SARS-CoV-2, the virus that causes COVID-19, is an airborne disease transmitted via aerosols, which are spread from the oral and nasal cavities—the mouth and the nose. In addition to the well-known division and spread of the virus in the cells of the respiratory tract, SARS-CoV-2 is also known to infect the cells of the lining of the mouth and the salivary glands.
A team of researchers led by Professor Kyoko Hida at Hokkaido University have shown that low concentrations of the chemical cetylpyridinium chloride, a component of some mouthwashes, has an antiviral effect on SARS-CoV-2. Their findings were published in the journal Scientific Reports.
Commercially available mouthwashes contain a number of antibiotic and antiviral components that act against microorganisms in the mouth. One of these, cetylpyridinium chloride (CPC), has been shown to reduce the viral load of SARS-CoV-2 in the mouth, primarily by disrupting the lipid membrane surrounding the virus. While there are other chemicals with similar effects, CPC has the advantage of being tasteless and odorless.
Cetylpyridinium chloride (CPC), the chemical tested in the study (Photo: Ryo Takeda)/CREDIT:Ryo Takeda
The researchers were interested in studying the effects of CPC in Japanese mouthwashes. Mouthwashes in Japan typically contain a fraction of the CPC compared to previously tested mouthwashes. They tested the effects of CPC on cell cultures that express trans-membrane protease serine 2 (TMPRSS2), which is required for SARS-CoV-2 entry into the cell.
They found that, within 10 minutes of application, 30–50 µg/mL of CPC inhibited the infectivity and capability for cell entry of SARS-CoV-2. Interestingly, commercially available mouthwashes that contain CPC performed better than CPC alone. They also showed that saliva did not alter the effects of CPC. Most significantly, they tested four variants of SARS-CoV-2—the original, alpha, beta and gamma variants—and showed that the effects of CPC were similar across all strains.
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This study shows that low concentrations of CPC in commercial mouthwash suppress the infectivity of four variants of SARS-CoV-2. The authors have already begun assessing the effect on CPC-containing mouthwashes on viral loads in saliva of COVID-19 patients. Future work will also focus on fully understanding the mechanism of effect, as lower concentrations of CPC do not disrupt lipid membranes.
Starting twice daily flushing of the mucus-lined nasal cavity with a mild saline solution soon after testing positive for COVID-19 can significantly reduce hospitalization and death, investigators report.
They say the technique that can be used at home by mixing a half teaspoon each of salt and baking soda in a cup of boiled or distilled water then putting it into a sinus rinse bottle is a safe, effective and inexpensive way to reduce the risk of severe illness and death from coronavirus infection that could have a vital public health impact.
“What we say in the emergency room and surgery is the solution to pollution is dilution,” says Dr. Amy Baxter, emergency medicine physician at the Medical College of Georgia at Augusta University
“By giving extra hydration to your sinuses, it makes them function better.
If you have a contaminant, the more you flush it out, the better you are able to get rid of dirt, viruses and anything else,” says Baxter.
“We found an 8.5-fold reduction in hospitalizations and no fatalities compared to our controls,” says senior author Dr. Richard Schwartz, chair of the MCG Department of Emergency Medicine. “Both of those are pretty significant endpoints.”
Drs. Richard Schwartz and Amy Baxter/Photo:Medical College of Georgia
The study appears to be the largest, prospective clinical trial of its kind and the older, high-risk population they studied — many of whom had preexisting conditions like obesity and hypertension — may benefit most from the easy, inexpensive practice, the investigators say.
They found that less than 1.3% of the 79 study subjects age 55 and older who enrolled within 24-hours of testing positive for COVID-19 between Sept. 24 and Dec. 21, 2020, experienced hospitalization. No one died.
Among the participants, who were treated at MCG and the AU Health System and followed for 28 days, one participant was admitted to the hospital and another went to the emergency room but was not admitted.
