- Scientists around the world are working on potential treatments and vaccines for the new coronavirus disease known as COVID-19.
- Several companies are working on antiviral drugs, some of which are already in use against other illnesses, to treat people who have COVID-19.
- Other companies are working on vaccines that could be used as a preventive measure against the disease.
With confirmed COVID-19 cases in the United States surpassing 9.4 million and continuing to grow, scientists are pushing forward with efforts to develop vaccines and treatments to slow the pandemic and lessen the disease’s damage.
On Oct. 22, the
The agency has also issued
An EUA allows doctors to use these drugs to treat people even before the medications have gone through the formal FDA approval process.
No vaccine that protects against SARS-CoV-2, the coronavirus that causes COVID-19, has received emergency use authorization or full approval in the United States. However, some countries have granted limited or early approval to certain vaccines.
Over the coming months, we may see additional drugs approved as COVID-19 treatments, depending on the outcome of clinical trials.
Experts also expect that a COVID-19 vaccine might be available in spring or summer 2021, although certain high-risk groups may have access to a vaccine earlier.
As we wait for additional treatments and a possible vaccine, there are still
“Even though technological advances allow us to do certain things more quickly, we still have to rely on social distancing, contact tracing, self-isolation, and other measures,” Dr. Bruce Y. Lee, a professor at the CUNY Graduate School of Public Health & Health Policy, told Healthline.
Vaccines are designed to protect people before they’re exposed to a virus — in this case SARS-CoV-2.
A vaccine basically
Vaccines also protect the community by reducing the spread of disease among people. This protection is known as herd, or community, immunity.
While many potential vaccines are in development, there is no guarantee any of these will work.
“There’s a lot of uncertainty with vaccine development,” Lee said. “Naturally, you have to make sure the vaccine is safe. But you also have to make sure the vaccine will elicit enough of an immune response.”
Like drugs, potential vaccines have to pass through
Scientists are testing 50 candidate vaccines in clinical trials in people.
Six vaccines, in China and Russia, have been given limited or early approval. These were released before the completion of phase 3 clinical trials, which has raised some concerns about safety.
Many scientists and public health experts caution that taking shortcuts with the vaccine approval process could damage the public’s faith in any approved vaccine.
“The public’s willingness to back quarantines and other public health measures to slow spread tends to correlate with how much people trust the government’s health advice,” Shibo Jiang, a virologist at Fudan University in China, wrote in the journal
“A rush into potentially risky vaccines and therapies will betray that trust and discourage work to develop better assessments,” he wrote.
Scientists began working on candidate vaccines to protect against SARS-CoV-2 in January after the virus’s genetic code, or genome, had been deciphered.
While vaccine development typically takes years, scientists hope to have a safe and effective COVID-19 vaccine sometime next year. This process has been sped up by recent advances in technology.
Experts say the likely timeline for distribution of a vaccine is spring or summer of 2021, although some high-risk groups could receive a vaccine as early as January.
Some scientists argue that a “human challenge trial” could speed up the vaccine clinical trials and answer questions about the vaccine’s efficacy and long-term protection.
In this type of trial, healthy volunteers are given a potential vaccine and then intentionally infected with the virus.
Usually, researchers wait for a person given a potential vaccine to be exposed naturally to the virus. Then they look at how well the person was protected by the vaccine.
There are no plans for this kind of study in the United States, but more than 38,000 people around the world have signed up to take part in this kind of trial.
In the United Kingdom, researchers are recruiting volunteers for a challenge trial. If the trial is approved by regulators, researchers plan to start in January.
A human challenge trial raises many ethical questions. One is that there’s still a lot we don’t know about this virus and disease, including who will get seriously ill or die from COVID-19.
That means people can’t really know the risks of participating in the study, so they wouldn’t be able to give high-quality informed consent. This is an essential part of modern clinical trials.
The World Health Organization released ethical guidelines to navigate these tricky waters.
Here’s a look at some of the ongoing COVID-19 vaccine projects:
Moderna / National Institutes of Health. The company began testing its two-dose messenger RNA (mRNA) vaccine in March in a phase 1 clinical trial, with promising results.
In late July, Moderna began phase 3 clinical trials of the vaccine.
In late August, company officials said preliminary phase 1 trial data showed that the vaccine elicited a promising immune response in 10 people between the ages of 56 and 70 as well as 10 people over age of 70.
