Kevin Kunzmann

As the Omicron variant of COVID-19 surges to 

 in the United States in terms of infections and hospitalizations it might be easy for the public to overlook that influenza has also spiked in recent weeks. The flu spike seems to have slowed in the 

 (see chart below) according to the Centers for Disease Control and Prevention (CDC), but not enough so that infection preventionists and other health care professionals don’t have to deal with the muddle of possible coinfection. Does the patient presenting with respiratory problems have influenza or 1 of the COVID-19 variants? Perhaps it’s just the common cold or allergies?

Being able to interpret early signs of disease is vital toward taking necessary steps to recovery and mitigation—receiving laboratory or at-home test result confirmation, referring to a clinician, taking necessary treatment, and possibly isolating from at-risk persons. While limited national testing availability and stunted turnaround time has plagued the US response to COVID-19 outbreaks since March 2020, massive data collection has given experts a more refined understanding of what is early signs of COVID-19, versus possibly the flu or otherwise.

 for identifying signs and symptoms, time from exposure to infection, and duration of illness for both COVID-19 and the flu.

Signs and Symptoms of COVID-19 and Influenza

While both diseases can present asymptomatically, the respiratory viruses share about a dozen common symptoms:

Persons with the flu often feel some or all of the above symptoms—with change in or loss of smell or taste being more frequently reported among patients with COVID-19. Young children with the flu are more susceptible to diarrhea than older patients.

Relative to the common cold, these symptoms occur abruptly in infected flu patients, with the below frequency:

Separately, COVID-19 cases include signs indicating need for emergent care that may sometimes differentiate from early flu signs and symptoms, including:

Pale, gray, or blue-colored skin, lips, or nail beds

Both COVID-19 and flu can become apparent or symptomatic as soon as 1 day post-infection. However, COVID-19 symptoms have frequently presented later in patients than symptoms of the flu—a difference of 2 to 14 days versus 1 to 4 days post-infection, respectively.

However, experts have observed that the highly transmissible and dominant Omicron variant of SARS-CoV-2 has been associated with expedited time from infection to presenting symptoms, and therefore, risk of spreading disease. This further stresses the need for identifying COVID-19 versus flu cases.

Flu is often associated with a recovery time anywhere between a few days to 2 weeks, notwithstanding severe cases or development of complications including sinus infections, pneumonia, myocarditis, encephalitis, myositis, organ failure, sepsis or more. Patients with the flu are also at greater risk of secondary bacterial infections than those with COVID-19, according to the CDC.

COVID-19 illness duration, unfortunately, is an interpretation still being researched. Cases of “long COVID” have been observed to last weeks to months following infection, regardless of patients’ disease severity or symptoms. Patients additionally face risk of complications including blood clots in the veins and arteries of the lungs, heart, legs, or brain, and development of multisystem inflammatory syndrome (MIS), any of which could warrant hospitalization and continued care.

Duration of contagious flu spread can begin as early as a full day before any symptom onset, and can last from 3 to 7 days for most patients, dependent on their age and health—older patients, infants, and those with weakened immune systems may be contagious for longer than a week.

COVID-19 can be spread 2 days prior to any symptom onset, and patients remain contagious for ≥10 days after apparent symptoms and/or a positive test result, per CDC—regardless of asymptomatic status. Those with severe disease and/or weakened immune systems may be contagious for ≥20 days.

This article was originally published on 

Source: Centers for Disease Control and Prevention

Articles

The highly transmissible and dominant Omicron variant of COVID-19 places added pressure on infection preventionists and other clinicians to determine just what they’re dealing with. 

Flu or Omicron? Diagnosis Must be Done Quickly

The at-home oral treatments for COVID-19 patients keep coming. Just 1 day after the US Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) to Pfizer’s nirmatrelvir and ritonavir tablet therapy (Paxlovir), the agency gave the EUA green light to Merck and Ridgeback Biotherapeutics’ molnupiravir. 

The investigative oral ribonucleoside analog that functions by inhibiting SARS-CoV-2 inhibition was authorized for adults with mild-to-moderate COVID-19 who are at risk of progressing to severe disease. The regimen is not intended for pediatric patients, those already hospitalized with COVID-19, for use over >5 consecutive days, or as a prophylaxis against the pandemic virus.

