But with the U.S. Food and Drug Administration (FDA) authorizing three COVID-19 vaccines for emergency use, the end of the pandemic could be drawing near. So far, 231 million vaccine doses have been administered in the U.S., according to the Centers for Disease Control and Prevention (CDC). Around 37 percent of all American adults are now full vaccinated, and close to 68 percent of those age 65 and up are completely inoculated. Still, we are not out of the woods yet, with more transmissible variants fueling an uptick in cases and COVID-19 surging in locations around the globe. Plus concerns about a potential link between the Johnson & Johnson Janssen vaccine and a handful of cases involving a rare blood-clotting disorder have complicated rollout of that one-dose option. Here’s where we stand now.
Johnson & Johnson Vaccine
The Johnson & Johnson (J&J) single-shot vaccine is the newest weapon in the fight against COVID-19 in the United States. On February 27, the FDA issued emergency use authorization for the J&J vaccine for people age 18 and older. Johnson & Johnson shared phase 3 trial data indicating that its Janssen vaccine had an overall efficacy rate of 72 percent in the United States. The vaccine demonstrated complete protection against COVID-related hospitalization and death and was shown to be 85 percent effective at preventing severe disease. The J&J vaccine is an adenovirus-vectored vaccine, which the CDC describes as a type that uses a genetically modified version of an adenovirus — a category of virus that includes the kind behind the common cold. The altered adenovirus, which can enter human cells but not replicate within them, delivers a gene that tells the cells to make part of a so-called spike protein, similar to the spike protein on the surface of the coronavirus. The immune system reacts by mounting a defense against the protein, creating “memory” cells and antibodies that remain in the blood stream to protect against future coronavirus infection. Johnson & Johnson set a goal of supplying 100 million doses to the United States in the first half of 2021. On April 13, however, the CDC and the FDA issued a joint statement recommending an immediate pause in the use of the vaccine after more than 6.8 million doses had been administered, following reports of six people developing a rare blood-clotting disorder. All were women between the ages of 18 and 48, with symptoms occurring 6 to 13 days after vaccination. While the joint statement said “these adverse events appear to be extremely rare,” it also cautioned that anyone who received the vaccine and developed symptoms like severe headache, abdominal or leg pain, or shortness of breath should contact their healthcare provider. Then, on April 23, the CDC and the FDA recommended lifting the pause on the J&J vaccine following a review of the available data. “We have concluded that the known and potential benefits of the Janssen COVID-19 vaccine outweigh its known and potential risks in individuals 18 years of age and older. We are confident that this vaccine continues to meet our standards for safety, effectiveness, and quality,” said Janet Woodcock, MD, the acting commissioner of the FDA, in a statement. RELATED: Coronavirus Alert: The Latest News, Data, and Expert Insights on the COVID-19 Pandemic
Pfizer-BioNTech Vaccine
On December 11, 2020, the FDA gave its first emergency use authorization for a coronavirus vaccine to Pfizer-BioNTech, making it available to people age 16 and older. Research published at the beginning of April 2021 involving 927 confirmed symptomatic cases of COVID-19 demonstrated that the Pfizer vaccine was 91.3 percent effective. The inoculation proved to provide protection for at least six months, and was 100 percent effective in preventing severe disease as defined by the CDC. In a forum hosted by CVS Health, Pfizer CEO Albert Bourla said that individuals will most likely need a booster dose of the COVID-19 vaccine within 12 months of getting fully vaccinated. “There are vaccines like polio where one dose is enough, and there are vaccines like flu that you need every year,” Bourla said. “The COVID virus looks more like the influenza virus than the polio virus.” The Pfizer vaccine relies on messenger RNA (mRNA) technology. This vaccine uses a genetic molecule called RNA (ribonucleic acid) to instruct human cells to make part of the spike protein, which stimulates an immune response against the coronavirus.
Moderna Vaccine
On December 18, the FDA granted emergency use authorization for the Moderna vaccine for people age 18 and up. The FDA go-ahead came after clinical trials in which 14,134 volunteers received the vaccine and 14,073 received placebo. The vaccine was 94.1 percent effective in preventing COVID-19 disease among these clinical trial participants, with 11 cases of COVID-19 in the vaccine group and 185 in the placebo group. At the time of the analysis of these 196 COVID-19 cases, none in the vaccine group and 30 in the placebo group were classified as severe. Research published April 6 in the The New England Journal of Medicine revealed that antibodies elicited by the two-dose Moderna immunization remain in the body after six months. Scientists are monitoring immune responses beyond six months and looking into the effect of a booster dose to extend the duration and breadth of activity against emerging viral variants. As with the Pfizer vaccine, the Moderna vaccines uses mRNA technology.
