Immune response kinetics to SARS-CoV-2 infection and COVID-19 vaccination among nursing home residents-Georgia, October 2020-July 2022.

BACKGROUND: Understanding the immune response kinetics to SARS-CoV-2 infection and COVID-19 vaccination is important in nursing home (NH) residents, a high-risk population. METHODS: An observational longitudinal evaluation of 37 consenting vaccinated NH residents with/without SARS-CoV-2 infection from October 2020 to July 2022 was conducted to characterize the immune response to spike protein due to infection and/or mRNA COVID-19 vaccine. Antibodies (IgG) to SARS-CoV-2 full-length spike, nucleocapsid, and receptor binding domain protein antigens were measured, and surrogate virus neutralization capacity was assessed using Meso Scale Discovery immunoassays. The participant's spike exposure status varied depending on the acquisition of infection or receipt of a vaccine dose. Longitudinal linear mixed effects modeling was used to describe trajectories based on the participant's last infection or vaccination; the primary series mRNA COVID-19 vaccine was considered two spike exposures. Mean antibody titer values from participants who developed an infection post receipt of mRNA COVID-19 vaccine were compared with those who did not. In a subset of participants (n = 15), memory B cell (MBC) S-specific IgG (%S IgG) responses were assessed using an ELISPOT assay. RESULTS: The median age of the 37 participants at enrollment was 70.5 years; 30 (81%) had prior SARS-CoV-2 infection, and 76% received Pfizer-BioNTech and 24% Moderna homologous vaccines. After an observed augmented effect with each spike exposure, a decline in the immune response, including %S IgG MBCs, was observed over time; the percent decline decreased with increasing spike exposures. Participants who developed an infection at least two weeks post-receipt of a vaccine were observed to have lower humoral antibody levels than those who did not develop an infection post-receipt. CONCLUSIONS: These findings suggest that understanding the durability of immune responses in this vulnerable NH population can help inform public health policy regarding the timing of booster vaccinations as new variants display immune escape.

Endemic coronavirus infections are associated with strong homotypic immunity in a US cohort of children from birth to 4 years.

BACKGROUND: The endemic coronaviruses OC43, HKU1, NL63 and 229E cause cold-like symptoms and are related to SARS-CoV-2, but their natural histories are poorly understood. In a cohort of children followed from birth to 4 years, we documented all coronavirus infections, including SARS-CoV-2, to understand protection against subsequent infections with the same virus (homotypic immunity) or a different coronavirus (heterotypic immunity). METHODS: Mother-child pairs were enrolled in metropolitan Cincinnati during the third trimester of pregnancy in 2017-18. Mothers reported their child's socio-demographics, risk factors, and weekly symptoms. Mid-turbinate nasal swabs were collected weekly. Blood was collected at 6 weeks, 6, 12, 18, 24 months and annually thereafter. Infections were detected by testing nasal swabs by an RT-PCR multi-pathogen panel and by serum IgG responses. Health care visits were documented from pediatric records. Analysis was limited to 116 children with high sample adherence. Re-consent for monitoring SARS-CoV-2 infections from June 2020 through November 2021 was obtained for 74 (64%) children. RESULTS: We detected 345 endemic coronavirus infections (1.1 infections/child-year) and 21 SARS-CoV-2 infections (0.3 infections/child-year). Endemic coronavirus and SARS-CoV-2 infections were asymptomatic or mild. Significant protective homotypic immunity occurred after a single infection with OC43 (77%) and HKU1 (84%), and after two infections with NL63 (73%). No heterotypic protection against endemic coronaviruses or SARS-CoV-2 was identified. CONCLUSIONS: Natural coronavirus infections were common and resulted in strong homotypic immunity but not heterotypic immunity against other coronaviruses, including SARS-CoV-2. Endemic coronavirus and SARS-CoV-2 infections in this US cohort were typically asymptomatic or mild.

Examination of SARS-CoV-2 serological test results from multiple commercial and laboratory platforms with an in-house serum panel.

