Ken reports on medical innovations and advances in practice and edits presentations for news and professional education publications. He previously taught and mentored pharmacy and medical students, and provided and managed pharmacy care and drug information services. He regularly contributes to Contagion Live, HCP Live, Neurology Live, and Pain Medicine News.

Kenneth Bender, PharmD, MA

"Long COVID" persisted for at least 6 months after recovery in more than half of over 250,000 survivors assessed in a systematic 

 of short-term and long-term postacute sequelae of COVID-19 (PASC).

Paddy Ssentongo, MD, PhD, MPH, Center for Neural Engineering, Department of Engineering, Science and Mechanics, The Pennsylvania State University, State College, PA, and colleagues conducted the review to estimate the overall and organ system-specific frequency of PASC.

"As we better understand the disease burden of PASC in COVID-19 survivors, we can develop precise treatment plans to improve clinical care in patients with COVID-19 who are at greatest risk of PASC and establish integrated, evidence-based clinical management for those affected," Ssentongo and colleagues opined.

 Ssentongo elaborated on their hope for improved approaches to PASC,"Machine learning models that use genomic, clinical, and socio-demographic information to predict patients with PASC will prove to be useful in guiding precision medicine," he said.

The investigators screened a total of 2,100 studies, with 57 meeting inclusion criteria containing 250,351 survivors of COVID-19, of whom 79% (197,777) had been hospitalized for the acute infection. The studies included randomized clinical trials, prospective and retrospective cohort studies, case series with at least 10 patients and case-control studies with reported PASC frequencies.

The median (interquartile range, IQR) of COVID-19 survivors experiencing at least 1 PASC was 54.0% (45.0-69.0%; 13 studies) at 1 month; 55% (34.8-65.5%; 38 studies) at 2 to 5 months; and 54% (31.0-67.0%; 9 studies at 6 or more months.The most common sequelae were pulmonary abnormalities, impaired mobility, neurologic and mental health disorders.

Persistent dyspnea was found in 29.7% (14.2-37.0%; 38 studies) and cough in 13.1% (5.3-22.6%; 26 studies).Increased oxygen requirement was reported in nearly two-thirds of survivors (65.0% (39.3-76.1%; 3 studies). Functional mobility declined in 20.2% (14.9-30.6; 6 studies) and exercise tolerance was reduced in 14.7% (10.6-18.%; 2 studies).

Neurological symptoms included difficulty concentrating in 23.8% (20.4-25.9%;4 studies), with other common symptoms including headaches, memory deficits, and cognitive impairment.Mental health disorders diagnosed after acute infection included anxiety in 29.6% (14.0-44.0%; 7 studies); sleep disorders in 27% (19.2-30.3%; 10 studies); depression in 20.4% (19.2-21.5%; 2 studies); and post-traumatic stress disorder in 13.3% (7.3-25.1%; 9 studies).

Ssentongo considered the question of whether neurologic disorders, as a possible direct effect of SARS-CoV-2, should be distinguished as a component of PASC from mental health disorders which can follow other serious illnesses, particularly in the context of a pandemic.

"It is plausible that the effects of the SARS-CoV-2 virus on the brain—either direct cytolytic effect or neuronal damage through indirect systemic effects such as secondary inflammatory response—can induce the reported mental health disorders," he indicated."Of course, future studies are necessary to delineate the psychological effect of the pandemic and the direct effect of the virus."

The investigators emphasize the importance of recognizing, not just the life lost from acute COVID-19 illness, but the disease burden experienced by so many due to PASC.They suggest that clinical management of PASC will require "a whole-patient perspective", with management tools like virtual rehabilitation platforms.They also recommend increasing the availability of "one-stop multidisciplinary clinics" to address the complex clinical presentations and avoid sending these patients on multiple referrals.

Ssentongo acknowledged, however, that such comprehensive approach to PASC is difficult within health care systems that have been exposed in the COVID-19 pandemic as often disjointed and inequitable.

