Mia Cokljat, M.B.Ch.B., from the University of Oxford in the United Kingdom, and colleagues compared the COVID-19 treatment guidelines of each World Health Organization (WHO) member state to the WHO COVID-19 therapeutic guidelines. The analysis included COVID-19 therapeutic national guidelines for 109 of the 194 WHO member states.

The researchers found considerable variation in guidelines and in disease severity stratifications. There were also substantial differences in therapeutic recommendations in many national guidelines versus the WHO guidelines. In late 2022, 93 percent of national guidelines were recommending at least one treatment that had been proven to be ineffective in large, randomized trials and was not recommended by WHO. For example, corticosteroids were not recommended in severe disease in nearly 10 percent of national guidelines, despite overwhelming evidence of their benefit. For countries categorized as low-resource settings, national guidelines showed the greatest divergence.

“The formalization of processes in the development of national guidelines for COVID-19 and other infectious diseases is essential for ensuring that these guidelines are grounded in the best available evidence,” the authors write. “A systematic and structured approach would not only enhance the credibility of the guidelines but could also contribute to their effectiveness in guiding public health interventions, especially in a pandemic setting.”

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The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) discussed vaccinations for COVID-19, influenza, respiratory syncytial virus (RSV), pneumococcal infections, and other infectious diseases and made some related recommendations during their first 2024 meeting, held February 28 to 29.

COVID-19 Vaccine Recommendations

The ACIP now recommends that persons 65 years of age and older should receive an additional dose of the updated (2023-2024) COVID-19 vaccine.¹ The additional dose must be administered at least 4 months following the previous dose of the updated vaccine.

Adults aged 65 years and older have expressed a high level of concern about COVID-19, with 68.4% of individuals indicating they would definitely receive another vaccine dose should it become available.² The effectiveness of an additional dose of COVID-19 vaccine is demonstrated by past recommendations.

The need for the recommended 4-month COVID-19 booster vaccine for those age 65 and older is supported by both hospitalization data and scientific reasoning. An estimated 67% of COVID-19 hospitalizations were among patients age 65 years and older between October 2023 and January 2024, according to ACIP current respiratory season calculations made using data from COVID-NET, a population-based hospitalization surveillance program.³ Moreover, hospitalizations were 5 times higher for those age 65 years and older vs those aged 50 to 64 years.

The need for booster protection is also indicated by data showing that older adults may not be able to generate robust, long-lasting neutralizing antibody responses or good memory cytotoxic T-cells as there are fewer naive T-cells that respond to new pathogens.²

Vaccine formulations for the next COVID-19 season are already underway.²

Notably, members of the ACIP expressed concern that offering booster vaccinations for those age 65 and older at 4-month intervals could create vaccine fatigue as well as confusion for providers, given that immunocompromised patients may receive a booster dose following a 2-month interval.

In their June 2024 meeting, the ACIP plans to propose revised time frames for COVID-19 vaccine development and vaccination that will allow health care providers ample time to prepare for the COVID-19 viral season.

RSV Vaccine Developments

An ACIP work group on RSV vaccination in older adults presented its recommendation that providers and patients “consider timing of the RSV vaccination as part of shared clinical decision-making discussions,” noting that for most older adults, RSV vaccination is most beneficial when received in late summer or early fall, before the start of RSV season.⁴

Although shared decision-making between patient and provider is currently recommended for determining whether or not an adult patient should receive the RSV vaccine, this recommendation may be replaced by a universal recommendation that adults above a certain age receive the RSV vaccine, and a risk-based recommendation that adults over age 50 years receive the vaccine, according to the work group report, “RSV Vaccination in Older Adults: Work Group Interpretations.”⁴

The ACIP also expressed its intention to discuss the potential approval of the GSK RSV vaccine, AREXVY, for those aged 50 to 59 at “increased risk of RSV disease” at their June meeting.  AREXVY is currently approved for use in adults aged 60 and above.⁴

In anticipation of RSV-related actions set for June, the ACIP reviewed RSV vaccine data related to the Moderna mRNA vaccine.^4,5 The committee also discussed concerns over the potential connection between currently approved RSV vaccines and an increased incidence of Guillain-Barré Syndrome (GBS).

Moderna mRNA RSV Vaccine

Moderna has been conducting a clinical trial for their mRNA-based RSV vaccine for adults age 60 years and older (ClinicalTrials.gov Identifier: NCT05127434), which works by encoding the RSV fusion (F) glycoprotein.⁵ According to an ACIP report on trial findings that was presented at the February meeting, the vaccine has been generally well tolerated, efficacious through a median 8.6 months of follow-up, and presented no safety concerns (including no concern over GBS).

The trial enrolled a total of 26,550 healthy adults age 60 years and older, including those with chronic, stable health conditions. The primary endpoint was vaccine efficacy in preventing the first episode of RSV lower respiratory tract disease (LRTD) between 14 days and 12 months post-vaccination. The secondary endpoint was vaccine efficacy in preventing the first episode of RSV acute respiratory disease (ARD) and first hospitalization between 14 days and 12 months.

Trial investigators found that vaccine efficacy for RSV-LRTD with 2 or more symptoms reached 83.7%, whereas efficacy for RSV-LRTD with 3 or more symptoms was calculated as 82.4%.⁵ The efficacy threshold for RSV-ARD was set at 68.4%. Vaccine efficacy met lower bounds of confidence interval criteria to exceed 20%.