COVID-19 Vaccines and Chronic Conditions
Certain chronic conditions, such as diabetes, can increase the risk of developing severe COVID-19, making vaccination especially vital. But people with underlying health issues may have concerns about the safety and effectiveness of COVID-19 vaccines, particularly if they have an autoimmune disorder such as rheumatoid arthritis and are on immunosuppressive medication. Individuals with migraine may fear that any potential short-term side effects of vaccination, such as headache, could trigger an attack. People who are temporarily immunocompromised — because they are undergoing chemotherapy for cancer, for instance — may have their own worries about whether the vaccine is safe for them. In general, doctors are urging patients with chronic health conditions to get a COVID-19 vaccine as soon as one is offered to them, though there may be factors to consider that warrant a conversation with a physician. For more information about the COVID-19 vaccine as it impacts chronic conditions, click on the following links:
Ankylosing spondylitisAsthmaCancerCOPDDiabetesEczemaHeart conditionsHepatitis CIBDLupusMigraineMultiple sclerosisPsoriasisRheumatoid arthritisUlcerative colitis
During a White House briefing on April 7, Rochelle Walensky, MD, MPH, director of the CDC, said that the variant, known as B.1.1.7, which was first identified in the United Kingdom, is “now the most common lineage circulating in the United States.” To beat these variants, she stressed that the U.S. must accelerate its vaccination efforts. An article in JAMA in March 2021 detailed how studies repeatedly have shown that the vaccines elicit lower levels of antibodies against virus variants, but they still might be sufficient to protect against COVID-19, or at least severe COVID-19. The CDC says so far, studies suggest that antibodies generated through currently authorized vaccines recognize these variants, and while they may have a weaker response, still offer protection. Pfizer and Moderna are conducting tests to see how effective their inoculations are against the variants, and are looking into developing booster shots. Johnson & Johnson conducted trials of its vaccine in South Africa, and while it was only 66 percent effective against the prevailing variant there as well as others, scientists still found that it was highly effective at preventing severe disease.
More Vaccine Contenders Are in the Pipeline
Keep on the lookout for the FDA to give emergency authorization to more vaccine candidates. The two below appear to be furthest along in the pipeline:
AstraZeneca
Like the Johnson & Johnson vaccine, the AstraZeneca vaccine is based on a weakened version of a common cold virus (adenovirus). On January 29, the European Medicines Agency authorized AstraZeneca’s COVID-19 vaccine for use in all adults over 18 in the European Union. The United Kingdom and the WHO have also authorized the shot. AstraZeneca is soon expected to apply to the FDA for authorization as it completes analysis of its U.S. clinical trial data. The company released interim analysis of study data on March 25 indicating that the vaccine has 76 percent efficacy against symptomatic COVID-19, 100 percent efficacy against severe disease and hospitalization, and 85 percent efficacy against symptomatic COVID-19 in participants age 65 and older. AstraZeneca, however, has been plagued with problems and is facing increasing skepticism. France and Germany had limited the shots to adults under the age of 65 due to a lack of data showing its efficacy in the older age group. On February 7, The New York Times reported that South Africa has stopped using the AstraZeneca vaccine after evidence emerged that the vaccine did not protect clinical trial volunteers from mild or moderate illness caused by the more contagious virus variant first seen in that country. Most recently, the European Medicines Agency (EMA) concluded that there is a possible link between the AstraZeneca vaccine and very rare cases of unusual blood clots and low blood platelets. Subsequently, several countries — including Britain, Belgium, and Australia — recommended limitations on the use of the vaccine. As the Wall Street Journal reported, Denmark and Norway have discontinued use of the vaccine altogether. Most of these rare clotting problems have occurred in women under 60 within two weeks of vaccination, and the EMA noted that benefits from the AstraZeneca shot still outweigh the risks. At the beginning of April, two papers published in The New England Journal of Medicine explained why the AstraZeneca vaccine may be leading to these rare clotting issues.