The company announced in late October that it had finished recruiting all 30,000 participants in the phase 3 trial. This included more than 7,000 people over the age of 65 and more than 5,000 younger people with chronic conditions that increase their risk of severe COVID-19.
In early October, company officials announced their vaccine won’t be available for wide distribution until spring 2021. Later in the month, Moderna’s CEO told investors that the trial’s data and safety monitoring board could start analyzing study data in November.
Pfizer / BioNTech / Fosun Pharma. Drugmaker Pfizer teamed up German biotech company BioNTech and Chinese drugmaker Fosun Pharma to develop a two-dose mRNA vaccine.
In mid-August, company officials said the vaccine had produced a “robust” response in a phase 1/2 clinical trial.
The company launched a phase 3 trial in late July, with a goal to recruit 30,000 people from the United States, Brazil, Argentina, and Germany. They later announced plans to increase this to 44,000 people. In October, the company said it received approval to enroll children as young as 12 years in the trial — the first American trial to include this age group.
As of late October, the trial had enrolled more than 42,000 people. At the time, the company had not yet conducted an interim analysis of the study data, which puts it behind its original goal of doing so by September. However, the company still expects to have enough data sometime in November to apply for emergency use authorization from the FDA.
Inovio. When COVID-19 appeared in December, drugmaker Inovio had already been working on a DNA vaccine for MERS, which is caused by another coronavirus. This allowed the company to quickly develop a potential COVID-19 vaccine.
Company officials announced at the end of April that it had enrolled 40 healthy volunteers in its phase 1 trial. In late September, the company announced that its phase 2/3 trial is on hold as the it responds to the FDA’s questions about the study.
Sanofi / Translate Bio. Drugmaker Sanofi announced in February that it would work with Translate Bio to develop an mRNA vaccine. Preclinical testing showed that the vaccine could elicit a strong immune response in mice and monkeys. The company expects results from its phase 2 trial in early December. After that, they will start a phase 3 study.
CanSino Biologics. Scientists at this Chinese company are also working on a potential vaccine that uses an adenovirus known as Ad5 to carry coronavirus proteins into cells.
In late July, they reported that participants in a phase 2 trial showed a strong immune response when given the vaccine. However, they noted older adults had a weaker response, suggesting two doses might be needed for that segment of the population.
The Chinese military approved the vaccine in June, allowing the vaccine to be given to its armed forces. In August, the company began phase 3 trials in Pakistan, Saudi Arabia, and Russia.
Gamaleya Research Institute. This Russian institute
In August, President Vladimir Putin announced that the country’s regulatory agency had approved the vaccine, even before phase 3 trials had started. Russian officials later said the vaccine had received a “conditional registration certificate.”
Results of a phase 1/2 trial found that the vaccine elicited an immune response with mild side effects. Phase 3 trials are currently under way in Russia, Belarus, United Arab Emirates, and India.
Johnson & Johnson. Drugmaker Johnson & Johnson announced in late July that it had begun a phase 1/2 trial in people after their adenovirus vaccine had shown promising results when used in monkeys.
In late September, the company announced it was starting a phase 3 trial of its one-dose vaccine with 60,000 participants. In mid-October, the company announced it was pausing this trial due to an “unexplained illness” with one of the participants. The company has since received permission to restart the study.
AstraZeneca / University of Oxford. A phase 1 clinical trial at the University of Oxford began in late April. The vaccine is based on a chimpanzee adenovirus, which shuttles coronavirus proteins into cells.
In August, AstraZeneca began phase 3 trials in Brazil, South Africa, and the
Sanofi / GSK / TranslateBio. Drugmaker Sanofi is pursuing two vaccines. The company is working with drugmaker GSK on a vaccine based on proteins from the coronavirus. When combined with another compound, called an adjuvant, the proteins elicit an immune response. They expect results from a phase 2 trial in early December, after which they will begin a phase 3 study.
Sanofi is also working with biotech company Translate Bio to develop an mRNA vaccine. They expect to start clinical trials in December.
Novavax. This company received up to $388 million in funding this spring from the Coalition for Epidemic Preparedness Innovations (CEPI), a group that has funded COVID-19 vaccine development. The vaccine is made by attaching virus proteins to microscopic particles.