RSV Vaccines and GBS

For the February ACIP meeting, CDC’s Immunization Safety Office and the US Food and Drug Administration (FDA) shared preliminary data from multiple surveillance systems on the risk for GBS after RSV vaccination.⁴

An elevated but rare risk for GBS was observed following administration of the GSK’s AREXY and Pfizer’s ABRYSVO vaccines for RSV.  According to the work group report on RSV Vaccination in Older Adults, current surveillance data “support a potential increased risk for GBS after RSV vaccination among adults aged ≥60 years.”⁴

The report went on to note that “there is currently insufficient evidence to confirm whether RSV vaccination is associated with increased risk for GBS in older adults, or to estimate the magnitude of any increase in GBS risk after RSV vaccination.”⁴

Currently, clinical trials are underway evaluating the safety of these vaccines, examining the association between RSV vaccines and the incidence of GBS. More conclusive evidence of potential risks following RSV vaccination will be available following RSV monitoring using self-controlled case series designs.

Influenza Immunization in Children With Asthma

The ACIP also assessed evidence evaluating the safety of the live attenuated influenza vaccine (LAIV4) in children with asthma.⁶ The evidence indicated that LAIV4 may be a suitable option for children age 5 years and older with asthma.

Evidence presented included a study assessing whether LAIV4 is noninferior to IIV4. The study included 151 patients between the ages of 5 and 7 years with persistent asthma who were randomly assigned to 2 groups: one receiving LAIV4 FluMist and the other receiving IIV4 Fluzone. On days 15 and 43, the 2 groups were evaluated for symptoms following vaccination. The study investigators compared the proportion of patients using LAIV4 vs IIV4 who experienced an asthma exacerbation during the 42 days following vaccination.

Study findings showed that in the 14 days following vaccination, 3 exacerbations were reported among those receiving LAIV4 vs 4 exacerbations among those receiving IIV4 (3.9% vs. 5.7%, P =.74). In the 42-day symptom assessment, 8 asthma exacerbations were documented among those receiving LAIV4 and 10 among those receiving IIV4 (10.8% vs. 14.7%, p = 0.74). The upper bound for noninferiority was set at 10% with a difference in proportion of 3.9 (CI: 90%: -0.15, 0.07).⁶ Researchers rejected the null hypothesis and proved LAIV4 noninferiority to IIV4.

Limitations of the study include the enrollment of fewer participants than intended, setting the power at 79% and the enrollment of patients within 2 separate flu seasons, which may have led to slightly different products.

Further discussion of the suitability of LAIV4 for children age 5 years and older with asthma is anticipated at future ACIP meetings.

Pneumococcal Vaccination: PCV21 Considerations

The ACIP also discussed incorporating a recently developed pneumococcal vaccine, V116, a 21-valent pneumococcal conjugate vaccine (PCV21), into its roster of recommended pneumococcal vaccines. Toward that end, the committee reviewed phase 3 clinical trial results for V116 (ClinicalTrials.gov Identifier: NCT05425732).

The ACIP reported that the following policy questions are being actively considered by its work group:⁷

1. Should PCV21 be recommended for US adults aged 19 and older who currently have a recommendation to receive a PCV?
2. Should PCV21 be recommended for US adults aged 50 to 64 years who do not have risk-based indication for the pneumococcal vaccine?
3. Should PCV21 be recommended for US adults aged 19 to 49 years who do not have risk-based indication for the pneumococcal vaccine?

About 30% to 40% of adult invasive pneumococcal disease (IPD) cases are caused by serotypes that are not contained in currently available pneumococcal vaccines.⁸ The PCV21 vaccine contains most of these serotypes and provides broader coverage. In a phase 3, randomized, double-blind, active comparator-controlled clinical study of the V116 PCV21 vaccine, V116 was concluded to be superior to PCV20 for 10 out of the 11 of its unique strains.

The work group concluded that pneumococcal disease is of public health importance to adults currently recommended for PCV vaccination. While it may be appropriate to expand vaccination to patients between the ages of 50 to 64, committee members concluded that epidemiology does not support expanding vaccination to younger adults without indication.

At its June meeting, the ACIP plans to consider official draft policies on PCV21 use in US adults.⁷

Jennifer Hammond, PhD, from Global Product Development at Pfizer in Collegeville, Pennsylvania, and colleagues randomly assigned adults with confirmed COVID-19 with symptom onset in the past 5 days to receive nirmatrelvir-ritonavir or placebo every 12 hours for five days (654 and 634 participants, respectively). From day 1 through day 28, participants logged the presence and severity of prespecified COVID-19 signs and symptoms daily.

The researchers found that the median time to alleviation of all targeted signs and symptoms of COVID-19 was 12 and 13 days in the nirmatrelvir-ritonavir and placebo groups, respectively. Five and 10 participants in the nirmatrelvir-ritonavir and placebo groups, respectively, were hospitalized for COVID-19 or died from any cause (difference, −0.8 percentage points; 95% CI, −2.0 to 0.4). The percentage of participants with adverse events was 25.8% and 24.1% for nirmatrelvir-ritonavir and placebo, respectively.

“Nirmatrelvir-ritonavir was not associated with a significantly shorter time to sustained alleviation of COVID-19 symptoms than placebo, and the usefulness of nirmatrelvir-ritonavir in patients who are not at high risk for severe COVID-19 has not been established,” the authors write.

