Jonna Lorenz is a freelance journalist with more than 20 years of experience. Her background is in business and health care news, including reporting, editing and research for newspapers and websites.

Jonna Lorenz

Investigators in China detailed a method for rapidly evaluating the vaccine effectiveness of COVID-19 vaccines against symptomatic infection with different SARS-CoV-2 variants by considering genetic distance.

, investigators at Chinese University of Hong Kong and Beth Bioinformatics Co. Ltd. analyzed data from 49 studies and nearly 2 million SARS-CoV-2 sequences. They found that the genetic distance of the receptor-binding domain of the spike protein was predictive of vaccine effectiveness.

“Traditionally, vaccine effectiveness (VE) can only be obtained after people have been vaccinated and a portion of the population has been infected,” corresponding author Maggie Haitian Wang, PhD, associate professor at Chinese University of Hong Kong, told 

. “Now with the technology presented in the paper, VE can be accurately predicted before vaccination and infection in silico for all types of vaccines.

“The method can be used in reverse to determine the optimal vaccine antigen that may lead to the maximum effectiveness against circulating viruses. This can facilitate the development of high efficacy vaccines against COVID-19, flu, and other pathogens.”

The investigators found that variations in the receptor-binding domain region had the strongest association with vaccine effectiveness. They used a mixed-effects model to control for variations in vaccine platforms and manufacturers and validated the results by published clinical trial data.

The study found that genetic distance of the receptor-binding domain accounted for 86.3% of the change in vaccine effectiveness against symptomatic infection in a mixed-effects model based on vaccine platform and 87.9% in a model based on manufacturer.

Using the model, investigators estimated the vaccine effectiveness of the mRNA vaccine platform against the Delta variant to be 82.8%, which is consistent with an observational study that showed 83% vaccine effectiveness. For the Omicron variant, the model estimated vaccine effectiveness ranging from 11.9% to 33.3%, varying by sublineage.

“Vaccine producers can use this technology to optimize vaccine composition against emerging variants and inform clinical trial design (where, when),” Wang said. “Clinicians, health care providers, and policy makers may be informed with estimates on vaccine effectiveness against new genetic variants, and estimate the scale of upcoming epidemics as new variants circulate.”

Using the computational framework, investigators were able to predict the drop in vaccine effectiveness against the Omicron variant months before traditional studies.

“We were among the earliest groups to know the threat of the Omicron,” Wang said. “As soon as the new variant was reported in Africa in November 2021, by the model we were very shocked to have obtained an extremely low VE by the in silico model and anticipated that this new variant will escape the immunity generated from existing vaccines against symptomatic infection. The first VE report for the Omicron by traditional studies was only available 3 months later.

“We were also surprised to find out very early that a large variation of VE was present among the Omicron sub-lineages, which infers that VE estimates would be population specific due to the diversified Omicron sub-lineage composition by geographical region.”

The computational framework was tailored from a bioinformatics approach previously developed to evaluate influenza viruses.

“The next steps of technology development include expanding the current VE framework to estimate other clinical outcomes of COVID-19, and incorporating individual level information for personalized risk estimation,” Wang said.

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A computational framework for estimating vaccine effectiveness based on genetic differences of SARS-CoV-2 variants showed promising results in a new study that verified the model with clinical trial data.

Predicting Vaccine Effectiveness Based on Genetic Distance of SARS-CoV-2 Variants


As world health officials work to understand an outbreak of acute hepatitis of unknown origin in children, new research from the Centers for Disease Control and Prevention suggests the number of cases is on par with pre-pandemic levels, and a common exposure has yet to be identified that would explain the origins of the condition.

The CDC released an interim analysis of acute hepatitis in children between October 2021 and June 2022 in its June 24 

, showing adenovirus infection in about 45% of cases and a history of SARS-CoV-2 infection in about 26%. The study included data on 123 cases.

