Interferon-inducer antivirals: Potential candidates to combat COVID-19

 Ashkan Bagheri a,b,c,d,1 , Seyed Mohammad Iman Moezzi a,b,c,d,1 , Pouria Mosaddeghi a,b,c,d , Sadra Nadimi Parashkouhi a,b,c,d , Seyed Mostafa Fazel Hoseini a,b,c,d , Fatemeh Badakhshan a,b,c,d , Manica Negahdaripour a,b,*

ABSTRACT 

Coronavirus disease 2019 (COVID-19) is an infective disease generated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the pandemic urgency and lack of an effective cure for this disease, drug repurposing could open the way for finding a solution. Lots of investigations are ongoing to test the compounds already identified as antivirals. On the other hand, induction of type I interferons are found to play an important role in the generation of immune responses against SARS-CoV-2. Therefore, it was opined that the antivirals capable of triggering the interferons and their signaling pathway, could rationally be beneficial for treating COVID-19. On this basis, using a database of antivirals, called drugvirus, some antiviral agents were derived, followed by searches on their relevance to interferon induction. The examined list included drugs from different categories such as antibiotics, immunosuppressants, anti-cancers, non-steroidal anti-inflammatory drugs (NSAID), calcium channel blocker compounds, and some others. The results as briefed here, could help in finding potential drug candidates for COVID-19 treatment. However, their advantages and risks should be taken into account through precise studies, considering a systemic approach. Even though the adverse effects of some of these drugs may overweight their benefits, considering their mechanisms and structures may give a clue for designing novel drugs in the future. Furthermore, the antiviral effect and IFN-modifying mechanisms possessed by some of these drugs might lead to a synergistic effect against SARS-CoV-2, which deserve to be evaluated in further investigations. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705326/pdf/main.pdf

Correlation of SARS-CoV-2 Breakthrough Infections to Time-from-vaccine; Prelim Study

 Roni Lotan, Sivan Gazit, Gabriel Chodik, Tal Patalon, Galit Perez, Amir Ben Tov, barak mizrahi, Nir Kalkstein, Asaf Peretz

doi: https://doi.org/10.1101/2021.07.29.21261317

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.07.29.21261317v1.full.pdf

Abstract

The short-term effectiveness of a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine was widely demonstrated. However, long term effectiveness is still unknown. A nationwide vaccination campaign was initiated early in Israel, allowing for a real-world evaluation of the interaction between protection and time-from-vaccine. The Delta (B.1.617.2) variant became the dominant strain in Israel in June 2021, as Israel is currently experiencing a new surge of cases. Leveraging the centralized computerized database of Maccabi Healthcare Services (MHS), we assessed the correlation between time-from-vaccine and incidence of breakthrough infection. We found that the risk for infection was significantly higher for early vaccinees compared to those vaccinated later. This preliminary finding should prompt further investigagions into long-term protection against different strains, and prospective clinical trials to examine the effect of a booster vaccine against breakthrough infection.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

This is a retrospective study

Funding Statement

Funded by Maccabi health care

https://www.medrxiv.org/content/10.1101/2021.07.29.21261317v1

Vaccinated, unvaccinated individuals have similar viral loads in communities with high prevalence of delta variant

 Kasen K Riemersma, Brittany E Grogan, Amanda Kita-Yarbro, Gunnar E Jeppson, David H O'Connor,  

View ORCID ProfileThomas C Friedrich, Katarina M Grande

doi: https://doi.org/10.1101/2021.07.31.21261387

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.07.31.21261387v1.full.pdf

Abstract

SARS-CoV-2 variant B.1.617.2 (delta) is associated with higher viral loads [1] and increased transmissibility relative to other variants, as well as partial escape from polyclonal and monoclonal antibodies [2]. The emergence of the delta variant has been associated with increasing case counts and test-positivity rates, indicative of rapid community spread. Since early July 2021, SARS-CoV-2 cases in the United States have increased coincident with delta SARS-CoV-2 becoming the predominant lineage nationwide [3]. Understanding how and why the virus is spreading in settings where there is high vaccine coverage has important public health implications. It is particularly important to assess whether vaccinated individuals who become infected can transmit SARS-CoV-2 to others. In Wisconsin, a large local contract laboratory provides SARS-CoV-2 testing for multiple local health departments, providing a single standard source of data using the same assay to measure virus burdens in test-positive cases. This includes providing high-volume testing in Dane County, a county with extremely high vaccine coverage. These PCR-based tests provide semi-quantitative information about the viral load, or amount of SARS-CoV-2 RNA, in respiratory specimens. Here we use this viral load data to compare the amount of SARS-CoV-2 present in test-positive specimens from people who self-report their vaccine status and date of final immunization, during a period in which the delta variant became the predominant circulating variant in Wisconsin. We find no difference in viral loads when comparing unvaccinated individuals to those who have vaccine "breakthrough" infections. Furthermore, individuals with vaccine breakthrough infections frequently test positive with viral loads consistent with the ability to shed infectious viruses. Our results, while preliminary, suggest that if vaccinated individuals become infected with the delta variant, they may be sources of SARS-CoV-2 transmission to others.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was supported by Centers for Disease Control and Prevention contracts 75D30120C09870 and 75D30121C11060 to D.H.O and T.C.F. The authors are also members of the Upper Midwest Regional Accelerator for Genomic Surveillance funded by the Rockefeller Foundation.