The study was funded by Pfizer.

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Editorial

Chad R. Wells, PhD, from the Yale School of Public Health in New Haven, Connecticut, and colleagues examined the effectiveness of an annual SARS-CoV-2 vaccination campaign in an age-structured dynamic transmission model in the US; the intervention included SARS-CoV-2 vaccination with an age-specific uptake similar to that of influenza vaccination.

The researchers found that in an annual vaccination campaign, the optimal timing between the first and second vaccine dose delivered to children younger than 2 years and adults aged 50 years and older was estimated to be 5 months. A second booster dose resulted in 123,869 fewer hospitalizations and 5524 fewer deaths compared with a single-dose campaign, averting $3.63 billion in costs over one year.

“Our study shows that adopting an annual vaccination campaign with the provision of a second dose to children younger than 2 years and adults aged 50 years or older can be a suitable approach to protect individuals against SARS-CoV-2 infection and associated outcomes,” the authors write.

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Austin E. Schumacher, PhD, from the Institute for Health Metrics and Evaluation in Seattle, and colleagues examined changes in mortality and life expectancy from 1950 to 2021, with special emphasis on changes that occurred during the 2020 to 2021 COVID-19 pandemic period, using 22,223 data sources.

The researchers found that over the study period, global all-cause mortality followed 2 distinct patterns: age-standardized mortality rates declined by 62.8% between 1950 and 2019, and increased 5.1% during the pandemic period. Child mortality continued to decline during the pandemic period, in contrast to the overall reversal in mortality trends, with 4.66 and 5.21 million global deaths among children younger than 5 in 2021 and 2019, respectively. In 2020 and 2021 combined, an estimated 131 million people died globally from all causes, of which 15.9 million were due to the COVID-19 pandemic (measured by excess mortality). In 80 countries and territories, excess mortality rates exceeded 150 deaths per 100,000 population during at least one year of the pandemic, while 20 nations had a negative excess mortality rate in 2020 or 2021. Global life expectancy at birth increased by 22.7 years between 1950 and 2021 (from 49.0 to 71.7 years); between 2019 and 2021, global life expectancy at birth decreased by 1.6 years.

“The comprehensive demographic metrics reported in this study show that marked reversals in adult mortality and life expectancy trends occurred during 2020 and 2021, leading to increased mortality and reduced life expectancy worldwide,” the authors write.

Several authors disclosed ties to industry.

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Routine vaccine coverage in the United States (US) declined during the COVID-19 pandemic and has not rebounded to prepandemic levels. Vaccine hesitancy may in part be due to the uncomfortable process of vaccination. This article discusses strategies to help combat needle anxiety among children.

The rate of routine vaccination in the US has dropped below the 95% needed to protect the general population, putting large groups of children at risk for potentially life-threatening illnesses. Adding to the number of unvaccinated children has been an increase in the vaccine exception rate. During the 2022-23 school year, the exemption rate increased 0.4 percentage points to 3.0%. Exemptions increased in 41 states, exceeding 5% in 10 states.¹

The US Centers for Disease Control and Prevention (CDC) reported that among kindergarten-aged children in the 2022 to 2023 school year, vaccination rates for measles, mumps, and rubella (MMR); diphtheria, tetanus, and acellular pertussis (DTaP); poliovirus; and varicella were below the target level, ranging between 92.7% for DTaP to 93.1% for MMR and poliovirus.¹

Addressing pediatric needle pain has been repeatedly identified as a priority in pediatric medicine, however, it remains undermanaged in the clinical setting. In addition, recommended approaches to managing pediatric procedural pain do not address anxiety about needle pain, which is a key driver for noncooperation.

Evelyn Chan, MBBS, MSc, DCH of Monash Children’s Hospital and Royal Children’s Hospital in Australia has investigated strategies for reducing anxiety among children during painful procedures.

To prepare children for vaccination, they should be aware of what to expect, according to Dr Chan. Children should be encouraged to ask any questions or to voice concerns and their perspectives should be validated and listened to actively. During vaccination, the goal should be to distract and to relax. This could mean bringing a stuffed animal, looking at a tablet, or breathing deeply. Throughout the process, vaccination should be encouraged through positive reinforcement, by informing the child about the health benefits and that with vaccination they are protected from illness.

To minimize the pain of vaccination, Dr Chan recommends employing the 3 ‘P’s: physical numbing, positioning, and psychological techniques.²

• Some patients may benefit from using a numbing cream or cold pack to reduce procedural pain.
• Certain positions during the procedure may facilitate a more relaxed vaccination process, for example, sitting on their parent’s lap, facing the parent, etc.
• Patients may engage in conversation, play with a stress-relieving toy, practice deep breathing, or use medical virtual reality to distract them during the procedure.

To combat needle phobia, some children may benefit from role-playing, in which the child and guardian take turns playing doctor and patient, thereby familiarizing themselves with the procedure through play.

Adults should avoid minimizing or dismissing a child’s fears over vaccines, pretending that the child won’t be receiving a vaccine during an appointment, sharing negative experiences related to vaccines with the child, and using bribery or threats to try and force the child into compliance as these strategies can exacerbate anxiety and/or make the experience more distressing.

