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Tuesday, May 11, 2021

Variables in Robust Protection by Vaccines Against SARS-CoV-2

 Pankaj Ahluwalia1Kumar Vaibhav2Meenakshi Ahluwalia2Ashis K. Mondal1Nikhil Sahajpal1Amyn M. Rojiani1 and Ravindra Kolhe1*

https://doi.org/10.3389/fimmu.2021.660019  


SARS-CoV-2 is the cause of a recent pandemic that has led to more than 3 million deaths worldwide. Most individuals are asymptomatic or display mild symptoms, which raises an inherent question as to how does the immune response differs from patients manifesting severe disease? During the initial phase of infection, dysregulated effector immune cells such as neutrophils, macrophages, monocytes, megakaryocytes, basophils, eosinophils, erythroid progenitor cells, and Th17 cells can alter the trajectory of an infected patient to severe disease. On the other hand, properly functioning CD4+, CD8+ cells, NK cells, and DCs reduce the disease severity. Detailed understanding of the immune response of convalescent individuals transitioning from the effector phase to the immunogenic memory phase can provide vital clues to understanding essential variables to assess vaccine-induced protection. Although neutralizing antibodies can wane over time, long-lasting B and T memory cells can persist in recovered individuals. The natural immunological memory captures the diverse repertoire of SARS-CoV-2 epitopes after natural infection whereas, currently approved vaccines are based on a single epitope, spike protein. It is essential to understand the nature of the immune response to natural infection to better identify ‘correlates of protection’ against this disease. This article discusses recent findings regarding immune response against natural infection to SARS-CoV-2 and the nature of immunogenic memory. More precise knowledge of the acute phase of immune response and its transition to immunological memory will contribute to the future design of vaccines and the identification of variables essential to maintain immune protection across diverse populations.

https://www.frontiersin.org/articles/10.3389/fimmu.2021.660019/full

Cannabidiol Inhibits SARS-CoV-2 Replication, Promotes Host Innate Immune Response

 Long Chi Nguyen, 

Dongbo YangVlad NicolaescuThomas J. BestTakashi OhtsukiShao-Nong ChenJ. Brent FriesenNir DraymanAdil MohamedChristopher DannDiane SilvaHaley GulaKrysten A. JonesJ. Michael MillisBryan C. DickinsonSavaş TayScott A. OakesGuido F. PauliDavid O. MeltzerGlenn RandallMarsha Rich Rosner

Just 2% of SARS-CoV-2−positive individuals carry 90% of virus in circulation

 

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PDF: https://www.pnas.org/content/pnas/118/21/e2104547118.full.pdf

Significance

We analyzed data from saliva-based COVID-19 screening deployed on the University of Colorado Boulder campus. Our dataset is unique in that all SARS-CoV-2−positive individuals reported no symptoms at the time of saliva collection, and therefore were infected but asymptomatic or presymptomatic. We found that 1) the distribution of viral loads observed in our asymptomatic college population was indistinguishable from what has been reported in hospitalized populations; 2) regardless of symptomatic status, approximately 50% of individuals who test positive for SARS-CoV-2 seem to be in noninfectious phases of the infection; and 3) just 2% of infected individuals carry 90% of the virions circulating within communities, serving as viral “supercarriers” and likely also superspreaders.

Abstract

We analyze data from the fall 2020 pandemic response efforts at the University of Colorado Boulder, where more than 72,500 saliva samples were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using qRT-PCR. All samples were collected from individuals who reported no symptoms associated with COVID-19 on the day of collection. From these, 1,405 positive cases were identified. The distribution of viral loads within these asymptomatic individuals was indistinguishable from what has been previously observed in symptomatic individuals. Regardless of symptomatic status, ∼50% of individuals who test positive for SARS-CoV-2 seem to be in noninfectious phases of the disease, based on having low viral loads in a range from which live virus has rarely been isolated. We find that, at any given time, just 2% of individuals carry 90% of the virions circulating within communities, serving as viral “supercarriers” and possibly also superspreaders.

https://www.pnas.org/content/118/21/e2104547118

CureVac says mass vaccine rollout thrown into doubt by U.S. restrictions

 Germany's CureVac (5CV.DE), which is gearing up to publish results of a key COVID-19 vaccine trial, said U.S. export restrictions on key materials are making it impossible to predict its short-term supply ramp-up in Europe.

