Following declarations from the US Department of Health and Human Services and World Health Organization ending the COVID-19 Public Health Emergency, the IARS COVID-19 Scientific Advisory Board (SAB) concluded its review of the scientific literature about SARS-CoV-2 in August. The SAB has reviewed more than 3,100 journal articles and published 1,076 article reviews over the past 42 months. It has been an enormous commitment from the SAB, and the IARS owes our dedicated physician volunteers a huge debt of gratitude for their unwavering participation in this initiative.

• COVID-19 Incidence and Mortality Among Unvaccinated and Vaccinated Persons Aged ≥12 Years by Receipt of Bivalent Booster Doses and Time Since Vaccination – 24 U.S. Jurisdictions, October 3, 2021-December 24, 2022. 2/9/2023. Johnson AG. MMWR Morb Mortal Wkly Rep.
  During the late BA.4/BA.5 period, unvaccinated persons had higher COVID-19 mortality and infection rates than persons receiving bivalent doses (mortality RR = 14.1 and infection RR = 2.8) and to a lesser extent persons vaccinated with only monovalent doses (mortality RR = 5.4 and infection RR = 2.5). Among older adults, mortality rates among unvaccinated persons were significantly higher than among those who had received a bivalent booster (65–79 years; RR = 23.7 and ≥80 years; 10.3) or a monovalent booster (65–79 years; 8.3 and ≥80 years; 4.2). The authors of this CDC MMWR conclude that, “For the best protection against severe COVID-19, all persons should stay up to date with recommended COVID-19 vaccination, including receipt of a bivalent booster by eligible persons.”
• Early Estimates of Bivalent mRNA Booster Dose Vaccine Effectiveness in Preventing Symptomatic SARS-CoV-2 Infection Attributable to Omicron BA.5- and XBB/XBB.1.5-Related Sublineages Among Immunocompetent Adults – Increasing Community Access to Testing Program, United States, December 2022-January 2023. 2/2/2023. Link-Gelles R. MMWR Morb Mortal Wkly Rep.
  This is a CDC report on the vaccine effectiveness (VE) against symptomatic infection of the bivalent mRNA vaccines against recent variants BA.5 and XBB/XBB1.5. Using data from the Increasing Community Access to Testing Program during December 1, 2022 to January 13, 2023, the authors used a test negative control format to evaluate 29,175 immunocompetent, adult patients with COVID-19-like symptoms who had received two or more monovalent mRNA vaccine/booster doses. In those who had additionally received a bivalent mRNA booster given 2 to 3 months earlier compared with no bivalent booster, VE in persons aged 18-49 years was 52% against symptomatic BA.5 infection and 48% against symptomatic XBB/XBB1.5 infection. Other age groups also had modest but real VE with a bivalent booster.
  SAB Comment: As featured in two articles in Newsletter Issue 159 (“Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Hospitalization Among Immunocompetent Adults Aged ≥65 Years – IVY Network, 18 States, September 8-November 30, 2022” and “Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults – VISION Network, Nine States, September-November 2022“) bivalent boosters reduce the incidence of hospitalizations and urgent care/emergency evaluations. This is the first evaluation of VE of the bivalent booster against symptomatic infections with the most recent BA.5 and XBB/XBB1.5 lineages and suggest all persons should stay up to date with recommended COVID-19 vaccines.
• SAB Comment: These well-done studies provide much anticipated bivalent vaccine effectiveness data, during a time when the omicron variants continue to evolve. Despite lab data that suggest viral neutralization after the bivalent vaccine is poor, these clinical studies document real but moderate protection against hospitalization and ED/UC encounters. This protection seems to be most prominent in older adults and was higher with increased time since the previous monovalent dose. Neither study addresses the long term durability of booster effectiveness. This information suggests that all persons should stay up to date with recommended COVID-19 vaccinations.
  • Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults – VISION Network, Nine States, September-November 2022. 12/29/22. Tenforde MW. MMWR Morb Mortal Wkly Rep.
    This is a bivalent vaccine effectiveness (VE) study from the VISION Network (nine US states) during September 13 to November 18, 2022, specifically looking at effectiveness against Emergency Department (ED) and Urgent Care (UC) encounters as well as hospitalizations. Among 78,303 ED/UC encounters in immunocompetent adults (over 18 years old), VE of the bivalent vaccine was 56% compared to no vaccination, 31% compared with receipt of last monovalent dose 2-4 months earlier, and 50% compared with receipt of last monovalent dose 11 months or more earlier. Among 15,527 hospitalizations of immunocompetent adults, the booster VE was similar to that in ED/UC patients.
  • Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Hospitalization Among Immunocompetent Adults Aged ≥65 Years – IVY Network, 18 States, September 8-November 30, 2022. 12/29/22. Surie D. MMWR Morb Mortal Wkly Rep.
    These IVY Network investigators from 18 US states sought to define vaccine effectiveness of the bivalent COVID-19 vaccine against hospitalization in elderly patients. Between September 8 and November 30, 2022, 798 patients hospitalized with a COVID-like illness were enrolled in this test-negative analysis. Among immunocompetent adults aged ≥65 years, a bivalent booster dose received after ≥2 monovalent mRNA doses provided good protection (73%) against COVID-19-associated hospitalization during this period of Omicron BA.5 or BQ.1/BQ.1.1 predominance. Compared to unvaccinated patients, the bivalent vaccine effectiveness was 84%. Substantial additional protection from a bivalent booster dose was observed when compared with remote monovalent-only mRNA vaccination.
• Paxlovid Associated with Decreased Hospitalization Rate Among Adults with COVID-19 — United States, April–September 2022. 12/2/22. Shah M. MMWR Morb Mortal Wkly Rep.
  This study reviewed electronic medical records to show that of 699,848 adults aged ≥18 years who were eligible for Paxlovid during April-August 2022, 28.4% received a Paxlovid prescription within 5 days of COVID-19 diagnosis (of whom 68.8% previously had received two or more doses of mRNA vaccine). Being prescribed Paxlovid was associated with a lower hospitalization rate among the overall study population (adjusted hazard ratio [aHR] = 0.49). The reduction was similar among those who had received ≥3 mRNA COVID-19 vaccines (aHR = 0.50) and across all age groups. The proportion of persons with in-hospital death was also lower among persons who received Paxlovid (0.01%) than among those who did not (0.04%). The authors state that Paxlovid should be prescribed to eligible adults to reduce the risk of COVID-19-associated hospitalization.
  SAB Comment: This study shows a significant real-world effect of Paxlovid during the Omicron era but with a reduction in hospitalization rate that is not nearly as large as that seen in the Paxlovid phase 2-3 trial done with unvaccinated patients during the Delta variant surge in 2021 (87.8% reduction of combined death or hospitalization).
• Effectiveness of a COVID-19 Additional Primary or Booster Vaccine Dose in Preventing SARS-CoV-2 Infection Among Nursing Home Residents During Widespread Circulation of the Omicron Variant – United States, February 14-March 27, 2022. 5/5/2022. Prasad N. MMWR Morb Mortal Wkly Rep.
  “Analysis … of data from approximately 15,000 skilled nursing facilities found that, compared with primary series vaccination only, an additional or booster dose provided greater protection (relative vaccine efficacy of 46.9%) against SARS-CoV-2 infection during Omicron variant predominance. ….All immune-compromised nursing home residents should receive an additional primary dose, and all nursing home residents should receive a booster dose, when eligible, to protect against COVID-19.” The analysis included 85,494 weekly reports of over 1.1 million residents from 14,758 Skilled Nursing Facilities. Over 90% had received mRNA COVID-19 vaccines. Approximately 22% had received only primary series vaccination, and 65% had received an additional or booster dose. Protection was slightly lower than during the Delta wave.
• Effectiveness of COVID-19 mRNA Vaccination in Preventing COVID-19-Associated Hospitalization Among Adults with Previous SARS-CoV-2 Infection – United States, June 2021-February 2022. 4/14/2022. Plumb ID. MMWR Morb Mortal Wkly Rep.
  A test-negative design was used in this CDC report to estimate effectiveness of COVID-19 mRNA vaccines in preventing subsequent COVID-19–associated hospitalization among adults aged ≥18 years with a previous positive nucleic acid amplification test or diagnosis of COVID-19. Using data from Cosmos, an aggregated data set from electronic health records, and vaccination status, 3,761 hospitalized case-patients were compared with 7,522 matched control-patients. After previous SARS-CoV-2 infection, estimated vaccine effectiveness against COVID-19–associated hospitalization was 47.5% after 2 vaccine doses and 57.8% after a booster dose during the Delta-predominant period, and 34.6% after 2 doses and 67.6% after a booster dose during the Omicron-predominant period. An increasing proportion of the U.S. population has had SARS-CoV-2 infection. COVID-19 vaccination offers additional protection against reinfection leading to hospitalization, with a booster dose(s) offering the highest level of protection.