The phase 3 NextCOVE study (ClinicalTrials.gov Identifier: NCT05815498) compared the safety, reactogenicity, relative vaccine efficacy and immunogenicity of mRNA-1283 to Moderna’s licensed COVID-19 vaccine, Spikevax^® (mRNA-1273.222). The randomized, observer-blind, active-controlled study enrolled approximately 11,400 participants aged 12 and older. 

Findings showed mRNA-1283 elicited a higher immune response against both Omicron BA.4/BA.5 and original virus strains of SARS-CoV-2, compared with mRNA-1273.222, particularly in individuals over the age of 65 years. The most common adverse reactions reported were injection site pain, headache, fatigue, myalgia and chills. The safety profile of mRNA-1283 was found to be similar to the currently approved Moderna COVID-19 vaccines.

“We are excited to announce our fourth infectious disease vaccine program with positive phase 3 data, further validating our robust mRNA platform,” said Stéphane Bancel, CEO  of Moderna. “mRNA-1283 is a critical component of our combination vaccine against flu and COVID-19, mRNA-1083, and this milestone gives us confidence in our ability to bring this much needed vaccine to market.”

In addition to a prefilled syringe presentation, mRNA-1283 is being developed with a longer shelf life and storage advantages. The Company expects these improvements will lessen the burden on providers and help increase access into new settings.

Pemgarda is a SARS-CoV-2 spike protein-directed attachment inhibitor. The EUA is supported by immunobridging data (based on the serum neutralization titer-efficacy relationships identified with other neutralizing human monoclonal antibodies against SARS-CoV-2) from the ongoing phase 3 CANOPY trial (ClinicalTrials.gov Identifier: NCT06039449). The study enrolled patients at least 18 years of age into 2 cohorts.

Cohort A (single-arm, open-label trial) included adults with moderate to severe immune compromise who received at least 1 dose of pemivibart. In Cohort B, adults without moderate to severe immune compromise were randomly assigned to receive either pemivibart or placebo.

The primary endpoint of Cohort A was to evaluate protection against symptomatic COVID-19 based on calculated titers against SARS-CoV-2 following pemivibart administration by immunobridging to historical data from the EVADE study (ClinicalTrials.gov Identifier: NCT04859517), which provided evidence of clinical efficacy of adintrevimab, the parent monoclonal antibody of pemivibart.

Results showed the trial met the primary immunobridging endpoint for Cohort A. Calculated serum neutralizing antibody titers against JN.1 (the current dominant variant circulating in the US) were consistent with the titer levels associated with efficacy in prior clinical trials of adintrevimab and certain other monoclonal antibody products previously authorized for the prevention of COVID-19. 

The most common adverse events reported with pemivibart were systemic and local infusion-related or hypersensitivity reactions, upper respiratory tract infection, viral infection, influenza-like illness, fatigue, headache, and nausea. Anaphylaxis was observed in 0.6% of study participants. The treatment should only be administered in settings in which health care providers have immediate access to medications to treat anaphylaxis and the ability to activate the emergency medical system, as necessary.

Pemgarda is supplied as a 500mg/4mL single-dose vial. Treatment is administered as a 4500mg single IV infusion; dosing may be repeated every 3 months from the date of the most recent dose. The product is expected to be available soon.

Carlo Brogna, MD, from the Craniomed Group Srl. Research Facility in Bresso, Italy, and colleagues studied the impact of specific antibiotics on recovery from COVID-19. The analysis included 211 COVID-19 patients (59 vaccinated).

The researchers found that early initiation of antibiotic therapy resulted in a significantly shorter recovery time (crude hazard ratio [HR], 4.74). Simultaneous use of nonsteroidal anti-inflammatory drugs did not shorten duration and in a multivariate analysis prolonged the disease. Longer recovery time was also seen in a subgroup of 42 patients receiving corticosteroids for a median of 3 days (crude HR, 0.542). Early initiation of antibiotics was associated with maintaining higher levels of blood oxygen saturation. Furthermore, a significant number of patients who received antibiotics in the first three days of acute illness for a duration of 7 days did not develop long COVID.

“The gut microbiome’s bacterial composition is highly dynamic, capable of producing proteins that interact with host cells, potentially triggering detrimental mechanisms,” the authors write. “This discovery implies a potential correlation between long COVID and a bacterial by-product within the microbiome, suggesting potential treatment alterations involving antibiotics and probiotics.”

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Adam de Havenon, MD, from Yale University in New Haven, Connecticut, and colleagues examined the burden of neurologic health care and incident neurologic diagnoses in the year after hospital-based care for COVID-19 vs influenza in an analysis of data from a large collection of electronic medical records for individuals aged 18 years or older during the index event. The study outcomes were subsequent health care encounters for 6 neurologic diagnoses during the following year. In addition, a composite of the 6 diagnoses was created, termed “incident neurologic diagnoses.”

The cohort included 77,272 individuals with COVID-19 and 77,272 with influenza after propensity score matching. The researchers found that patients with COVID-19 had a lower risk for subsequent care for migraine, epilepsy, neuropathies, movement disorders, stroke, or dementia compared with patients with influenza (hazard ratios, 0.645, 0.783, 0.567, 0.644, 0.904, and 0.931, respectively). In 2.79 and 4.91% of the COVID-19 and influenza cohorts, respectively, postinfection incident neurologic diagnoses were observed.

“While the results were not what we expected to find, they are reassuring in that we found being hospitalized with COVID did not lead to more care for common neurologic conditions when compared to being hospitalized with influenza,” coauthor Brian C. Callaghan, MD, from the University of Michigan in Ann Arbor, said in a statement.