Though Paxlovir reached an EUA a day prior, the months-long promise of a regulated pill for the treatment of COVID-19 has been associated with molnupiravir for some time. Interim trial data 

 of this year from the pivotal, global phase 3 MOVe-OUT trial showed molnupiravir reduced patient risk of COVID-19 hospitalization or death by approximately 50%.

Just 28 (7.3%) of patients to receive molnupiravir experienced either outcome, versus 53 (14.1%) patients administered placebo (

 = .0012). No patients to receive molnupiravir had died through 29 days post-randomization, versus 8 patients to receive placebo.

Final data from MOVe-OUT showed reduced relative risk of COVID-19-related hospitalization and death was actually only reduced by 30% with molnupiravir versus placebo, however. Approximately 6.8% of the participants treated with molnupiravir were hospitalized or died, as compared to 9.7% of the placebo recipients.

A month later, it received authorization from the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA), making it the 

 to be regulated by a global health authority.

FDA Antimicrobial Drugs Advisory Committee

 voted to support Merck and Ridgeback’s application on the basis of the supporting phase 3 trial findings.

Now, with the EUA, molnupiravir will be available at a recommended dose of 4 capsules, 200 mg each, taken orally every 12 hours over 5 days, to reduce the risk of severe COVID-19 progression in high-risk, infected adults.

“Based on the strong science behind molnupiravir—a single oral medicine that interrupts replication of the SARS-CoV-2 virus, with data demonstrating a significant reduction in the risk of hospitalizations and deaths—molnupiravir has the potential to become an important tool for healthcare professionals and appropriate patients,” Dr. Dean Y. Li, president of Merck Research Laboratories, said in a statement. “We are immensely grateful to all of our collaborators, including trial patients and clinical investigators, for their important contributions to this milestone.”

In the space of 2 days, the FDA approved at-home oral treatments for patients with mild-to-moderate COVID-19, drug that were months in development. Today, it was Merck and Ridgeback Biotherapeutics’ turn.

COVID-19 Pill Molnupiravir Gets EUA Approval by FDA

Moderna plans to have what the company considers pretty convincing data when it seeks approval for its COVID-19 vaccine for children. Unpublished, interim data from Moderna’s phase 2/3 pediatric trial showed a lesser dose of the company’s 2-dose 

 mRNA-1273 is associated with a significant neutralizing antibody response in children aged 6 to <12 years old.

The shared data from the ongoing KidCOVE trial, which includes a cohort of 4753 pediatric participants, will be used in Moderna’s application to the US Food and Drug Administration (FDA) for regulated use of the mRNA vaccine in preventing COVID-19 among the pediatric age group.

The randomized, blinded, placebo-controlled KidCOVE is an expansion assessment of 2-dose 50 mcg mRNA-1273 in health children aged 6 months to <12 years old. Though the trial is continuing to enroll children aged 6 months to <6 years old in North America, Moderna has reached its endpoint for assessment of the cohort aged 6 to <12 years old.

Investigators assessed a comparison of SARS-CoV-2 neutralizing antibody response in vaccinated children versus that observed in young adults included in Moderna’s phase 3 COVE trial, using a geometric mean ratio (GMR). At 1 month following the second dose of 50 mcg mRNA-1273, GMR of response from observed children versus young adults was 1.5 greater (95% CI, 1.3 – 1.8), with a seroresponse rate of 99.3% (difference, 0.6%; 95% CI, -2.8 to 2.8).

The vaccine was generally well tolerated in children aged 6 to <12 years old, with a safety and tolerability profile consistent with that observed in adolescents and adults from the phase 3 trial. Adverse events were generally mild or moderate in severity, and the most commonly reported events included fatigue, headache, fever, and injection site pain.

 accompanying the data, which is yet to be peer reviewed, Stephane Bancel, Moderna chief executive officer, expressed optimism brought on by the newest pediatric COVID-19 vaccination metrics.