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for COVID-19 diagnosis. Serological tests are valuable tools for serosurveillance programs and establishing correlates of protection from disease. This study evaluated the performance of one in-house enzyme linked immunosorbent assay (ELISA) utilizing the pre-fusion stabilized ectodomain of SARS-CoV-2 spike (S), two commercially available chemiluminescence assays Ortho VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Abbott SARS-CoV-2 IgG assay and one commercially available Surrogate Virus Neutralization Test (sVNT), GenScript USA Inc., cPass SARS-CoV-2 Neutralization Antibody Detection Kit for the detection of SARS-CoV-2 specific antibodies. Using a panel of rRT-PCR confirmed COVID-19 patients' sera and a negative control group as a reference standard, all three immunoassays demonstrated high comparable positivity rates and low discordant rates. All three immunoassays were highly sensitive with estimated sensitivities ranging from 95.4-96.6 %. ROC curve analysis indicated that all three immunoassays had high diagnostic accuracies with area under the curve (AUC) values ranging from 0.9698 to 0.9807. High positive correlation was demonstrated among the conventional microneutralization test (MNT) titers and the sVNT inhibition percent values. Our study indicates that independent evaluations are necessary to optimize the overall utility and the interpretation of the results of serological tests. Overall, we demonstrate that all serological tests evaluated in this study are suitable for the detection of SARS-CoV-2 antibodies.

Factors Associated With Prolonged Respiratory Virus Detection From Polymerase Chain Reaction of Nasal Specimens Collected Longitudinally in Healthy Children in a US Birth Cohort.

BACKGROUND: Respiratory viral shedding is incompletely characterized by existing studies due to the lack of longitudinal nasal sampling and limited inclusion of healthy/asymptomatic children. We describe characteristics associated with prolonged virus detection by polymerase chain reaction (PCR) in a community-based birth cohort. METHODS: Children were followed from birth to 2 years of age in the PREVAIL cohort. Weekly nasal swabs were collected and tested using the Luminex Respiratory Pathogen Panel. Weekly text surveys were administered to ascertain the presence of acute respiratory illnesses defined as fever and/or cough. Maternal reports and medical chart abstractions identified healthcare utilization. Prolonged virus detection was defined as a persistently positive test lasting ≥4 weeks. Factors associated with prolonged virus detection were assessed using mixed effects multivariable logistic regression. RESULTS: From a sub-cohort of 101 children with ≥70% weekly swabs collected, a total of 1489 viral infections were detected. Prolonged virus detection was found in 23.4% of viral infections overall, 39% of bocavirus infections, 33% of rhinovirus/enterovirus infections, 14% of respiratory syncytial virus (RSV) A infections, and 7% of RSV B infections. No prolonged detection was found for influenza virus A or B, coronavirus 229E or HKU1, and parainfluenza virus 2 or 4 infections. First-lifetime infection with each virus, and co-detection of another respiratory virus were significantly associated with prolonged detection, while symptom status, child sex, and child age were not. CONCLUSIONS: Prolonged virus detection was observed in 1 in 4 viral infections in this cohort of healthy children and varied by pathogen, occurring most often for bocavirus and rhinovirus/enterovirus. Evaluating the immunological basis of how viral co-detections and recurrent viral infections impact duration of virus detection by PCR is needed to better understand the dynamics of prolonged viral shedding.

SARS-CoV-2 shedding and evolution in patients who were immunocompromised during the omicron period: a multicentre, prospective analysis.