"Similar to the barriers that exist in traditional physical medicine, PASC treatment centers and clinics may be concentrated in urban areas," he observed."Therefore, traditional health care disparities may perpetuate in PASC treatment. Nevertheless, establishing these clinics will steer us in the right direction in treating PASC."

Articles

PASC (postacute sequelae of COVID-19) was found to persist for at least 6 months in more than half of those contracting the infection.

Course of COVID-19 Likely to Go Long

Just over half of US adults are planning to get vaccinated for influenza despite urging by health officials concerned with potential influenza resurgence during the COVID-19 pandemic, according to a new 

 by the National Foundation for Infectious Diseases (NFID).

The survey, conducted August 12-16, 2021, found that although 61% agree that flu vaccination is the best preventive measure against flu-related deaths and hospitalizations, 44% of US adults are either unsure or do not plan to get the vaccination. The NFID-sponsored survey was conducted by NORC, a social research institution at the University of Chicago.

 announcing the survey findings, Rochelle Walensky, MD, MPH, director, Centers for Disease Control and Prevention (CDC), emphasized the importance of the influenza vaccination.

"While we do not know what the activity will be like this fall, I urge everyone age 6 months and older to get vaccinated. If you are unsure about getting a flu vaccine, please take the time to get the information you need to make the right choice for your health and to get vaccinated," Walensky urged. "The COVID-19 pandemic is not over, and the risk of both flu and COVID-19 circulating could put additional strain on hospitals and frontline healthcare professionals."

An NFID statement indicated that the survey was conducted to obtain a better understanding of the beliefs about flu and pneumococcal disease, as well as attitudes and practices around vaccination, and how these may be affected by the COVID-19 pandemic. The survey included 1126 complete responses, with 1064 via the web and 62 via telephone, from US adults age 18 years and older representing all US states and the District of Columbia.

Among those not planning to get vaccinated, the most frequent reasons were: do not think vaccine works very well (39%); never get the flu (36%); concern about potential side effects (25%); don't think flu is serious illness (20%); concern about getting flu from vaccine (19%).

The prospect of low vaccination rates poses particular hazard to those at highest risk for flu-related complications, according to the health experts at the news conference.They noted that nearly 1 in 4 (23%) adults who are at high risk had indicated that they were not planning to get vaccinated this season, not only leaving them vulnerable, but increasing likelihood of transmission.

"Amid the ongoing pandemic, we remain extremely concerned about patients with chronic health conditions who are at higher risk for pneumococcal disease and complications from flu and COVID-19," indicated Cedric Rutland, MD, West Coast Lung, Newport Beach, CA.

Patricia Stinchfield, RN, MS, NFID president-elect highlighted the youngest, vulnerable population."Children age 6 years and younger are at higher risk of serious flu-related illness, and we need to ensure our children are protected before flu starts spreading in schools and communities. Flu vaccines can be life saving for children," she declared.

Laura Riley, MD, Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, noted that the current 55% vaccination coverage of pregnant women was similar to the prior season."Nearly half of pregnant women and their infants remain unprotected against flu," Riley said. "All pregnant women should get a flu vaccine to protect themselves and their newborn babies from severe complications."

77% would be willing to take an antiviral medication if prescribed to reduce severe flu symptoms

Among respondents who had not received at least one dose of a COVID-19 vaccine, 63% won't, and 28% are not sure whether they will get a COVID-19 vaccine,

51% are not familiar with pneumococcal disease, although about a third (32%) of those at higher risk report having been advised to receive pneumococcal vaccine.

54% report they will wear a mask at least sometimes during the flu season.

Black adults (73%) and Hispanic adults (62%) are more likely than White adults (46%) to report they will wear a mask during flu season.

"Survey findings highlight the importance of raising awareness and addressing misconceptions about flu, pneumococal disease, and COVID-19 vaccines, and the importance of healthcare professionals strongly recommending vaccines for their patients," the NFID indicated in the press release.

New survey finds little more than half of US adults are planning to obtain vaccination against influenza despite urging by health officials.

National Survey Finds Low Interest in Influenza Vaccination

 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 healthcare 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."