“We are encouraged by the immunogenicity and safety profile of mRNA-1273 in children aged 6 to under 12 years and are pleased that the study met its primary immunogenicity endpoints,” Bancel said. “We look forward to filing with regulators globally and remain committed to doing our part to help end the COVID-19 pandemic with a vaccine for adults and children of all ages.”

Pediatric immunity from COVID-19 continues to be an under-addressed issue in pandemic response; 

data from the American Association of Pediatrics (AAP)

 show children comprise more than 16% of all US cases—a rate has been on the rise in past months. For the week ending October 14, children made up 25.5% of the weekly reported COVID-19 cases, despite only comprising 22.2% of the country’s population.

Moderna’s phase 2/3 pediatric trial showed a lesser dose of the company’s 2-dose COVID-19 vaccine mRNA-1273 is associated with a significant neutralizing antibody response in children aged 6 to <12 years old.

Moderna Praises Its COVID-19 Child Vaccine Data   

Just who should get a COVID-19 booster shot and when continues to be 

 as the delta variant rages on, deaths climb (

, according to Johns Hopkins University), and while the Centers for Disease Control and Infection say that breakthrough infections are very rare, the agency only counts breakthrough infections that lead to hospitalizations and/or death. So, who knows?

Well, Johnson & Johnson thinks that it may have the answer.

The company announced to-be-published phase 3 data from a real-world evidence trial showing that their single-dose adenovirus-based 

 Ad26.COV2.S was associated with 79% overall efficacy for the prevention of COVID-19 and 81% effective for the prevention of hospitalizations associated with the virus.

The new data from the company’s pivotal ENSEMBLE trial program also included data from ENSEMBLE 2, an assessment of a two-dose regimen of Ad26.COV2.S. A booster dose provided 56 days after the first dose was associated with a 94% efficacy in preventing symptomatic COVID-19 in the US, and 75% efficacy worldwide.

The company is now seeking US Food and Drug Administration (FDA) authorization of their booster dose regimen on the basis of this data, which has yet to be peer-reviewed.

In the preprint data from Johnson & Johnson’s cohort assessment of nearly 400,000 participants vaccinated with Ad26.COV2.S, investigators sought to observe the single-dose vaccine’s effectiveness in preventing COVID-19 and related hospitalizations in US clinical practice. They additionally wanted to observe its duration of protection over a longer, real-world observation, as well as its efficacy in preventing infection via more transmissible delta variants.

Trial participants were newly vaccinated adults aged ≥18 years old, matched with up to 10 unvaccinated persons with similar demographics and COVID-19 risk factors. Vaccine effectiveness was estimated for observed COVID-19 infections and related hospitalizations, and was stratified by age, immunocompromised status, calendar time, and regions/states with greater incidence of the circulating delta variant.

The trial population included 390,517 vaccinated and 1,524,153 unvaccinated individuals.

Estimated vaccine effectiveness was 79% (95% CI, 77 – 80) for COVID-19 and 81% (95% CI, 79 – 84) for COVID-19 hospitalizations. An assessment of calendar months from March – July 2021 showed overall vaccine effectiveness did not “meaningfully” vary over time:

Investigators additionally observed a greater vaccine effectiveness in persons aged <50 years (83%; 95% CI, 81 – 85), and a lower effectiveness in immunocompromised patients (64%; 95% CI, 57 – 70).

Among participants in states with high incidence of delta variant infection, COVID-19 prevalence was greater among both vaccinated and unvaccinated cohorts. Investigators observed, however, an overall vaccine effectiveness of 79% (95% CI, 75 – 83) and 78% effectiveness versus hospitalization (95% CI, 73 – 82) in these states during June and July—the observed months when delta variant incidence was at its greatest.

That said, this estimated data does not entail sequence-specific information, meaning there is no specific certainty of the vaccine effectiveness of Ad.COV2.S in preventing delta variant-driven infection.

Nonetheless, investigators concluded the population-based US data demonstrate the “high and stable effectiveness” of the single-dose COVID-19 vaccine across both high-risk patient subpopulations, as well as residents in areas more adversely affected by the delta variant.

“As the COVID-19 pandemic continues and variants evolve the observed effectiveness may change in the future as new variants emerge,” they concluded. “Our data and data to be generated over the coming months using this system of claims data contribute important and otherwise unattainable evidence to policymakers, physicians, and patients.”