BACKGROUND: Prolonged SARS-CoV-2 infections in people who are immunocompromised might predict or source the emergence of highly mutated variants. The types of immunosuppression placing patients at highest risk for prolonged infection have not been systematically investigated. We aimed to assess risk factors for prolonged SARS-CoV-2 infection and associated intrahost evolution. METHODS: In this multicentre, prospective analysis, participants were enrolled at five US medical centres. Eligible patients were aged 18 years or older, were SARS-CoV-2-positive in the previous 14 days, and had a moderately or severely immunocompromising condition or treatment. Nasal specimens were tested by real-time RT-PCR every 2-4 weeks until negative in consecutive specimens. Positive specimens underwent viral culture and whole genome sequencing. A Cox proportional hazards model was used to assess factors associated with duration of infection. FINDINGS: From April 11, 2022, to Oct 1, 2022, 156 patients began the enrolment process, of whom 150 were enrolled and included in the analyses. Participants had B-cell malignancy or anti-B-cell therapy (n=18), solid organ transplantation or haematopoietic stem-cell transplantation (HSCT; n=59), AIDS (n=5), non-B-cell malignancy (n=23), and autoimmune or autoinflammatory conditions (n=45). 38 (25%) participants were real-time RT-PCR-positive and 12 (8%) were culture-positive 21 days or longer after initial SARS-CoV-2 detection or illness onset. Compared with the group with autoimmune or autoinflammatory conditions, patients with B-cell dysfunction (adjusted hazard ratio 0·32 [95% CI 0·15-0·64]), solid organ transplantation or HSCT (0·60 [0·38-0·94]), and AIDS (0·28 [0·08-1·00]) had longer duration of infection, defined as time to last positive real-time RT-PCR test. There was no significant difference in the non-B-cell malignancy group (0·58 [0·31-1·09]). Consensus de novo spike mutations were identified in five individuals who were real-time RT-PCR-positive longer than 56 days; 14 (61%) of 23 were in the receptor-binding domain. Mutations shared by multiple individuals were rare (<5%) in global circulation. INTERPRETATION: In this cohort, prolonged replication-competent omicron SARS-CoV-2 infections were uncommon. Within-host evolutionary rates were similar across patients, but individuals with infections lasting longer than 56 days accumulated spike mutations, which were distinct from those seen globally. Populations at high risk should be targeted for repeated testing and treatment and monitored for the emergence of antiviral resistance. FUNDING: US Centers for Disease Control and Prevention.

Monoclonal Antibodies as SARS-CoV-2 Serology Standards: Experimental Validation and Broader Implications for Correlates of Protection.

COVID-19 has highlighted challenges in the measurement quality and comparability of serological binding and neutralization assays. Due to many different assay formats and reagents, these measurements are known to be highly variable with large uncertainties. The development of the WHO international standard (WHO IS) and other pool standards have facilitated assay comparability through normalization to a common material but does not provide assay harmonization nor uncertainty quantification. In this paper, we present the results from an interlaboratory study that led to the development of (1) a novel hierarchy of data analyses based on the thermodynamics of antibody binding and (2) a modeling framework that quantifies the probability of neutralization potential for a given binding measurement. Importantly, we introduced a precise, mathematical definition of harmonization that separates the sources of quantitative uncertainties, some of which can be corrected to enable, for the first time, assay comparability. Both the theory and experimental data confirmed that mAbs and WHO IS performed identically as a primary standard for establishing traceability and bridging across different assay platforms. The metrological anchoring of complex serological binding and neuralization assays and fast turn-around production of an mAb reference control can enable the unprecedented comparability and traceability of serological binding assay results for new variants of SARS-CoV-2 and immune responses to other viruses.

Use of Updated COVID-19 Vaccines 2023-2024 Formula for Persons Aged ≥6 Months: Recommendations of the Advisory Committee on Immunization Practices - United States, September 2023.

COVID-19 vaccines protect against severe COVID-19-associated outcomes, including hospitalization and death. As SARS-CoV-2 has evolved, and waning vaccine effectiveness has been noted, vaccine formulations and policies have been updated to provide continued protection against severe illness and death from COVID-19. Since September 2022, bivalent mRNA COVID-19 vaccines have been recommended in the United States, but the variants these vaccines protect against are no longer circulating widely. On September 11, 2023, the Food and Drug Administration (FDA) approved the updated (2023-2024 Formula) COVID-19 mRNA vaccines by Moderna and Pfizer-BioNTech for persons aged ≥12 years and authorized these vaccines for persons aged 6 months-11 years under Emergency Use Authorization (EUA). On October 3, 2023, FDA authorized the updated COVID-19 vaccine by Novavax for use in persons aged ≥12 years under EUA. The updated COVID-19 vaccines include a monovalent XBB.1.5 component, which is meant to broaden vaccine-induced immunity and provide protection against currently circulating SARS-CoV-2 XBB-sublineage variants including against severe COVID-19-associated illness and death. On September 12, 2023, the Advisory Committee on Immunization Practices recommended vaccination with updated COVID-19 vaccines for all persons aged ≥6 months. These recommendations will be reviewed as new evidence becomes available or new vaccines are approved and might be updated.

