Antibody response to symptomatic infection with SARS-CoV-2 Omicron variant viruses, December 2021 to June 2022 (preprint)

To describe humoral immune responses to symptomatic SARS-CoV-2 infection, we assessed immunoglobulin G binding antibody levels using a commercial multiplex bead assay against SARS-CoV-2 ancestral spike protein receptor binding domain (RBD) and nucleocapsid protein (N). We measured binding antibody units per mL (BAU/mL) during acute illness within 5 days of illness onset and during convalescence in 105 ambulatory patients with laboratory-confirmed SARS-CoV-2 infection with Omicron variant viruses. Comparing acute- to convalescent phase antibody concentrations, geometric mean anti-N antibody concentrations increased 47-fold from 5.5 to 259 BAU/mL. Anti-RBD antibody concentrations increased 2.5-fold from 1258 to 3189 BAU/mL.

Anti-SARS-CoV-2 Antibody Levels Associated with COVID-19 Protection in Outpatients Tested for SARS-CoV-2, US Flu VE Network, October 2021 to June 2022 (preprint)

BackgroundWe assessed the association between antibody concentration [≤]5 days of symptom onset and COVID-19 illness among patients enrolled in a test-negative study MethodsFrom October 2021[boxh]June 2022, study sites in seven states enrolled and tested respiratory specimens from patients of all ages presenting with acute respiratory illness for SARS-CoV-2 infection using rRT-PCR. In blood specimens, we measured concentration of anti- SARS-CoV-2 antibodies against the ancestral strain spike protein receptor binding domain (RBD) and nucleocapsid (N) antigens in standardized binding antibody units (BAU/mL). Percent reduction in odds of symptomatic COVID-19 by anti-RBD antibody was estimated using logistic regression modeled as (1-adjusted odds ratio of COVID-19)x100, adjusting for COVID-19 vaccination status, age, site, and high-risk exposure. ResultsA total of 662 (33%) of 2,018 symptomatic patients tested positive for acute SARS- CoV-2 infection. During the Omicron-predominant period, geometric mean anti-RBD binding antibody concentrations measured 823 BAU/mL (95%CI:690[boxh]981) among COVID-19 case- patients versus 1,189 BAU/mL (95%CI:1,050[boxh]1,347) among SARS-CoV-2 test-negative patients. In the adjusted logistic regression, increasing levels of anti-RBD antibodies were associated with reduced odds of COVID-19 for both Delta and Omicron infections. ConclusionHigher anti-RBD antibodies in patients were associated with protection against symptomatic COVID-19 during emergence of SARS-CoV-2 Delta and Omicron variants.

Work Attendance during Acute Respiratory Illness Before and During the COVID-19 Pandemic, United States, 2018-2022 (preprint)

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza viruses can be transmitted by infected persons who are pre-symptomatic or symptomatic. To assess impact of the COVID-19 pandemic on work attendance during illness, we analyzed prospectively collected data from persons with acute respiratory illness (ARI) enrolled in a multi-state study during 2018-2022. Persons with prior experience working from home were significantly less likely than those without this experience to work onsite on the day before illness and during the first 3 days of illness; the effect was more pronounced for the COVID-19 pandemic period than the pre-pandemic influenza seasons. Persons with influenza or COVID-19 were significantly less likely to work onsite than persons with other ARIs. Among persons for whom positive COVID-19 test results were available by the second or third day of illness, few worked onsite. Work-from-home policies may reduce the likelihood of workplace exposures to respiratory viruses.

Prior SARS-CoV-2 Infection and COVID-19 Vaccine Effectiveness against Outpatient Illness during Widespread Circulation of SARS-CoV-2 Omicron Variant, US Flu VE Network (preprint)