https://www.medrxiv.org/content/10.1101/2021.07.31.21261387v1

Spike in reported increase of COVID-19 deaths was skewed by old data

 A massive 300 percent hike in nationwide COVID-19 deaths recorded Friday by Johns Hopkins University was skewed by states dumping data – that in one case dated back as far as last spring, according to a report.

The university, which has been a trusted source of coronavirus information since the start of the pandemic, reported that US deaths surged from 321 on Thursday to 891 on Friday, as the Delta variant quickly spreads throughout much of the country.

Florida was responsible for a huge chunk of the increase, with 409 of Friday’s death toll coming from that state, according to The Daily Mail. However, Florida only releases weekly data on Friday, making the day-to-day totals reported by the university unclear and overblown, the outlet said.

Figures released by Delaware also added to the surging daily increase, as that state announced 130 new deaths Friday, the tabloid reported. The dramatic figure was misleading because those deaths actually occurred between mid-May 2020 and late last month, and were added after The First State reviewed death certificates, according to the article.

People wait in line at a Miami-Dade County COVID-19 testing site in Hialeah, Florida.

Lynne Sladky/AP

Data from Michigan, which only releases statistics biweekly, also reportedly added to the distorted total.

The true day-to-day increase of nationwide COVID-19 deaths was actually only 2.5 percent, according to the outlet.

https://nypost.com/2021/07/31/spike-in-reported-increase-of-covid-19-deaths-skewed-by-old-data/

California Biggest Public Sector Union Opposes Newsom's Vaccine Order

 by Tom Ozimek via The Epoch Times,

California’s biggest public sector union has come out in opposition to Gov. Gavin Newsom’s order requiring state workers to show proof of vaccination against COVID-19 or undergo regular testing.

Richard Louis Brown, president of SEIU Local 1000, which represents some 96,000 employees of the State of California, on Wednesday shared a letter from the union to the California Department of Human Resources (CalHR) objecting to Newsom’s vaccine mandate.

“The new policy constitutes a unilateral change in violation of the obligation to give notice and the opportunity to meet and confer prior to implementation,” reads the letter, signed by SEIU Local 1000 chief counsel Anne Giese.

Giese called on CalHR and the State of California to “cease and desist enforcing this requirement or imposing an immediate deadline” until the union has had the chance to meet and confer.

The move came in response to the Democrat governor’s order, issued on Monday, requiring all of California’s state employees, some 246,000 people, to get vaccinated starting Aug. 2 or be subjected to weekly COVID-19 testing.

COVID-19 is the disease caused by the CCP (Chinese Communist Party) virus.

In announcing the vaccine mandate, Newsom pointed to the spread of the Delta variant of the CCP virus, which the Centers for Disease Control and Prevention (CDC) lists as a “variant of concern” and considers to be more transmissible and potentially more resistant to vaccines.

“We are now dealing with a pandemic of the unvaccinated, and it’s going to take renewed efforts to protect Californians from the dangerous Delta variant,” Newsom said in a statement.

“As the state’s largest employer, we are leading by example and requiring all state and health care workers to show proof of vaccination or be tested regularly.”

So far, opposition by SEIU Local 1000 marks the only union objection to Newsom’s order.

On Friday, Newsom’s office shared statements in support of his order issued by a number of local leaders and associations.

“Newsom’s new vaccine policy is a reasonable compromise that we can get behind,” said Glen Stailey, president of the Correctional Peace Officers Association.

“It provides for regular testing at work for those who have chosen not to get vaccinated—this will prevent the spread of the virus among correctional officers and incarcerated individuals alike.”

Denise Duncan, president of the United Nurses Association of California said in a statement that, “COVID-19 transmissions are high, we’re in a fourth surge, and we know that unvaccinated people are suffering the most. This is a forward-thinking order from Governor Newsom which will save lives by protecting patients and caregivers both.”

Federal, state, and local government officials have pushed vaccinations harder as cases linked to the Delta variant have risen.

