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

BACKGROUND: We assessed associations between binding antibody (bAb) concentration <5 days of symptom onset and testing positive for COVID-19 among patients in a test-negative study. METHODS: From October 2021─June 2022, study sites in seven states enrolled patients aged ≥6 months presenting with acute respiratory illness. Respiratory specimens were tested for SARS-CoV-2. In blood specimens, we measured concentrations 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 change in odds of COVID-19 by increasing anti-RBD bAb was estimated using logistic regression as (1-adjusted odds ratio of COVID-19)x100, adjusting for COVID-19 mRNA vaccine doses, age, site, and high-risk exposure. RESULTS: Out of 2,018 symptomatic patients, 662 (33%) tested positive for acute SARS-CoV-2 infection. Geometric mean RBD bAb were lower among COVID-19 cases than SARS-CoV-2 test-negative patients during both the Delta-predominant (112 vs. 498 BAU/mL) and Omicron-predominant (823 vs. 1,189 BAU/mL) periods. Acute phase ancestral spike RBD bAb associated with 50% lower odds of COVID-19 were 1,968 BAU/mL against Delta and 3,375 BAU/mL against Omicron; thresholds may differ in other laboratories. CONCLUSION: During acute illness, antibody concentrations against ancestral spike RBD were associated with protection against COVID-19.

Hybrid immunity and SARS-CoV-2 antibodies: results of the HEROES-RECOVER prospective cohort study.

BACKGROUND: There are limited data on whether hybrid immunity differs by count and order of immunity-conferring events (SARS-CoV-2 infection or COVID-19 vaccination). From a cohort of health care personnel, first responders, and other frontline workers in six US states, we examined heterogeneity of the effect of hybrid immunity on SARS-CoV-2 antibody levels. METHODS: Exposures included event-count (sum of infections and vaccine doses) and event-order, categorized into seven permutations of vaccination and/or infection. Outcome was level of serum binding antibodies against receptor binding domain (RBD) of the ancestral SARS-CoV-2 spike protein (total RBD-binding Ig), measured by enzyme-linked immunosorbent assay. Mean antibody levels were examined up to 365 days after each of the 1st-7th events. RESULTS: Analysis included 5,793 participants measured from August 7, 2020 to April 15, 2023. Hybrid immunity from infection before one or two vaccine doses elicited modestly superior antibody responses after the 2nd and 3rd events (compared to infections or vaccine-doses alone). This superiority was not evident after the 4th and 5th events (additional doses). Among adults infected before vaccination, adjusted geometric mean ratios (95% CI) of anti-RBD early response (versus vaccinated-only) were 1.23 (1.14-1.33), 1.09 (1.03-1.14), 0.87 (0.81-0.94), and 0.99 (0.85-1.15) after the 2nd-5th events, respectively. Post-vaccination infections elicited superior responses: adjusted geometric mean ratios (95% CI) of anti-RBD early response (versus vaccinated-only) were: 0.93 (0.75-1.17), 1.11 (1.06-1.16), 1.17 (1.11-1.24), and 1.20 (1.07-1.34) after the 2nd-5th events, respectively. CONCLUSIONS AND RELEVANCE: Findings reflecting heterogeneity in antibody levels by permutations of infection and vaccination history could inform COVID-19 vaccination policy.

Estimates of SARS-CoV-2 Seroprevalence and Incidence of Primary SARS-CoV-2 Infections Among Blood Donors, by COVID-19 Vaccination Status - United States, April 2021-September 2022.

Changes in testing behaviors and reporting requirements have hampered the ability to estimate the U.S. SARS-CoV-2 incidence (1). Hybrid immunity (immunity derived from both previous infection and vaccination) has been reported to provide better protection than that from infection or vaccination alone (2). To estimate the incidence of infection and the prevalence of infection- or vaccination-induced antibodies (or both), data from a nationwide, longitudinal cohort of blood donors were analyzed. During the second quarter of 2021 (April-June), an estimated 68.4% of persons aged ≥16 years had infection- or vaccination-induced SARS-CoV-2 antibodies, including 47.5% from vaccination alone, 12.0% from infection alone, and 8.9% from both. By the third quarter of 2022 (July-September), 96.4% had SARS-CoV-2 antibodies from previous infection or vaccination, including 22.6% from infection alone and 26.1% from vaccination alone; 47.7% had hybrid immunity. Prevalence of hybrid immunity was lowest among persons aged ≥65 years (36.9%), the group with the highest risk for severe disease if infected, and was highest among those aged 16-29 years (59.6%). Low prevalence of infection-induced and hybrid immunity among older adults reflects the success of public health infection prevention efforts while also highlighting the importance of older adults staying up to date with recommended COVID-19 vaccination, including at least 1 bivalent dose.*,†.