Early Detection and Surveillance of the SARS-CoV-2 Variant BA.2.86 - Worldwide, July-October 2023.

Early detection of emerging SARS-CoV-2 variants is critical to guiding rapid risk assessments, providing clear and timely communication messages, and coordinating public health action. CDC identifies and monitors novel SARS-CoV-2 variants through diverse surveillance approaches, including genomic, wastewater, traveler-based, and digital public health surveillance (e.g., global data repositories, news, and social media). The SARS-CoV-2 variant BA.2.86 was first sequenced in Israel and reported on August 13, 2023. The first U.S. COVID-19 case caused by this variant was reported on August 17, 2023, after a patient received testing for SARS-CoV-2 at a health care facility on August 3. In the following month, eight additional U.S. states detected BA.2.86 across various surveillance systems, including specimens from health care settings, wastewater surveillance, and traveler-based genomic surveillance. As of October 23, 2023, sequences have been reported from at least 32 countries. Continued variant tracking and further evidence are needed to evaluate the full public health impact of BA.2.86. Timely genomic sequence submissions to global public databases aided early detection of BA.2.86 despite the decline in the number of specimens being sequenced during the past year. This report describes how multicomponent surveillance and genomic sequencing were used in real time to track the emergence and transmission of the BA.2.86 variant. This surveillance approach provides valuable information regarding implementing and sustaining comprehensive surveillance not only for novel SARS-CoV-2 variants but also for future pathogen threats.

SARS-CoV-2 shedding and evolution in immunocompromised hosts during the Omicron period: a multicenter prospective analysis.

Background: Prolonged SARS-CoV-2 infections in immunocompromised hosts may predict or source the emergence of highly mutated variants. The types of immunosuppression placing patients at highest risk for prolonged infection and associated intrahost viral evolution remain unclear. Methods: Adults aged ≥18 years were enrolled at 5 hospitals and followed from 4/11/2022 - 2/1/2023. Eligible patients were SARS-CoV-2-positive in the previous 14 days and had a moderate or severely immunocompromising condition or treatment. Nasal specimens were tested by rRT-PCR every 2-4 weeks until negative in consecutive specimens. Positive specimens underwent viral culture and whole genome sequencing. A Cox proportional hazards model was used to assess factors associated with duration of infection. Results: We enrolled 150 patients with: B cell malignancy or anti-B cell therapy (n=18), solid organ or hematopoietic stem cell transplant (SOT/HSCT) (n=59), AIDS (n=5), non-B cell malignancy (n=23), and autoimmune/autoinflammatory conditions (n=45). Thirty-eight (25%) were rRT-PCR-positive and 12 (8%) were culture-positive ≥21 days after initial SARS-CoV-2 detection or illness onset. Patients with B cell dysfunction had longer duration of rRT-PCR-positivity compared to those with autoimmune/autoinflammatory conditions (aHR 0.32, 95% CI 0.15-0.64). Consensus (>50% frequency) spike mutations were identified in 5 individuals who were rRT-PCR-positive >56 days; 61% were in the receptor-binding domain (RBD). Mutations shared by multiple individuals were rare (<5%) in global circulation. Conclusions: In this cohort, prolonged replication-competent Omicron SARS-CoV-2 infections were uncommon. Within-host evolutionary rates were similar across patients, but individuals with infections lasting >56 days accumulated spike mutations, which were distinct from those seen globally.

Genomic Surveillance for SARS-CoV-2 Variants: Circulation of Omicron Lineages - United States, January 2022-May 2023.

CDC has used national genomic surveillance since December 2020 to monitor SARS-CoV-2 variants that have emerged throughout the COVID-19 pandemic, including the Omicron variant. This report summarizes U.S. trends in variant proportions from national genomic surveillance during January 2022-May 2023. During this period, the Omicron variant remained predominant, with various descendant lineages reaching national predominance (>50% prevalence). During the first half of 2022, BA.1.1 reached predominance by the week ending January 8, 2022, followed by BA.2 (March 26), BA.2.12.1 (May 14), and BA.5 (July 2); the predominance of each variant coincided with surges in COVID-19 cases. The latter half of 2022 was characterized by the circulation of sublineages of BA.2, BA.4, and BA.5 (e.g., BQ.1 and BQ.1.1), some of which independently acquired similar spike protein substitutions associated with immune evasion. By the end of January 2023, XBB.1.5 became predominant. As of May 13, 2023, the most common circulating lineages were XBB.1.5 (61.5%), XBB.1.9.1 (10.0%), and XBB.1.16 (9.4%); XBB.1.16 and XBB.1.16.1 (2.4%), containing the K478R substitution, and XBB.2.3 (3.2%), containing the P521S substitution, had the fastest doubling times at that point. Analytic methods for estimating variant proportions have been updated as the availability of sequencing specimens has declined. The continued evolution of Omicron lineages highlights the importance of genomic surveillance to monitor emerging variants and help guide vaccine development and use of therapeutics.