Just under half of the U.S. population is fully vaccinated, according to the CDC.

Vaccine mandates have become a hot-button issue, with advocates welcoming them as a measure to help stem the spread of the CCP virus and protect vulnerable populations, while opponents object on a range of grounds, including concerns about side effects, that the COVID-19 vaccines are currently under emergency use authorization, and that mandates infringe on personal liberties.

https://www.zerohedge.com/political/california-biggest-public-sector-union-opposes-newsoms-vaccine-order

Gottlieb estimates up to 1M Americans infected with Covid daily as delta spreads

 Dr. Scott Gottlieb told CNBC on Friday he believes the coronavirus is significantly more widespread in the U.S. than official case counts reflect as the highly contagious delta variant sweeps the nation.

“I wouldn’t be surprised if, on the whole, we’re infecting up to a million people a day right now, and we’re just picking up maybe a 10th of that or less than a 10th of that,” the former Food and Drug Administration commissioner said in an interview on “Squawk Box.” Gottlieb now serves on the board of Covid vaccine maker Pfizer.

The current seven-day average of new daily coronavirus cases in the U.S. is roughly 67,000, according to a CNBC analysis of Johns Hopkins University data. That’s up 53% compared with a week ago, as the country grapples with a surge in new infections driven largely by delta, first discovered in India and now the dominant variant in the U.S.

“What it reflects is a reality where you have a highly transmissible variant that’s widely spread across the U.S. right now that’s spreading mostly in a population that’s either vaccinated and developing mild symptoms or no symptoms at all; or spreading in a younger population that’s also less likely to develop symptoms because they’re younger, healthier,” Gottlieb said, when asked by “Squawk Box” co-host Andrew Ross Sorkin how the physician arrived at his “staggering” estimation of 1 million new infections a day. 

“Most of the spread and most of the people who are showing up in the hospital are younger people. If that’s where the infection is occurring, then there must be a lot more infection underneath the small numerator that’s showing up in the hospital,” added Gottlieb, who led the FDA from 2017 to 2019 in the Trump administration. He’s become a closely watched voice during the pandemic, routinely appearing on CNBC and other media outlets to offer his analysis on the health crisis. 

The highest seven-day day average of new Covid cases recorded in the U.S. was roughly 251,000 on Jan. 8, according to CNBC’s analysis. Case counts had dropped off dramatically in the spring as the country’s vaccination campaign picked up speed.

But in recent weeks, as U.S. cases again started to accelerate, Gottlieb has said a large number of coronavirus infections were likely going unreported, partly because the testing landscape is different now than at previous stages in the pandemic. In the early days, Gottlieb suggested the actual case counts were much higher than official tallies due to scarce testing resources.

Now, he has said it’s a different situation, where the discrepancy between case counts and true infection levels stems from people who remain asymptomatic or develop only mild symptoms not going to get tested. Additionally, Gottlieb previously told CNBC people can now complete at-home tests and those results are unlikely to make their way to health authorities and then show up in official case counts.

On Friday, Gottlieb reiterated his view that the U.S. is much further into the surge of delta-driven infections than others believe. “This delta wave will pass, probably at some point in September,” he predicted.

Gottlieb’s comments Friday came after The Washington Post and other media organizations, including CNBC, reported on a leaked Centers for Disease Control and Prevention document about the risks presented by the delta variant. 

The public health agency’s document, authenticated to CNBC by the U.S. agency, said the delta variant is as transmissible as chickenpox and suggested vaccinated people may be able to pass on the virus strain to others as easily as unvaccinated individuals. 

The studies and data included in the document were seen as key factors in the CDC reversing course on masks earlier this week. The agency now recommends all people, even those who are vaccinated, wear face coverings indoors in areas with high transmission.

https://www.cnbc.com/2021/07/30/dr-scott-gottlieb-estimates-up-to-1-million-americans-infected-with-covid-daily-as-delta-spreads.html

COVID-19 rates a worry as 1 million head for Iowa State Fair

 With coronavirus cases rising throughout Iowa and around the nation, health experts are becoming increasingly worried about next month’s Iowa State Fair, which will bring more than 1 million people to Des Moines from around the state, including many from counties with low vaccination rates and increasing prevalence of the disease.

Iowa’s biggest annual event comes at a time when giant summer events will draw crowds throughout the nation, including in states that are experiencing more virus infections due to low vaccination rates and growth of the delta variant. They range from the Sturgis Motorcycle Rally in South Dakota to the Minnesota State Fair, which typically draws more than 2 million people.

In Iowa, officials have encouraged people to get vaccinated, but the state's Republican-majority legislature and governor have blocked local governments from imposing vaccination or mask requirements, so there will be no limits on who can attend the fair when the event begins its 11-day run on Aug. 12.