Lessons learned from the implementation of integrated serosurveillance of communicable diseases in the Americas.

Objective: Systematize the experience and identify challenges and lessons learned in the implementation of an initiative for integrated serosurveillance of communicable diseases using a multiplex bead assay in countries of the Americas. Methods: Documents produced in the initiative were compiled and reviewed. These included concept notes, internal working papers, regional meetings reports, and survey protocols from the three participating countries (Mexico, Paraguay, and Brazil) and two additional countries (Guyana and Guatemala) where serology for several communicable diseases was included in neglected tropical diseases surveys. Information was extracted and summarized to describe the experience and the most relevant challenges and lessons learned. Results: Implementing integrated serosurveys requires interprogrammatic and interdisciplinary work teams for the design of survey protocols to respond to key programmatic questions aligned to the needs of the countries. Valid laboratory results are critical and rely on the standardized installment and roll-out of laboratory techniques. Field teams require adequate training and supervision to properly implement survey procedures. The analysis and interpretation of serosurveys results should be antigen-specific, contextualizing the responses for each disease, and triangulated with programmatic and epidemiological data for making decisions tailored to specific population socioeconomic and ecologic contexts. Conclusions: Integrated serosurveillance as a complementary tool for functional epidemiological surveillance systems is feasible to use and key components should be considered: political engagement, technical engagement, and integrated planning. Aspects such as designing the protocol, selecting target populations and diseases, laboratory capacities, anticipating the capacities to analyze and interpret complex data, and how to use it are key.

Shedding of Culturable Virus, Seroconversion, and 6-Month Follow-up Antibody Responses in the First 14 Confirmed Cases of Coronavirus Disease 2019 in the United States.

We aimed to characterize presence of culturable virus in clinical specimens during acute illness, and antibody kinetics up to 6 months after symptom onset, among 14 early patients with coronavirus disease 2019 in the United States. We isolated viable severe acute respiratory syndrome coronavirus 2 from real-time reverse-transcription polymerase chain reaction-positive respiratory specimens collected during days 0-8 after onset, but not after. All 13 patients with 2 or more serum specimens developed anti-spike antibodies; 12 developed detectable neutralizing antibodies. We did not isolate virus after detection of neutralizing antibodies. Eight participants provided serum at 6 months after onset; all retained detectable anti-spike immunoglobulin G, and half had detectable neutralizing antibodies. Two participants reported not feeling fully recovered at 6 months.

Development of a Measles and Rubella Multiplex Bead Serological Assay for Assessing Population Immunity.

Serosurveys are important tools for estimating population immunity and providing immunization activity guidance. The measles and rubella multiplex bead assay (MBA) offers multiple advantages over standard serological assays and was validated by comparison with the enzyme-linked immunosorbent assay (ELISA) and the measles plaque reduction neutralization (PRN) assay. Results from a laboratory-produced purified measles virus whole-virus antigen MBA (MeV WVAL) correlated better with ELISA and PRN than results from the baculovirus-expressed measles nucleoprotein (N) MBA. Therefore, a commercially produced whole-virus antigen (MeV WVAC) was evaluated. Serum IgG antibody concentrations correlated significantly with a strong linear relationship between the MeV WVAC and MeV WVAL MBAs (R = 0.962 and R2 = 0.926). IgG concentrations from the MeV WVAC MBA showed strong correlation with PRN titers (R = 0.846), with a linear relationship comparable to values obtained with the MeV WVAL MBA and PRN assay (R2 = 0.716 and R2 = 0.768, respectively). Receiver operating characteristic (ROC) curve analysis of the MeV WVAC using PRN titer as the comparator resulted in a seroprotection cutoff of 153 mIU/ml, similar to the established correlate of protection of 120 mIU/ml, with a sensitivity of 98% and a specificity of 83%. IgG concentrations correlated strongly between the rubella WVA MBA and ELISA (R = 0.959 and R2 = 0.919). ROC analysis of the rubella MBA using ELISA as the comparator yielded a cutoff of 9.36 IU/ml, similar to the accepted cutoff of 10 IU/ml for seroprotection, with a sensitivity of 99% and a specificity of 100%. These results support use of the MBA for multiantigen serosurveys assessing measles and rubella population immunity.