Several authors disclosed ties to the biotechnology industry.

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Zhitao Yang, MD, from Ruijin Hospital in Shanghai, and colleagues conducted a randomized clinical trial involving adults with mild-to-moderate COVID-19 and within 5 days of SARS-CoV-2 infection. Participants were randomly allocated to receive VV116 or nirmatrelvir-ritonavir (165 and 180 patients, respectively) for 5 days.

The researchers found that viral load rebound occurred in 20.0 and 21.7% of patients in the VV116 and nirmatrelvir-ritonavir groups, respectively. Symptom rebound occurred in 25.6 and 24.5% of patients in the VV116 and nirmatrelvir-ritonavir groups, respectively. For 24 rebound cases, viral whole-genome sequencing showed the same lineage at baseline and viral load rebound.

“Effective treatment options in addition to the drug per se, especially the potential prolongation of treatment duration, as well as the interplay of viral infection, host immunity, and antiviral treatment in the process of rebound, warrant investigation in future studies,” the authors write.

VV116 and nirmatrelvir-ritonavir tablets were provided by the Shanghai Junshi Biosciences.

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Yun Lu, PhD, from the Food and Drug Administration in Silver Spring, Maryland, and colleagues examined stroke risk after administration of either brand of the COVID-19 bivalent vaccine, COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine on the same day (concomitant administration), and influenza vaccine.

The researchers observed no significant associations between either brand of the COVID-19 bivalent vaccine and stroke outcomes during the one- to 21-day or 22- to 42-day risk window vs the 43- to 90-day control window among the 11,001 beneficiaries who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine. There was a statistically significant association noted between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window for the BNT162b2 COVID-19 bivalent vaccine and between vaccination and transient ischemic attack during the one- to 21-day risk window for the mRNA-1273.222 COVID-19 bivalent vaccine among the 4596 beneficiaries who experienced stroke after concomitant administration. A significant association was seen between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window among the 21,345 beneficiaries who experienced stroke after influenza vaccination.

“The study by Lu et al illustrates the value of a timely, well-designed analysis and has provided reassurance about the COVID-19 boosters,” Kathryn M. Edwards, MD, and Marie R. Griffin, MD, MPH, from Vanderbilt University in Nashville, Tennessee, write in an accompanying editorial.

Several authors disclosed employment with Acumen.

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Editorial (subscription or payment may be required)

Núria Mercadé-Besora, from the University of Oxford, and colleagues conducted a staggered cohort study based on national vaccination campaigns using electronic health records from the United Kingdom, Spain, and Estonia to examine the association between COVID-19 vaccination and the risk for post-COVID-19 cardiac and thromboembolic complications. Outcomes included heart failure, venous thromboembolism (VTE), and arterial thrombosis/thromboembolism (ATE) recorded at 0 to 30, 31 to 90, 91 to 180, and 181 to 365 days after SARS-CoV-2 infection.

The analyses included 10.17 million vaccinated and 10.39 million unvaccinated individuals. The researchers found that vaccination was associated with reduced risks for acute and postacute COVID-19 VTE, ATE, and heart failure, with meta-analytic subhazard ratios of 0.22, 0.53, and 0.45 and 0.53, 0.72, and 0.61 for 0 to 30 days and 91 to 180 days after SARS-CoV-2 infection, respectively.

“Vaccination against SARS-CoV-2 substantially reduced the risk of acute post-COVID-19 thromboembolic and cardiac complications, probably through a reduction in the risk of SARS-CoV-2 infection and the severity of COVID-19 disease due to vaccine-induced immunity,” the authors write.

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As of March 9, 2024, only FDA-approved Paxlovid (manufactured and labeled in accordance with the New Drug Application) may be dispensed for the treatment of mild to moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death. 

According to the FDA, all EUA-labeled Paxlovid, regardless of labeled or extended expiration date, must be returned to the manufacturer or disposed of in accordance with all federal, state, and local regulations.

The EUA continues to allow the use of Paxlovid in pediatric patients 12 years of age and older weighing at least 40kg who are at high risk for progression to severe COVID-19, including hospitalization or death. Additionally, state-licensed pharmacists are still authorized to prescribe Paxlovid.

Through December 31, 2024, Medicare and Medicaid beneficiaries, and uninsured individuals who do not have a prescription drug benefit may apply to receive Paxlovid for free through the PAXCESS program. Commercially insured patients may be eligible for the co-pay assistance program.

Households across the country have been able to order four free rapid antigen tests through COVID.gov. since November. All orders placed on or before Friday will be fulfilled, according to the Administration for Strategic Preparedness and Response (ASPR), a division of the US Department of Health and Human Services.

“ASPR has delivered over 1.8 billion free COVID-19 tests to the American people through COVID.gov and direct distribution pathways and will continue distributing millions of tests per week to long-term care facilities, food banks, health centers and schools,” an ASPR spokesperson told CNN.

The decision reflects the reality that COVID-19 cases are falling as the respiratory virus season winds down.

COVID-related hospitalizations are still elevated, but they are dropping in certain areas of the country, CDC data shows.

The federal government previously suspended the free rapid test program last May after the public health emergency of the pandemic was officially ended. Residents who haven’t placed an order since then can now place two, which will provide eight tests in total, according to COVID.gov.

