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A second antimalarial treatment is being seriously considered and evaluated for its efficacy against COVID-19. The treatment is from the plant Artemisia annua, which most people know as sweet wormwood or sweet Annie. Research over the past few decades has revealed multiple health benefits from this plant with an uncommon name.
Another plant in the same family, Artemisia absinthium, has a different history. It has been used in the development of absinthe, an alcoholic beverage which is up to 80% alcohol prepared by macerating the leaves and distilling them.1
However, it is the Artemisia annua, or sweet wormwood, that is a current focus of research. Sweet wormwood is a traditional Chinese medicine that has been used for more than 2,000 years. Research by Chinese scientists in the 1970s initiated what the World Health Organization calls “one of the most important advances in malaria control in modern times.”2
Wormwood and sweet wormwood belong to the Asteraceae family, which includes coneflowers, dandelions, ragweed and goldenrod.3 The plant is adaptable, hardy and in some cases considered invasive. Gardeners often plant it for the sweet-smelling foliage and its yellow flowers.4
Artemisia Annua May Hold One Key to COVID-19
Researchers isolated a class of compounds in sweet wormwood that demonstrated activity against cancer, schistosomiasis and malaria.5 More recently, it was discovered that the plant is bioactive against certain viruses such as cytomegalovirus, hepatitis B and C, and members of the herpes family, including herpes virus type 1 and Epstein-Barr.6
Following the SARS outbreak in 2003, researchers began evaluating the effectiveness of Chinese medicinal herbs against the virus.7 Four extracts showed promise, including Artemisia annua.
Building on this and other research, scientists at the Max Planck Institute in Germany collaborated with those at Freie Universität Berlin to carry out laboratory studies evaluating the bioactive compounds in the plant against SARS-CoV-2. Peter H. Seeberger, who was one of two scientists who oversaw the research, commented:8
"Having worked with compounds derived from A. annua plants, I was familiar with the interesting activities of the plants against many different diseases, including a range of viruses. Therefore, we felt that exploring the activity of this plant against COVID-19 was worth the undertaking.”
Stronger Antiviral Activity With Coffee
Seeberger was also encouraged by the international collaboration as scientists work together to find compounds that may improve the treatment and management of people with COVID-19. He said:9
“Given the encouraging results of Chinese colleagues in 2005 and similarities between the new virus and the one that caused SARS, plant extracts and artemisinin derivatives need to be tested as quickly as possible. This international collaboration makes this possible.”
After demonstrating antiviral capability in the lab, researchers moved to testing sweet wormwood in a human trial. They are using a cultivated line of seeds developed by ArtemiLife Inc. from Kentucky. The researchers found that when the compounds were extracted from this particular line, they demonstrated the strongest antiviral activity.
Klaus Osterrieder from Freie Universität Berlin conducted the activity assays in which they discovered that using an ethanolic extract of Artemisia and coffee produced the best results. When tested alone, the artemisinin didn’t demonstrate much antiviral activity. Osterrieder found the results remarkable:10
"I was surprised to find that A. annua extracts worked significantly better than pure artemisinin derivatives and that the addition of coffee further enhanced the activity.”
If they find success in the human trials, it may mean the discovery of a treatment for COVID-19 that meets many criteria. These include being widely available, relatively inexpensive, effective and safe.11
Pick-the-Winner Study Design Scales Up Traditional Research
The extract is being added to an ongoing University of Kentucky clinical trial in which researchers are evaluating experimental treatments for COVID-19. In the race to find a viable treatment, clinical trials are taking on unique designs.
In this case, the researchers developed a “pick-the-winner” format that lets scientists quickly evaluate the results of the therapies being tested and move patients into clinical arms that appear to be working. Dr. Susanne Arnold, a medical oncologist from the University of Kentucky Markey Cancer Center, commented on the distinctive study design:12
“While there is no standard treatment for COVID-19, this trial gives us the ability to test multiple therapies rapidly in order to identify the most promising agents. This rapid assessment means that the trial can quickly include and test new therapies such as Artemisia annua.”
This study design is different from the remdesivir research that, according to The HighWire, appeared to be manipulated as the scientists changed the outcome measures, the number of study participants and the type of placebo used as the study moved forward.13
The adaptive U.K. wormwood study aims to move as many patients into successful treatments as possible as results are tabulated, while the data collection is ongoing. The treatments are also being reserved for patients assessed to be at high risk, who are either at home or in the hospital and have tested positive for COVID-19. Patients who have the symptoms but have not developed severe symptoms can also be included if they are in a high-risk category.
The researchers use a multidisciplinary committee to choose therapies allowed in the trial. Some of the criteria used to consider are those that “have excellent safety profiles and are readily available, rapidly scalable and relatively inexpensive.”
Those who choose to enroll in the trial are assigned one of four types of treatment, including Artemisia annua. Once the team has identified the most promising therapies from this study, they plan to enroll a larger number of patients in a traditional placebo-controlled trial.
