Covid Updates as of March 20th & Final Thoughts

     It's a little over a year since the national shutdowns that send students home from school, adults home from work, and the country into a state of disarray (re: empty toilet paper shelves). Now, we are at 77,000,000 Americans with their first dose and over 10% fully vaccinated. More than 500,000 people have died in just a year.

    As of March 20th, cases have declined since the horrendous winter outbreak that had the US facing nearly 200,000 cases each day at some points. Still, the virus continues to spread with about 55,000 new cases a day, which still is relatively high considering the prior lockdown points over the past year. What's more concerning than this is the variants that continue to spread. The East Coast states have been struggling to reduce Covid cases amidst a public pushing for businesses to open such as bars, gyms, and casinos. Air travel was also at its highest rate since the pandemic hit, which could mean another surge in the weeks to come.    

    We as a country seem to be at a pivotal turning point in terms of curbing the transmission of the virus and increasing to see case numbers dwindle, and a so-called "fourth wave". Much of Europe right now is locking back down amid extremely high case counts in places aside from the United Kingdom. If I've learned anything from a year on this rollercoaster ride and through Humans and Viruses, it's that we need to pay attention to transmission and incidence and not just "trends". A little rain may seem inconsequential after a hurricane just hit, but it still is a weather event. We must not neglect our still high number of cases especially when variants could pose a risk to vaccination efforts. I don't know where we will be come March 2022, but I know the skills I've learned from class will equip me well to think critically about data and about habits as a population trying to curb a virus.

https://www.nytimes.com/live/2021/03/19/world/covid-vaccine-coronavirus-cases 

-Sammy

CRISPR Treatment for Flu AND Covid-19?

 At the Georgia Institute of Technology, researchers have developed a new treatment utilizing CRISPR to target RNA molecules. The treatment would theoretically be given to humans via a nebulizer, which would be a relatively easy way to distribute the treatment once in the hands of patients.

            The researchers had the mRNA technology code for a protein, Cas13a, that destroys parts of code that viruses use to replicate in the lungs. They were able to devise the treatment for flu and COVID-19 because the only change required was the guide strand—which is what tells the Cas13a protein where to attach to the RNA and destroy it. For the flu, the protein goes for the polymerase genes in replication. The treatment also is able to attack SARS-CoV-2 at conserved targets even given the variants circulating. As we know, influenza and SARS-CoV-2 have incredibly different genomes; this subtle change based upon each viruses’ genetic code is an amazing opportunity for multi-purpose treatment for respiratory viruses.

 

            The research trials showed that the protein can work for 99% of flu strains circulating, and also produced no side effects in animal models and helped them to fully recover. More work must be done on the safety of these treatments before human trials can begin; however, the mRNA does not get into your nucleus and affect the DNA and is relatively transient in the body as well. After successful vaccines so far, the data on successful treatments is very encouraging to see.  - Sammy

https://globalbiodefense.com/2021/03/19/mrna-treatment-shows-promise-for-stopping-flu-and-covid-19-viruses/ 

Controlling Avian Influenza

     There have been over 30 outbreaks of "High Pathogenicity Avian Influenza" (HPAI) in poultry and wild fowl in Japan since October 30, 2020 alone. Influenza A virus H5N8, a virus commonly known as one of the HPAIV has caused the outbreak. In order to keep this virus from spreading, uncovering the route for introduction of the virus is essential as is finding out how to halt its transmission route.

    At Hokkaido University, with Professor Yoshihiro at the helm, scientists found one possible route of introduction of HPAIV into Japan. The route they discovered was via migratory birds coming from Europe. They also concurrently found that human anti-influenza drugs could be used to treat the virus in poultry and foul, as opposed to killing the birds. HPAI in poultry leads to large economic and material losses, and the main way to control the spread is usually by killed all the infected birds. The virus can also infect wild birds in zoos and sanctuaries which would lead to the death of potential endangered species.

    Scientists collected duck samples from Lake Komuke in Hokkaido in October 2020. The H5N8 presence was molecularly confirmed, which was related to outbreaks in Europe in 2019 and 2020 as well as variants in Korea and Japan. They ascertained from this that it must have spread due to migratory birds going from Europe to Asia in a ten month span. A pressing concern is that there is yet another H5N8 variant wreaking havoc in Europe which could mean that the north is a reservoir for the disease.

    As a Humans and Viruses student, an equally and if not more pressing concern is the relationship between HPAI and influenza in humans, given that strains from poultry have made the cross into humans before. For example, in February 2021 in Russia a zoonotic strain emerged within the human population. Thus, halting the spread of HPAI not only has implications for the poultry market, but for entire human populations as well. Given we are currently in a pandemic, viral surveillance especially in animals should be of the utmost importance.