Schwartz says Baxter brought him the idea early in the pandemic and he liked that it was inexpensive, easy to use and could potentially impact millions at a time where, like other health care facilities, the Emergency Department of the AU Health System was starting to see a lot of SARS-CoV-2-positive patients.
They knew that the more virus that was present in your body, the worse the impact, Baxter says. “One of our thoughts was: If we can rinse out some of the virus within 24 hours of them testing positive, then maybe we can lower the severity of that whole trajectory,” she says, including reducing the likelihood the virus could get into the lungs, where it was doing permanent, often lethal damage to many.
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Additionally, the now-infamous spiky SARS-CoV-2 is known to attach to the ACE2 receptor, which is pervasive throughout the body and in abundance in locations like the nasal cavity, mouth and lungs. Drugs that interfere with the virus’ ability to attach to ACE2 have been pursued, and Baxter says the nasal irrigation with saline helps decrease the usual robust attachment. Saline appears to inhibit the virus’ ability to essentially make two cuts in itself, called furin cleavage, so it can better fit into an ACE2 receptor once it spots one.
Participants self-administered nasal irrigation using either povidone-iodine, that brown antiseptic that gets painted on your body before surgery, or sodium bicarbonate, or baking soda, which is often used as a cleanser, mixed with water that had the same salt concentration normally found in the body.
But their experience indicates the saline solution alone sufficed. “It’s really just the rinsing and the quantity that matter,” Baxter says.
The investigators also wanted to know any impact on symptom severity, like chills and loss of taste and smell. Twenty-three of the 29 participants who consistently irrigated twice daily had zero or one symptom at the end of two weeks compared to 14 of the 33 who were less diligent.
Those who completed nasal irrigation twice daily reported quicker resolution of symptoms regardless of which of two common antiseptics they were adding to the saline water.
Others have shown the nasal irrigation, also called lavage, can also be effective in reducing duration and severity of infection by a family of viruses that include the coronaviruses, which are also known to cause the common cold, as well as the influenza viruses, the investigators write. “SARS-CoV-2 infection was another perfect situation for it,” Baxter says.
In fact, nasal irrigation is something that has been done for millennia in Southeast Asia, and Baxter had noted lower death rates from COVID-19 in countries like Laos, Vietnam and Thailand. “Those were places that I knew from having been there where they use nasal irrigation as a normal part of hygiene just like brushing their teeth,” she says. A 2019 pre-COVID study provided evidence that regular nasal irrigation in Thailand can improve nasal congestion, decrease postnasal drip, improve sinus pain or headache, improve taste and smell and improve sleep quality.
Saline water
Schwartz said the simplicity and safety of the treatment had him recommending nasal irrigation to positive patients early on and the published results make him even more confident in recommending nasal irrigation to essentially anyone who tests positive.
“Many of the people who have been using this now for months have told me their seasonal allergies have gone away, that it really makes a huge difference in any of the things that go through the nose that are annoying.”
A study released in September 2020 indicated that gargling with a saline-based solution can reduce viral load in COVID-19, and another released in 2021 suggested that saline works multiple ways to reduce cold symptoms related to infection with other coronaviruses and might work as well as a first-line intervention for COVID-19.
Despite the two nostrils, the nasal sinus is just one cavity, so the water is pushed into one side and comes out the other, Baxter notes.
Mutated versions of the 80r and m396 antibodies can be produced and given as a therapeutic to fight the Covid-19 infection
A researcher, using computer models to understand the structure of viruses at the molecular level, has figured out how the old 2002 SARS coronavirus virus functions vis-a-vis the novel coronavirus or SARS-COV-2 that causes Covid-19. He discovered that sequence differences prevent 80R and m396 from binding to COVID-19 using ‘in silico’ analysis to fast-track passive immunity.
Since both illnesses (SARS-CoV and SARS-CoV-2) share the same spike protein, the entry key that allows the virus into the human cells, Padilla-Sanchez plans to take the antibodies found in the first outbreak in 2002 — 80R and m396 — and reengineer them to fit the current COVID-19 virus.
