Silver Bullet Sept 3 - building a case for booster shots, antibodies, mechanisms of mortality
A biweekly update on all things COVID-19. News, public health guidance, trends, breakthroughs, and thousands of scientific papers distilled down to what you need to know right now.
More than 80% of Americans now have Covid-19 antibodies
A new, nationwide survey of US blood donations by the CDC shows that a large majority of donors had antibodies to SARS-CoV-2. The prevalence of antibodies in blood samples (seroprevalence) increased from 3.5% in July 2020—before vaccines were available—to 20.2% for infection-induced antibodies and 83.3% for combined infection- and vaccination-induced antibodies in May 2021. The results of the survey do not reflect population levels of immunity (herd immunity), which may not be accurately reflected by the presence of antibodies. Notably, the US experienced a significant surge driven by the Delta variant after May 2021 in spite of more than 80% seroprevalence. The study also showed that there were about 2.1 actual infections for every officially documented infection. The current number of reported infections in the US is 39.7 million. At a ratio of 2.1 to 1, that would be 83.37 million total cases.
Treatment with antibody duo can keep high risk patients out of the hospital
High risk patients with Covid-19 infection were 60-70% less likely to require hospitalization when treated with a combination of two monoclonal antibody treatments—casirivimab and imdevimab. And of those admitted to the hospital, the need for treatment in the ICU and mortality were both reduced. That’s according to a study of nearly 1400 patients at the Mayo Clinic between Dec. 2020 and April 2021 published in The Lancet’s EClinicalMedicine.
On the other hand, a study from Michigan Medicine published in The New England Journal of Medicine shows no benefit for convalescent plasma, a therapy that was pioneered early in the pandemic when virtually no other treatments were available. The trial was terminated in Feb. 2021 due to lack of efficacy in a planned interim analysis. The data collected from 450 patients who visited emergency departments with laboratory-confirmed Covid-19 diagnoses and symptoms found that convalescent plasma was no more effective at preventing progression of the disease than vitamins and saline. Lead author on the study Frederick Korley said, “Convalescent plasma may still be useful if given very early in the course of illness and in doses that are much higher than doses used in our study. There are other sub-groups of patients that may benefit from convalescent plasma, and that is what we need to figure out with future research.”
Mortality linked to high viral load in lungs
One of the continuing mysteries of Covid-19 is why it causes such severe, devastating illness in some people, while only causing mild illness for most. Some of the theories include an overreaction of the immune system called a “cytokine storm,” or secondary bacterial infection. Researchers from New York University investigated the viral load and respiratory tract microbiome of 142 patients with Covid-19. Their results showed that secondary infections are not driving mortality in Covid-19. Rather, patients who died had significantly greater quantities of virus in their lungs—on average 10 times more—compared to those that survived. “Our findings suggest that the body’s failure to cope with the large numbers of virus infecting the lungs is largely responsible for COVID-19 deaths in the pandemic,” says study lead author Imran Sulaiman, MD, PhD, an adjunct professor in the Department of Medicine at NYU Langone Health. Another contributor to mortality was a weaker immune response.
Another study related to the mechanisms of Covid-19 mortality in the Journal of Clinical Investigation details the role of an enzyme (sPLA2-IIA) in driving severity of the disease. The enzyme is similar to an enzyme in rattlesnake venom, and in healthy people it aids in defense against bacterial infections. However, it was found in unusually high amounts in the tissues of people who had succumbed to Covid-19. At those high levels, the enzyme causes damage by “shredding” vital organs. The significance of this discovery is that it could be used as a predictor for disease severity in Covid-19 patients, as a target for development of therapeutics, and it could also shed light on long Covid.
Newly discovered antibody neutralizes all coronaviruses
Antibody therapies attack the virus that causes Covid-19, SARS-CoV-2, by binding to it and deactivating it. The most potent antibodies against the virus have been found to target a small section of the spike protein that attaches to the cell it is attacking. This section is called the receptor binding domain (RBD). A team of scientists studied a panel of antibodies targeting the RBD and found one, S2H97, that not only binds tightly to all strains of SARS-CoV-2, but also binds tightly to all viruses in the sarbecovirus lineage of betacoronaviruses, including the SARS virus. Their findings are published in the journal Nature. When the antibody was given to hamsters prior to infection with SARS-CoV-2, replication of the virus was reduced by more than 10,000 fold compared to control animals. Not only does this antibody have potential to treat or prevent all current and future strains of Covid-19, it also points the way toward development of new vaccines and therapeutics that are robust in the face of viral evolution and immune escape.
Nursing home study shows steep decline in vaccine antibodies after six months
A study from Harvard University, Case Western Reserve, and Brown University found that antibody levels decreased more than 80% in nursing home residents and nursing home health care workers. The results, published as a preprint on Medrxiv, support the case for booster shots, particularly for the elderly.
Two FDA officials, Marion Gruber, director of the FDA’s vaccines office, and her deputy Philip Krause, handed in their resignations over the Biden administration’s announcement that adults would receive a Covid booster shot eight months after completing their initial vaccination, according to reporting by The New York Times. They believed there was not enough data to support the booster shot plan, and that the announcement put inappropriate pressure on the agency to authorize them quickly. The Biden administration’s plan was contingent on FDA authorization of the shots, and was endorsed by senior federal health officials, including acting FDA commissioner Janet Woodcock.
