By Marie Rosenthal, MS, and Ethan Covey
Now that more people are out and about, other respiratory viruses, which had been at historically low levels, are inching back up. We are more than a year into the pandemic, and many people are still putting off that trip to the doctor’s office. Antibiotic use increased during the early days of the pandemic, probably because doctors didn’t know what they were dealing with, and there is concern about more resistance developing. To slow transmission worldwide, more countries need access to vaccines, and let’s end on a high note: Scientists are working on a new vaccine that could protect against all strains and variants of coronaviruses.
Outside of COVID-19, Viral Circulation Was Low, but Now Rising
The circulation of respiratory viruses in the United States has been at historically low levels during the COVID-19 pandemic.
However, rates have varied among viruses, and many have returned to pre-pandemic levels, even exhibiting atypical, off-season spread (MMWR Morb Mortal Wkly Rep 2021;70[29]:1013-1019).
“This report describes how respiratory viruses, like flu, spread at historically low levels during the first year and a half of the COVID-19 pandemic, likely because of measures used to stop the spread of COVID-19, which included staying home,” said Sonja J. Olsen, PhD, an epidemiologist with the CDC’s Influenza Division, National Center for Immunization and Respiratory Diseases. “However, spread of some of these viruses is now increasing, and there could be more widespread respiratory circulation this fall and winter.”
The study focused on virologic data available from U.S. laboratories available through the World Health Organization Collaborating Laboratories System and CDC’s National Respiratory and Enteric Virus Surveillance System and focused on influenza activity from Oct. 3, 2020, to May 22, 2021, as well as activity of other respiratory viruses from Jan. 4, 2020, to May 22, 2021.
From October 2020 through the end of the survey period, U.S. influenza activity was lower than at any time since 1997, when public data became available. In clinical specimens, only 0.2% tested positive for influenza, as did 0.05% of specimens tested at public health laboratories.
Like influenza, respiratory syncytial virus circulated at historically low levels throughout 2020. However, rates of respiratory syncytial virus have been increasing across the country since April 2021. Activity of common human coronaviruses and parainfluenza viruses decreased during 2020, but have since bounced back to pre-pandemic levels, including rates of activity that differ from typical seasonal trends. Rhinoviruses and enteroviruses remained at low levels through May 2020, and have since risen to near–pre-pandemic levels.
The authors of the report noted that clinicians need to be aware of how these various viruses have rebounded, and the potential for further spread caused by decreases in COVID-19 mitigation practices.
“It is important to continue everyday preventive actions, like avoiding close contact with people who are sick, staying home when sick, covering coughs and sneezes, and frequent handwashing,” Dr. Olsen said. “In addition, influenza vaccination for persons six months and older will be important in preventing flu.”
Still Missing Medical Appointments Due to COVID-19
More than a year into the pandemic, concerns about exposure to the coronavirus still affect health care decision making for some U.S. adults. In April 2021, more than one in 10 adults younger than 65 years of age reported delaying or going without health care in the past 30 days due to fear of virus exposure, while nearly one in 10 parents delayed or did not seek care for their children for the same reason, according to two analyses.
Hispanic and Black adults, as well as those with lower incomes, delayed care at even higher rates.
The analyses funded by the Robert Wood Johnson Foundation and prepared by Urban Institute researchers assess delayed or forgone health care in April 2021 among adults 18 to 64 years of age and parents of children under 19. Researchers found:
Hispanic and Black adults delayed or did not get care at higher rates than white adults (16.2% and 13.3% vs. 8.7%).
Adults with incomes below 250% of the federal poverty level were more likely than those with higher incomes to avoid care (14.9% vs. 8.2%).
Adults with multiple chronic health conditions were more likely than adults with no conditions to report unmet care needs (16.7% vs. 7.6%).
Among parents with children under 19, the researchers found:
About 9.2% of parents reported they had delayed or forgone at least one type of care for their children in the past 30 days over worries about exposure to the coronavirus, and 5.5% reported their children had missed out on multiple types of care for this reason.
Parents with family incomes below 250% of the federal poverty level were more likely than those with higher incomes to report delaying or forgoing care for their children (12.3% vs. 6.5%).
The most common type of delayed or forgone care for both adults and their children was dental care. Just under 7% of adults surveyed delayed dental care, and 5.3% delayed this care for their children.
“Even as COVID-19 cases fell from their peak, delayed and forgone health care over worries about exposure to coronavirus persisted in April 2021,” said Dulce Gonzalez, MA, a research associate at the Urban Institute. “Unmet health care needs can adversely affect health and other daily activities for both children and adults.”