These tests can be taken at home and used whether or not someone has symptoms. They should work through the end of the year; some of the dates on the labels may show that they’re expired, but the U.S. Food and Drug Administration has extended those expiration dates.

The CDC recommends that people test if they have any COVID symptoms including a sore throat, a runny nose, loss of smell or taste or a fever.

Just last week, the agency relaxed its COVID isolation guidance and said people no longer need to stay home for five days and could instead return to work or school once symptoms start subsiding and they haven’t had a fever for at least 24 hours without medication.

More information

Visit the CDC for more on COVID testing.

SOURCE: COVIDtest.gov.; CNN

This is despite the fact that cancer survivors are more likely to be vaccinated against COVID-19 and just as likely as the general population to be infected with SARS-CoV-2. These findings were published in the Journal of the National Cancer Institute.

For this study, researchers evaluated data from the National Health Interview Survey in 2021 and 2022. The cohort from 2021 included 3428 cancer survivors and 26,023 control individuals without a cancer history. The cohort from 2022 included 3218 cancer survivors and 24,393 control individuals.

The cancer survivors were more likely than control individuals to have received 2 or more COVID-19 vaccines in 2021 (66.6% and 62.3%, respectively; P =.003) and 2022 (77.0% and 72.4%, respectively; P <.001).

However, cancer survivors were just as likely as control individuals to report having COVID-19 in 2021 (14.1% and 14.2%, respectively; P =.93) and 2022 (39.9% and 39.3%, respectively; P =.55).

Cancer survivors were more likely than control individuals to report moderate to severe COVID-19 symptoms in 2021 (62.5% and 54.2%, respectively; P =.02). In 2022, there was a trend toward more moderate and severe COVID-19 among cancer survivors, but the difference between cancer survivors and control individuals was not statistically significant (54.5% and 51.3%, respectively; P =.13).

However, the data from 2022 showed that cancer survivors were more likely than control individuals to have symptoms of long COVID (20.6% and 17.3%, respectively; P =.04). There were no data on long COVID from 2021.

“With the continuing high infectious rate and seasonal resurgences of COVID-19 infections and ongoing recommendations for vaccination, especially for vulnerable populations, monitoring the impact of COVID-19 infection and the effectiveness of prevention and control strategies continue to be a public health priority,” the researchers wrote. “Our findings suggest the need for tailored efforts to prevent and control COVID-19 infection for cancer survivors.”

Mahan Ghafari, PhD, from the University of Oxford in the United Kingdom, and colleagues examined the population prevalence of persistent SARS-CoV-2 infections, their viral load kinetics, and evolutionary dynamics over the course of infections. Overall, 381 individuals with SARS-CoV-2 RNA at high-titer persisting for at least 30 days were identified; of these individuals, 54 had viral RNA persisting for at least 60 days (“persistent infections”).

The researchers found that the odds of self-reporting long COVID-19 were more than 50% higher for individuals with persistent infection compared with those with nonpersistent infection. An estimated 0.1 to 0.5% of infections may become persistent, lasting for at least 60 days, and with typically rebounding high viral loads. Many viral amino acid substitutions were identified in some patients, indicating periods of strong positive selection, while others had no consensus change in the sequences for prolonged periods, indicating weak selection. These substitutions included lineage-defining mutations for SARS-CoV-2 variants and at target sites for monoclonal antibodies; they were also commonly found in immunocompromised individuals.

“Our observations highlight the continuing importance of community-based genomic surveillance both to monitor the emergence and spread of new variants and to gain a fundamental understanding of the natural history and evolution of novel pathogens and their clinical implications for patients,” the authors write.

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Jennifer DeCuir, PhD, from the CDC in Atlanta, and colleagues used a test-negative case-control study design with data from 2 CDC vaccine effectiveness (VE) networks to assess VE of an updated COVID-19 vaccine dose against COVID-19-associated emergency department or urgent care encounters and hospitalization among immunocompetent adults during September 2023 to January 2024.

The researchers found that VE against COVID-19-associated emergency department/urgent care encounters was 51 and 39% during the first seven to 59 and 60 to 119 days, respectively, after an updated dose. From 2 CDC VE networks, VE estimates against COVID-19-associated hospitalization were 52 and 43%, respectively, with corresponding median intervals of 42 and 47 days from the updated dose.

“CDC will continue monitoring VE of updated COVID-19 vaccines,” the authors write. “These results support CDC recommendations for updated 2023-2024 COVID-19 vaccination.”

Several authors disclosed ties to the pharmaceutical industry.

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Instead, the CDC recommends “returning to normal activities when, for at least 24 hours, symptoms are improving overall, and if a fever was present, it has been gone without use of a fever-reducing medication.”

This is the first time the agency has loosened its COVID-19 isolation guidelines since 2021. The thinking behind it is to come more in line with advisories for other common respiratory infections.

“The new guidance brings a unified approach to addressing risks from a range of common respiratory viral illnesses, such as COVID-19, flu and RSV, which can cause significant health impacts and strain on hospitals and health care workers,” the CDC said in a statement announcing the change.

Once people with COVID do return to “normal activities,” they should still take precautions over the next five days to help stop spreading the infection to others.

Those precautions include “enhancing hygiene practices, wearing a well-fitting mask, keeping a distance from others and/or getting tested for respiratory viruses [including COVID-19],” the agency said.

Why the changes now?