Assessment of Anti-SARS-CoV-2 antibody levels among university students vaccinated with different COVID-19 primary and booster doses - fall 2021, Wisconsin.

BACKGROUND: University students commonly received COVID-19 vaccinations before returning to U.S. campuses in the Fall of 2021. Given likely immunologic variation among students based on differences in type of primary series and/or booster dose vaccine received, we conducted serologic investigations in September and December 2021 on a large university campus in Wisconsin to assess anti-SARS-CoV-2 antibody levels. METHODS: We collected blood samples, demographic information, and COVID-19 illness and vaccination history from a convenience sample of students. Sera were analyzed for both anti-spike (anti-S) and anti-nucleocapsid (anti-N) antibody levels using World Health Organization standardized binding antibody units per milliliter (BAU/mL). Levels were compared across categorical primary COVID-19 vaccine series received and binary COVID-19 mRNA booster status. The association between anti-S levels and time since most recent vaccination dose was estimated by mixed-effects linear regression. RESULTS: In total, 356 students participated, of whom 219 (61.5%) had received a primary vaccine series of Pfizer-BioNTech or Moderna mRNA vaccines and 85 (23.9%) had received vaccines from Sinovac or Sinopharm. Median anti-S levels were significantly higher for mRNA primary vaccine series recipients (2.90 and 2.86 log [BAU/mL], respectively), compared with those who received Sinopharm or Sinovac vaccines (1.63 and 1.95 log [BAU/mL], respectively). Sinopharm and Sinovac vaccine recipients were associated with a significantly faster anti-S decline over time, compared with mRNA vaccine recipients (P <.001). By December, 48/172 (27.9%) participants reported receiving an mRNA COVID-19 vaccine booster, which reduced the anti-S antibody discrepancies between primary series vaccine types. CONCLUSIONS: Our work supports the benefit of heterologous boosting against COVID-19. COVID-19 mRNA vaccine booster doses were associated with increases in anti-SARS-CoV-2 antibody levels; following an mRNA booster dose, students with both mRNA and non-mRNA primary series receipt were associated with comparable levels of anti-S IgG.

Respiratory Syncytial Virus Infection Among Hospitalized Infants in Four Middle-Income Countries.

BACKGROUND: Understanding respiratory syncytial virus (RSV) global epidemiology is important to inform future prevention strategies. METHODS: Hospitalized infants <1-year-old with acute illness were enrolled prospectively in Albania, Jordan, Nicaragua, and Philippines during respiratory seasons in 2015-2017. Medical chart review, parental interview, and post-discharge follow up were conducted. Respiratory specimens were tested using real-time RT-PCR for RSV. Infant characteristics associated with very severe illness (intensive care unit [ICU] admission or receipt of supplemental oxygen) were assessed using logistic regression to adjust for potential confounders (age, sex, study site, and preterm birth). RESULTS: Of 3634 enrolled hospitalized infants, 1129 (31%) tested positive for RSV. The median age of RSV-positive infants was 2.7 (IQR: 1.4-6.1) months and 665 (59%) were male. Very severe illness in 583 (52%) RSV-positive infants was associated with younger age (aOR 4.1, 95% CI: 2.6-6.5 for 0-2 compared to 9-11-months; P < .01), low weight-for-age z-score (aOR 1.9, 95% CI: 1.2-2.8; P < .01), ICU care after birth (aOR 1.6, 95% CI: 1.0-2.5; P = .048), and cesarean delivery (aOR 1.4, 95% CI: 1.0-1.8; P = .03). RSV subgroups A and B co-circulated at all sites with alternating predominance by year; subgroup was not associated with severity (aOR 1.0, 95% CI: 0.8-1.4). Nine (0.8%) RSV-positive infants died during admission or within ≤30 days of discharge, of which 7 (78%) were <6-months-old. CONCLUSIONS: RSV was associated with nearly a third of infant acute illness hospitalizations in four middle-income countries during the respiratory season, where, in addition to young age, factors including low weight-for-age might be important predictors of severity. RSV prevention strategies targeting young infants could substantially reduce RSV-associated hospitalizations in middle-income countries.