Even before the recent surge, non–COVID-19 health care had not returned to baseline, according to Katherine Hempstead, a senior policy adviser at the Robert Wood Johnson Foundation, in New Jersey. “Skipping needed care can endanger the health of adults and children, especially those with chronic conditions.”
The analyses draw on data from the Urban Institute’s April 2021 Health Reform Monitoring Survey. The survey was fielded April 2-20, with a sample size of 9,067 adults 18 to 64 years of age.
Antimicrobial Use Grew During COVID-19 Pandemic
A study of data from hospitals in South Carolina found that use of antimicrobial agents increased steeply during the pandemic.
The results, which were presented at the World Microbe Forum virtual meeting, raise concerns that such use may cause increases in antimicrobial resistance and undo efforts of antimicrobial stewardship programs (poster WMF21-0194).
“As antimicrobials are a precious resource, we all have a vested interest in stopping inappropriate use,” said Pamela Bailey, DO, an assistant professor of medicine at the University of South Carolina School of Medicine, in Columbia, and a co-author of the poster.
The study includes data from 22 hospitals in South Carolina, which report antimicrobial usage data to the National Healthcare Safety Network and Antimicrobial Stewardship Collaborative of South Carolina. Usage was tabulated for all antibacterial agents, broad-spectrum antibacterial agents and antibacterial agents predominantly used for resistant gram-positive infections, and compared between the b period of March to June 2019, and pandemic period of March to June 2020.
While hospitals that did not admit patients with COVID-19 did not demonstrate higher antimicrobial use during the pandemic, use increased significantly in hospitals that did admit COVID-19 patients. The mean level of antimicrobial usage, reported as days of therapy per 1,000 days present in 2020, was 565.8 versus 530.9 in 2019.
- The overall standardized antimicrobial administration ratio rose from 0.84 during 2019 to 0.92 in 2020.
- And use of broad-spectrum agents, specifically beta-lactams for Pseudomonas and agents for methicillin-resistant Staphylococcus aureus agents increased from a rate of 122.3 during 2019 to 142.5 a year later.
Some, although likely not all, of the increased use may be tied to confusion regarding COVID-19 during the early days of the pandemic and efforts made by health care professionals to triage patient care.
“The novel aspect of SARS-CoV-2 infection was a struggle in the early days of the pandemic—we knew so little, and were understandably cautious,” Dr. Bailey said.
“This meant using antimicrobials to treat the presumed coinfections, extrapolated from what we knew about other viral respiratory infections.
“Relatively quickly,” Dr. Bailey added, “we learned that bacterial coinfections were not as common as we thought and that we needed to scale back our antimicrobial use in COVID-19 patients.”
Staffing changes and in-hospital priority shifts during the early days of the pandemic likely resulted in changes to existing antimicrobial stewardship programs, likely contributing to higher antimicrobial use.
“We know from our study that we were inappropriately using antimicrobials in the early days of the pandemic, and we have launched efforts to scale back this inappropriate use,” Dr. Bailey said. “The concern is that in the coming years, we will see more resistance in our communities due to this inappropriate use—only time will tell.”
All Countries Need Access to Vaccines to Slow Transmission
The allocation of COVID-19 vaccines among countries has thus far tended toward vaccine nationalism, wherein countries stockpile vaccines to prioritize access for their citizenry over equitable vaccine sharing. The extent of vaccine nationalism, however, may strongly affect global trajectories of COVID-19 case numbers and increase the potential emergence of novel variants, according to a study from Princeton University and McGill University (Science 2021 Aug 17. doi:10.1126/science.abj7364).
“Certain countries such as Peru and South Africa that have had severe COVID-19 outbreaks have received few vaccines, while many doses have gone to countries experiencing comparatively milder pandemic impacts, either in terms of mortality or economic dislocation,” said co-first author Caroline Wagner, PhD, an assistant professor of bioengineering at McGill University, in Montreal, who previously served as a postdoctoral research associate in Princeton’s High Meadows Environmental Institute (HMEI).
“Our goal was to explore the effects of different vaccine-sharing schemes on the global persistence of COVID-19 infections—as well as the possibility for the evolution of novel variants—using mathematical models,” said co-first author Chadi Saad-Roy, a Princeton graduate student in ecology and evolutionary biology and the Lewis-Sigler Institute for Integrative Genomics, in New Jersey.
The researchers projected forward the incidence of COVID-19 cases under a range of vaccine dosing regimens, vaccination rates and assumptions related to immune responses. They did so in two model regions: one with high access to vaccines (a high-access region) and a low-access region. The models also allowed for the regions to be coupled either through case importation, or the evolution of a novel variant in one of the regions.