Novavax
In March, Novavax released results from a late-stage trial in the United Kingdom, finding that its vaccine is 96.4 percent effective against mild, moderate, and severe disease caused by the original COVID-19 strain, and 86.3 percent effective against the U.K. variant. In a separate trial in South Africa, however, the Novavax vaccine only demonstrated an overall efficacy of 48.6 percent against predominant variant strains there. According to an investigation by The Wall Street Journal published February 23, early data suggests that the Novavax shot may be one of the first shown to stem asymptomatic spread of the coronavirus and also potentially provide longer-lasting protection. The two-dose Novavax immunization is called a “subunit vaccine” and includes only parts of the virus or bacteria, or subunits. The Novavax COVID-19 shot is produced by creating a genetically engineered baculovirus (a group of large DNA viruses that infect insects) containing a gene for a modified COVID-19 spike protein, and the vaccine includes this protein and an adjuvant (a substance that can boost the immune response). As of April 7, data from a late-stage U.S. trial are still pending, but during a Washington Post Live event on February 24, Gregory Glenn, MD, the head of research and development for Novavax, told reporters that he expected results in April, after which Novavax will apply for emergency use authorization. In a hearing with the House Committee on Energy and Commerce on February 23, representatives from Novavax said that it is “prepared to deliver the 110 million doses … by the third quarter of this year.”
Doctors Have a Number of COVID-19 Treatment Options
Several treatments have been shown to reduce the symptoms and harmful effects of COVID-19. Some have been given emergency use authorization by the FDA, and others are still under investigation, but trials so far have been promising. Here are a few of the top therapies:
Remdesivir
In October of 2020, Veklury (remdesivir) became the first medication approved by the FDA for the treatment of COVID-19 in hospitalized patients. The antiviral medication, manufactured by Gilead Sciences and originally developed for the treatment of Ebola, was given the green light after studies showed that it helped patients with COVID-19 recover more quickly by inhibiting the replication of the virus. “The drug can now be openly prescribed by healthcare providers for patients who are hospitalized with COVID-19 infection, so I think that’s definitely a step forward,” says Susan Kline, MD, MPH, a professor of medicine in the division of infectious diseases and international medicine at the University of Minnesota in Minneapolis, and a principal investigator for one of the studies. In Dr. Kline’s investigation (the results of which were published November 5 in The New England Journal of Medicine), remdesivir shortened recovery time in hospitalized patients with COVID-19 and evidence of lower respiratory tract infection to a median of 10 days compared with 15 days for those who were taking a placebo. Data also showed a trend toward reducing mortality. Recently, researchers from Johns Hopkins University confirmed the drug’s effectiveness. Their investigation, published in JAMA Network Open in March 2021, revealed that the antiviral was associated with faster clinical improvement in hospitalized COVID-19 patients. Matthew Heinz, MD, a hospitalist (hospital physician) in Tucson, Arizona, who has treated COVID-19 patients with remdesivir, says that remdesivir is not a cure. “I would almost compare it with Tamiflu therapy for influenza — it reduces viral load and may reduce the length of the disease overall, and it seems to diminish the intensity of it, especially for those with a lot of comorbidities [two or more health conditions that occur in the same person at the same time].” Remdesivir can cause side effects — it can elevate liver enzymes and trigger allergic reactions — so for now it is only recommended for hospitalized patients, who can be closely monitored. On February 9, the FDA granted emergency use authorization for the monoclonal antibodies bamlanivimab and etesevimab to be administered together. Data released by pharmaceutical company Eli Lilly on March 10 revealed that this monoclonal combo therapy reduced the risk of hospitalizations and deaths from COVID-19 by 87 percent in high-risk patients recently diagnosed with mild-to-moderate disease. (The drug was not authorized for use in patients who are hospitalized or who require supplemental oxygen.) Back in November, the FDA had granted emergency use authorization for bamlanivimab on its own to treat patients who fit this description. But on April 16, the FDA rescinded this authorization after finding that virus variants had become increasingly resistant to this treatment. As of mid-March, about 20 percent of viruses sequenced in the U.S. were reported as variants expected to be resistant to bamlanivimab alone, increasing from about 5 percent in mid-January. The FDA stressed that bamlanivimab and etesevimab, administered together, have proven to be very effective against COVID-19. RELATED: A Brief History of COVID, 1 Year In
Casirivimab and Imdevimab
In November 2020, Regeneron’s antibody “cocktail” of casirivimab and imdevimab (called REGEN-COV) was green-lighted for emergency use by the FDA to treat mild-to-moderate COVID-19 in adults and pediatric patients at high risk for progressing to severe disease (but who are not hospitalized with COVID-19 or requiring supplemental oxygen). Clinical research found that the drug combination could reduce COVID-19-related hospitalization or emergency room visits in patients at high risk for disease progression within 28 days after treatment when compared with placebo. Regeneron announced January 27 that the casirivimab and imdevimab antibody cocktail successfully neutralized coronavirus variants first identified in the United Kingdom and South Africa; more research is ongoing.
