Kenneth Bender, PharmD, MA

 to assess concomitant administration of any vaccine with either an adenoviral vector or mRNA COVID-19 vaccine found the combination with influenza vaccine is safe, produces immunogenicity associated with separate vaccination, and supports the combination as an efficient intervention against the possible “twindemic.”

Validation of a more efficient means to vaccinate against these viral infections is particularly welcome as flu season has commenced in the US and northern hemisphere countries, and a recent 

 from the National Foundation for Infectious Diseases (NFID) shows that 44% of the US population are unsure or do not plan to get vaccinated against influenza.

Rajeka Lazarus, DPhil, Department of Microbiology, University Hospitals Bristol and Weston, NHS Foundation Trust, Bristol, UK, and colleagues of the ComFluCOV Trial Group anticipate that concomitant administration would reduce burden on health care systems, and report, “concomitant vaccination raises no safety concerns and preserves the immune response to both vaccines.”

The investigators recruited 679 participants who had received the first dose of either the adenoviral vector SARS-CoV-2 vaccine ChAd0x1 (AstraZeneca) or the mRNA vaccine BNT162b2 (Pfizer/BioNTech) and randomized 1:1 to receive either placebo or an age-appropriate dosed influenza vaccine (adjuvanted trivalent or cellular or recombinant quadrivalent) with their second COVID-19 vaccine dose. Follow-up monitoring was available for 665 participants.

The study monitored for adverse effects and assessed laboratory indicators of immunogenicity from April 1 through June 26, 2021, outside influenza season. The study was interrupted April 8 when notice was received of thomboembolic events associated with ChAd0x1, and resumed April 9 with exclusion of participants with risk factors for thrombotic events.

The primary outcome was one or more solicited reports of systemic reaction within 7 days after vaccination such as fever, chills, or joint pains. Secondary outcomes involving safety and adverse response included solicited local reactions such as pain or tenderness and unsolicited adverse events, including medically-attended adverse events.

The secondary outcome of immune response was determined from measures including SARS-CoV-2 S-protein immunoglobulin G (anti-S IgG) concentration in serum collected on day of vaccination (D0) and day 21; and hemagglutinin antibody inhibition (HAI) against the 4 strains of influenza contained in the 2020/21 formulations, on D0, day 21 and day 42. Other immunological measures that will be in a subsequent report include neutralizing antibodies against SARS-CoV-2 on D0 and day 21 and mucosal immune responses to COVID-19 vaccines in saliva.

Lazarus and colleagues reported that, overall, 555/665 (83.5%) of participants had at least one solicited local adverse reaction after vaccination on DO; in 85.2% of those receiving concomitant vaccinations and 81.7% with placebo in lieu of influenza. The numbers with local reactions 7 days after injection were similar in both groups, although higher among those receiving the active combination at day 21. Rates of medically assisted adverse events were similar between groups following both D0 and day 21.

The Anti-S IgG geometric mean units (GMU) at day 21 were similar between those who received either SARS-CoV-2 vaccine alone or with concomitant influenza vaccine. Seroconversion rates (SCR) ranged from 89-100% and 79-93% 21 days after either BNT162b2 or CHAd0x1, respectively, whether administered alone or in combination with influenza vaccine. There were no significant differences in the HAI GMR for any influenza strain 21 days after influenza concomitant vaccination with SARS-CoV-2 vaccine compared to previously studied cohorts receiving influenza vaccination alone.

“By performing the trial in relation to the second rather than the first dose of COVID-19 vaccine, we have evaluated safety and immunogenicity in primed individuals,” Lazarus and colleagues point out. “Therefore, the findings are also likely to be more relevant to the question of concomitant administration of booster doses and seasonal influenza vaccines, which over time may become the 'norm' in many parts of the world.”

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Twofer Vaccine in the Making Works Against ‘Twindemic’ of Flu, COVID-19

Repercussions from the COVID-19 pandemic will be measured for years to come. For instance, according to investigators with the University of Wisconsin, it appears as if there were fewer antibiotics prescribed for respiratory symptoms during the pandemic than in the comparable pre-pandemic period. Their findings came from data collected from patients at the University of Wisconsin Health system and were recently published in a 

Alexander Lepak, MD, an assistant professor in the infections disease department at the University of Wisconsin School of Medicine and Public Health, and colleagues found that while antibiotic prescribing rates increased during the pre-pandemic winter respiratory viral season, they decreased in the short-term and remained low throughout the corresponding pandemic period.

“One way to interpret the study is to draw a conclusion about how much inappropriate antibiotic use was occurring for respiratory viruses in the pre-pandemic period,” said Lepak, the study’s corresponding author. “But I think there is another side to this story, and that this is a huge success story. We had massive COVID-19 surges, with unprecedented numbers of patients with respiratory complaints, especially in the fall between October and December, yet antibiotics were not prescribed, for the most part, in patients with respiratory complaints during this period—keeping in mind they had indistinguishable symptoms from other respiratory viruses where antibiotics were previously prescribed.”

Lepak and colleagues—Lepak emphasized that the study was a “huge collaborative effort”—compared the number of antibiotic prescriptions provided at the more than 80 ambulatory clinic sites of UW Health with 7 million annual ambulatory encounters, in the pre-pandemic period of July 2018 to February 2020 and April 2020 to February 2021 during the pandemic. The number of ambulatory encounters during those periods were similar: 637,000 and 662,000 per month, respectively.

The winter seasonal viruses, including influenza, respiratory syncytial virus (RSV), and seasonal coronavirus, demonstrated seasonal variation during the pre-pandemic but not the pandemic period. The number of patients presenting with seasonal viruses decreased from approximately 4800 per month pre-pandemic to 12 per month in the pandemic period. Other respiratory virus detections also decreased, from 560 per month pre-pandemic to 228 per month during the pandemic.

The investigators reported that, adjusting for seasonality, monthly antibiotic prescription for respiratory tract infections (the indication for antibiotic prescriptions is required by UW Health Pharmacy) fell 79%, from 10.5 to 2.2 prescriptions per 1000 patient encounters.

“Antibiotic prescribing for respiratory complaints was best correlated with activity of seasonal coronaviruses, rhinoviruses, RSV, metapneumovirus, etc., and it was not as well correlated with influenza and wasn’t correlated at all with COVID-19 activity,” Lepak commented. “The difference between these is that we have accessible and timely diagnostics for the latter two, but not necessarily the former group, at least for ambulatory care patients.

“Based on these findings, our hypothesis is that providing more comprehensive respiratory viral testing that is accessible and timely to ambulatory providers and patients may be able to significantly curb antibiotic prescribing for respiratory viruses,” Lepak said.

Although the investigators found other studies which have showed relatively quick declines in rates of viral infections or antimicrobial prescribing, they characterize theirs as “the first to combine respiratory virus activity and antibiotic prescriptions that were indexed to the number of encounters over a prolonged period that includes the typical respiratory virus season.”

This represents a “huge success” for providers who were able to deal with COVID-19 and other respiratory diseases properly, says one of the authors of the study. 

Kenneth Bender, PharmD, MA

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Twofer Vaccine in the Making Works Against ‘Twindemic’ of Flu, COVID-19

COVID-19 Pandemic May Have Helped Cut Antibiotic Prescribing