The phase 3 ENSEMBLE 2 trial is a randomized, double-blind, placebo-controlled clinical trial assessing the efficacy and safety of 2-dose Ad26.COV2.S regimen administered at a 56-day interval, versus placebo among an international population of adults with varying risk for severe COVID-19.

Median follow-up in the trial, according to Johnson & Johnson, was 36 days since the second dose administration; just 29% of trial participants had ≥2 months of follow-up data after receiving the investigative booster dose.

Investigators observed 100% vaccine effectiveness (95% CI, 33 – 100) against severe or critical COVID-19 in ≥14 days post-booster dose. They additionally observed 75% overall effectiveness (95% CI, 55 – 87) versus symptomatic COVID-19 in patients globally, and 94% overall effectiveness (95% CI, 58 – 100) in US patients.

The company stated that a booster dose of Ad26.COV2.S was associated with a 4- to 6-fold increase in antibody titers versus a lone single-dose administration at 2 months. At 6 months, the booster dose was associated with a 12-fold increase in antibodies.

Johnson & Johnson intends to submit the full ENSEMBLE 2 study data for publication in the coming months.

In a statement accompanying the reported data, Paul Stoffels, MD, Johnson & Johnson Vice Chairman of the Executive Committee and Chief Scientific Officer, called it “critical” to prioritize prevention of hospitalization and death during the continued COVID-19 pandemic.

“A single-shot COVID-19 vaccine that is easy to use, distribute and administer, and that provides strong and long-lasting protection is crucial to vaccinating the global population,” Stoffels said. “At the same time, we now have generated evidence that a booster shot further increases protection against COVID-19 and is expected to extend the duration of protection significantly.”

Investigators concluded that their data demonstrate the “high and stable effectiveness” of the single-dose COVID-19 vaccine across both high-risk patient subpopulations, as well as residents in areas more adversely affected by the delta variant.

Johnson & Johnson Touts COVID-19 Vaccine Booster Shot 

Eight months after the Food and Drug Administration (FDA) granted emergency use authorization (EAU) to the Pfizer/BioNTech COVID-19 vaccine, the agency today gave the vaccine full approval. As 

, the FDA’s move might go a long way to mitigate vaccine hesitancy, not only 

 as well. Infection preventionists are often tasked with the job of 

 their hesitant fellow heath care workers into getting vaccinated.

The Pfizer/BioNTech vaccine becomes the first COVID-19 vaccine given Biologics License Application (BLA)—or full approval. The BLA was given for the companies’ 

 BNT162b2 (Comirnaty). The fully approved vaccine is for people 16 and older; the EUA version is available for children aged 12–15 years and as a third “booster” dose in immunocomrpomised patients.

Health care experts have been pushing the FDA to grant full approval to the COVID-19 vaccines as soon as possible as a way of inducing the vaccine hesitant to get inoculated in the hope that that will stem the rising tide of the delta variant, which has become the 

The FDA’s granting full approval of the Pfizer/BioNTech vaccine comes at a time of a renewed push for 

This newest decision by the FDA comes while new cases of the pandemic virus have reached their highest in the US this year and COVID-19 vaccination rates nearly plateaued last month, although the Centers for Disease Control and Prevention (CDC) has seen a 

 in vaccination rates the last few weeks. The CDC states that as “of August 19, the 7-day average number of administered vaccine doses reported (by date of CDC report) to CDC per day was 823,355, a 17.78% increase from the previous week.” Yesterday, the White House reported that more than 800,000 vaccine doses were administered; marking the fifth consecutive days that about 700,000 COVID-19 vaccine doses have been administered. That’s an increase of 25% in the last 2 weeks

BNT162b2 is a nucleoside-modified messenger RNA (mRNA) vaccine encoded with the SARS-CoV-2 full-length Spike protein glycoprotein. It was selected for continued assessment against 3 other candidates by Pfizer and BioNTech investigators in July 2020, and was granted Fast Track Designation by the FDA around the same time.