Evaluation of Ortho VITROS and Roche Elecsys S and NC Immunoassays for SARS-CoV-2 Serosurveillance Applications.

SARS-CoV-2 seroprevalence studies are instrumental in monitoring epidemic activity and require well-characterized, high-throughput assays, and appropriate testing algorithms. The U.S. Nationwide Blood Donor Seroprevalence Study performed monthly cross-sectional serological testing from July 2020 to December 2021, implementing evolving testing algorithms in response to changes in pandemic activity. With high vaccine uptake, anti-Spike (S) reactivity rates reached >80% by May 2021, and the study pivoted from reflex Roche anti-nucleocapsid (NC) testing of Ortho S-reactive specimens to parallel Ortho S/NC testing. We evaluated the performance of the Ortho NC assay as a replacement for the Roche NC assay and compared performance of parallel S/NC testing on both platforms. Qualitative and quantitative agreement of Ortho NC with Roche NC assays was evaluated on preselected S/NC concordant and discordant specimens. All 190 Ortho S+/Roche NC+ specimens were reactive on the Ortho NC assay; 34% of 367 Ortho S+/Roche NC- specimens collected prior to vaccine availability and 43% of 37 Ortho S-/Roche NC+ specimens were reactive on the Ortho NC assay. Performance of parallel S/NC testing using Ortho and Roche platforms was evaluated on 200 specimens collected in 2019 and 3,903 study specimens collected in 2021. All 200 pre-COVID-19 specimens tested negative on the four assays. Cross-platform agreement between Roche and Ortho platforms was 96.4% (3,769/3,903); most discordant results had reactivity close to the cutoffs on the alternate assays. These findings, and higher efficiency and throughput, support the use of parallel S/NC testing on either Roche or Ortho platforms for large serosurveillance studies. IMPORTANCE Seroprevalence studies like the U.S. Nationwide Blood Donor Seroprevalence Study (NBDS) have been critical in monitoring SARS-CoV-2 epidemic activity. These studies rely on serological assays to detect antibodies indicating prior infection. It is critical that the assays and testing algorithms used in seroprevalence studies have adequate performance (high sensitivity, high specificity, ability to discriminate vaccine-induced and infection-induced antibodies, etc.), as well as appropriate characteristics to support large-scale studies, such as high throughput and low cost. In this study we evaluated the performance of Ortho's anti-nucleocapsid assay as a replacement for the Roche anti-nucleocapsid assay and compared performance of parallel anti-spike and anti-nucleocapsid testing on both platforms. These data demonstrate similar performance of the Ortho and Roche anti-nucleocapsid assays and that parallel anti-spike and anti-nucleocapsid testing on either platform could be used for serosurveillance applications.

COVID-19 Surveillance After Expiration of the Public Health Emergency Declaration - United States, May 11, 2023.