“We looked at a broad number of exposures and from that information essentially there are no common exposures that were found in terms of foods that were consumed, intoxicants, medication, common exposures like pet exposures among the cases for which we’ve been able to do this more extensive look,” study co-author David Sugerman, MD, of the CDC told 

An analysis published in the CDC’s June 17 

 suggested that compared with pre-pandemic levels, there was no increase in hepatitis-associated emergency department visits or hospitalizations, liver transplants or adenovirus types 40/41 infections among US children.

“This is an ongoing investigation,” Sugerman said. “I think it’s going to take collectively our work here in the United States and other countries time to have more answers.”

In April, the World Health Organization reported 169 

 of unknown origin in children in a dozen countries, leading to one death and 17 transplants. In response, the CDC issued a request calling on health care providers to report additional cases in children younger than 10.

 305 patients under investigation in 42 states and territories, including 11 deaths, and 20 liver transplants. Cases also have risen globally, with the 

 650 probable cases in 33 countries as of May 26, the European Centers for Disease Prevention and Control reporting 402 cases in 20 countries as of June 9, and the United Kingdom reporting 260 cases as of June 13. Most cases have been in children younger than 5.

“This is still a very rare condition,” Sugerman said. “We’re looking at less than 10 cases per million population in the United States if we consider there are around 40 million children less than 10 years of age in the United States. So it’s an incredibly rare condition.”

The CDC is investigating possible causes, including adenovirus infection, SARS-CoV-2 infection or other viruses, environmental triggers or ingested toxins. Among those who were tested for adenovirus infection, 44.6% tested positive. About 10% tested positive for acute SARS-CoV-2 infection, and a history of SARS-CoV-2 infection was reported among 26%. No common exposures such as travel, food, or toxicants have been identified.

“Adenovirus has the strongest signal of the things we’re looking for, but still, 45% is not 80% or 100%,” Sugerman said. “So, it’s there but it’s not telling us the whole story potentially and there’s more work to be done.”

Adenovirus has not been part of the standard workup for children with hepatitis. Sugerman urged clinicians to cast a wide net, including specialized testing for adenovirus 40/41 in the workup of children with acute hepatitis.

 for testing patients under investigation for acute hepatitis along with 

 for collection and submission of specimens.

The CDC is investigating whether recent cases may be associated with the return to regular activities, leaving children vulnerable to viral illnesses they avoided due to COVID-19 mitigation strategies.

“It might be we’re detecting something that was there all along. There’s not a surge in adenovirus. What could have happened is that there was a re-exposure adenovirus,” Sugerman said. “So, the thought is that children are re-exposed to a number of viruses that they weren’t during the mitigation efforts with coronavirus.”

Sugerman said ongoing research will include controlled studies to better understand a possible link between adenovirus and hepatitis and looking back in time to see whether adenovirus may have been present in some previous cases of hepatitis with unknown cause.

“Likely, it’s multifactorial,” he said.

The Centers for Disease Control and Prevention (CDC) is seeking more data on a possible cause of acute hepatitis in children, calling on clinicians to screen for adenovirus infections along with a broad range of possible exposures.

CDC Identifies Adenovirus Infections in 45% of Acute Hepatitis Cases in Children

Ferring Pharmaceuticals’ investigational drug RBX2660 for recurrent 

 infection (CDI) was associated with consistent improvements to fecal microbiome and bile acid compositions, according to a recent analysis of data from 3 clinical trials.

The subgroup analysis, presented at the American Gastroenterology Association’s 

 in San Diego, included data from three clinical trials of RBX2660 – PUNCH CD2, PUNCH CD3 and PUNCH OLS.

“The biggest takeaway from our DDW presentation was that our analysis of 3 large clinical trials revealed consistent, large, and statistically significant shifts to the fecal microbiome and bile acid compositions from before to after administration of RBX2660,” lead author Ken Blount, PhD, chief scientific officer at Rebiotix and vice president of microbiome research at Ferring Pharmaceuticals, told 

The microbiota-based live biotherapeutic was associated with shifts from opportunistic bacteria and primary bile acids to beneficial Bacteroidia- and Clostridia-class bacteria and secondary bile acids.