In his June 2020 publication in the online journal, Research Ideas and Outcomes, he describes efforts to unravel this problem using computer simulation based on his discovery that sequence differences prevent 80R and m396 from binding to COVID-19.
“Understanding why 80R and m396 did not bind to the SARS-CoV-2 spike protein could pave the way to engineering new antibodies that are effective,” Padilla-Sanchez said. “Mutated versions of the 80r and m396 antibodies can be produced and administered as a therapeutic to fight the disease and prevent infection.”
Supercomputing Process
His docking experiments showed that amino acid substitutions in 80R and m396 should increase binding interactions between the antibodies and SARS-CoV-2, providing new antibodies to neutralize the virus. “Now, I need to prove it in the lab,” he said.
Structural model of SARS-CoV-2 infection. This structural model was built with UCSF Chimera using high-performance computers (Bridges Large and Frontera). The model shows 16 viruses, with the spike proteins shown in green (PDB ID: 6VSB) and an actual lipid bilayer membrane, with ACE2 dimers shown in magenta. All these structures are at atomic resolution. The length of the membrane is approximately 1 micrometer / CREDIT: Victor Padilla-Sanchez
For this research, Padilla-Sanchez used supercomputing resources and ran the docking experiments for computational modeling and analysis of protein structures. The software virtually binds the proteins then provides a score for each binding experiment. “If you find a good docking position, then you can recommend that this new, mutated antibody should go to production.”
Currently, various labs across the world are already testing vaccines. “If we don’t find a vaccine in the near term we still have passive immunity, which can prevent infection for several months as long as you have the antibodies,” Padilla-Sanchez said. “Of course, a vaccine is the best outcome. However, passive immunity may be a fast track in providing relief for the pandemic.”
As of July 2020, COVID-19 has infected more than 16 million people worldwide with more than 630,000 deaths with no vaccine or therapeutics to fight the disease.
As schools in the United States are gearing up to open, anew study has come out stating that children are equally susceptible to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but exhibit mild symptoms compared with adults. Though data is sparse on children, they do spread respiratory and gastrointestinal illnesses far wider than previously thought.
Early reports did not find strong evidence of children as major contributors to SARS-CoV-2 spread owing to school closures ahead of the pandemic and no large-scale investigations of schools in community transmission had been conducted, said the researchers. Now that public health systems ponder to reopen schools and day cares, the new study on children’s transmission potential has sent alarm bells to public health officials in the US and elsewhere.
The study conducted between March 23 and April 27, 2020 on replication of SARS-CoV-2 in older children found similar levels of viral nucleic acid as adults, but significantly greater amounts of viral nucleic acid among those younger than 5 years. The SARS-CoV-2 reverse transcriptase–polymerase chain reaction (PCR) was performed on nasopharyngeal swabs collected at various hospitals and clinics including drive-through testing sites at a pediatric tertiary medical center in Chicago, Illinois.
This cohort included all individuals aged younger than 1 month to 65 years who tested positive for SARS-CoV-2 or those with symptoms suggestive of a COVID-19–compatible illness and/or high-risk exposures. In all, 145 patients with mild to moderate illness within 1 week of symptom onset were tested.
Divided in 3 groups — young children younger than 5 years, older children aged 5 to 17 years, and adults aged 18 to 65 years — researchers found young children had significantly equivalent or more viral nucleic acid in their upper respiratory tract compared with older children and adults. Some had even 100-fold greater amount of SARS-CoV-2 in the upper respiratory tract.
Thus, the study suggests that young children can potentially be important drivers of SARS-CoV-2 spread in the general population, and are more likely to transmit. “Behavioral habits of young children and close quarters in school and day care settings raise concern for SARS-CoV-2 amplification in this population as public health restrictions are eased,” wrote authors in their paper published in the journal JAMA Pediatrics.