    As for controlling virus spread in animals, the findings of two antivirals baloxavir carboxyl and peramivir being used to treat HPAI is very peculiar and could have implications for future outbreak situations.  BXM and permavir drugs were both successful in improving survival outcomes for infected poultry. As for now, however, the strongest method to stop transmission is to enact surveillance measures and continue to look at migratory birds. Finding suitable treatment is also a key step into not damaging the poultry industry or human populations with deadly diseases. - Sammy

https://www.sciencedaily.com/releases/2021/03/210311123449.htm

Chronic hepatitis C infection and opioid use

 Opioid abuse and overdose are one of the major public health threats of our time. A study by Butt et al. shows that a higher risk of prescription opioid use might be higher among chronic hepatitis C patients due to higher comorbidity burden and social vulnerability. All individuals with a confirmed chronic Hepatitis C infection from the Electronically Retrieved Cohort of HCV Infected Veterans data set were included in this study. Butt et al. measured acute and long-term prescription opioid use defined as having a drug supply of 90 days or more. Statistical analyses included chi-square and t-tests to determine the proportion of individuals with acute and chronic long term prescription opioid use by various social factors such as race, gender, homelessness, poverty (annual income <$45,200), rural/non-rural residence, alcohol use and diagnosis of psychiatric illness. Logistic regression analyses were also included to determine the risks of factors associated with the outcome of interest. The results show that among 160,856 chronic hepatitis C cases, 38.4% had acute prescription opioid use. This was significant with a p-value of 0.01. Additionally, those with chronic Hepatitis C were 60% more likely to develop chronic long term prescription opioid use (95%CI 1.63, 1.69). Black females who experienced homelessness were at the highest risk for developing chronic long term POU. Individuals with chronic hepatitis C had, in general, more social vulnerability factors compared to control groups. 

Although Butt et al. the long term effects of prescription use of opioids do require further study, this study adds to the pile of evidence that calls for addressing the public health threat that is opioid drug overdose and abuse. 

-Bethel 

https://www.nature.com/articles/s41598-021-85283-6

Hepatitis B chronicity: some light shed on cccDNA formation

 Approximately 257 million people are living with hepatitis B infection worldwide. Hepatitis B is caused by the hepatitis B virus of the hepadnaviridae family which is a DNA virus. The virus is transmitted through the parenteral route with exposure to infected bodily fluids and replicates in hepatocytes (liver cells). Hepatitis B is a disease of the liver with symptoms including jaundice, light or grey stools, hepatic tenderness and enlargement of the liver (hepatomegaly). While most adults recover, 90% of infants, 30-50% of children between the ages 1 and 5 years and 5% of adults with the disease progress to chronic HBV that causes serious diseases such as cirrhosis and hepatocellular carcinoma. The development of chronic HBV is established through persistence of the virus due to the formation of covalently closed circular DNA (cccDNA). Wei and Ploss showed in their study for the first time how cccDNA is formed from relaxed circular DNA (rcDNA). 

The genome of the virion is a double-stranded relaxed circular DNA with four lesions. These lesions are the covalently linked viral polymerase and DNA flap on the 5’-end of the negative strand and the 5’-capped RNA primer and ssDNA gap on the positive strand. After entry through the bile acid transporter (NTCP), the viral rcDNA is released into the nucleus and the four lesions on the rcDNA are repaired to form a stable cccDNA. In addition to establishing chronicity, cccDNA serves as a template for the HBV viral transcripts.  Both viral factors and host repair factors are involved in the repair process. Though Wei and Ploss identified the human factors involved in this process namely proliferating cell nuclear antigen (PCNA), the replication factor C (RFC) complex, DNA polymerase delta, flap endonuclease 1 (FEN-1), and DNA ligase 1 (LIG1), the exact mechanism by which these lead to the repair of the four lesions was not known. In their recently published work, they first showed that all five human factors are necessary for the repair of the lesions on the positive strand, whereas only FEN-1 and LIG1 are required to repair the lesions on the negative strand. Then they proceeded to understand the repair mechanism of each strand individually by monitoring the intermediates. The removal of the covalently attached viral polymerase was found to be required in the repair process with the product deproteinated rcDNA a critical repair intermediate. This research shows that the repair of the positive and negative strands are independent events with the positive strand repair resembling the maturation of Okazaki fragments. The negative-strand repair process involves a slow removal of 5’ protein adduct and removal of the DNA flap by FEN-1 leaving a nick that subsequently seals.

This remarkable work is going to be very essential in the development of therapeutics for chronic HBV infection. 

-Bethel 

https://www.nature.com/articles/s41467-021-21850-9 

https://www.cdc.gov/vaccines/pubs/pinkbook/hepb.html

WHO is getting vaccinated on the African continent?

