By Marie Rosenthal, MS
Stanford University researchers found that the second shot of COVID-19 vaccine is crucial for activating the best immune response, while another group found the vaccines are still effective in preventing disease among health care workers. U.K. researchers think they figured out why blood clots occur in some COVID-19 patients. Unfortunately, the pandemic has had a negative effect on another epidemic: opioid abuse. Overdoses are at record highs. And finally, researchers look at infants: Those hospitalized for a bacterial infection are more likely to be positive for COVID-19 if there is a high rate of circulating virus in the community.

Don’t Skip the Second Shot

The second dose of a COVID-19 vaccine induces a powerful boost to a part of the immune system that provides broad antiviral protection, according to a study led by the Stanford University School of Medicine, in California (Nature 2021 Jul 12 https://doi.org/10.1038/s41586-021-03791-x). So, don’t skip the second shot.

The chief immunologic basis for approval of traditional vaccines has been their ability to induce neutralizing antibodies. “Antibodies are easy to measure,” said Bali Pulendran, PhD, the Violetta L. Horton Professor II at Stanford. “But the immune system is much more complicated than that. Antibodies alone don't come close to fully reflecting its complexity and potential range of protection.”

The innate immune system is the body's sixth sense, whose constituent cells are the first to become aware of a pathogen's presence. Although they do not distinguish among separate pathogens, they secrete signaling proteins that launch the response of the adaptive immune system—the B and T cells that attack specific viral or bacterial species or strains. During the week or so it takes for the adaptive immune system to rev up after vaccination, innate immune cells perform the task of holding incipient infections at bay by gobbling up—or firing noxious substances, albeit somewhat indiscriminately, at—whatever looks like a pathogen to them.

In December 2020, Stanford Medicine began giving the Pfizer-BioNTech vaccine. The team selected 56 healthy volunteers and drew blood samples from them at multiple time points preceding and following the first and second shots. The researchers found that the first shot increases SARS-CoV-2?specific antibody levels, as expected, but not nearly as much as the second shot does. 

“The second shot has powerful beneficial effects that far exceed those of the first shot,” Dr. Pulendran said. “It stimulated a manifold increase in antibody levels, a terrific T-cell response that was absent after the first shot alone, and a strikingly enhanced innate immune response.”

Unexpectedly, Dr. Pulendran said, the vaccine—particularly the second dose—caused the massive mobilization of a newly discovered group of first responder cells that normally are scarce and quiescent.

These cells—a small subset of monocytes that express high levels of antiviral genes—barely budge in response to an actual COVID-19 infection. But the Pfizer vaccine induced them to action.

This special group of monocytes constituted only 0.01% of all circulating blood cells prior to vaccination. But after the second Pfizer vaccine shot, their numbers expanded 100-fold to account for a full 1% of all blood cells. In addition, their disposition became less inflammatory but more intensely antiviral. They seem uniquely capable of providing broad protection against diverse viral infections, Dr. Pulendran said.

“The extraordinary increase in the frequency of these cells, just a day following booster immunization, is surprising,” he said. “It's possible that these cells may be able to mount a holding action against not only SARS-CoV-2, but against other viruses as well.”

mRNA Vaccines Slash Risk for COVID-19 Infection by 91% in Fully Vaccinated People

Despite breakthrough infections, people who receive mRNA COVID-19 vaccines are up to 91% less likely to develop the disease than those who are unvaccinated, according to a new nationwide study of eight sites, including Salt Lake City. 

For the few vaccinated people who do experience a breakthrough case, the study suggests that vaccines reduce the severity of COVID-19 symptoms and shorten its duration.
These results are among the first to show that mRNA vaccination benefits even those individuals who have breakthrough infections (N Engl J Med 2021;385:320-329 DOI: 10.1056/NEJMoa2107058). 

“One of the unique things about this study is that it measured the secondary benefits of the vaccine," said Sarang Yoon, DO, a study co-author, an assistant professor at the University of Utah Rocky Mountain Center for Occupational and Environmental Health (RMCOEH), and principal investigator of the RECOVER (Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel) study in Utah.

The study was designed to measure the risks and rates of infection among workers on the front lines of the pandemic.

“We gave these vaccines to some of the highest-risk groups in this country—doctors, nurses and first responders,” Dr. Yoon said. “These are the people who are getting exposure to the virus day in and day out, and the vaccine protected them against getting the disease. Those who unfortunately got COVID-19 despite being vaccinated were still better off than those who didn't.”