In August, Novavax launched a phase 2 trial in South Africa. A month later, the company began a phase 3 trial in the United Kingdom. It plans to start another phase 3 trial in the United States by the end of November.
University of Queensland in Australia / CSL. Researchers at the university developed a vaccine by growing viral proteins in cell cultures. They began preclinical testing stages in early April. The phase 1 trial in people began in early July. A phase 2/3 trial is expected to start late this year.
Wuhan Institute of Biological Products / Sinopharm. Chinese company Sinopharm is testing an inactivated virus vaccine developed by the Wuhan Institute of Biological Products. After a successful
Beijing Institute of Biological Products / Sinopharm. Sinopharm is testing a second inactivated virus vaccine developed by Beijing Institute of Biological Products.
Phase 3 trials began in June in the UAE and in September in Argentina. In September, the UAE approved the vaccine for use on healthcare workers even before the results of the phase 3 trials.
Sinovac Biotech. This Chinese company launched phase 3 trials of its inactivated virus vaccine in Brazil in July, Indonesia in August, and Turkey in September. In August, the Chinese government issued emergency approval for the vaccine for use on high-risk groups.
Bharat Biotech / Indian Council of Medical Research / Indian National Institute of Virology. Indian company Bharat announced in late October that it was beginning a phase 3 trial of its inactivated virus vaccine.
Murdoch Children’s Research Institute in Australia is conducting a phase 3 trial of the bacillus Calmette-Guérin (BCG) tuberculosis vaccine to see if it also protects people from the coronavirus. This trial is being run in Australia, Brazil, the Netherlands, Spain, and the United Kingdom.
Some scientists think the polio vaccine might boost the immune system just enough to fight off the new coronavirus, although there’s no evidence yet to confirm this theory.
Two U.S. researchers also suggested that the measles, mumps, rubella (MMR) vaccine might offer protection against inflammation and sepsis in people with COVID-19. They recommend starting a clinical trial with the MMR vaccine in healthcare workers.
Antivirals are drugs that are used for treating viral infections. Some antivirals target specific viruses, while others work against a number of viruses.
These drugs can work in different ways such as preventing the virus from entering host cells, replicating, or releasing viral particles to infect other cells.
Here are some of antivirals being eyed as treatments for COVID-19. Many of these have been approved for other conditions or have been tested on other viruses.
Remdesivir (brand name Veklury). Developed a decade ago, remdesivir failed in clinical trials against Ebola in 2014. But it was found to be generally safe in people.
Research with MERS, a disease caused by a different coronavirus, showed that the drug blocked the virus from replicating.
In April, drugmaker Gilead Sciences announced that preliminary data from a trial of remdesivir overseen by the National Institute of Allergy and Infectious Diseases (NIAID) had “met its primary endpoint.”
Based on these results, the FDA
In August, the agency
The results of a phase 3 trial published in October in the New England Journal of Medicine showed that remdesivir shortened the hospital stay of COVID-19 patients by about 5 days.
People taking remdesivir also had a lower risk of dying compared to those who had been given an inactive control substance.
On Oct. 22, the FDA
Not all clinical trials have found that remdesivir is effective.
Preliminary results from a World Health Organization trial released in October found that remdesivir had little effect on how long people stayed in the hospital and no effect on their risk of dying.
Remdesivir is also being tested in many COVID-19 clinical trials around the world, including in combination with other drugs such as
In mid-September, officials at Eli Lilly announced that in early stage trials their anti-inflammatory drug baricitinib when added to remdesivir can shorten hospital stays by 1 day for people with COVID-19.
Olumiant, which is the name baricitinib is sold under, is already used to treat rheumatoid arthritis and other conditions that involve overactive immune systems.
The drug is also being tested in children with moderate to severe COVID-19.
AT-527. This drug was developed by Boston biotech Atea Pharmaceuticals and is being developed in partnership with drugmaker Roche.
Atea began a phase 2 trial in May, testing the drug in people hospitalized with moderate COVID-19.
The company plans to test the drug next year outside the hospital setting, and test to see if the drug can work in people recently exposed to the coronavirus.
EIDD-2801. This drug was created by scientists at a nonprofit biotech company owned by Emory University.
Research in mice has shown that it can reduce replication of multiple coronaviruses, including SARS-CoV-2.