• Cardiac Complications After SARS-CoV-2 Infection and mRNA COVID-19 Vaccination – PCORnet, United States, January 2021-January 2022. 4/7/2022. Block JP. MMWR Morb Mortal Wkly Rep.
  In this CDC report, data from electronic health records in 40 health care systems found that cardiac complications including myocarditis, pericarditis and multisystem inflammatory syndrome were rare but the risk was significantly higher after SARS-CoV-2 infection than after a first or second mRNA COVID-19 vaccination for both males and females in all age groups. Relative risk ratios varied among age, sex, specific complications, and first or second shot, and ranged from 1.8 to 115. The study population consisted of 15,215,178 persons aged ≥5 years, including 814,524 in the infection cohort. Confidence intervals were wide for some estimates due to the rarity of outcomes.
• Effectiveness of mRNA Vaccination in Preventing COVID-19-Associated Invasive Mechanical Ventilation and Death – United States, March 2021-January 2022. 3/24/22. Tenforde MW. MMWR Morb Mortal Wkly Rep.
  To better evaluate vaccine effectiveness (VE) of both mRNA vaccines in preventing COVID-19 invasive mechanical ventilation (IMV) and death, these authors from 21 US centers used a case control design to study 1440 COVID-19 patients between March 2021 and January 2022. Though vaccinated patients were older, had more comorbidities (especially immunocompromising conditions) than unvaccinated patients, receiving 2 or 3 doses of an mRNA vaccine was associated with a 90% reduction in risk for COVID-19 IMV or death. Protection of 3 mRNA vaccine doses during the period of Omicron predominance was 94%. The authors conclude that COVID-19 mRNA vaccines provide strong protection against severe COVID-19 resulting in respiratory failure or death.
• Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance — VISION Network, 10 States, Aug. 2/11/2022. Ferdinands J. MMWR Morb Mortal Wkly Rep.
  This CDC study examines mRNA vaccine effectiveness (VE) in 241,204 emergency department/urgent care (ED/UC) encounters and 93,408 hospitalizations across 10 states between August 26, 2021 and January 22, 2022. During both the Delta and Omicron periods, VE after receipt of a third dose was always higher than VE following a second dose; however, VE waned with increasing time since vaccination. During the Omicron-predominant period, mRNA vaccination was highly effective against both ED/UC encounters (VE = 87%) and hospitalizations (VE=91%) within 2 months after a third dose, but effectiveness declined to 66% for prevention of ED/UC encounters by the 4th month, and 78% for hospitalizations.
  SAB Comment: This study shows VE after a third dose of mRNA vaccine is excellent against Omicron, though it does wane somewhat with time. The takeaway is that all persons should stay up to date with recommended vaccinations.
• Laboratory-Confirmed COVID-19 Among Adults Hospitalized with COVID-19–Like Illness with Infection-Induced or mRNA Vaccine-Induced SARS-CoV-2 Immunity — Nine States, January–September 2021. 10/29/21. Bozio C. MMWR Morb Mortal Wkly Rep.
  This is a CDC-led study in nine US states which looked at the protective immunity produced by a COVID-19 illness compared to that of the mRNA vaccines. Among COVID-19-like illness hospitalizations among adults aged 18 years or older whose previous infection or vaccination occurred 90-179 days earlier, the adjusted odds of laboratory-confirmed COVID-19 among unvaccinated adults with previous SARS-CoV-2 infection were 5.49-fold higher than the odds among fully vaccinated recipients of an mRNA COVID-19 vaccine who had no previous documented infection. The authors conclude that all eligible persons should be vaccinated, including unvaccinated persons previously infected with SARS-CoV-2.
• Comparative Effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions – United States, March-August 2021. 9/23/21. Self WH. MMWR Morb Mortal Wkly Rep.