“The microbiome shifts are important because Bacteroidia and Clostridia are known to help resist intestinal colonization by pathogens like 

Blount said. “The bile acid shifts are important because secondary bile acids are known to repress 

 and in animal studies. Across these three trials we also observed significant shifts of the MHI-A microbiome biomarker of antibiotic-related dysbiosis—from more dysbiotic MHI-A before RBX2660 administration to a healthier MHI-A after RBX2660 administration.”

The shifts were greatest among participants who were clinical responders to RBX2660, defined as no CDI recurrence at eight weeks after treatment.

“We believe this analysis may reveal possible mechanisms by which RBX2660 significantly reduced recurrence of 

 infections in these clinical trials,” Blount said. To our knowledge this is the largest analysis to date of microbiome and bile acid changes associated with administration of an investigational live biotherapeutic.”

The findings were consistent with the earliest clinical trial of the treatment and offer strong evidence given the size of the analysis, which included more than 300 participants from 3 clinical trials.

“We were intrigued to find that the shifts were so consistent among the three trials in this combined analysis, including the MHI-A biomarker data,” Blount said.

During nearly a decade of research of the potential first-in-class biotherapeutic, investigators have conducted six controlled clinical trials with more than 1000 participants. The Food and Drug Administration has granted the therapy Fast Track, Orphan, and Breakthrough Therapy designations.

The analysis of microbiome and bile acid compositions was among four abstracts presented at DDW regarding RBX2660. Investigators also presented data showing RBX2660 had a 68.3% 

 when administered following antibiotic treatment, versus a 55% success rate in a placebo group, and that 

Currently antibiotics are the standard of care for treating CDI but they also present the primary risk factor for recurrence by destroying health bacters. RBX2660 aims to prevent recurrence of CDI by restoring the microbiome and halting the cycle of antibiotic-induced dysbiosis and CDI recurrence.

“We believe the exploratory analysis presented at DDW underpins the clinical efficacy observed in our trials by revealing possible mechanisms by which RBX2660 may be reducing rCDI,” Blount said.

Patients with recurrent Clostridioides difficile infection saw improvements in fecal microbiome and bile acid after treatment with the investigational microbiota-based live biotherapeutic RBX2660.

RBX2660 for Recurrent CDI Associated with Microbiome and Bile Acid Restoration

The emergence of the Omicron variant of SAR-CoV-2 rendered traditional public health measures insufficient to protect against the spread of COVID-19, a new study suggests.

The study, highlighted in a research letter in

, examined routine surveillance and vaccination efforts during the fall semester at Cornell University from Aug. 26 through Dec. 18, when Omicron emerged as the predominant variant.

“Based on analysis of routinely collected population surveillance data, Cornell’s experience shows that traditional public health interventions were not a match for Omicron,” wrote the authors, led by Genevive Meredith, DrPH, MPH, of Cornell University. “While vaccination protected against severe illness, it was not sufficient to prevent rapid spread, even when combined with other public health measures including widespread surveillance testing.”

Working in partnership with the Tompkins County Health Department, Cornell opened for instruction in the fall 2021 with public health measures including COVID-19 vaccines mandated for students and encouraged for employees, a mask mandate on campus, surveillance testing, and isolation and contact tracing for positive COVID-19 cases.

Between Aug. 23 and Sept. 10, 480 COVID-19 cases were identified among 15,503 undergraduate students, 2873 graduate students and 2803 employees, or an average of 22.9 cases a day. Between Sept. 12 and Nov. 27, cases were limited to 330 before a sharp increase after the university’s five-day Thanksgiving break. Cases rose to 75 between Nov. 28 and Dec. 4, 655 from Dec. 5-11, and 1,559 from Dec. 12-18, and case positivity rates surged to 5.7% from 0.5%.

The surge occurred while 97.9% of people were fully vaccinated and despite efforts to mitigate spread.

“Support teams helped cases isolate safely, investigation identified exposures, and contact tracing identified contacts who were instructed to monitor for symptoms, test, and/or quarantine,” the authors wrote.