Background: We estimated combined protection conferred by prior SARS-CoV-2 infection and COVID-19 vaccination against COVID-19-associated acute respiratory illness (ARI). Methods: During SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant circulation between October 2021 and April 2022, prospectively enrolled adult patients with outpatient ARI had respiratory and filter paper blood specimens collected for SARS-CoV-2 molecular testing and serology. Dried blood spots were tested for immunoglobulin-G antibodies against SARS-CoV-2 nucleocapsid (NP) and spike protein receptor binding domain antigen using a validated multiplex bead assay. Evidence of prior SARS-CoV-2 infection also included documented or self-reported laboratory-confirmed COVID-19. We used documented COVID-19 vaccination status to estimate vaccine effectiveness (VE) by multivariable logistic regression by prior infection status. Results: 455 (29%) of 1577 participants tested positive for SARS-CoV-2 infection at enrollment; 209 (46%) case-patients and 637 (57%) test-negative patients were NP seropositive, had documented previous laboratory-confirmed COVID-19, or self-reported prior infection. Among previously uninfected patients, three-dose VE was 97% (95% confidence interval [CI], 60%, 99%) against Delta, but not statistically significant against Omicron. Among previously infected patients, three-dose VE was 57% (CI, 20%, 76%) against Omicron; VE against Delta could not be estimated. Conclusions: Three mRNA COVID-19 vaccine doses provided additional protection against SARS-CoV-2 Omicron variant-associated illness among previously infected participants.

Population-based hospitalization burden estimates for respiratory viruses, 2015-2019 (preprint)

Background: Acute respiratory infections (ARIs) result in millions of illnesses and hundreds of thousands of hospitalizations annually in the US. The responsible viruses include influenza, parainfluenza, human metapneumovirus, coronaviruses, respiratory syncytial virus (RSV), and human rhinoviruses. This study estimated the population-based hospitalization burden of 18 respiratory viruses (RV) over 4 years, from 7/1/2015 to 6/30/2019 among adults ≥18 years of age for Allegheny County (Pittsburgh), Pennsylvania. Methods: We used population-based statewide hospital discharge data, health system electronic medical record (EMR) data for RV tests, census data, and a published method to calculate burden. Results: Among 26,211 eligible RV tests, 67.6% were negative for any virus. The viruses detected were rhinovirus/enterovirus (2,552; 30.1%), influenza A (2,299; 27.1%), RSV (1,082; 12.7%), human metapneumovirus (832; 9.8%), parainfluenza (601; 7.1%), influenza B (565; 6.7%), non-SARS-CoV-2 coronavirus (420; 4.9% 1.5 years of data available), and adenovirus (136; 1.6%). Most tests were among female (58%) and white (71%) patients with 60% of patients ≥65 years, 24% 50-64 years and 16% 18-49 years. The annual burden, ranged from 137-174/100,000 population for rhinovirus/enterovirus; 99-182/100,000 for influenza A; 56-81/100,000 for RSV. Among adults <65 years, rhinovirus/enterovirus hospitalization burden was higher than influenza A; whereas the reverse was true for adults ≥65 years. RV hospitalization burden increased with increasing age. Conclusions: These virus-specific ARI population-based hospital burden estimates showed significant non-influenza burden. These estimates can serve as the basis for several areas of research that are essential for setting funding priorities and guiding public health policy.

Agent-based Investigation of the Impact of Low Rates of Influenza on Next Season Influenza Infections (preprint)

Introduction Interventions to curb the spread of SARS-CoV-2 during the 2020-21 influenza season essentially eliminated influenza during that season. Given waning antibody titers over time, future residual population immunity against influenza will be reduced. The implication for the subsequent 2021-22 influenza season is unknown. Methods We used an agent-based model of influenza implemented in the FRED (Framework for Reconstructing Epidemiological Dynamics) simulation platform to estimate cases and hospitalization over two succeeding influenza seasons. The model uses a synthetic population to represent an actual population, and individual interactions in workplaces, school, households and neighborhoods. The impact of reduced residual immunity was estimated as a consequence of increased protective measures (e.g., social distancing and school closure) in the first season. The impact was contrasted by the level of similarity (cross-immunity) between influenza strains over the seasons. Results When the second season strains were dissimilar to the first season (have a low level of cross immunity), a low first season has limited impact on second season cases. When a high level of cross-immunity exists between strains in the 2 seasons, the first season has a much greater impact on the second season. In both cases this is modified by the transmissibility of strains in the 2 seasons. In the context of the 2021-22 season, the worst case scenario is a highly transmissible strain causing increased cases and hospitalizations over average influenza seasons, with a possible significant increase in cases in some scenarios. The most likely overall scenario for 2021-22 is a more modest increase in flu cases over an average season. Discussion Given the light 2020-21 season, we found that a large, compensatory second season might occur in 2021-22, depending on cross-immunity from past infection and transmissibility of strains. Furthermore, we found that enhanced vaccine coverage could reduce this high, compensatory season. Young children may be especially at risk in 2021-22 since very young children were unlikely to have had any exposure to infection and most immunity in that age group would be from vaccination, which wanes quickly.