COVID-19 vaccine candidate shows early promise

New data from a phase 1/2 clinical trial of a vaccine candidate being developed by Pfizer and German biopharmaceutical company BioNTech show the vaccine produced a robust immune response and was tolerable in healthy adults. The results appeared today in Nature.

The trial, which involved 45 healthy volunteers aged 18 to 55, compared different dose levels of BNT162b1, a nucleoside-modified messenger RNA (mRNA) vaccine that encodes the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Twelve participants per dose level (10 μg and 30 μg) were vaccinated on days 1 and 21, and 12 volunteers received a 100-μg dose on day 1. Nine participants received a placebo.

For all three dose levels, the geometric mean concentrations (GMCs) of RBD-binding IgG at 21 days after the first dose ranged from 534 to 1,778 units per milliliter (U/mL). By comparison, convalescent serum drawn from 38 patients with SARS-CoV-2 infection 14 days after diagnosis had an RBD-binding IgG GMC of 602 U/mL. By 7 days after the second dose for the volunteers in 10-μg and 30-μg groups, RBD-binding IgG GMCs had increased to 4,813 to 27,872 U/mL.

Highly elevated RBD-binding antibody concentrations remained so until 14 days after the second dose—the last time-point evaluated—and were roughly 8- to 50-fold higher than that of the convalescent serum panel. For the volunteers who received a 100-μg dose, RBD-binding antibody concentrations did not increase beyond 21 days after vaccination.

For all doses, small increases in SARS-CoV-2 neutralizing geometric mean titers (GMTs) were observed 21 days after the first dose, with substantially greater neutralizing GMTs observed 7 days after the second 10-μg and 30-μg dose. Neutralizing GMTs further increased by 14 days after the second dose, to 180 at the 10-μg level and 437 at the 30-μg level, compared with 94 for the convalescent serum panel.

The most common reactions were pain at the injection site, mild to moderate fatigue, and headache. Systematic events, including fever, increased with the dose level and were more frequent after the second dose in the 10-μg and 30-μg groups but resolved within a few days. Based on the reactogenicity after the first dose, participants in to 100-μg group did not receive a second dose.

The authors say the results provide a benchmark for the magnitude of the vaccine-elicited response and the vaccine's potential to provide protection, but they note that efficacy will ultimately be determined in a phase 3 trial.
Aug 12 Nature abstract

Study supports rapid COVID-19 testing at nursing homes after case identification

A new study by the Centers for Disease Control and Prevention's (CDC's) COVID-19 response team and seven state and local health departments suggests that rapid facility-wide testing at nursing homes after identification of an index case could help reduce transmission among residents and staff.

The seven health departments conducted initial facility-wide testing of residents and health care personnel (HCP) at 288 nursing homes from Mar 24 to Jun 14. Two of the health departments conducted testing in 195 nursing homes as part of facility-wide testing of all nursing homes in their states, and the other 5 targeted initial facility-wide testing to nursing homes with a newly reported case in a resident or staff member.

The two health departments using a statewide testing strategy (North Dakota and South Carolina) conducted tests in 195 nursing homes in low-incidence areas and found that in the 125 nursing homes that had no reported cases, 95 of 22,977 people (0.4%) tested positive. The five health departments using the targeted testing strategy (Arkansas, New Mexico, Utah, Vermont, and Detroit) tested at 93 nursing homes (88 of which had a documented COVID-19 case) and found that 1,619 of 13,443 residents and HCP (12%) tested positive. In 79% of the 93 nursing homes, new cases were detected.

The number of days from identification of the index case to completion of facility-wide testing ranged from 1 to 41 (median = 7 days). Population average estimates from regression analyses showed that each additional day from index case identification to completion of facility-wide testing was associated with identification of 1.3 additional cases. 