Baricitinib
The FDA granted an emergency use authorization to Eli Lilly for the rheumatoid arthritis drug baricitinib (Olumiant) in combination with remdesivir, for the treatment of suspected or laboratory-confirmed COVID-19 in hospitalized adults and pediatric patients 2 years or older requiring supplemental oxygen or invasive mechanical ventilation. Baricitinib is a pill that seems to work against COVID-19 by reducing inflammation and producing an antiviral reaction. Research published December 2020 in The New England Journal of Medicine showed that baricitinib taken in conjunction with the antiviral remdesivir reduced time to recovery for people hospitalized with COVID-19. Severely ill patients who needed a high dose of supplemental oxygen or a noninvasive form of ventilation had the biggest response, and they recovered eight days faster when baricitinib was included in their drug regimen compared with the control group.
Dexamethasone
Dexamethasone is a corticosteroid commonly used to relieve inflammation (swelling, heat, redness, and pain) for people with arthritis, as well as severe allergies and asthma, and skin, blood, kidney, eye, thyroid, and intestinal disorders (such as colitis). Doctors also prescribe the drug to treat certain types of cancer. Widely used and relatively affordable, this medication may also help save lives. The NIH now recommends that COVID-19 patients on mechanical ventilators or in need supplemental oxygen may benefit from dexamethasone. If that’s not available, they may take other corticosteroids, such as prednisone, methylprednisolone, or hydrocortisone. The drug has been touted as first to reduce deaths among COVID-19 patients. In a report published February 25 in The New England Journal of Medicine, scientists from Oxford followed thousands of hospitalized subjects who were either receiving dexamethasone or getting the usual care (the control group). Among those on ventilators, the incidence of death was 29.3 percent in the dexamethasone group versus 41.4 percent in the control group. Among those receiving supplemental oxygen, the death incidence was 23.3 percent versus 26.2 percent. Studies appearing in the JAMA, including a meta-analysis of seven randomized trials published in September 2020, have further supported the benefit of dexamethasone for patients with severe or critical COVID-19. Following the release of these results, the WHO strongly recommended the use of these medications. The FDA lists dexamethasone on its list of drugs used for hospitalized patients with COVID-19. In March, the National Health Service (NHS) in England said that the steroid has saved around one million lives worldwide since its discovery as an effective treatment for COVID-19.
Tocilizumab
Although the monoclonal antibody tocilizumab (brand name Actemera) from Roche is not yet approved by the FDA, clinical trial results released on February 11 indicate that the drug commonly used to treat rheumatoid arthritis could help prevent 1 in 25 deaths among patients hospitalized with COVID-19. A total of 2,022 patients were randomly allocated to receive tocilizumab by intravenous infusion and were compared with 2,094 patients randomly allocated to usual care alone. A total of 82 percent of patients were taking a systemic steroid such as dexamethasone. Treatment with tocilizumab significantly reduced deaths: 596 (29 percent) of the patients in the tocilizumab group died within 28 days compared with 694 (33 percent) patients in the usual care group. Scientists from the University of Oxford, reporting on this preliminary study, wrote: “This means that for every 25 patients treated with tocilizumab, one additional life would be saved.”
Convalescent Plasma, Now Under Question
Convalescent plasma is blood from people who have recovered from COVID-19 that contains different types of antibodies to fight the virus. In August, the FDA had granted emergency use of the treatment in hospitalized patients, but based on new research, the FDA revised its authorization on February 4, limiting its use specifically to hospitalized patients early in the disease course. RELATED: Convalescent Plasma Receives FDA Emergency Use Authorization as a COVID-19 Treatment Research published in the British Medical Journal on January 14 found convalescent plasma may cut deaths in patients not on ventilation and an investigation in the journal JCI Insights published in February in February found that convalescent plasma treatment significantly improved clinical outcomes. But a major trial looking at several potential treatments for severely ill COVID-19 patients who are in intensive care announced that it had halted recruitment to its convalescent plasma arm because the treatment showed no benefit to these patients. The NIH has said that there is insufficient data at this time to “recommend either for or against the use of COVID-19 convalescent plasma for the treatment of COVID-19.”