FDA granted the vaccine EUA in December 2020

, based on supporting data showing a 95% overall vaccine efficacy in preventing symptomatic COVID-19 among Phase 3 trial participants without previous SARS-CoV-2 infection prior to 7 days after their second vaccine dose.

The EUA was also backed by a 17-4-1 vote 

in favor of the vaccine’s benefit-risk profile

 from the Vaccines and Related Biological Products Advisory Committee (VRBPAC) at the time. Pfizer and BioNTech’s BLA submission was 

granted Priority Review by the FDA last month

, streamlining the regulatory review and decision-making timeline for the vaccine.

Peter Hotez, MD, PhD, Professor in the Departments of Pediatrics, Molecular Virology & Microbiology at Baylor College of Medicine, told 

’s sister publication, that one of the benefits of the FDA’s approval is that it will come with new prescribing capabilities granted through the BLA, noting physicians will now have “more wiggle room” in strategically reducing COVID-19 risk among their patients.

Carlos del Rio, MD, Executive Associate Dean of Emory School of Medicine & Grady Health System, expressed concern that vaccine-hesitant groups will continue to reject the validity of COVID-19 vaccines regardless of FDA designations. He told 

 that the BLA, in regard to public response, may land somewhere between a small win and a non-factor; he estimated that 1 or 2 of every 10 unvaccinated US adults may be now persuaded to seek immunization because of the BLA.

Del Rio believes the full approvals will rather change the scope of employer-level 

 and public work industries—including transportation—have already begun to establishing COVID-19 vaccination mandates for workers.

“Full approvals are going to make mandates a lot easier, and that will make people get vaccinated,” del Rio explained. “You’re going to see an explosion of mandates happening when the full approval occurs.”

The delta variant has been largely to blame for this newest spike in COVID-19 cases, hospitalizations, and deaths. Per the CDC, the now-prominent strain is estimated to be more than 2-fold more contagious than previous SARS-CoV-2 variants, has been linked to more severe illness among unvaccinated persons and more breakthrough infections in vaccinated persons.

However, the CDC reiterates the benefit of authorized COVID-19 vaccines in reducing risk of infection, serious illness, and death from the delta variant, as well as in reducing risk of virus spread from a vaccinated person to others.

Other vaccine regulation strategies are currently at play in the US. Earlier this month, 

 to Pfizer/BioNTech and Moderna for third “booster” doses of their respective mRNA vaccines in severely immunocompromised patients. Days later, a report revealed the Biden administration’s plan to advocate for

 COVID-19 vaccine booster dose availability for all Americans at 8 months

 following their final dose. Their timeline, dependent on FDA allowance, would authorize booster doses for the adults by mid-September.

The national push for booster dose-improved immunity against a surging virus, as well as expanded vaccine indications to include children, will likely to play out in the coming months. Today’s designation by the FDA marks a new precedent for the scientific response against COVID-19—a mark which Hotez anticipates Moderna and Johnson & Johnson developers will also reach soon.

“I welcome the development and think it will happen for all 3 vaccines we have, hopefully before the end of the year,” he said.

Health care experts hope that the move will induce the vaccine hesitant—in the public, and among health care professionals—to get inoculated in the hope that that will stem the rising tide of the delta variant.

FDA Grants Full Approval to Pfizer/BioNTech Vaccine

Medical experts, including those with the 

Centers for Disease Control and Prevention

, have been urging Americans to get vaccinated if for no other reason than that the COVID-19 vaccines have proven somewhat effective in beating back the delta variant. New research out of the UK seems to back this up. It finds that two-dose 

 effectiveness rates remain high against symptomatic disease brought on by the delta variant.

Investigators at Public Health England showed 2-dose administration of Pfizer-BioNTech mRNA vaccine BNT162b2 and AstraZeneca-University of Oxford adenovirus vaccine ChAdOx1 nCoV-19 were associated with 88% and 67% effectiveness against symptomatic delta variant-derived COVID-19, respectively. The findings, published today in 

, provide support for 2-dose vaccine uptake in the wake of surging cases driven by the highly transmissible delta variant.

The vaccines’ highly efficacious benefit in symptomatic COVID-19 prevention has been observed largely in clinical trials and real-world research involving the first prominent B.1.1.7 (alpha) variant, the study notes.