"For these reasons, testing of all residents and HCP in a nursing home with efficient turnaround time is recommended as soon as possible after identifying a new COVID-19 case," the authors wrote yesterday in Morbidity and Mortality Weekly Report (MMWR). "Facility-wide testing after identification of an index case might maximize the benefits of infection prevention and control interventions by enabling early identification of unrecognized cases, cohorting and isolation of resident cases, and exclusion of infected HCP from the workplace through nonpunitive sick-leave policies."
Aug 11 MMWR study

Study shows nearly half of household contacts of kids with COVID-19 also had symptoms

A new study based on pediatric patients in Atlanta who sought hospital treatment for COVID-19 shows 46.5% of the patients' household contacts also had symptoms of the virus, but children were the index case in only roughly 22% of the households. The study was published yesterday in the Journal of the Pediatric Infectious Diseases Society.

To conduct the study, researchers tracked children under the age of 18 with laboratory-confirmed SARS-CoV-2 between Mar 16 and Jun 14 who were seen by a healthcare provider at a Children's Healthcare of Atlanta facility. A total of 138 patients were identified, among which 32 households participated in follow-up parental interviews. Overall, 144 household contacts were identified among the 32 households: 58 (40%) children and 86 (60%) adults.

In total, 67 (46.5%) household contacts developed symptoms of COVID-19 either before or after the pediatric patients. In the 32 households studied, 7 reported the child was the likely index case (22%).

"Differences in child and adult transmission rates are likely affected by differences in their social isolation practices. For a majority of our study period, children were not attending school or daycare," the authors said.

They also noted that over half of the households had adults who were essential workers and continued to work during the pandemic, increasing their own risk of exposure and secondary transmission.
Aug 11 J Pediatric Infect Dis Soc study

Studies yield more clues on COVID-19 exposure in healthcare workers

Two new studies shed more light on COVID-19 exposure patterns in healthcare workers, with both suggesting that compliance with recommended personal protective equipment (PPE) protocols kept workers safe.

Writing in a JAMA Internal Medicine research letter yesterday, a group from St Francis Hospital in Roslyn, NY, looked at the rate among healthcare workers, based on reverse transcriptase-polymerase chain reaction (RT-PCR) testing and antibody testing in March and April, a time when the state was one of the nation's COVID-19 hotspots.

Of 3,046 employees, 56% had antibody testing and 20% underwent RT-PCR testing, with 12% receiving both.

Antibody tests were positive in 9.8% of employees, a rate that didn't vary by job title or work area and was significantly lower than for the Long Island general public, which had a rate of 16.7%. The authors concluded that the lower rate in healthcare workers, who are likely exposed to much higher virus levels, provides strong evidence that current PPE practices are protective, which is reassuring. However, they noted that the single-center results from a hospital that adequately supplied PPE to all health workers may not apply to all health settings.
Aug 11 JAMA Intern Med research letter

In the second study, researchers from the Cleveland VA Medical Center examined sources of exposure in health personnel infected with COVID-19 between the middle of March and the middle of July. They published their findings yesterday in the American Journal of Infection Control.

Over the 4-month study period, 1,534 healthcare workers were tested for COVID-19, 72.4% due to symptoms and 27.6% as part of contact tracing. Of those, 6.3% (96) were positive for the virus, including 93.4% who had symptoms and 6.3% who didn't.

Of those who tested positive, 25% had high-risk exposure at work and 14% were exposed in the community.

All of the higher-risk exposures to infected patients occurred in non–COVID-19 units, typically when the disease wasn't initially suspected. Higher-risk exposures to coworkers often involved gaps in compliance with masking in nonpatient areas such as nursing stations or break rooms. The authors added that a notable finding was that no staff working on the COVID-19 ward or in the intensive care unit contracted COVID-19, suggesting that compliance with universal masking was excellent. The team also noted that better detection in patients with atypical symptoms and reducing high-risk contacts among workers may help reduce the risk of COVID-19 infections in healthcare workers.
Aug 11 Am J Infect Control abstract