The study found that mRNA COVID-19 vaccines were:

• 91% effective in reducing risk for infection once participants were "fully" vaccinated, two weeks after the second dose; and 
• 81% effective in reducing risk for infection after "partial" vaccination, two weeks after the first dose but before the second dose was given.
  

The HEROES-RECOVER network recruited 3,975 participants at eight sites. In addition to Salt Lake City, sites included Miami; Temple, Texas; Portland, Ore.; Duluth, Minn.; and Phoenix and Tucson, as well as other areas in Arizona. Participants submitted samples for COVID-19 testing on a weekly basis for 17 weeks between Dec. 13, 2020 and April 10, 2021. Participants also reported weekly whether they had COVID-19?like symptoms, including fever, shortness of breath, and loss of taste and smell.
Only 204 (5%) of the participants eventually tested positive for SARS-CoV-2, the virus that causes COVID-19. Of these, 156 were unvaccinated, 32 had an indeterminate vaccine status, and 16 were fully or partially vaccinated. The fully or partially vaccinated participants who developed breakthrough infections had milder symptoms than those who were unvaccinated:

• Presence of fever was reduced 58% among those vaccinated with a breakthrough infection.
• Days spent sick in bed were reduced by 60% among those who developed a breakthrough infection.
• Detection of the virus was reduced by 70% among those with breakthrough infections, from 8.9 to 2.7 days.
  

Three people who were hospitalized were not immunized, meaning that no one who developed a breakthrough infection was hospitalized.

These findings also suggest that fully or partially vaccinated individuals who get COVID-19 might be less likely to spread the virus to others. The researchers found that infected study participants who had been fully or partially vaccinated when infected had 40% less detectable virus in the nose and did so for six fewer days compared with those who were unvaccinated.

Overall, the researchers concluded that the study's findings support the CDC's recommendation to get fully vaccinated as soon as possible.

ED Visits Related to Opioid Overdoses Increase During COVID-19 

Although ED visits overall decreased by 14% in 2020, visits caused by an opioid overdose increased by 10.5% (Ann Emerg Med 2021 Mar 19 DOI: 10.1016/j.annemergmed.2021.03.013).

Opioid overdoses were responsible for one in every 313 visits, which is up from one in every 400 visits during the previous two years. 

This trend is supported by preliminary data recently released by the CDC, which recorded more than 93,000 opioid overdose deaths in 2020. That's a 29.4% increase from the previous year and the most opioid overdose deaths ever recorded in the United States.

“COVID-19, and the disruptions in every part of our social and work lives, made this situation even harder by increasing the risk of opioid misuse and relapse because people were separated from their social support and normal routines,” said Molly Jeffery, PhD, a researcher in the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery and senior author of the study. 

More than 70% of drug overdose deaths in 2019 involved an opioid, according to the CDC, although trends were leveling off before the COVID-19 pandemic. Since then, that trend has reversed significantly, data show.

The research team studied visits to 25 EDs in six states—Alabama, Colorado, Connecticut, Massachusetts, North Carolina and Rhode Island—from January 2018 through December 2020. Opioid-related overdose visits increased to 3,486 in 2020 from 3,285 and 3,020 in 2019 and 2018, respectively. 

In addition, the evidence indicates that the percentage of people who experience an overdose but did not go to the ED is likely increasing, suggesting overdose rates may be even higher.

Treatments such as buprenorphine and methadone for opioid misuse need to be more accessible, as does naloxone, an opioid overdose reversal drug, according to Dr. Jeffery. 

Additionally, use of telemedicine has remained high and could increase accessibility to psychiatric care, she said. “We think this may be an important way to increase the accessibility of care for many people with opioid misuse disorder or addiction,” Dr. Jeffery said.

Thrombosis May Be Related to Abnormal Antibody Response

Inflammation and thrombosis seen in very severe cases of COVID-19 may be caused by the antibodies sent to fight the disease activating unnecessary platelet activity in the lungs (Blood 2021 Jul 28 DOI: 10.1182/blood.2021011871).

New research shows how antibodies produced to protect against COVID-19 are triggering increased function of platelets, which may be causing fatal blood clots in patients with severe disease. 