On January 31, 2020, the U.S. Department of Health and Human Services (HHS) declared, under Section 319 of the Public Health Service Act, a U.S. public health emergency because of the emergence of a novel virus, SARS-CoV-2.* After 13 renewals, the public health emergency will expire on May 11, 2023. Authorizations to collect certain public health data will expire on that date as well. Monitoring the impact of COVID-19 and the effectiveness of prevention and control strategies remains a public health priority, and a number of surveillance indicators have been identified to facilitate ongoing monitoring. After expiration of the public health emergency, COVID-19-associated hospital admission levels will be the primary indicator of COVID-19 trends to help guide community and personal decisions related to risk and prevention behaviors; the percentage of COVID-19-associated deaths among all reported deaths, based on provisional death certificate data, will be the primary indicator used to monitor COVID-19 mortality. Emergency department (ED) visits with a COVID-19 diagnosis and the percentage of positive SARS-CoV-2 test results, derived from an established sentinel network, will help detect early changes in trends. National genomic surveillance will continue to be used to estimate SARS-CoV-2 variant proportions; wastewater surveillance and traveler-based genomic surveillance will also continue to be used to monitor SARS-CoV-2 variants. Disease severity and hospitalization-related outcomes are monitored via sentinel surveillance and large health care databases. Monitoring of COVID-19 vaccination coverage, vaccine effectiveness (VE), and vaccine safety will also continue. Integrated strategies for surveillance of COVID-19 and other respiratory viruses can further guide prevention efforts. COVID-19-associated hospitalizations and deaths are largely preventable through receipt of updated vaccines and timely administration of therapeutics (1-4).

Neutralizing Antibody Responses to Messenger RNA Coronavirus Disease 2019 Vaccines Versus Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Pregnant Women and Vaccine-Induced Antibody Transfer to Infants.

Background: Early coronavirus disease 2019 (COVID-19) vaccine trials excluded pregnant women, resulting in limited data about immunogenicity and maternal-fetal antibody transfer, particularly by gestational timing of vaccination. Methods: In this multicenter observational immunogenicity study, pregnant and nonpregnant women receiving COVID-19 vaccines were prospectively enrolled. Participants had sera collected before vaccination, at 14-28 days after each vaccine dose, at delivery (umbilical cord and peripheral), and from their infants at 3 and 6 months. Geometric mean titers (GMTs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ID50 neutralizing antibody (nAb) against D614G-like viruses were compared by participant characteristics. Results: Overall, 23 nonpregnant and 85 pregnant participants (trimester of first vaccine dose: 10 first, 47 second, 28 third) were enrolled. Ninety-three percent (76/82 with blood samples) of pregnant participants had detectable SARS-CoV-2 nAb after 2 vaccine doses, but GMTs (95% confidence intervals) were lower in pregnant participants than nonpregnant participants (1722 [1136-2612] vs 4419 [2012-9703]; P = .04). By 3 and 6 months, 28% and 74% of infants, respectively, of vaccinated participants had no detectable nAb to D614G-like viruses. Among the 71 pregnant participants without detectable nAb before vaccination, cord blood GMTs at delivery were 5-fold higher among participants vaccinated during the third versus first trimester, and cord blood nAb titers appeared inversely correlated with weeks since first vaccine dose (R2 = 0.06, P = .06). Conclusions: Though most pregnant women develop nAb after 2 doses of mRNA COVID-19 vaccines, this analysis suggests that infant protection from maternal vaccination varies by gestational timing of vaccination and wanes. Additional prevention strategies such as caregiver vaccination may warrant consideration to optimize infant protection.

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.

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: Four hundred fifty-five (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.

Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibody Responses After Community Infections in Children and Adults.

Background: We compared postinfection severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (nAb) responses among children and adults while the D614G-like strain and Alpha, Iota, and Delta variants circulated. Methods: During August 2020-October 2021, households with adults and children were enrolled and followed in Utah, New York City, and Maryland. Participants collected weekly respiratory swabs that were tested for SARS-CoV-2 and had sera collected during enrollment and follow-up. Sera were tested for SARS-CoV-2 nAb by pseudovirus assay. Postinfection titers were characterized with biexponential decay models. Results: Eighty participants had SARS-CoV-2 infection during the study (47 with D614G-like virus, 17 with B.1.1.7, and 8 each with B.1.617.2 and B.1.526 virus). Homologous nAb geometric mean titers (GMTs) trended higher in adults (GMT = 2320) versus children 0-4 (GMT = 425, P = .33) and 5-17 years (GMT = 396, P = .31) at 1-5 weeks postinfection but were similar from 6 weeks. Timing of peak titers was similar by age. Results were consistent when participants with self-reported infection before enrollment were included (n = 178). Conclusions: The SARS-CoV-2 nAb titers differed in children compared to adults early after infection but were similar by 6 weeks postinfection. If postvaccination nAb kinetics have similar trends, vaccine immunobridging studies may need to compare nAb responses in adults and children 6 weeks or more after vaccination.