Between Nov. 28 and Dec. 31, a total of 2,797 cases were reported, or an average of 82.3 per day. Most were mild (82.2%), and 98.6% were breakthrough cases. The investigators also noted that more close contacts were subsequently diagnosed with COVID-19 during this time – 22.6% compared with 4.4% between Aug. 23 and Nov. 27.

“Something had clearly changed in the university setting, as similar outbreaks were not yet being seen in the off-campus community or neighboring counties,” the authors wrote.

The investigators determined that by Dec. 11, 89.1% of cases were from the Omicron variant. Additional mitigation measures were instituted on or after Dec. 10, including limiting in-person interactions, prohibiting student gatherings, and moving examinations online.

The study contributes to research showing that the emergence of the Omicron variant changed the shape of the pandemic. The variant, which brought

 of existing treatments. Still, the variant has caused 

Public health officials continue to discuss 

High vaccination rates at Cornell University prevented severe disease during the Omicron surge of the COVID-19 pandemic but didn’t stop the rapid spread of the virus, even with comprehensive public health measures.

Routine Surveillance Details Rapid Spread of COVID-19 at Cornell University During Omicron Surge


Nonhospitalized patients with COVID-19 who took the antiviral drug molnupiravir were less likely to need respiratory interventions and had fewer acute care visits, a secondary analysis of the phase 3 trial found.

, included 1433 nonhospitalized patients at 107 sites around the world who received either 800 mg of molnupiravir or a placebo every 12 hours for 5 days.

“The findings suggest there are additional important clinical benefits of molnupiravir beyond reduction in hospitalization and death,” the study authors, led by Matthew Johnson, MD, of Merck, wrote.

Molnupiravir, invented at Drug Innovations at Emory (DRIVE) and developed by Merck and Ridgeback Biotherapeutics, was granted an 

 (EUA) by the Food and Drug Administration (FDA) for the treatment of COVID-19 in December. The approval came one day after the 

 for Pfizer’s antiviral Paxlovid as the first oral antiviral for treating COVID-19.

The MOVe-OUT trial showed molnupiravir reduced patient risk of COVID-19 hospitalization or death by approximately 50%.

The secondary analysis of the randomized controlled clinical trial, MOVe-OUT, included patients with mild to moderate COVID-19 and risk factors for progressing to severe disease. Investigators analyzed the effects of molnupiravir on biomarkers, respiratory interventions and medical services.

Participants in the molnupiravir group saw faster normalization of C-reactive protein (CRP) concentration and oxygen saturation (SpO2) compared with those in the placebo group by Day 29. Improvements began on Day 3 of treatment and continued through Day 29.

“The continuous decreases in CRP concentration and increases in SpO2 with molnupiravir indicate subsiding systemic inflammation and recovering respiratory function,” the authors wrote.

The relative risk reduction for requiring the use of respiratory interventions was 34.3% among the patients in the treatment group. Those who received molnupiravir also had RRRs of 23.5% for conventional oxygen therapy, 26.1% for high-flow heated and humidified oxygen treatment, 75.4% for noninvasive mechanical ventilation, 64.1% for invasive mechanical ventilation.

“The decreased need for invasive mechanical ventilation is particularly relevant because patients with COVID-19 who receive this respiratory intervention have mortality rates up to 50%,” the authors wrote.

Among a subgroup of patients who required hospitalization, the RRR for all respiratory interventions was 21.3%. The median number of days before discharge also was lower among the treatment group – 9, compared with 12 for those in the placebo group.

Those in the treatment group had an RRR for acute care visits of 32.1% and 33.8% for COVID-19-related acute care visits.

“Altogether, these findings suggest there is added clinical value of molnupiravir for the treatment of nonhospitalized adults with mild to moderate COVID-19,” the authors wrote. “Meaningful benefits of molnupiravir to patients and health care systems may exceed the previously demonstrated benefits of reducing hospitalizations or death due to disease progression as well as alleviating symptoms in high-risk patients.”

