID-19

American Heart Association Quells Vaccine Myocarditis Fears Amid Growing Public Concern

As concerns regarding mRNA vaccine-caused myocarditis skyrocket on social media and news outlets, researchers have published a study in the American Heart Association’s Circulation journal with statistics regarding the potential side effect.

Google Search interest in “COVID vaccine myocarditis” from December 6, 2020 to December 6, 2021. / trends.google.com

Myocarditis is a condition that causes inflammation in the heart, which can weaken its ability to regularly pump blood throughout the body. It can lead to heart failure, abnormal heartbeat, and sudden death. Most cases of myocarditis are caused by viruses, but the rare heart condition has been noticed as a potential side effect of mRNA vaccines for COVID-19.

The study published in Circulation statistically analyzed cases in patients younger than 21 years old who had received an mRNA vaccine within 30 days of showing symptoms of myocarditis. Researchers found that, in general, young people who experience myocarditis as a side effect of the COVID-19 vaccine recover quickly and completely.

The Circulation study found that 90.6% of adolescent and young adult patients who experienced myocarditis after vaccination were male. In most cases, symptoms presented 2 days after vaccination. The most common symptom was chest pain, which presented in 99.3% of the patients. 18.7% of the patients had low left ventricular ejection fraction (LVEF), meaning that not enough blood was pumping out of their hearts. However, all patients with low LVEF who followed up had fully recovered with normalized function.

Another study published in the New England Journal of Medicine reported that only 2.13 in 100,000 people who received the mRNA vaccine experienced myocarditis. This is much lower than the 150 in 100,000 rate of myocarditis in unvaccinated patients infected with COVID-19 as reported by the Morbidity and Mortality Weekly Report. This means that unvaccinated people infected with COVID-19 had about 70 times greater incidence of myocarditis than any person receiving the mRNA vaccine.

The Circulation study’s first author, Dr. Dongngan T. Truong, told the American Heart Association Newsroom that the data showed that “most cases of suspected COVID-19 vaccine-related myocarditis in people younger than 21 are mild and resolve quickly.”

As the data shows that myocarditis as a side effect of COVID-19 vaccination is extremely rare (2.13 in 100,000) and that almost all of those patients recovered quickly and completely, the American Heart Association continues holding its position that COVID-19 vaccines are safe and highly effective (preventing hospitalization and death in 91% of severe infections). Dr. Donald M. Lloyd-Jones, president of the AHA, said that COVID-19 vaccines were “fundamental to saving lives, protecting our families and communities against COVID-19, and ending the pandemic,” then urging parents to vaccinate their children as soon as possible.

References

Note from the Editors

This article does not offer medical advice. It is a review of statements and data offered by the American Heart Association. Consult with a doctor regarding concerns related to health effects from the COVID-19 vaccine.

Categories
COVID-19

Mutation of Nucleocapsid, Not Spike Protein, Responsible for Delta Variant’s Increased Transmissibility

Since the emergence of the Delta variant as the world’s predominant variant of SARS-CoV-2, little has been discovered regarding its mechanism for increased transmissibility. Researchers from the Gladstone Institute of Data Science and Biotechnology (San Francisco, CA) and the Innovative Genomics Institute at UC Berkeley (Berkeley, CA) believe they have found a key site of genetic mutations in the nucleocapsid that could be responsible for the Delta variant’s increased transmissibility.

One author of the study, Abdullah Syed, described in a press release that the life cycle of a virus can be divided into three parts:

  • Entry: the virus is enters a cell
  • Replication: the virus hijacks the cell, causing it to create more copies of proteins and genetic material that comprise the virus
  • Assembly: the copied proteins and genetic material are packaged into new virus particles

The nucleocapsid, a multifunctional structural protein, is critical to the efficiency of the assembly stage in the coronavirus. Though it was previously hypothesized that mutations in the spike protein were causing increased efficiency during the entry stage, the researchers found that mutations in the nucleocapsid were the most significant contributor to Delta’s higher infectivity.

Typically, researching the nucleocapsid would require real viruses, because unlike the spike protein, it is located inside of the virus. This has caused nucleocapsid research to be overlooked, as working with real viruses is inherently dangerous due to the possibility of infecting researchers.

Taha Taha of the Gladstone Institute of Virology described the method that enabled the researchers to study virus replication without using live SARS-CoV-2 virions. They used virus-like particles (VLPs), which have the same structure as the virus, but lack any genetic material for replication. This means that researchers do not risk infection, as the VLPs are unable to replicate. VLPs are also easier to mutate than live viruses.

The researchers genetically engineered the VLPs to express luciferase (the enzyme that causes fireflies to glow), as the light it gives off can be used to gauge activity of a protein-expressing gene. By mutating the nucleocapsid with the mutations found in the Delta variant, an increase in luciferase expression (measured by light) would signal that the mutations increase the functionality of the nucleocapsid.

This was confirmed as one single amino acid mutation (the most basic mutation possible) in the nucleocapsid was found to cause a tenfold increase of luciferase expression, meaning that the mutated virus-assembly protein was ten times as active. Syed noted that this matched the tenfold increase in viral load observed in patients infected with the Delta variant.

The researchers further proved that the mutations increased the activity of the nucleocapsid by infecting cells with real SARS-CoV-2 virions in a highly controlled lab setting, finding that the real mutated virus also demonstrated faster reproduction.

This research has the potential to completely redirect the focus of scientists searching for culprit mutations in new variants of SARS-CoV-2, as research has largely focused on the spike protein until now. An improved understanding of the mechanisms of improved infectivity is important to researchers developing new therapies.

The novel virus-like particle method used could also prove to change virus research forever, as Taha states that this faster and safer alternative to using real viruses could also be used to test existing therapeutics (like vaccines) on new variants. Syed mentioned that the VLP method could even be used to find out if certain animal coronaviruses are capable of infecting humans, to develop new methods of therapy for COVID-19, or to do research on newly emerging viruses that are potentially too dangerous to work with.

This article is based on the following sources

– A. M. Syed et al., Science. (2021, November 4). Rapid assessment of SARS-Cov-2 evolved variants using virus-like particleshttps://doi.org/10.1126/science.abl6184
– Henderson, H. (2021, November 4). New method sheds light on why some SARS-Cov-2 variants are more infectious. Innovative Genomics Institute (IGI). https://innovativegenomics.org/news/sars-cov-2-variants-infection/
– Peters Kostman, M. (2021, May 17). Free COVID-19 (SARS-Cov-2) illustrations. Innovative Genomics Institute (IGI). https://innovativegenomics.org/free-covid-19-illustrations