“Unfortunately our current leadership has turned their back on science and turned their back on what’s available to us to fight this pandemic and leaving Iowans struggling against what could be prevented,” said Dr. Megan Srinivas, an Iowa-based infectious disease physician nationally recognized for her research, which includes COVID-19.

She said people have the misconception that being outdoors ensures safety, when the virus actually can spread in large dense crowds such as state fairs and large concert venues.

“Anytime we see a large congregation of people especially with the mixed vaccination status, we’re going to see high risk for transmission and increases in transmission,” she said.

In addition, the delta variant is two to three times more transmissible than prior virus strains, creating an additional risk among fairgoers as they stand in line for food, share condiment dispensers and hop into carnival rides, Srinivas said.

The Iowa State Fair will be in Polk County, where health department spokeswoman Nola Aigner Davis expressed concern about the state’s virus trends and a reluctance to get vaccinated or wear masks.

“We know what the numbers say. We know that our cases are going up. We know trends are going up. What is the safe thing to do when people can’t get vaccinated? They need to wear a mask,” Davis said.

Asked Wednesday if she was concerned about infections at the Iowa State Fair, Gov. Kim Reynolds didn't directly answer but advised potential fairgoers to get vaccinated and noted most people hospitalized with COVID-19 have not been vaccinated.

“So it’s a decision that they’ve made,” she said. “They’ve made the calculation on whether to do it or not and so I don’t feel that we should punish everybody because some have made the decision not to.”

The Centers for Disease Control and Prevention reported Wednesday that 49% of Iowans were fully vaccinated, ranking the state 21st in the nation. In at least 18 of Iowa's 99 counties, fewer than 40% of the population is vaccinated, and CDC data shows 35 counties with a high rate of spread and 12 counties with substantial spread of the virus.

Iowa also has the sixth-lowest testing rates in the nation among states reporting the data, which could make it difficult to pinpoint an outbreak if one occurs.

Srinivas said she's also concerned by RAGBRAI, an annual week-long bike ride across Iowa that continues through Saturday, drawing about 15,000 cyclists from around the country to small towns in counties with some of the state's lowest vaccination rates.

She called it the “perfect environment for outbreaks to occur.”

In South Dakota, the Sturgis Motorcycle Rally is expected to attract over 700,000 people. The event went forward last year amid the pandemic, leading to 463 infections traced among rallygoers. Many health experts labeled the event “a superspreader.” Cell phone data shows that, for two weeks in August, the rally turns the normally-sleepy city of Sturgis into a travel hub comparable to a major U.S. city. The event is scheduled this year for Aug. 6-15.

“It’s sort of the perfect storm for pandemic spread,” said Dr. Doug Lehmann, a doctor who runs a health clinic in Rapid City.

While South Dakota this summer has seen significantly lower case rates compared to last year, local doctors are still worried the massive crowds could lead to a fresh surge.

“This year, there’s a lot of forces that are coming together to make it potentially worse (than last year),” said Dr. Jim Buchanan, a retired physician.

Only about 37% of people in Meade County -- where the rally will be held -- have been fully vaccinated, according to the Centers for Disease Control and Prevention.

In Chicago, the city’s top public health officials said Tuesday that she’s still comfortable with the four-day Lollapalooza music festival set to begin Thursday. Organizers are requiring attendees to show proof of full vaccination or a negative COVID-19 test result, Dr. Allison Arwady said Tuesday. People attending all four days will have to be tested at least twice.

The festival — the city’s largest music event — is expected to draw 100,000 people each day to Chicago’s Grant Park. Those who are not fully vaccinated must wear face masks when they are attending the festival.

The Minnesota State Fair will be back starting Aug. 26 after a one-year hiatus due to the pandemic. It typically draws more than 2 million visitors during its 12-day run, which ends on Labor Day.

Nearly all of Minnesota’s pandemic restrictions have been lifted, so fair officials don’t anticipate daily attendance limits. As things currently stand, masks will not be required for guests but are “strongly encouraged” for anyone not fully vaccinated. Proof of vaccination will not be required. Hand sanitizer will be provided at locations throughout the 322-acre fairgrounds in the St. Paul suburb of Falcon Heights.

Garth Brooks fans will have a chance to be vaccinated against COVID-19 when the country music star performs at Arrowhead Stadium on Aug. 7. Chiefs president Mark Donovan said Monday the team plans to take every opportunity to offer vaccinations at Arrowhead, The Kansas City Star reported.

https://abcnews.go.com/Entertainment/wireStory/covid-19-rates-worry-million-head-iowa-state-79126119