Limitations of the study include that analysis was conducted retrospectively, despite the data being collected prospectively for the MOVe-OUT trial. The study also didn’t include any vaccinated patients, so it could not assess the possible impact of vaccination or the time elapsed since vaccination on findings. Potential financial impact was not assessed.

Merck’s antiviral drug molnupiravir may benefit nonhospitalized patients with mild or moderate COVID-19, according to a secondary analysis of phase 3 clinical trial data.



Secondary Analysis of Molnupiravir Trial for Shows Additional Benefits for COVID-19 Patients

The antiviral drug tecovirimat may improve outcomes for people infected with monkeypox, a recent study in Britain suggests.

The small retrospective observational study, published in 

, included 7 patients who were treated for monkeypox at high consequence infectious diseases centers in Britain between Aug. 15, 2018, and Sept. 10, 2021 and aimed to describe the clinical course of the disease and response to novel antiviral therapies.

“The single biggest takeaway is the excellent clinical and virological response to the oral antiviral tecovirimat in one patient with monkeypox who received this agent,” lead author Hugh Adler, PhD, of Liverpool University Hospitals NHS Foundation Trust told 

. “We definitely need well-powered, prospective studies to validate this finding, but it is a strong signal, and may be of use to clinicians managing patients with monkeypox in the current outbreak in the Western Hemisphere.”

Three patients were treated with 200 mg of brincidofovir weekly before developing elevated liver enzymes and ending treatment. One patient received 600 mg of tecovirimat twice a day for two weeks and experienced a shorter duration of illness and viral shedding.

The study included patients who tested positive after traveling from Nigeria along with transmission to a healthcare worker and within a family household. All seven of the patients in the study developed skin lesions, and all made a full recovery.

“We were surprised to find positive monkeypox PCR results in blood and upper respiratory swabs, and particularly surprised that the throat swabs remained PCR positive long after the resolution of the rash in some cases,” Adler said. “We don't yet know the implications for infection control advice, etc. (after all, don't forget that patients with COVID can remain PCR positive for weeks despite no longer being infectious), but it merits consideration when managing patients in the current outbreak, and warrants dedicated research (eg with viral culture) to settle the question once and for all.”

Three patients in the study spent more than three weeks in isolation because of prolonged positivity. The disease was mild in all of the patients involved in the study, with none experiencing pneumonia or sepsis. Unexpected symptoms included mild relapse six weeks after discharge in one patient and a deep tissue abscess that required drainage in another. Isolation led to low mood in patients.

“We wanted to draw attention to the prolonged illness and hospitalization our patients experienced, even with ultimately ‘uncomplicated’ monkeypox, so that healthcare providers can prepare to psychologically support patients with this infection, and for policymakers to consider whether self-isolation at home is an option for selected patients,” Adler said. “And most importantly, we want healthcare providers and readers everywhere to know that monkeypox remains a significant public health problem in West and Central Africa, where there is an urgent unmet need for antiviral treatments, vaccines and more evidence-based infection control protocols.

Monkeypox is endemic in Africa, but global health officials have been closely monitoring the 

 of the disease outside of Africa. About 300 cases of monkeypox have been reported in a dozen countries.

“Clinicians, including the authorship of this paper, remain involved in the clinical and public health response to the ongoing unprecedented monkeypox outbreak in the UK, Europe and beyond, and I am confident that this will be brought under control,” Adler said. “There are plans to undertake further research to explain our finding of positive monkeypox viral PCR testing in upper respiratory throat swabs and understand the infection control implications of this. And internationally I am pleased that there is a trial recruiting in the Democratic Republic of the Congo looking at the role of smallpox vaccination for healthcare staff caring for patients with monkeypox, and an expanded access program for tecovirimat in the Central African Republic.”

A recent study in the United Kingdom suggests that more research into the possible benefits of antiviral drug tecovirimat for treating monkeypox may be warranted after showing positive results in one patient.

Jonna Lorenz

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