Jonna Lorenz

About a third of patients with coronavirus disease 2019 (COVID-19) reported persistent symptoms in a survey completed an average of 6 months after the onset of their illness, a small study from the University of Washington found.

The longitudinal prospective cohort study, published in 

, included 177 people who completed follow-up questionnaires between 31 and 300 days after illness onset at an average of 169 days.

“The primary take home message is that even in relatively young, healthy individuals, and even in those who have a mild case of COVID-19, symptoms can last for months after infection and can adversely impact quality of life,” co-author Denise J. McCulloch, MD, MPH, infectious disease fellow at the University of Washington, told 

Most of those surveyed—150 (84.7%)—were outpatients who reported mild symptoms, 11 (6.2%) were asymptomatic and 16 (9%) were hospitalized with moderate or severe illness.

People age 65 and older were most likely to report persistent symptoms (43.3% of 30 patients), followed by those aged 40 to 64 (30.1% of the 83), and patients aged 18 to 39 (26.6% of the 64).

“I was surprised at how many people reported persistent symptoms 6 months after their infection,” McCulloch said. “Persistent symptoms have been more widely reported in cohorts of hospitalized patients, so we were surprised to see how often it occurred in this group of people who were fairly young and healthy, the vast majority of whom did not require hospitalization for their illness.”

Among those outpatients who originally reported mild symptoms, 49 (32.7%) reported at least 1 persistent symptom during the follow-up survey, compared with 5 (31.3%) of those hospitalized and 1 (4.8%) in the healthy control group. Among patients with hypertension or diabetes, 11 (35.5%) reported persistent symptoms.

“I would want clinicians to encourage COVID-19 vaccination for 

 of their patients when it is available to them, not just those who are considered high risk,” McCulloch said. “I believe our results underscore the importance of COVID vaccination even in young, healthy individuals, in order to help prevent COVID-19 infection and the potential for long-term symptoms.”

The most common persistent symptoms reported in the follow-up survey were fatigue and loss of taste or smell, both of which were reported among 24 patients (13.6%). Other symptoms included brain fog (2.3%). Health-related quality of life (HRQoL) was worse for 51 (30.7%) outpatients and hospitalized patients, and 14 patients (7.9%) reported negative impacts on at least 1 activity of daily living such as household chores.

“We plan to continue to survey the individuals in our study for 2 years to see whether their symptoms improve over time,” McCulloch said. “Also, many medical centers, including the University of Washington, are creating post-COVID clinics to help care for these patients following their illness. I hope that in partnership with these post-COVID clinics, researchers can work to understand what causes prolonged symptoms, and how these symptoms can be alleviated.”

The study is consistent with previous research, including a 

 by investigators at the University of Geneva that found that 33% of patients who were diagnosed with SARS-CoV-2 infection but did not require hospitalization still reported lingering symptoms 6 weeks after their diagnosis.

The long-term consequences of COVID-19 have been a growing concern during the pandemic.

On Feb. 23, the National Institutes of Health 

 to study cases of COVID-19 in which symptoms persist long past the initial stages of the illness. Referred to informally as COVID-19 long haulers or long COVID, the NIH has termed these prolonged health consequences as Post-Acute Sequelae of SARS-CoV-2 infection (PASC).

The NIH PASC Initiative announced its first Research Opportunity Announcements (ROAs), which offer open funding for ongoing and new research studies that address PASC as part of $1.15 billion in funding over four years passed by Congress in December.

The Infectious Diseases Society of America (IDSA) recently held a 

 addressing the increasing need for clinics focusing on the aftermath of COVID-19.

Articles

Symptoms of COVID-19 can persist for months in about a third of cases, including among those with mild illness, a new study confirms.

A Third of COVID-19 Patients Report Persistent Symptoms 6 Months After Illness 

Black, American Indian, Hispanic and older adults have been underrepresented in vaccine clinical trials during the past decade, according to a new analysis.

, included 230 clinical trials based in the United States and registered on ClinicalTrials.com between July 1, 2011 and June 30, 2020. The trials studied involved 219,555 participants.

“I believe there are three big takeaways from our research,” first author Laura Flores, BA, a PhD candidate at the University of Nebraska Medical Center, told 

®. “Our study highlighted a decade's worth of disparities—with Hispanic or Latino, Black or African American, American Indian/Alaska Native and older populations often left out of vaccine clinical trial research.

“Additionally, the lack of race and ethnicity reporting in 

 was a startling finding. With missing ethnicity data in over 60% percent of trials, and missing race data in 40% of trials, it is difficult to assess the true representation among clinical trials participants.

“Female adults were overrepresented overall and within all phases of vaccine clinical trial research over the last decade.”

Age and sex of participants were reported for every trial, race was reported for 134 (58.3%) and ethnicity was reported for 79 (34.3%).