Pharmaceutical company Merck and Ridgeback Biotherapeutics LP signed an agreement in May to develop this drug. A phase 1 trial of this drug began in April in the United Kingdom, followed in July by a phase 2 trial.
Unlike remdesivir, EIDD-2801 can be taken orally, which would make it available to a larger number of people.
Favipiravir (brand name Avigan). This drug, which is manufactured by the Japanese company Fujifilm Toyama Chemical Co., Ltd., is approved in some countries outside the United States to treat influenza.
Japan, where the medication is made, is sending the drug to 43 countries for clinical trial testing in people with mild or moderate COVID-19. Canadian researchers are testing to see whether the drug can help fight outbreaks in long-term care homes.
In September, Fujifilm released the results of a phase 3 trial that began in March. COVID-19 patients taking the drug improved after 12 days on average versus more than 14 days on average for people taking an inactive placebo.
The company is seeking approval of the drug in Japan as a treatment for COVID-19.
Kaletra. This is a combination of two drugs — lopinavir and ritonavir — that work against HIV.
Clinical trials are being done to see whether this drug combo also works against SARS-CoV-2. There have been mixed results.
One small study published May 4 in the journal Med by Cell Press found that lopinavir/ritonavir didn’t improve outcomes in people with mild or moderate COVID-19 compared to those receiving standard care.
Another study, published May 7 in the New England Journal of Medicine, found that the drug combination wasn’t effective for people with severe COVID-19.
Merimepodib (VX-497). This drug, developed by ViralClear Pharmaceuticals Inc., has been previously shown to have antiviral and immune-suppressing effects. It was tested against hepatitis C but had only modest effects.
The company is running a phase 2 trial of this drug. People with advanced COVID-19 will be randomized to receive either merimepodib with remdesivir, or remdesivir plus a placebo.
The company ended its phase 2 trial in October after concerns about the drug’s safety.
Niclosamide. ANA Therapeutics began a phase 2 and 3 trial in October of oral niclosamide, a drug that’s been used for more than 50 years to treat tapeworms, to see whether it helps people with COVID-19. Earlier studies showed the drug had antiviral and immune-modulating activities.
Umifenovir (brand name Arbidol). This antiviral was tested along with the drug lopinavir/ritonavir as a treatment for COVID-19.
Researchers reported in mid-April that the three-drug combination didn’t improve the clinical outcomes for people hospitalized with mild to moderate cases of COVID-19.
Monoclonal antibodies trigger the immune system to attack a virus. Like antibodies made by the body’s immune system, these lab-made molecules target a specific invader, such as SARS-CoV-2.
AstraZeneca received funding in October to begin phase 3 trials of its anti-SARS-CoV-2 antibody combo drug AZD7442. One study will examine whether the drug can provide protection for up to 12 months.
The drug is made of two antibodies discovered by Vanderbilt University Medical Center, isolated from the blood of a couple from Wuhan, China.
Celltrion. This South Korean company began a phase 3 trial in October of its monoclonal antibody treatment, CT-P59. It’s being tested in people who have been in close contact with a person with COVID-19 to see whether the drug can prevent infection.
Edesa Biotech Inc. received approval to begin a phase 2 trial of its monoclonal antibody drug, EB05. The company thinks its drug could reduce the overactive immune responses associated with acute respiratory distress syndrome (ARDS).
Eli Lilly. In early October, Eli Lilly reported that a new treatment involving two antibodies showed promising results in reducing SARS-CoV-2 levels. The treatment was given to people with COVID-19 who hadn’t been hospitalized.
The results were published in the New England Journal of Medicine. People who received the antibodies had significantly reduced virus levels after 11 days. They also had slightly less severe symptoms compared to participants who received an inactive placebo.
In mid-October, the National Institutes of Health paused the phase 3 trial of Eli Lilly’s antibody over potential safety concerns. The drug was being tested in combination with the antiviral remdesivir.
Regeneron Pharmaceuticals Inc. is testing a two-antibody combination in four groups: people hospitalized with COVID-19; people with symptoms of the disease but not hospitalized; healthy people at high risk for getting sick with COVID-19; and healthy people who have had close contact with someone with COVID-19.
On Oct. 7, the company asked the FDA for emergency approval of its antibody mixture, or “cocktail.” The announcement came a few days after President Trump was treated with the drug for COVID-19. Regeneron officials said doses for 50,000 people would initially be available.