The study took antibodies produced to fight the coronavirus's spike protein from people with severe infections and cloned them in a lab for study. The team found that the small sugars found on the surface of these antibodies differed from antibodies of healthy individuals, and when the cloned antibodies were introduced in vivo to blood cells from healthy donors, an increase in platelet activity was observed.

The study team also found that it was possible to reduce or stop platelets from responding by treating blood with active ingredients from different medications that inhibit platelet function or immune responses. The findings suggest it may be possible for drugs that are currently used to treat immune system disorders to reduce or stop the cells from producing an exaggerated platelet response.

A trial led by Imperial College London and Imperial College Healthcare NHS Trust, called MATIS, is already testing these drugs in clinical trials with patients at hospital sites across the United Kingdom to see whether they will reduce serious clotting in hospitalized COVID-19 patients.

The lab-based study of human cells provides key evidence to support the scientific basis for the MATIS trial and, while there are yet to be any results reported from this clinical trial, the two teams will continue to work closely together as the clinical trial develops.

“One way to think of what is happening is that the immune response that is designed to protect you from the infection in some cases, particularly in severely ill patients, actually causes more damage. In this case, the antibodies that are produced to stop COVID-19 from spreading trigger infected cells to induce platelet activity which causes clotting, even though there is no wound that needs healing,” said Professor Jon Gibbins, the director of the Institute for Cardiovascular and Metabolic Research at the University of Reading, in the United Kingdom.

COVID-19 Prevalence Among Hospitalized Infants Varies

How common COVID-19 is among infants may depend on the extent of the pandemic virus circulating in a community, according to a new study (Pediatr 2021 Jun 30  e2020044685; DOI: https://doi.org/10.1542/peds.2020-044685).

The study found specifically that rates of infection with the virus that causes COVID-19 were higher among infants hospitalized not for COVID-19, but because they were being evaluated for a potential serious bacterial infection (SBI) during periods of high COVID-19 circulation in New York City. The study also found rates of COVID-19 positivity in this age group were lower when infection rates in the city were low.

Led by researchers from NYU Langone Health, the study also examined the clinical course of the infection in infants and found that the most common presentation of COVID-19 was a fever without other symptoms.

“Enhancing our knowledge of how COVID-19 infection affects young infants is important for informing clinical practice, and for planning public health measures such as vaccination distribution,” said Vanessa N. Raabe, MD, an assistant professor in NYU Langone's Departments of Medicine and Pediatrics, in the Division of Pediatric Infectious Diseases, and one of the study's principal investigators.

New York City was the early epicenter of COVID-19 in the United States, with more than 190,000 reported infections during the peak of the city’s epidemic between March and May 2020. Of the reported cases, 3% were in children younger than 18 years of age, although these numbers may underestimate the true incidence given the lack of adequate testing. Most children infected with the disease were asymptomatic or had mild symptoms. However, cases of severe illness have been reported and some reports suggest young infants may be at higher risk for severe disease than older children.

Babies are often treated with antibiotics in the hospital when they run a fever until doctors can determine they don't have a serious bacterial infection, such as meningitis or a bloodstream infection, the study authors said.

“Because fever is a common symptom of COVID-19 in children, clinicians must consider COVID-19 as a potential cause of fever and not solely rely on laboratory or imaging results to guide decision making on whether or not to test hospitalized infants for COVID-19,” Dr. Raabe said.

The current study analyzed data from infants younger than 90 days of age, admitted for SBI evaluation at NYU Langone Health hospitals and NYC Health and Hospitals/Bellevue Hospital between March and December 2020. Of 148 infants, 15% tested positive for COVID-19, and two of the 22 infants with COVID-19 required ICU admission, but were discharged safely. Specifically, the team found that only 3% of infants tested positive during periods of low community virus circulation, compared with 31% in communities with high infection rates.

The team also found a relatively low incidence (6%) of infection of the hospitalized infants with other commonly occurring viruses, whether or not they had COVID-19. “This likely reflects community-wide decreases in other respiratory viruses reported in New York during the study period due to enhanced infection control practices, like social distancing and mask wearing, at the height of the pandemic,” Dr Raabe said.

The researchers recommended that clinicians continue to assess young infants who present with fever for bacterial infections, regardless of COVID-19 status and given the potential severe consequences if not treated.

Additional research is needed in infants evaluated in a wider range of settings, including the ED and outpatient clinics, to truly understand the full impact of COVID-19 in this age group.