"Due to the Defense Production Act we are not getting certain goods out of the USA," CureVac Chief Executive Franz-Werner Haas told weekly Der Spiegel.

The Defense Production Act is a decades old U.S. law that gives federal agencies the power to prioritize procurement orders related to national defence, but it has also widely been used in non-military crises such as natural disasters.

"We are not getting all the materials that we need," he was quoted as saying.

"At times we live from hand to mouth. That makes it hard to build up a stockpile," Haas said, when asked how much the company would be able to deliver during the summer months.

He added that items in short supply include special plastic containers and nucleotides, which are the chemical building blocks that make up the genetic code in the vaccine's active ingredient, the so-called messenger RNA.

Unlike rival German vaccine developer BioNTech (22UAy.DE), which struck a partnership with pharma giant Pfizer (PFE.N), CureVac has not teamed up with a U.S. partner. BioNTech and Pfizer continue to increase global production and have not cited the Defense Production Act as a hindrance. 

As CureVac's only major supply deals, the European Union in November last year secured up to 405 million doses of the immunisation.

The biotech firm has said it expects to file for European authorization in late May or early June. read more

Nasdaq-listed CureVac, which is backed by investors Dietmar Hopp, GlaxoSmithKline (GSK.L) as well as the German government, has said it aims to produce up to 300 million doses of the vaccine in 2021 and up to 1 billion in 2022.

https://www.reuters.com/business/healthcare-pharmaceuticals/curevac-says-mass-vaccine-rollout-thrown-into-doubt-by-us-restrictions-2021-05-04/

Resuming in-person learning at Texas schools last fall accelerated spread of COVID-19: study

 When Texas schools returned to in-person education last fall, the spread of the coronavirus “gradually but substantially accelerated,” leading to at least 43,000 additional cases and 800 additional deaths statewide, according to a study released Monday.

Covid booster shots 'will also be free to the public'

 Covid-19 booster shots will be free to the public if they are needed to control the ongoing pandemic, David Kessler, chief science officer of the White House Covid-19 response team, told U.S. lawmakers Tuesday.

“We do have the funds to purchase the next round and to assure if there are boosters that they are free just as the last round,” Kessler said at a Senate hearing. “Beyond 2022, I look to your guidance for at what point do you transition back to a commercial market, but I think for this coming round we are going to proceed as we have proceeded,” he said.

Kessler said it is still unclear if the booster shots will be necessary to protect against future variants of the coronavirus. The U.S. is making the preparations in case they are needed, he said. Antibodies that protect against the virus wane over time and new variants that reduce the effectiveness of some vaccines “all increase the probability that booster doses may be needed,” he said.

Kessler said the U.S. needs to speed its work in developing an oral antiviral drug that can be easily distributed to help combat the virus. The U.S. has granted emergency approval of a few drugs that use antibodies to fight Covid-19, but they have to be administered via an IV drip and haven’t been widely used by health providers.

“People who are immunosuppressed, who do not mount an immune response for a number of reasons or choose not to be vaccinated will continue to be vulnerable and we need options for them,” Kessler said. “The antibody treatments are one approach, but a simple oral antiviral can add to our armamentarium to bring this epidemic under control.”

If booster shots are deemed necessary by federal health officials, seniors and people with underlying conditions would likely be the first to have access to them, as they did during the first round of vaccines.

Moderna is already running tests on a potential booster shot to be administered after a patient is fully vaccinated with both previous doses of the vaccine. The Moderna booster shot already shows promising results against the B.1.351 and P.1 variants first detected in South Africa and Brazil, respectively.

https://www.cnbc.com/2021/05/11/us-official-says-covid-booster-shots-will-also-be-free-to-the-public-.html