  This CDC study compared the real-life vaccine effectiveness (VE) against hospitalization of patients who had the three vaccines which were approved in the US. The vaccination status of 1,682 patients hospitalized with COVID-19 was compared with the vaccination status of 2,007 control patients admitted without COVID-19 during March to August 2021. VE against COVID-19 hospitalization was slightly lower for the Pfizer vaccine (88%) than the Moderna vaccine (93%), with this difference driven by a decline in VE after 120 days for the Pfizer but not for the Moderna vaccine. The Janssen (Johnson and Johnson) VE was 71%.
  SAB Comment: As viral variants were not determined in this study, and time since vaccination is increasing, the VE of various vaccines may be changing. Note that in the first week of May 2021, 1.6% of all COVID-19 infections in the US were thought to be caused by Delta, whereas in the last week of September, 99% of US cases were Delta.
• Effectiveness of COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Frontline Workers Before and During B.1.617.2 (Delta) Variant Predominance – Eight U.S. Locations, December 2020-August 2021. 8/26/21. Fowlkes A. MMWR Morb Mortal Wkly Rep.
  Data from the prospective frontline worker HEROES-RECOVER Cohorts showed that from 12/24/20-4/10/21 the Pfizer-BioNTech and Moderna vaccines were ~90% effective in preventing symptomatic and asymptomatic SARS-CoV-2 infection. Adjusted efficacy was 80%. The estimate was 85% among participants for whom less than 120 days had elapsed since full vaccination and 73% among those for whom 150 or more days had elapsed. Once Delta became the predominant variant, adjusted efficacy decreased from 91% to 66%. However, this trend should be interpreted with caution as effectiveness might also have declined due to greater time since vaccination. In addition, there were few weeks of observation and low numbers of infections.
• COVID-19 Vaccine Safety in Adolescents Aged 12-17 Years – United States, December 14, 2020-July 16, 2021. 8/5/21. Hause AM. MMWR Morb Mortal Wkly Rep.
  A statistical analysis of the Pfizer COVID-19 vaccine in children 12 years or older in the US demonstrated its safety. Reactions to the vaccine are uncommon and mostly mild. Myocarditis is one rare but severe reaction more common in boys after the second vaccination and that resulted in no deaths.
• Hospitalization of Adolescents Aged 12-17 Years with Laboratory-Confirmed COVID-19 – COVID-NET, 14 States, March 1, 2020-April 24, 2021. 6/10/21. Havers FP. MMWR Morb Mortal Wkly Rep.
  In the US, “Most COVID-19-associated hospitalizations occur in adults, but severe disease occurs in all age groups, including adolescents aged 12–17 years. COVID-19 adolescent hospitalization rates from COVID-NET peaked at 2.1 per 100,000 in early January 2021, declined to 0.6 in mid-March, and rose to 1.3 in April. Among hospitalized adolescents, nearly one third required intensive care unit admission, and 5% required invasive mechanical ventilation; no associated deaths occurred. Recent increased hospitalization rates in spring 2021 and potential for severe disease reinforce the importance of continued COVID-19 prevention measures, including vaccination and correct and consistent mask wearing among persons not fully vaccinated or when required.” –MMWR Summary
• COVID-19 Vaccine Breakthrough Infections Reported to CDC – United States, January 1-April 30, 2021. 5/27/21. CDC COVID-19 Vaccine Breakthrough Case Investigations Team. MMWR Morb Mortal Wkly Rep.
  In this brief weekly report, the CDC provides an important glimpse into the post-vaccination scenario in the US. During the 4 months ending April 30, 2021, a total of 10,262 breakthrough infections have been reported. Of those, 63% were female, median age 58 years, of which 27% were asymptomatic, 10% hospitalized and 2% died. By the end of the study, although 100 million individuals had been vaccinated in the US, SARS-CoV-2 transmission was still in full swing with 355,000 new cases daily. Variants were detected at a similar rate among vaccinated and non-vaccinated patients. Underreporting of asymptomatic cases and limited RNA sequencing represent current and future limitations to these statistics. Notably, beginning May 1, 2021, the CDC transitioned from monitoring all reported COVID-19 vaccine breakthrough infections to investigating only those among patients who are hospitalized. Monthly reports and additional information on vaccination breakthrough initiatives by the CDC can be found here.
• Provisional Mortality Data – United States, 2020. 4/8/2021. Ahmad FB. MMWR Morb Mortal Wkly Rep.