Some good news about MIS-C
Most children recover quickly and do not suffer longterm complications from MIS-C. That’s according to a research letter published online in JAMA Pediatrics. Although children may be severely ill with systemic inflammation and require care in the ICU, most children in a cohort of 68 children had normal laboratory testing results at 50 days after hospital admission. And most children who presented with aneurysms had resolution of the aneurysm fairly quickly, as well. Although the study is limited because it is small, the authors said, “it is reassuring that the majority of patients had good outcomes with no significant medium- or long-term sequelae.”
Learning more about breakthrough infections
Breakthrough infections occur when the virus overcomes the defenses of fully vaccinated people to cause an infection. Although the Covid-19 vaccines have a high level of effectiveness for preventing infection (anywhere from 60-80% in various studies), some people will inevitably still get sick. We already know that those people are much less likely to have severe disease requiring hospitalization or mechanical ventilation, and they are much less likely to die. Now, a report in The Lancet Infectious Diseases based on data collected from the COVID Symptom Study mobile phone app shows that breakthrough infections are twice as likely to be asymptomatic and half as likely to lead to long-Covid syndrome. Frail older adults were more likely to experience post-vaccination infection, and thus are more at risk of transmitting infection, particularly when living in long term care facilities. In addition to underlining the benefits of vaccines, the study also emphasizes the importance of regular Covid testing of vaccinated individuals who work with vulnerable populations.
Moderna submits vaccine application to the FDA
Moderna has completed submission of its application for full approval of its Covid-19 vaccine. The vaccine was given emergency use authorization in 2020, and has been used widely in mass vaccination programs in the US and around the world. The company has also filed for emergency use authorization of its vaccine for adolescents 12 and older. The FDA recently approved the Pfizer-BioNTech Covid-19 vaccine for people 16 and older.
JnJ booster produces nine times more antibodies
Johnson and Johnson reported results of a Phase 1/2 clinical trial in the New England Journal of Medicine showing that a second shot of its Covid-19 vaccine produced an increase in antibodies against the viral spike protein that was nine times higher than the amount of antibodies present 28 days after the initial dose. The company is in discussion with the FDA, the CDC, and European regulatory authorities regarding recommendations for a JnJ booster shot.
CDC: vaccines remain highly effective against hospitalization
Although there has been some loss of vaccine effectiveness for preventing infection, the CDC says that the currently authorized vaccines are still highly effective for preventing illness severe enough to warrant hospitalization. That’s according to a presentation given Aug. 30 to the CDC’s Advisory committee on Immunization Practices. In that presentation, the CDC contemplated a risk-based approach toward distributing booster vaccines, prioritizing those at highest risk of severe disease. The agency has also released new data (note: unpublished, not peer reviewed) showing that unvaccinated adults are 17 times more likely to require hospitalization than vaccinated adults. Those who were fully vaccinated and hospitalized with Covid-19 were generally older, more likely to reside in nursing homes, and had three or more underlying conditions. Nearly one third had medical conditions that suppressed their immune systems.
Israel data show booster doses reduce infection risk by 68%
Israel, an early leader in its mass vaccination program, instituted a third dose campaign in August. A retrospective study (not yet peer reviewed) evaluating short-term effectiveness of three doses compared to two doses showed a significant advantage for the three dose regimen. Seven to 13 days after the third shot, there was a 46-69% reduced probability of testing positive for SARS-CoV-2, and at 14-20 days the difference was 70-85%. These are reductions in the odds of breakthrough infection compared to protection already provided by two doses of vaccine. Although waning immunity over time and partial escape by the Delta variant could account for the effectiveness of the third shot, maturation of the immune response to the initial vaccination may also play a role. Many vaccines are given in series with gaps of six months or more to optimize the immune response. Anthony Fauci, director of the NIAID, said that a three dose series could become the standard for Covid-19 vaccination. “The reason I say that is that it is very clear, when you give a prime and maybe a second shot as a boost, but give the immune system enough chance to mature in both affinity maturation and maturation of the B cell repertoire, it is entirely understandable why the results that I just reported from the Israeli boosters are so dramatic,” he explained.
Other science news
Defibrillator drone could save lives
In a small clinical trial, Swedish researchers showed that an automated external defibrillator (AED) could be delivered by drone about two minutes ahead of the arrival of an ambulance, on average. This time difference could be crucial, as the chances of surviving an out-of-hospital cardiac arrest without CPR and defibrillation decrease by 7 to 10 percent for each minute that passes. In a typical year, only about 10% of people suffering OHCAs in Sweden survive. However, none of the AEDs deployed during the study were removed from the drones before the ambulance arrived. The researchers say more work is needed to educate bystanders on the use of the device. Additionally, some kinks still need to be worked out with dispatching and the mechanicals.
‘Lite salt’ reduces cardiovascular events
A large study in over 20,000 people from 600 villages in rural China suggests that the use of a salt substitutes in home cooking could save lives. Half of the participants, whose average age was about 65, were given a supply of a salt substitute that had reduced sodium and added potassium (similar to Morton’s ‘Lite Salt’ in the US), and instructed to use it sparingly to minimize sodium consumed. The other half of the group continued to use regular salt as usual. After five years, there were over 4000 deaths, 3000 strokes, and 5000 cardiovascular events. Statistical analysis showed a significant reduction in those outcomes among the group using the salt substitute. The researchers believe that use of salt substitutes nationally in China could save 460,000 people per year by preventing early deaths connected to sodium consumption. One complication in implementing this sort of change on a large scale is that outside of rural China, people eat more processed foods, so the change would have to be made in food production as well as in homes.
Has Delta peaked? by David Leonhardt and Ashley Wu, The New York Times
A lucky few seem ‘resistant’ to Covid-19. Scientist want to know why by Amitha Kalaichandran, Statnews