Artemisia Annua Has a 30-Year History Treating Malaria
Artemisia annua has a long history of use as one of the best treatments for malaria.14 In a press release from Max-Planck-Gesellschaft, it was noted that artemisinin-based combinations are used throughout the world, they show little toxicity and are even used to treat malaria in newborns.15
There have been some reports of liver damage when using products containing artemisia annua.16 However, studies show the liver damage from sweet wormwood is both rare and self-limiting.17 The most severe cases reported were in people getting other antimalarial drugs with known hepatotoxicity. Symptoms appeared in days or weeks after starting Artemisia annua.
As the study at the University of Kentucky gets underway, the Malagasy Institute of Applied Research (IMRA) in Madagascar has already developed a product based on one of their traditional medicines from sweet wormwood. The director general, Dr. Charles Andrianjara, began work in January when COVID-19 was first announced.18
The group combed through their catalog of thousands of medicinal herbs collected since 1957. Their hypothesis was that if they could find a treatment for “the cough, respiratory difficulties, the aches, the fever, then we could treat the virus.”19
Some Concerned Monotherapy May Drive Malarial Resistance
The IMRA is well-respected in a country where many of the residents turn first to herbal medicine before looking for pharmaceutical drugs. They refined some and contributed to research that led to discovering pharmaceutical treatments that are internationally recognized, including a drug that helps with diabetes management and another now being used to treat certain cancers.
At the time of the announcement and launch of Covid-Organics (CVO) in Madagascar, fewer than 20 patients had used the treatment. This is likely since the country has had a low number of people with the virus — 405 confirmed cases as of May 22, 2020, as reported by Time.20
The team had developed an herbal tea that combined Artemisia with other ingredients. Although the numbers were low, Andrianjara was encouraged since the remedies included in the tea have no known side effects. He went on to explain to Time:21
“’They have been thoroughly tested for toxicity, and they have been on the market for 30 years, so we already know their efficacy.’ He likens CVO to common Western treatments like painkillers, which some studies show do not work on everyone. ‘You can give 20 people paracetamol. It won’t harm any of them, but it won’t cure all of their headaches either. If CVO can cure 60% of the population, to me that’s good. It’s not the best, but it’s good.’”
This relatively nontoxic compound is the cornerstone of a combination therapy that has significantly brought down the number of deaths from malaria. Kevin Marsh from the University of Oxford has been studying malaria in Kenya for decades. He worries about the resistance the parasite may develop to artemisinin if it's used in Africa as a monotherapy.22
When used to treat malaria, a second drug is included in the cocktail to reduce the potential for drug resistance, although the question of resistance is not clear as others don't believe it will be an issue since pharmacies in Africa have sold artemisinin monotherapy for many years.
After the announcement of CVO, several African nations requested information about shipments to their countries.23 This prompted a statement from the World Health Organization on May 4, 2020, in which they expressed concern and rebuked unsubstantiated claims, writing:24
“… caution must be taken against misinformation, especially on social media, about the effectiveness of certain remedies. Many plants and substances are being proposed without the minimum requirements and evidence of quality, safety and efficacy.
The use of products to treat COVID-19, which have not been robustly investigated can put people in danger, giving a false sense of security and distracting them from hand washing and physical distancing which are cardinal in COVID-19 prevention, and may also increase self-medication and the risk to patient safety.”
It’s Not Clear What’s in the Madagascar Brew
Health officials gave three reasons for their concern over the promotion of an herbal remedy like CVO to prevent and treat the novel coronavirus.25 At the time of the promotion there was no scientific evidence to show the extract could work in humans. The fear is this would give users a false sense of security, leading people to stop social distancing and hand-washing.
The second concern was that the herbal tea or capsule can contain a cocktail of other bioactive compounds that may have side effects not associated with artemisinin. And third, widespread use may trigger resistant strains of malaria for people living in regions where the disease is endemic.
Chemical & Engineering News reports southeast Asia currently has an artemisinin-resistant malaria parasite, and signs of rising resistance are appearing in Papua New Guinea, Guyana and Rwanda. The African Union has requested that the government of Madagascar explain, scientifically, how the wormwood-based cocktail works.26
Andrianjara’s statements are the result of observation from a handful of patients. It will also be difficult for others to validate the effects of CVO as the IMRA has not released the ingredients. While it is being promoted by the country’s president, the Madagascar National Academy of Medicine has not cleared it for distribution.
However, as some contemplate where the profit is being funneled from the sale of CVO, it is important to note that unlike remdesivir, which is being sold for $3,100 for a full course of treatment,27 the cost to consumers for sweet wormwood treatments is relatively low. Covid-Organics can be found in almost every supermarket for the equivalent of 20 cents for a single serving and $1.50 for a box of 10 tea bags. Adrianjara suggests28
“Instead of researching something new that costs a lot of money that we cannot afford, let’s go back and revisit our traditional knowledge. We have a lot of wealth in our traditions and culture, and maybe we don’t exploit it enough.”