Total and Subgenomic RNA Viral Load in Patients Infected With SARS-CoV-2 Alpha, Delta, and Omicron Variants.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic and subgenomic RNA levels are frequently used as a correlate of infectiousness. The impact of host factors and SARS-CoV-2 lineage on RNA viral load is unclear. METHODS: Total nucleocapsid (N) and subgenomic N (sgN) RNA levels were measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in specimens from 3204 individuals hospitalized with coronavirus disease 2019 (COVID-19) at 21 hospitals. RT-qPCR cycle threshold (Ct) values were used to estimate RNA viral load. The impact of time of sampling, SARS-CoV-2 variant, age, comorbidities, vaccination, and immune status on N and sgN Ct values were evaluated using multiple linear regression. RESULTS: Mean Ct values at presentation for N were 24.14 (SD 4.53) for non-variants of concern, 25.15 (SD 4.33) for Alpha, 25.31 (SD 4.50) for Delta, and 26.26 (SD 4.42) for Omicron. N and sgN RNA levels varied with time since symptom onset and infecting variant but not with age, comorbidity, immune status, or vaccination. When normalized to total N RNA, sgN levels were similar across all variants. CONCLUSIONS: RNA viral loads were similar among hospitalized adults, irrespective of infecting variant and known risk factors for severe COVID-19. Total N and subgenomic RNA N viral loads were highly correlated, suggesting that subgenomic RNA measurements add little information for the purposes of estimating infectivity.

Use of Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Tests by US Infectious Disease Physicians: Results of an Emerging Infections Network Survey, March 2022.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests have had limited recommended clinical application during the coronavirus disease 2019 (COVID-19) pandemic. To inform clinical practice, an understanding is needed of current perspectives of United States-based infectious disease (ID) physicians on the use, interpretation, and need for SARS-CoV-2 antibody tests. Methods: In March 2022, members of the Emerging Infections Network (EIN), a national network of practicing ID physicians, were surveyed on types of SARS-CoV-2 antibody assays ordered, interpretation of test results, and clinical scenarios for which antibody tests were considered. Results: Of 1867 active EIN members, 747 (40%) responded. Among the 583 who managed or consulted on COVID-19 patients, a majority (434/583 [75%]) had ordered SARS-CoV-2 antibody tests and were comfortable interpreting positive (452/578 [78%]) and negative (405/562 [72%]) results. Antibody tests were used for diagnosing post-COVID-19 conditions (61%), identifying prior SARS-CoV-2 infection (60%), and differentiating prior infection and response to COVID-19 vaccination (37%). Less than a third of respondents had used antibody tests to assess need for additional vaccines or risk stratification. Lack of sufficient evidence for use and nonstandardized assays were among the most common barriers for ordering tests. Respondents indicated that statements from professional societies and government agencies would influence their decision to order SARS-CoV-2 antibody tests for clinical decision making. Conclusions: Practicing ID physicians are using SARS-CoV-2 antibody tests, and there is an unmet need for clarifying the appropriate use of these tests in clinical practice. Professional societies and US government agencies can support clinicians in the community through the creation of appropriate guidance.

Spike Gene Target Amplification in a Diagnostic Assay as a Marker for Public Health Monitoring of Emerging SARS-CoV-2 Variants - United States, November 2021-January 2023.

Monitoring emerging SARS-CoV-2 lineages and their epidemiologic characteristics helps to inform public health decisions regarding vaccine policy, the use of therapeutics, and health care capacity. When the SARS-CoV-2 Alpha variant emerged in late 2020, a spike gene (S-gene) deletion (Δ69-70) in the N-terminal region, which might compensate for immune escape mutations that impair infectivity (1), resulted in reduced or failed S-gene target amplification in certain multitarget reverse transcription-polymerase chain reaction (RT-PCR) assays, a pattern referred to as S-gene target failure (SGTF) (2). The predominant U.S. SARS-CoV-2 lineages have generally alternated between SGTF and S-gene target presence (SGTP), which alongside genomic sequencing, has facilitated early monitoring of emerging variants. During a period when Omicron BA.5-related sublineages (which exhibit SGTF) predominated, an XBB.1.5 sublineage with SGTP has rapidly expanded in the northeastern United States and other regions.