  The estimated age-adjusted death rate in the US increased by 15.9% from 2019 to 2020, representing the first increase since 2017. COVID-19 caused or contributed to 377,883 or 11.3% of total death and ranked third behind heart disease (21%) and cancer (17%). When sorted by age, race, ethnicity and sex, this report by the CDC’s National Vital Statistics System found age-adjusted death rates to be highest in the over 85-year old population, the non-Hispanic Black and the non-Hispanic American Indian or Alaska Native people. Males died at 33% higher rate from COVID than females.
  These provisional data are the result of a streamlined reporting mechanism which provides expanded mortality data for 2020 with a mere 4 month (prior 11 month) delay.
• Racial and Ethnic Disparities in COVID-19 Incidence by Age, Sex, and Period Among Persons Aged <25 Years – 16 U.S. Jurisdictions, January 1-December 31, 2020. 3/18/21. Van Dyke ME. MMWR Morb Mortal Wkly Rep.
  This is a data-rich CDC report on nearly 700,000 COVID-19 cases in young people from jurisdictions representing 23% of the US population. (Included cases represent 77% of total cases due to absent ethnicity data in the remainder.) Incidences among multiple minorities ranged from 0.77 to 4.57 relative to non-Hispanic Whites and disparities evolved during 2020. Large disparities January–April generally decreased May–December, primarily due to higher incidence among Whites. Children <10 rarely tested positive, however incidence increased stepwise from ages 10-24. The largest persistent disparities involved Native Hawaiian and Pacific Islanders, Native Americans, and Hispanics. Ethnic minorities often live in multigenerational homes and include essential workers unable to shelter at home. Equitable and timely access to testing, prevention, and vaccination is urged.
• Body Mass Index and Risk for COVID-19-Related Hospitalization, Intensive Care Unit Admission, Invasive Mechanical Ventilation, and Death – United States, March-December 2020. 3/11/2021. Kompaniyets L. MMWR Morb Mortal Wkly Rep.
  From March-December 2020, the authors evaluated the association between body mass index (BMI) and risk for severe COVID-19 outcomes in 148,494 adults who were diagnosed with COVID-19 during an emergency department or inpatient visit at 238 US hospitals. Of those patients, 28.3% were overweight and 50.8% were obese. Authors conclude that being overweight and obesity are risk factors for hospitalization, ICU admission, and death among patients aged ≥65 years. There was a downslope for death in patients with BMIs of 23.7 to 25.9; an upswing was similar for patients with a median age of 55 years at the dynamic point. The authors discuss the clinical and public health implications of higher BMI, the need for COVID-19 illness management, vaccine prioritization and policies to increase access to nutrition and physical activities to help address the increases in obesity severity.
• Association of State-Issued Mask Mandates and Allowing On-Premises Restaurant Dining with County-Level COVID-19 Case and Death Growth Rates — United States, March 1–December 31, 2020. 3/5/21. Guy GP. MMWR Morb Mortal Wkly Rep.
  During March 1-December 31, 2020, state-issued mask mandates applied in 2,313 (73.6%) of the 3,142 U.S. counties. Mandating masks was associated with a decrease in daily COVID-19 case and death growth rates within 20 days of implementation. During the study period, states allowed restaurants to reopen for on-premises dining in 3,076 (97.9%) U.S. counties. This was associated with an increase in daily COVID-19 case growth rates 41–100 days after implementation and an increase in daily death growth rates 61–100 days after implementation. The study did not distinguish between indoor and outdoor on-premises dining.
• Factors Associated with Positive SARS-CoV-2 Test Results in Outpatient Health Facilities and Emergency Departments Among Children and Adolescents Aged <18 Years – Mississippi, September-November 2020. 12/17/20. Hobbs CV. MMWR Morb Mortal Wkly Rep.
  This investigation included children and adolescents younger than 18 years who received RT-PCR testing for presence of SARS-CoV-2 in nasopharyngeal swab specimens at outpatient testing health care centers or the ED during September 1–November 5, 2020. Of 397 participants, children and adolescents who received positive test results for SARS-CoV-2 were more likely than were similarly aged participants who had negative test results to have had close contact with persons with COVID-19. Exposure was attributed to gatherings with persons outside the household, and a lack of consistent mask use in school. However, attending school or childcare was not associated with receiving positive SARS-CoV-2 test results.