“I believe the lack of data reporting was a big shock to the entire team,” Flores said. “We can’t begin to solve inequalities in clinical trial research without the whole picture.”

Compared with U.S. census data, white Americans were overrepresented in vaccine clinical trials, accounting for 77.9% of adult participants, while those underrepresented included Black or African American individuals at 10.6%, American Indian or Alaska Native individuals 0.4% and Hispanic of Latino individuals at 11.6%. Asian individuals were equally represented to the US census data at 5.7%.

Adult trials included more female participants (56%). Those age 65 and older were underrepresented (12.1%).

Pediatric trials also showed a underrepresentation among Black participants (10.1%) and Hispanic participants (22.5%)

“Our study highlighted some good news in that we are close to reflecting the racial makeup of the US population in vaccine clinical trials,” Flores said. “With race, the gaps we identified are much smaller than in other research areas, like oncology clinical trials, and this signals we might be on the right track. That being said, we believe it is important to note that small inequities are still important inequities. We are doing a genuine disservice to these populations by not reaching out, and not keeping records, and not including them in trials that might benefit them.”

The NIH Revitalization Act of 1993 directed the National Institutes of Health to establish guidelines for including women and minorities in clinical trials. In 2017, the NIH amended the policies for reporting data, and the US Food and Drug Administration (FDA) issued a 

 stressing the importance of diversity in clinical trials.

Missing data on race and ethnicity deprives studies of important context for understanding health disparities such as socioeconomic barriers, implicit bias and increased burden of comorbidities.

Flores said she hopes the study leads to better demographic reporting by investigators.

“Enrolling the right populations and in particular the most impacted populations in clinical trials is not a luxury but a necessity,” author Carlos del Rio, MD, of Emory University School of Medicine told 

. “I am hopeful that the National Academy of Science Engineering and Medicine Committee will come up with good recommendations that will help improve the representation of diverse populations in clinical trials and research.”

Author Michele Andrasik. PhD EdM, of Fred Hutchinson Cancer Research Center, emphasized the importance of building trustworthy relationships with communities to ensure good public health for all.

“We need concerted efforts to ensure the inclusion of diverse participants in clinical trials,” Andrasik told 

®. “This will require going beyond guidelines and potentially implementing sample requirements going forward. The same is true for the collection of race and ethnicity data. The large incidence of missing data is unacceptable.”

The coronavirus disease 2019 (COVID-19) pandemic has brought additional challenges to clinical trials. Last year, the FDA 

 for conducting clinical trials during the pandemic, acknowledging challenges brought by quarantines, site closures, travel limitations and interruptions to the supply chain and urging measures such as increased safety monitoring, shifting to telemedicine platforms and including explanation for any missing data due to disruptions.

Vaccine clinical trials have fallen short of diversity guidelines during the past decade, with minority groups underrepresented and key data missing in many trials, a new study found.

Minorities Are Underrepresented in Vaccine Clinical Trials

A variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identified in association with a recent surge in coronavirus diseases 2019 (COVID-19) in Southern California is spreading rapidly, new research suggests.

Investigators at Cedars-Sinai Medical Center (CSMC) conducted phylogenetic analysis of 185 samples taken during a surge of COVID-19. The study, published in 

, found that the variant, CAL.20C, accounted for about 36% (67 of 185) of samples collected at CSMS between Nov. 22 and Dec. 28.

“The spread of the new CAL.20C strain of the SARS-CoV-2 virus is likely a reflection of increased COVID-19 cases due to social behavior over the winter holidays,” study's co-senior author, Jasmine Plummer, PhD, a research scientist at the Cedars-Sinai Center for Bioinformatics and Functional Genomics and associate director of the Applied Genomics, Computation & Translational Core at Cedars-Sinai told 

®. “This development is a reminder that social distancing, wearing a mask, washing hands and staying home where possible, plus also getting vaccinated when you are able to, can help curb this pandemic.”

CAL.20C originated from a group of viruses tracked from Europe to New York early in the pandemic and was first detected in California in July. It reemerged in October and became more prevalent, accounting for about 35% of all coronavirus strains in California and 44% of those in Southern California on Jan. 22. CAL.20C is distinct from variants identified in the United Kingdom (B.1.1.7), South Africa (B.1.351), and Brazil (B.1.1.248) and had been detected in 26 states and several other countries by Jan. 22.

“We initially began this research at a time when the hospital was overwhelmed post-holidays with increased COVID-19 positive cases, and the UK variant was reported and spreading,” Plummer said. “So we first looked for the UK variant and instead found the new CAL.20C strain, which was prevalent in Southern California and accounted for almost 40% of cases within our hospital population.”

The variation includes 3 mutations in the spike protein, which is a target of vaccines and monoclonal antibodies, raising concerns about the potential implications for disease severity and infectivity. Functional effects remain uncertain.