In mid-October, the company reported its antibody mixture had performed well in a clinical trial involving hamster and rhesus macaque monkeys.
In late October, the company announced it would stop recruiting participants who need high levels of supplemental oxygen into its phase 2 and 3 trial due to potential safety concerns. People who need low or no supplemental oxygen will continue to be enrolled.
Sorrento Therapeutics. This small biotech company announced in May that it has an antibody drug that’s been effective in early testing in blocking SARS-CoV-2.
The company says the drug could potentially be used to treat people with COVID-19 as well as help prevent infection.
A preprint study published in September found that the antibody protected Syrian golden hamsters that were infected with SARS-CoV-2.
Vir Biotechnology has isolated antibodies from people who survived SARS, a disease caused by another coronavirus. The company is working with Chinese firm WuXi Biologics to test them as a treatment for COVID-19.
In October, Vir and drugmaker GlaxoSmithKline began a phase 3 trial of its antibody therapy VIR-7831.
In early November, Reuters reported that a large-scale plan by the World Health Organization to supply COVID-19 drugs to poorer countries would focus on antibody treatments and steroids but not include remdesivir.
Along the same lines, the FDA has
The theory is that their plasma contains antibodies that will attack this particular coronavirus.
In late March, the New York Blood Center began collecting plasma from people who have recovered from COVID-19.
In late May, researchers reported that 19 of 25 people with COVID-19 who were treated with convalescent plasma transfusions at Houston Methodist Hospital in Texas had improved. Eleven of those patients have been released from the hospital.
Mayo Clinic and Michigan State University are also leading convalescent plasma programs.
In late August, the FDA approved an emergency use authorization for convalescent plasma therapy to treat COVID-19. Some experts, however, said more research needs to be done on this type of treatment.
A phase 2 trial published in
In some people with COVID-19, the immune system goes into overdrive, releasing large amounts of small proteins called cytokines.
Scientists think this “cytokine storm” may be the reason certain people with severe COVID-19 develop ARDS and need to be put on a ventilator.
Several immune suppressants are being tested in clinical trials to see whether the drugs can quell the cytokine storm and reduce the severity of ARDS.
Dexamethasone. The inexpensive corticosteroid is already approved for other conditions and can be given orally or intravenously.
Preliminary results published in July in the New England Journal of Medicine found that a moderate dose of dexamethasone reduced death in people hospitalized with COVID-19 on a ventilator and people receiving supplemental oxygen but not on a ventilator.
Other drugs being tested include baricitinib, a drug for rheumatoid arthritis, and IL-6 inhibitors.
Eli Lilly announced in October that baricitinib in combination with remdesivir reduced recovery time and improved clinical outcomes in people with COVID-19. The largest benefits were seen in those receiving supplemental oxygen or noninvasive ventilation.
In October, the National Institutes of Health began a
The FDA has also approved a device that
Athersys Inc. began a phase 2 and 3 trial that will examine whether the company’s stem cell treatment could potentially benefit people with ARDS.
Mesoblast has also developed a potential stem cell treatment for ARDS. The company is enrolling people with moderate to severe ARDS into a phase 2 and 3 clinical trial in the United States. As of October, the company had enrolled more than half of the participants for the phase 3 trial.
Scientists are also looking at other ways to target the virus or treat the complications of COVID-19.
Antibody cocktail. In late July, researchers at Columbia University in New York announced some initial success in using a mix of antibodies to potentially treat people with a SARS-CoV-2 infection.
They said the antibodies were collected from people hospitalized with COVID-19. The drug mixtures were tested on human cells as well as hamsters.
If proven safe and effective, the antibodies would be given via blood transfusions to people who recently contracted the virus.
Apilimod. In late July, Yale University announced it’s conducting a trial with AI Therapeutics on a drug known as apilimod.
Yale officials said the medication has been proven safe in treating autoimmune diseases and follicular lymphoma.
They said preliminary research indicates apilimod can block cellular entry of the new coronavirus.
The drug has been granted fast-track status by the FDA.
Blood thinners. In mid-September, U.S. researchers announced they’ve started two clinical trials to look at the possibility of using blood thinners to treat COVID-19.
One trial would focus on people with COVID-19 who have been hospitalized while the other would center on those with COVID-19 who weren’t hospitalized.