New clinical trial is first to describe concomitant administration of any vaccine with either an adenoviral vector or mRNA COVID-19 vaccine.



Concomitant COVID-19 and Influenza Vaccination Tested Against Twindemic


Israel was the first country to make a third booster dose of an mRNA vaccine against COVID-19 available for the elderly, before expanding to those 12 years or older, and a new large population 

 of the initial offering confirms that it reduced infection rate compared with a 2-dose vaccination regimen.

In the study report, lead author Yinon Bar-On, MSc, Weizmann Institute of Science, Rehovot, Israel, and colleagues recount that Israel had addressed an increase in cases attributed to the Delta variant by approving the third dose for high-risk populations on July 12, and then for those 60 years of age or older on July 30.

Although the action was based on evidence that the booster of the Pfizer-BioNTech BNT162b2 vaccine increases antibody neutralization levels by an approximate factor of 10 compared with levels after the 2nd dose, Bar-On and colleagues point out that it remained to be determined whether that would correspond to increased protection.

“It is thought that increased neutralization titer could lead to increased protection against infection and severe illness,” Bar-On and colleagues indicated. ”However, in terms of real-world effectiveness, the size of such an effect remains unclear.”

For that real-world data, the investigators accessed records from the Israeli Ministry of Health database for over 1 million persons who were 60 years of age or older and had received the 2-dose vaccination (1,137,804 participants met inclusion criteria).They then compared infection rates during the study period from July 30 through August 2021 between those who did or did not receive a third dose. The booster had been administered at least 5 months after a 2-dose vaccination. The rate of infections was calculated from confirmed cases which occurred at least 12 days after the respective vaccinations, in the period of expected immunologic efficacy.

The non-booster group included approximately 5.2 million person-days of risk, with 4439 confirmed infections and 294 cases of severe illness.The booster group included 10.6 million person-days of risk with 934 confirmed infections and 29 cases of severe illness.

The investigators reported the confirmed infection rate was lower in the booster group than in the nonbooster group by a factor of 11.3 (95% Confidence Interval [CI] 10.4-12.3). The absolute between-group difference in rate of confirmed infection was 86.6 infections per 100,000 person-days.

The relative rate of severe illness was further lowered in the booster group relative to the nonbooster, by a factor of 19.5 (12.9-29.5)The absolute between-group difference in the rate of severe illness was 7.5 cases per 100,000 person-days.

“Our findings give clear indications of the effectiveness of a booster dose even against the currently dominant delta variant,” Bar-On and colleagues concluded.“Further studies will help determine the long-term effectiveness of the booster dose against current and emerging variants.”

 Editor-in-Chief, Eric Rubin, MD, PhD, and Deputy Editor, Lindsey Baden, MD, discussed the Israel study within an interview conducted by Stephen Morrissey, PhD. Although they note that these data can be difficult to apply to practice, with communities that may engage vaccines and health behaviors differently, the large size of the studied population and analyses conducted to reduce bias support the reliability of the findings.

“The fundamental finding of a differential attack rate of COVID infection in those who received a boost looks pretty real," Baden commented.

Rubin agreed that the benefit was apparent, and particularly notable given that the studied population included immunocompromised individuals along with the elderly who were the in the first group to receive the third booster dose. That demographic, however, could also limit generalizing the findings, he cautioned.

"What that would mean for the rest of the population is not so clear," Rubin said. "It may be that there isn't that much of an effect for everybody else, and there's no way of telling from these population level data if that is true."

"So I think there are more important data to come," he added.

With the expansion of booster vaccinations to the wider population in Israel, and the current discussions about which populations in the US should have that access, Rubin offered a final caution."It's also important to remember that these are the data upon which people are acting right now.They're making important public health decisions, and I think that everyone should know that the data aren't perfect."

Although these data are not from randomized controlled trials which supported the initial vaccinations, Rubin recognized that these are the available data. "We're going to have to be using incomplete data or imperfect data to inform what we do," he acknowledged.

A third dose booster vaccination given to persons 60 years of age or over in Israel was confirmed to lower their rate of COVID-19 infection compared to a 2-dose regimen.