COVID-19 Research at the KPNW Center for Health Research

The Kaiser Permanente Northwest Center for Health Research (CHR) has been conducting COVID-19 research since April 2020. Since that time, new findings have emerged, and new studies are underway at CHR and at Kaiser Permanente Northwest (KPNW).

Current studies

Since the start of the pandemic, CHR researchers under the direction of Distinguished Investigator Allison Naleway, PhD, have been involved in numerous regional and national studies on the safety and effectiveness of COVID-19 vaccines in real world settings outside of trials.

COVID-19 Vaccine Bivalent Booster

Under the direction of Distinguished Investigator Stephen Fortmann, MD, bivalent vaccines (those with two strains of the COVID-19 virus) as a booster were tested at KPNW to determine their safety, tolerability and immunogenicity. The bivalent boosters were found to be more effective at boosting the immune response than monovalent boosters, providing added protection against severe infection in people who previously had been vaccinated or boosted. This study is continuing for continuing observation and will likely end in late 2023.

CASCADIA

CHR, in collaboration the University of Washington, is enrolling 3,500 participants in the Portland/Vancouver (WA) and Seattle metropolitan areas to determine vaccine effectiveness against COVID-19. Participants in the CASCADIA prospective cohort study, which is funded by the Centers for Disease Control and Prevention (CDC), will complete baseline surveys, baseline and annual blood draws, and weekly nasal swabs, and share updated vaccination status and other information through monthly surveys. Each week, swab specimens will be tested for SARS-CoV-2 and other respiratory pathogens using the highly accurate real-time polymerase chain reaction test (RT-PCR), and additional testing will be conducted on blood specimens to determine immune response from infection and vaccination.

VISION Network

The VISION Network is a multistate collaboration between the Centers for Disease Control and Prevention (CDC) and health care systems with integrated medical, laboratory and vaccination records. The VISION Network performs assessments of COVID-19 vaccine effectiveness in emergency department, urgent care and hospital settings. CHR researchers have contributed to numerous reviews.

Recent publications:

Vaccine Safety Datalink

The Vaccine Safety Datalink (VSD) is a three-decade long research network established to conduct post-licensure observational studies of vaccine safety. The VSD is a collaboration of KPNW and twelve other integrated health systems and the Centers for Disease Control and Prevention. The VSD is led at CHR by Allison Naleway, PhD, Distinguished Investigator. The VSD utilizes standardized electronic health record-derived data on insurance enrollment, demographic characteristics, medical encounters from all settings, vaccination and prescribed medications to examine the safety of vaccines, including vaccines against COVID-19.

Near Real-Time Safety Surveillance

Since 2006, the Vaccine Safety Datalink has conducted weekly vaccine surveillance known as Rapid Cycle Analysis. When the first COVID-19 vaccine was administered in December 2020, weekly monitoring of this new vaccine started immediately. VSD investigators developed an internal dashboard to facilitate visualization and rapid reviews of large weekly automated vaccine safety surveillance data on COVID-19 vaccines. This report includes interim findings on risk of adverse events after receipt of mRNA COVID-19 vaccines through June 2021.

Another VSD study identified and tracked cases and incidence of Guillain-Barre Syndrome (GBS) following COVID-19 vaccination and assessed the risk of GBS after vaccination for Ad.26.COV2.S (Janssen) and mRNA vaccines. GBS has occurred in the past following other vaccinations so it was important to study it in this context.

The VSD updated previously reported comparisons of myocarditis and pericarditis incidence during a risk interval after mRNA vaccination versus a later comparison interval and presented new head-to-head comparisons assessing whether risk differs between the two mRNA vaccines.

COVID-19 Vaccine Safety in Pregnancy

The Vaccine Safety Datalink is one of four systems used by the CDC to monitor the safety of COVID-19 vaccines after pregnancy.

A retrospective cohort study of live births from eight Vaccine Safety Datalink health care organizations evaluated risks for preterm birth (<37 weeks' gestation) and small-for-gestational-age at birth (birthweight <10th percentile for gestational age) after COVID-19 vaccination (receipt of ≥1 COVID-19 vaccine doses) during pregnancy. Results consistently showed no increased risk when stratified by mRNA COVID-19 vaccine dose, or by second or third trimester vaccination, compared with risk among unvaccinated pregnant women.

In a study of COVID-19 vaccines and acute adverse events, the VSD evaluated the incidences of 25 medically attended events (known reactogenic adverse events and clinically serious outcomes) among vaccinated women compared with unvaccinated matched controls. COVID-19 vaccines were not associated with an increased risk of the clinically serious acute adverse events that were evaluated.

The VSD conducted case-control surveillance of COVID-19 vaccination during pregnancy and spontaneous abortion. Among women with spontaneous abortions, the odds of COVID-19 vaccine exposure were not increased in the prior 28 days compared with women with ongoing pregnancies. Another study aimed to understand how time since vaccine roll-out or other methodologic factors could affect results.

COVID-19 Vaccination in Children

The VSD studied the safety of COVID-19 vaccination among children ages 5-11, analyzing data from three safety monitoring systems to study v-safe, the voluntary smartphone-based system that monitors reactions and health effects; the Vaccine Adverse Events Reporting System (VAERS), the national spontaneous reporting system comanaged by the CDC and Food and Drug Administration; and the Vaccine Safety Datalink.