With mass vaccination advances in developed countries, there is an ongoing worry some of the poor nations in the world are being left behind. By the end of February, per 100 people the UK has given out 31 doses, the U.S. 22, Asia just over 2 and Africa less than 0.3. As the World Health Organization has been emphasizing for months now, vaccinating individuals in all corners of the world is absolutely essential in curbing the spread of the SARS-CoV-2 virus. While some African nations have only started vaccination programs recently with the COVAX vaccines, deals with other countries and donations, some are still on the waiting line and a few countries have completely opted out of vaccinating citizens. 

The major source of vaccines for the continent is the COVAX initiative formed by WHO, CEPI and GAVI in efforts to address inequities in vaccine distribution and vaccinate 20% of Africa’s population. So far, a growing number of African countries including the first country to receive COVAX vaccines, Ghana, Kenya, Ethiopia, Ivory Coast, Nigeria, South Africa, Angola and Zimbabwe. A number of African nations have gotten vaccine donations from countries like China, Russia, India and the United Arab Emirates as well as from manufacturing companies such as Pfizer. A select number of African nations such as Senegal and Morrocco are buying their vaccines from donating countries as well. In addition, AU has allocated millions of doses to provide for member nations to help reach the goal of vaccinating the 20% African population. 

However, will vaccinating 20% of the population be enough? The head of Africa Centres for Disease Control stated that countries would need to vaccinate at least 60% of their populations to “get the pandemic out”. As a challenge to reaching this goal other than lack of resources and vaccines, there is the added burden of mistrust and resistance to getting vaccinated among the public within the continent. An online pan-African research network, Afrobarometer that collects and analyses data from more than 30 out of 54 African countries, showed that 60% of respondents of a survey said they are unlikely to try getting vaccinated. With the recent suspension of the AstraZeneca vaccines in European countries from fear of blood clot formations, this number might even be increasing. In addition, Tanzania, Burundi and Madagascar have indicated they will not be seeking vaccines at the moment until more scientific data is acquired on the vaccines. Many challenges lay ahead with shimmering hopes of death rates going down hopefully manifesting with vaccinations. 

- Bethel 

https://www.bbc.com/news/56100076 

https://www.afro.who.int/news/covax-expects-start-sending-millions-covid-19-vaccines-africa-february 

https://www.washingtonpost.com/politics/2021/03/12/africa-has-started-vaccinating-against-covid-do-citizens-trust-their-governments-vaccine-safety/ WHO is getting vaccinated on the African continent?

Controversies regarding AstraZeneca vaccine safety: the risk/benefit game

 European countries including Germany, France, Italy, Spain, Denmark, Norway and the Netherlands, among others, have paused the use of the AstraZeneca COVID-19 vaccine after reports of blood clots forming following the administration of the vaccine. In response, AstraZeneca released an update on the14th of March reassuring nations of the safety of the vaccine based on scientific evidence. 

The company reported that of the 17 million people vaccinated across EU member nations and the UK, 15 events of deep vein thrombosis and 22 cases of pulmonary embolism are reported as of March 8. The company also assured monthly safety reports to be made public with complete transparency next week. The Chief Medical Officer added, “The nature of the pandemic has led to increased attention in individual cases and we are going beyond the standard practices for safety monitoring of licensed medicines in reporting vaccine events, to ensure public safety.”

Since the clinical trial data and reports of adverse side effects following administration vaccines thus far have not shown alarming flags in terms of safety, the viability of vaccines during storage, shipments and distribution is another area to examine. This was also included in the safety update released by the company in which it reports ‘no confirmed issues’ in different batches of vaccines being distributed across the EU, UK and the rest of the world. 

The nations that suspended the use of the vaccine indicated that they are waiting for pending analysis from European authorities and regulators. WHO officials and the European Medicines Agency along with many health officials have been releasing statements that they are ‘firmly convinced’ the vaccine’s benefits far outweigh the risks. WHO officials are recommending the continued use of the vaccine and further highlighted the major challenge in the global fight against the pandemic is access to vaccines not concerns of blood clots. 

While European nations who halted the use of the AstraZeneca vaccine did so as precautionary efforts, the magnitude of the concern that resulted in this decision is questionable. Moreover, such powerful nations stopping vaccines in such a worry has an impact on the public’s perception of vaccines that is very concerning. This decision could feed into existing fears and mistrust of vaccines and even spark concerns among the public around the world. Did these countries act prematurely?

 

-Bethel

https://www.aljazeera.com/news/2021/3/15/which-countries-have-halted-use-of-astrazenecas-covid-vaccine 

https://www.washingtonpost.com/nation/2021/03/15/coronavirus-covid-live-updates-us/#link-4BVATIYKYFAL5J2ZC5IMBCEXT4 

https://www.astrazeneca.com/media-centre/press-releases/2021/update-on-the-safety-of-covid-19-vaccine-astrazeneca.html