“Data on the effectiveness of COVID-19 vaccines against clinical outcomes with (delta) variant have been limited,” they write. In their conclusion they write that “the findings are observational and should be interpreted with caution. Low sensitivity or specificity of PCR testing could result in cases and controls being misclassified, which would attenuate the estimates of vaccine effectiveness.”

’s Editorial Advisory Board, notes that “the data from the United Kingdom which reports that the Pfizer mRNA vaccine is 88% effective against symptomatic infections appears to be in stark contrast to the 41% effectiveness reported by the Ministry of Health in Israel. The difference can be explained by waning of immunity over time and the vaccine dosage schedule in the two countries.”

Israel was one of the first countries to administer vaccines to their population and has a dosage schedule similar to the US. The UK, on the other hand, spaced the 2 doses apart by up to 3 months, says Kavanagh.

“Thus, most in Israel completed their vaccination schedule far ahead of those in the United Kingdom,” says Kavanagh. “Israel is currently administering boosters to those above the age of 60 and more than 5 months since vaccination. The United Kingdom is planning to start booster shots in September.”

In the UK study, a team led by Jamie Lopez Bernal, PhD, sought to interpret the effectiveness of currently available 2-dose vaccines in the UK against the B.1.617.2 (delta) variant of SARS-CoV-2—at a time when cases borne from the variant were spreading from India to dozens other countries, while investigators had little indication of the COVID-19 vaccines’ effectiveness in curbing it.

Investigators conducted a test-negative case-control assessment to estimate vaccine effectiveness against symptomatic disease caused by the delta or alpha variant. They identified variants based on sequencing and spike (S) gene status observation, using data from all symptomatic cases of COVID-19 sequenced in England to determine proportion of cases with either variant according to vaccination status.

The team included 19,109 sequenced cases which included persons ≥16 years old, appropriately vaccinated with either BNT162b2 or ChAdOx1 nCoV-19 regimens, with symptomatic COVID-19 caused by either alpha or delta variant. They observed the alpha variant in 14,837 (77.6%) cases, and delta in 4272 (22.4%).

More than one-third of observed patients in each variant population were aged 16-29 at the time of sequencing; approximately 99% of both populations did not have a history of travel that would implicate international SARS-CoV-2 infection risk. A total of 307 (2.1%) sequenced COVID-19 cases from either variant group were linked to health or social care workers.

In observing a single dose of either regimen, Lopez Bernal and colleagues observed significantly lower vaccine effectiveness versus the delta variant: 30.7% (95% CI, 25.2 – 35.7). Single-dose vaccine effectiveness versus the alpha variant was 48.7% (95% CI, 45.5 – 51.7).

Two-dose BNT162b2 was associated with a 93.7% vaccine effectiveness versus the alpha variant (95% CI, 91.6 – 95.3), compared to an 88.0% effectiveness versus the delta variant (95% CI, 85.3 – 90.1).

Two-dose ChAdOx1 nCoV-19 was associated with a 74.5% vaccine effectiveness versus the alpha variant (95% CI, 68.4 – 79.4) and a 67.0% effectiveness versus the alpha variant (95% CI, 61.3 – 71.8).

“A clear effect was noted with both vaccines, with high levels of effectiveness after 2 doses,” investigators noted. “Vaccine effectiveness against either variant was smaller after the receipt of 2 doses of the ChAdOx1 nCoV-19 vaccine than after the receipt of 2 doses of the BNT162b2 vaccine, a finding that is consistent with reported clinical trial findings.”

Investigators concluded that their findings show “high levels of vaccine effectiveness” with 2-dose vaccination against symptomatic COVID-19 brought on by the delta variant.

“These estimates were only modestly lower than the estimate of vaccine effectiveness against the alpha variant,” they wrote. “Our finding of reduced effectiveness after the first dose would support efforts to maximize vaccine uptake with two doses among vulnerable groups in the context of circulation of the delta variant.”

The original version of this article appeared in

The findings provide support for 2-dose vaccine uptake in the wake of surging cases driven by the highly transmissible delta variant.