According to CDC Director Dr Mandy Cohen, the update “reflects the progress we have made in protecting against severe illness from COVID-19. However, we still must use the commonsense solutions we know work to protect ourselves and others from serious illness from respiratory viruses — this includes vaccination, treatment and staying home when we get sick.”

Some recommendations remain unchanged, including staying up to date on vaccinations. That includes this week’s CDC recommendation that Americans 65 and older receive another COVID booster shot this spring, to help maintain immunity.

The guidance also recommends “practicing good hygiene by covering coughs and sneezes, washing or sanitizing hands often, and cleaning frequently touched surfaces,” and seeking out cleaner air by “bringing in more fresh outside air, purifying indoor air or gathering outdoors.”

The agency noted that COVID-19 is far less of a threat than it was during the pandemic, because it is “far less likely to cause severe illness because of widespread immunity and improved tools to prevent and treat the disease.”

The new guidance came after some states initiated similar changes, and the CDC noted that those states “have not seen increased hospitalizations or deaths related to COVID-19.”

Lower rates of COVID hospitalizations were among the reasons California shortened its five-day isolation recommendation in January, urging people to stay home until they are fever-free for 24 hours and their symptoms are mild and improving. Oregon made a similar move last May.

Michael Osterholm, an infectious disease expert at the University of Minnesota, said the new recommendations make sense, now that the urgency of the pandemic has passed.

“Public health has to be realistic,” he told the Washington Post recently. “In making recommendations to the public today, we have to try to get the most out of what people are willing to do. … You can be absolutely right in the science and yet accomplish nothing because no one will listen to you.”

Not everyone is happy with the new guidance, however.

Loosening the guidelines “sweeps this serious illness under the rug,” Dr Lara Jirmanus told the Post recently. She’s a clinical instructor at Harvard Medical School and a member of the People’s CDC, a coalition of health care workers, scientists and advocates focused on reducing the harmful effects of COVID-19.

Public health officials should treat COVID differently from other respiratory viruses because it’s deadlier than the flu and poses a risk for lingering symptoms known as Long COVID, she said. Nearly 7% of Americans report having lingering COVID symptoms such as fatigue, trouble breathing, brain fog and joint pain, CDC data show.

Doctors say the best way for sick people to protect their communities is to mask or avoid trips outside the home if infected.

“You see a lot of people with symptoms — you don’t know if they have COVID or influenza or RSV — but in all three of those cases, they probably shouldn’t be at Target, coughing and looking sick,” Dr. Eli Perencevich, an internal medicine professor at the University of Iowa, told the Post.

More information

Visit the U.S. Centers for Disease Control and Prevention for current guidance on COVID.

SOURCE: U.S. Centers for Disease Control and Prevention, news release, March 1, 2024, Washington Post

The latest guidance, voted on by a vaccine advisory panel and endorsed by the US Centers for Disease Control and Prevention, states that a second booster is fine as long as at least 4 months have passed since a patient’s last COVID-19 shot.

“Today’s recommendation allows older adults to receive an additional dose of this season’s COVID-19 vaccine to provide added protection,” CDC Director Mandy Cohen, MD, said in an agency statement announcing the new recommendation. “Most COVID-19 deaths and hospitalizations last year were among people 65 years and older. An additional vaccine dose can provide added protection that may have decreased over time for those at highest risk.”

So far, this season’s COVID-19 booster has proved 54% effective against infection with the predominant COVID-19 variant, known as JN.1.

“Data continues to show the importance of vaccination to protect those most at risk for severe outcomes of COVID-19,” the CDC said. “An additional dose of the updated COVID-19 vaccine may restore protection that has waned since a fall vaccine dose, providing increased protection to adults ages 65 years and older.”

COVID-19 is still a serious disease: There are more than 20,000 hospitalizations and more than 2,000 deaths each week due to the coronavirus, according to the CDC. And people 65 years and older have the highest hospitalization and death rates, the data show.

“Adults 65 years and older are disproportionately impacted by COVID-19, with more than half of COVID-19 hospitalizations during October 2023 to December 2023 occurring in this age group,” the CDC noted, adding that people who are immunocompromised are already eligible for additional doses of COVID-19 vaccines.

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Noting that the ACTT risk profile previously demonstrated that hospitalized patients in the high-risk quartile benefit most from remdesivir, Catharine I. Paules, MD, from the Penn State Health Milton S. Hershey Medical Center, and colleagues examined potential baricitinib-related treatment effects by risk quartile in a post hoc analysis of the ACTT-2 trial, conducted in 999 adults hospitalized with COVID-19 at 67 trial sites in 8 countries. Participants received baricitinib plus remdesivir or placebo plus remdesivir.

The researchers found that baricitinib plus remdesivir was associated with a reduced risk for death, reduced progression to invasive mechanical ventilation or death, and improved recovery rate compared with placebo plus remdesivir in the high-risk quartile (hazard ratios, 0.38, 0.57, and 1.53, respectively). Compared with control participants, those receiving baricitinib plus remdesivir had significantly larger increases in absolute lymphocyte count and significantly larger decreases in absolute neutrophil count after five days, with the largest effects seen in the high-risk quartile.

“To our knowledge, no other clinical trials have assessed clinical benefit from an immunomodulator with relation to dynamics in hematologic parameters, and these data suggest the relevance of these measurements in predicting treatment response,” the authors write.