“In this way, we could assess the dependence of our epidemiological projections on different immunological parameters; regional characteristics, such as population size and local transmission rate; and our assumptions related to vaccine allocation,” Dr. Wagner said.
Senior author C. Jessica E. Metcalf, PhD, an associate professor of ecology and evolutionary biology at Princeton and public affairs and associated faculty in HMEI, added: “High case numbers in unvaccinated populations will likely be associated with higher numbers of hospitalizations and larger clinical burdens compared to highly vaccinated populations.”
The authors also drew on a framework developed in their prior work to begin trying to quantify the potential for viral evolution under different vaccine-sharing schemes. In their model, repeat infections in individuals with partial immunity, either from an earlier infection or a vaccine could foster more variants, which plays a role in sustaining transmission, they explained.
“Global vaccine coverage will reduce the clinical burden from novel variants, while also decreasing the likelihood that these variants emerge,” Mr. Saad-Roy said.
A new study boosts hopes for a broad vaccine to combat COVID-19 variants and future coronavirus outbreaks.
What We Need Is a Dream Vaccine
Scientists from Duke-NUS (National University of Singapore) Medical School and the National Centre for Infectious Diseases found that 2003 SARS (severe acute respiratory syndrome) survivors who have been vaccinated with the Pfizer-BioNTech messenger RNA (mRNA) vaccine produced highly potent functional antibodies that are capable of neutralizing not only all known SARS-CoV-2 variants of concern (VOCs), but other animal coronaviruses that have the potential to cause human infection (N Engl J Med 2021 Aug 18. doi:10.1056/NEJMoa2108453).
This is the first time that such cross-neutralizing reactivity has been demonstrated in humans, and further boosts hopes of developing an effective and broad-spectrum next-generation vaccine against different coronaviruses.
Among the coronavirus family, one subgroup relies on the angiotensin-converting enzyme 2 (ACE2) molecule to enter human cells. Both SARS-CoV-1 and SARS-CoV-2 belong to this group as well as a number of coronaviruses circulating in animals, such as bats, pangolins and civets. While the exact route of transmission remains unknown, these viruses have the potential to jump from animals to humans and could start the next pandemic. Collectively, this group of viruses is called sarbecovirus.
“We explored the possibility of inducing pan-sarbecovirus neutralizing antibodies that can block the common human ACE2–virus interaction, which will be protective not only against all known and unknown SARS-CoV-2 VOCs, but also future sarbecoviruses,” said Chee Wah Tan, PhD, a senior research fellow with Duke-NUS’s Emerging Infectious Diseases (EID) program and co-first author of the study.
To test their hypothesis, researchers recruited eight people who recovered from SARS-CoV-1, which was responsible for the 2003 SARS epidemic, as well as 10 healthy people and 10 COVID-19 survivors. They then compared the immune response of the three groups before and after they were vaccinated with the mRNA vaccine. In particular, they wanted to understand whether the neutralizing antibodies developed in the SARS-vaccinated group could wipe out both SARS-CoV-1 and SARS-CoV-2 viruses as well as other sarbecoviruses, including potentially zoonotic sarbecoviruses that have been identified in bats and pangolins.
“Prior to vaccination, SARS-CoV-1 survivors had detectable neutralizing antibodies against SARS-CoV-1 but no or low-level anti–SARS-CoV-2 neutralizing antibodies. After receiving two doses of the mRNA vaccine, all displayed high levels of neutralizing antibodies against both SARS-CoV-1 and SARS-CoV-2,” said Wanni Chia, PhD, a research fellow at the Duke-NUS’s EID program and co-first author of the study. “Most importantly, they are the only group with a broad spectrum of neutralizing antibodies against 10 sarbecoviruses that were chosen to be examined.”
This research points to a novel strategy for developing the next-generation vaccines, they said.
The team conducted their investigation using an improved version of the surrogate virus neutralization test (sVNT) developed by Duke-NUS in early 2020. The team invented the sVNT assay (cPass, GenScript), which has been granted emergency use authorization by the FDA to determine SARS-CoV-2–specific neutralizing antibodies in human sera following infection or vaccination. Drs. Tan and Chia are part of Professor Wang’s team and co-inventors of the sVNT. The improved multiplex sVNT allows simultaneous detection of neutralizing antibodies against different sarbecoviruses in a single tube, thus playing a pivotal role in studies like this that require accurate side-by-side comparison of neutralizing antibody levels against different viruses.
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