Cannabinoid drug ARDS-003. In mid-September, officials at Canada-based Tetra Bio-Pharma announced they had received FDA approval to start a phase 1 trial of a synthetic cannabinoid drug to treat COVID-19.
Company officials said the medication may provide protection against ARDS, a condition that’s the most common cause of death for people with severe COVID-19.
Diabetes drug. In late September, researchers reported that the diabetes drug sitagliptin reduced death and improved clinical outcomes in people with type 2 diabetes who were given the drug after being hospitalized for COVID-19.
Researchers said it’s possible that sitagliptin could also help people without type 2 diabetes who develop COVID-19.
Feline coronavirus drug. In early September, a study reported that a drug sometimes used to treat a coronavirus illness in cats showed promise in a trial against COVID-19 in humans.
The drug hasn’t been approved by the FDA for use in cats or people, but researchers say it’s shown indications it can stop SARS-CoV-2 from replicating by targeting a key part of the virus’s cellular machinery.
Ibuprofen. In early June, scientists started a clinical trial to see whether the pain medication could be used for people hospitalized with COVID-19.
Their theory is that ibuprofen’s anti-inflammatory qualities could help ease breathing difficulties associated with the illness.
Interferon beta. In mid-July, scientists in the United Kingdom reported success in initial tests with a protein called interferon beta. The body produces this protein during viral infections.
The researchers said the protein is inhaled directly into the lungs of someone with a SARS-CoV-2 infection in hopes of stimulating an immune response.
They said the protein reduced the odds of developing a severe form of the disease in hospitalized patients by 79 percent.
Preliminary results from a study by the World Health Organization found that interferon beta didn’t help people with COVID-19.
Nasal spray. In late September, officials at Australian biotech company Ena Respiratory reported that a nasal spray used to treat colds and flu was highly effective in an animal study in reducing SARS-CoV-2 replication. Human trials are scheduled to start soon.
Nitric oxide. In October, Nitric Oxide Innovations (NOI) LLC announced plans to begin a phase 2B and 3A outpatient clinical study of NOviricid, an oral lozenge that stimulates the production of nitric oxide in the body.
The study will enroll African Americans, a group that has been disproportionately affected by COVID-19.
Earlier research has suggested that nitric oxide might work as a treatment for COVID-19 by improving blood vessel function. It may also prevent certain viruses from replicating.
Synthetic antibodies. In mid-August, scientists at the University of California, San Francisco announced they had created synthetic antibodies that may neutralize the new coronavirus.
The compound still has to go through clinical trials, but the scientists said it could be available within a few months in a nasal spray or inhaler.
Hydroxychloroquine and chloroquine. These drugs received emergency use authorization from the FDA at the end of March.
On June 15, the FDA
At the time of the FDA authorization in March, manufacturer Novartis donated about 30 million doses of hydroxychloroquine and 1 million doses of chloroquine to the nation’s existing Strategic National Stockpile.
The United States is now left with 63 million doses of hydroxychloroquine and 2 million doses of chloroquine in its emergency stockpile.
Clinical results for the drugs have been mixed. Studies published in May in the New England Journal of Medicine and
In late May, the World Health Organization announced it was halting its clinical trials of hydroxychloroquine due to safety concerns.
In mid-June, the National Institutes of Health
In late June, British officials announced they would restart a global clinical trial on hydroxychloroquine and chloroquine.
In late July, scientists in Brazil announced that hydroxychloroquine given alone or with other drugs didn’t improve the condition of people hospitalized with mild to moderate COVID-19.
In late September, researchers at the University of Pennsylvania reported that hydroxychloroquine was no more effective in preventing the contraction of the new coronavirus in people who took the drug as opposed to those who didn’t.
- Phase 1. The drug is given to a small number of healthy people and people with a disease to look for side effects and figure out the best dose.
- Phase 2. The drug is given to several hundred people who have the disease, looking to see whether it works and if there are any side effects that weren’t caught during the initial testing.
- Phase 3. In this large-scale trial, the drug is given to several hundred or even up to 3,000 people. A similar group of people take a placebo, or inactive compound. The trial is usually randomized and can take 1 to 4 years. This stage provides the best evidence of how the drug works and the most common side effects.
- Phase 4. Drugs that are approved for use undergo continued monitoring to make sure there are no other side effects, especially serious or long-term ones.