Data Mining Safety Assessments

Complementing its real-time surveillance for pre-specified health outcomes using pre-specified risk intervals, the VSD conducts tree-based data-mining to look for clustering of a broad range of health outcomes after COVID-19 vaccination. In one study, the VSD used this untargeted, hypothesis-generating approach to assess the safety of first booster doses of Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273) and Janssen (Ad26.COV2.S) COVID-19 vaccines.

Completed Studies

Remdesivir

Immediately after COVID-19 was declared a global pandemic, CHR launched a randomized clinical trial that tested the antiviral drug remdesivir (brand name Veklury) as a treatment for Kaiser Permanente Northwest members hospitalized with COVID.

Distinguished Investigator Richard Mularski, MD, lead the study comparing treatment for five days with treatment for 10 days. Distinguished Investigator Stephen Fortmann, MD, a study Co-Investigator, reported that equivalent results between the groups led health care providers to select a five-day regimen of remdesivir for members hospitalized with COVID in most cases.

A different remdesivir study conducted by the National Institutes of Health (NIH), which CHR was not a part of, found that patients with severe COVID who received remdesivir recovered more quickly than patients who received a placebo.

Two more studies funded by NIH and led by Dr. Mularski were completed at KPNW’s Sunnyside and Westside hospitals. These studies tested the addition of other treatments to remdesivir.

The first of these studies centered on baricitinib (brand name Olumiant), a drug used to treat rheumatoid arthritis. More than 1,000 people were enrolled in the study, which compared remdesivir plus a placebo with remdesivir plus baricitinib.

The results, published in December 2020 in the New England Journal of Medicine, showed that combining remdesivir and baricitinib was a more effective way to treat COVID-19 than remdesivir alone. More patients recovered in the group receiving the combination, and patients in this group had a shorter time to recovery. Hospitalized patients needing oxygen appeared to benefit the most.

Kaiser Permanente Northwest and CHR were the only KP sites nationally participating in this trial.

The second study compared remdesivir plus a placebo with remdesivir plus interferon-beta 1a (brand name Rebif), a drug used to treat multiple sclerosis. The study did not find a benefit of adding interferon to remdesivir in treating patients hospitalized with COVID-19.

COVID-19 Vaccine vs Placebo

This was the first trial of the innovative mRNA-based vaccine against COVID-19 (BNT162b2) developed by Pfizer and BioNTech, which has since been given to millions of people. It began in July 2020 — 6 months after the COVID-19 virus (SARS-CoV-2) was identified, which was an unprecedented speed. The study enrolled more than 44,000 individuals worldwide, including 98 KPNW members. Half of the members received the active vaccine (the first individuals in Portland to receive it) and half the placebo, and no one, including the CHR investigators (led by Dr. Fortmann), was aware of who received the vaccine and who the placebo.

Thanks in part to the large number of participants, the trial provided clear evidence that the vaccine was safe and effective. It prevented over 90% of infections; as well, virtually none of those vaccinated became sick enough to need hospitalization, and none died. The vaccine was approved by the FDA and CDC for use in the public less than 6 months after the trial started. After it was found to be effective, KPNW was authorized to “break the blind” and give the placebo group the active vaccine in December 2020.

COVID-19 Vaccine Booster vs Placebo

This study tested whether a booster dose (of BNT162b2) was effective in preventing COVID-19 among healthy individuals who had received two doses of the vaccine at least 6 months previously. The study helped establish the effectiveness of such a strategy. Dr. Fortmann led the study at CHR.

RECOVER-HEROES

The RECOVER-HEROES network was a CDC-funded, multi-state prospective cohort study involving health care personnel, first responders and other essential and frontline workers in Portland who were followed from Spring 2020 to early 2023. The objective was to examine the effectiveness of COVID vaccines in preventing infection and/or reducing the severity of SARS-CoV-2 infection. The vaccines were found to be highly effective in preventing infection.

Key publications:

VITALS

The Viral Testing and Local Surveillance study (VITALS) was a CDC-funded project to explore potential gaps in clinician-ordered testing for SARS-CoV-2. One aim was to describe the incidence, clinical testing patterns and characteristics of less severe COVID-19 in KPNW’s ambulatory and virtual care settings. Using comprehensive electronic health records, researchers were able to describe the clinical-care trajectory of members who presented for COVID-19-related care through virtual visits. The second aim was to enhance surveillance of COVID-19 by testing nasal swabs for both influenza and COVID-19 from people who were referred for COVID-19 testing but didn’t complete the test at the time.

eESPI

The Epidemiology of SARS-CoV-2 in Pregnancy and Infancy (ESPI) Network: Electronic Cohort (eESPI) collected health record data of a retrospective cohort of pregnant women and their infants who were born during the COVID-19 pandemic. This CDC-funded network used data from a large, diverse cohort of pregnant people receiving antenatal and peripartum care at KPNW and two other integrated health care networks in the United States during the first year of the COVID-19 pandemic.

ESPI publications:

COVID-19 Vaccination and Mortality

To assess mortality not associated with COVID-19 after vaccination against the disease in a general population setting, members from seven VSD sites, including the Center for Health Research, conducted a cohort study among approximately 11 million people enrolled in VSD sites. After standardizing mortality rates by age and sex, the study found that COVID-19 vaccine recipients had lower non-COVID-19 mortality than did unvaccinated individuals.