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Cristina V. Cardemil, MD, MPH, from the National Institutes of Health in Rockville, Maryland, and colleagues quantified protection against infection from maternally derived vaccine-induced antibodies in the first 6 months of an infant’s life. Full-length spike (Spike) immunoglobulin G (IgG), pseudovirus 614D, and live virus D614G and omicron BA.1 and BA.5 neutralizing antibody (nAb) titers were measured at delivery among infants born to mothers vaccinated during pregnancy with 2 or 3 doses of a messenger RNA COVID-19 vaccine.

The researchers found that Spike IgG, pseudovirus, and live nAb titers were significantly higher at delivery for 204 infants of boosted mothers than for 271 infants of nonboosted mothers; infants of boosted mothers were 56% less likely to acquire infection in the first six months. The infant’s risk for acquiring infection was reduced by 47% for each 10-fold increase in Spike IgG titer at delivery, irrespective of boost. Risk reductions of 30, 46, 56, and 60% were seen in association with 10-fold increases in pseudovirus titers against Wuhan Spike, live virus nAb titers against D614G, and omicron BA.1 and BA.5 at delivery, respectively.

“We show that a monovalent booster dose during pregnancy leads to higher binding and nAb titers at delivery that are effective against omicron, for an age group that has the highest COVID-19-associated hospitalization rate in pediatrics since the emergence and ubiquitous spread of omicron variants,” the authors write.

Several authors disclosed ties to the pharmaceutical industry.

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Quan M. Vu, from the US Centers for Disease Control and Prevention in Atlanta, and colleagues estimated the incidence rates of post-COVID-19 fatigue and chronic fatigue by analyzing electronic health record data for 4589 patients with confirmed COVID-19 during February 2020 to February 2021 and 9022 propensity score-matched non-COVID-19 controls. Patients were followed for a median of 11.4 months.

The researchers found that the incidence rate of fatigue and chronic fatigue was 10.2 and 1.8 per 100 person-years, respectively, among COVID-19 patients. The hazard ratios were 1.68 and 4.32 for fatigue and chronic fatigue, respectively, compared with non-COVID-19 controls.

“Our data indicate that COVID-19 is associated with a significant increase in new fatigue diagnoses, and physicians should be aware that fatigue might occur or be newly recognized more than one year after acute COVID-19,” the authors write. “The high incidence rates of fatigue reinforce the need for public health actions to prevent infections, to provide clinical care to those in need, and to find effective treatments for post-acute COVID-19 fatigue.”

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Nicole D. Ford, PhD, from the CDC in Atlanta, and colleagues analyzed data from noninstitutionalized US adults participating in the 2022 Behavioral Risk Factor Surveillance System to examine the prevalence of long COVID, defined as the self-report of any symptoms lasting 3 or more months that were not present before COVID-19.

The researchers found that 6.4% of noninstitutionalized US adults reported ever having experienced long COVID, nationally. There was variation observed in the weighted age- and sex-standardized prevalence, from 1.9 to 10.6% for the US Virgin Islands and West Virginia, respectively; in 7 states, prevalence exceeded 8.8% (the highest prevalence quintile cutoff). In New England and the Pacific, prevalence tended to be lower, while higher prevalence was seen in the South, Midwest, and West.

“Given the increased health care needs among persons experiencing long COVID, ongoing assessment of state- and territory-level prevalence data could guide policy, planning, or programming,” the authors write. “State-level estimates might also help identify geographic disparities in long COVID across the US that could guide interventions to promote health equity.”

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An advisory panel to the CDC is expected to vote on whether to recommend a spring booster during a February 28 meeting, a source close to the panel told NBC News. The panel is expected to focus on the safety of high-risk Americans, including people 65 and older and anyone with a weakened immune system.

“The discussion will be aimed at the people who are most accepting of public health recommendations,” Dr. William Schaffner, an infectious diseases expert at Vanderbilt University Medical Center in Nashville, Tennessee, told NBC News. “The committee, in its rigorous fashion since the question has come up, will be considering a second dose for people at high risk or for people who wish to get it.”

A spring booster would be the same shot approved last fall, which targets the XBB.1.5 subvariant. Luckily, that booster formulation also works well against the JN.1 subvariant, the leading cause of most COVID infections in the United States at the moment.

Experts said a spring booster shot makes sense.

“Waiting till the fall, I think, is a mistake,” Michael Osterholm, an infectious disease expert and director of the Center for Infectious Disease Research and Policy at the University of Minnesota, told NBC News. “We have clear evidence that either vaccine or previous infection probably gives four to six months of relative protection against serious illness, hospitalizations and deaths, but wanes substantially after that.”

Still, even vulnerable groups like transplant patients, who tend to follow their doctors’ advice, are feeling vaccine fatigue, Dr. William Werbel, associate director of epidemiology and quantitative sciences with the Johns Hopkins Transplant Research Center in Baltimore, told NBC News.

“Some people have had seven, eight vaccines,” Werbel said. “Transplant recipients would be more receptive and much more likely to follow recommendations, particularly if recommended by the transplant center, but the ceiling is kind of lowered because of this societal fatigue and societal disenchantment with COVID.”

Experts generally recommend that even high-risk patients wait at least two months after a COVID vaccination or COVID infection before getting another shot.

Recent research has shown that people who got the latest booster shot were 54% less likely to be infected with COVID this winter.

More information

The U.S. Centers for Disease Control and Prevention has more on COVID vaccines.

SOURCE: NBC News