“Using the advanced technology known as next-generation sequencing and finding new versions of the SARS-CoV-2 virus can help promote public health surveillance and arm clinicians with information about what may be presented to them as cases emerge in the healthcare system,” Plummer said. “Research like ours allows scientists the opportunity to ensure virus variants have no adverse effects, and if they do, that we can modify vaccines in a way to address this development.”

Functional studies are underway to examine the infectiousness and clinical outcomes of CAL.20C.

Prevalent strains in the United States appear to be sensitive to therapeutics, but emerging variants raise concerns that the virus could develop resistance, an 

 by John R. Mascola, MD; Barney S. Graham, MD, PhD; and Anthony S. Fauci, MD, of the National Institute of Allergy and Infectious Diseases. They noted that studies have suggested the B.1.1.7 variant is 30% to 80% more effectively transmitted and associated with a 30% increased risk of death.

Surveillance, tracking, and vaccine deployment will be key to addressing these new variants and could benefit from the infrastructure and process used for updating influenza vaccines.

“SARS-CoV-2 will be with the global population for some time and has clearly shown its tendency toward rapid antigenic variation, providing a ‘wake-up call’ that a sustained effort to develop a pan-SARS-CoV-2 vaccine is warranted,” the NIAID authors wrote.

 first identified in Europe and Africa in December also has made its way to the United States. B.1.525 shares a mutation found in the Brazilian and South African variants that raise concerns about the possibility of resistance to antibodies.

 variant spreading predominantly in the South and Southwest was first identified in October and has spread to account for about 27% of all sequenced SARS-CoV-2 genomes in Louisiana and 11% of those in New Mexico.

The emergence of more transmissible variants highlights the need for improved sequence-based surveillance along with testing and contact tracing to improve prevention measures as the disease evolves, Adam S. Lauring, MD, PhD, told 

Investigators at Cedars-Sinai Medical Center identified a variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), called CAL.20C, which accounted for about 44% of samples in Southern California in January.

Variant of SARS-CoV-2 Found in Southern California Is Spreading Rapidly

Children in households where someone had coronavirus disease 2019 (COVID-19) were about about half as likely to test positive for the disease as adults, according to a new study, which also found children to be less likely to pass the disease on to others.

, examined data from 637 households in Bnei Brak, Israel, including 3,353 individuals to analyze the susceptibility and infectivity of children compared with adults. Among the households included in the study, at least one member tested positive for COVID-19. Excluding these index cases, 25% of children and 44% of adults tested positive for COVID-19.

“Our research provides evidence that the susceptibility of children to infection with SARS-CoV-2 is significantly lower than that of adults (approximately by half),” Yair Goldberg, PhD, associate professor, at the Faculty of Industrial Engineering & Management at Technion Israel Institute of Technology told 

®. “We also estimated somewhat lower infectivity for children who are infected, though results are less clear-cut in this regard.”

PCR testing determined that 1,510 of 3,353 household members were positive for COVID-19. The study found that susceptibility to COVID-19 among children younger than 20 was 43% (95% CI: [31%, 55%]) of the susceptibility of adults and infectivity of children was 63% (95% CI: [37%, 88%]) of infectivity of adults.

The study found that the odds of testing positive for COVID-19 increased with age until about age 20 and remained constant thereafter.

“When we looked at the data we were surprised by the fact that the chance for a child to have been tested positive increased with the age of the child,” Goldberg said. “We were also surprised by the large percentage of infected people in the families we studied (45%).”

Data from serological testing among a subset of participants and PCR testing showed that infections are under-detected and that is more substantial among children.

That difference was expected based on previous findings that children are more likely to have mild or no symptoms. For example, one 

 found that about 36% of children who tested positive for COVID-19 were asymptomatic.

However, the difference in under-detection isn’t significant enough to explain the difference in positivity rates between children and adults. Even after adjusting for under-detection, the data still showed lower infections rates for children.

“While there is now good evidence that children are less susceptible to infection than adults when exposed to infected people, and it is clear that children display milder symptoms when infected, it should be kept in mind that transmission is context-dependent and that higher contact rates among children in settings such as schools can offset the effect of lower susceptibility and lead to outbreaks,” Goldberg said. “Therefore, efforts must still be made to protect children, in particular since currently they are not vaccinated.”

Some have feared that COVID-19 may become more severe among children over time. So far that doesn’t seem to be the case, according to 

, that found that the proportions of deaths caused by COVID-19 in children was stable across May, June and July.

More research is needed to better understand the factors that affect transmission along with the role of children in spreading the disease as the pandemic evolves.

“It is important to evaluate the effect of new strains on transmission,” Goldberg said. “While there is strong evidence that new strains are more transmissible, it is not clear whether they change the picture regarding the lower relative susceptibility of children. This an issue that needs to be investigated in the future and household studies such as ours are one useful way to do so.”

Children are about half as susceptible as adults to contracting COVID-19, according to new research from Israel.