Seroprevalence of SARS-CoV-2 Among Frontline Health Care Personnel in a Multistate Hospital Network - 13 Academic Medical Centers, April-June 2020.

Health care personnel (HCP) caring for patients with coronavirus disease 2019 (COVID-19) might be at high risk for contracting SARS-CoV-2, the virus that causes COVID-19. Understanding the prevalence of and factors associated with SARS-CoV-2 infection among frontline HCP who care for COVID-19 patients are important for protecting both HCP and their patients. During April 3-June 19, 2020, serum specimens were collected from a convenience sample of frontline HCP who worked with COVID-19 patients at 13 geographically diverse academic medical centers in the United States, and specimens were tested for antibodies to SARS-CoV-2. Participants were asked about potential symptoms of COVID-19 experienced since February 1, 2020, previous testing for acute SARS-CoV-2 infection, and their use of personal protective equipment (PPE) in the past week. Among 3,248 participants, 194 (6.0%) had positive test results for SARS-CoV-2 antibodies. Seroprevalence by hospital ranged from 0.8% to 31.2% (median = 3.6%). Among the 194 seropositive participants, 56 (29%) reported no symptoms since February 1, 2020, 86 (44%) did not believe that they previously had COVID-19, and 133 (69%) did not report a previous COVID-19 diagnosis. Seroprevalence was lower among personnel who reported always wearing a face covering (defined in this study as a surgical mask, N95 respirator, or powered air purifying respirator [PAPR]) while caring for patients (5.6%), compared with that among those who did not (9.0%) (p = 0.012). Consistent with persons in the general population with SARS-CoV-2 infection, many frontline HCP with SARS-CoV-2 infection might be asymptomatic or minimally symptomatic during infection, and infection might be unrecognized. Enhanced screening, including frequent testing of frontline HCP, and universal use of face coverings in hospitals are two strategies that could reduce SARS-CoV-2 transmission.

Decline in SARS-CoV-2 Antibodies After Mild Infection Among Frontline Health Care Personnel in a Multistate Hospital Network - 12 States, April-August 2020.

Most persons infected with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), develop virus-specific antibodies within several weeks, but antibody titers might decline over time. Understanding the timeline of antibody decline is important for interpreting SARS-CoV-2 serology results. Serum specimens were collected from a convenience sample of frontline health care personnel at 13 hospitals and tested for antibodies to SARS-CoV-2 during April 3-June 19, 2020, and again approximately 60 days later to assess this timeline. The percentage of participants who experienced seroreversion, defined as an antibody signal-to-threshold ratio >1.0 at baseline and <1.0 at the follow-up visit, was assessed. Overall, 194 (6.0%) of 3,248 participants had detectable antibodies to SARS-CoV-2 at baseline (1). Upon repeat testing approximately 60 days later (range = 50-91 days), 146 (93.6%) of 156 participants experienced a decline in antibody response indicated by a lower signal-to-threshold ratio at the follow-up visit, compared with the baseline visit, and 44 (28.2%) experienced seroreversion. Participants with higher initial antibody responses were more likely to have antibodies detected at the follow-up test than were those who had a lower initial antibody response. Whether decay in these antibodies increases risk for reinfection and disease remains unanswered. However, these results suggest that serology testing at a single time point is likely to underestimate the number of persons with previous SARS-CoV-2 infection, and a negative serologic test result might not reliably exclude prior infection.

Contribution of dendritic cells to measles virus induced immunosuppression.

Measles virus (MV) remains an important pathogen in children worldwide. The morbidity and mortality of MV is associated with severe immune suppression. Dendritic cells (DCs) were identified as initial target cells in vivo, and DCs were efficiently infected by MV in vitro. MV infection of DCs likely contributes to functional deficiency in these cells; therefore playing a role in MV-induced immunosuppression. DCs appeared to mature phenotypically; however, the ability of infected cells to stimulate T cells was compromised. Phenotypic maturation of infected immature DCs was partially controlled by IFN production; however, infected DCs also maintained markers of an immature phenotype such as the continued uptake of antigen and lack of expression of chemokine receptor CCR7. Furthermore, mature DCs did not appear to maintain phenotypic maturation following infection demonstrated by decreased MHC and co-stimulatory molecule expression. Several mechanisms of MV-induced DC dysfunction have been suggested, each likely contributing to the immunosuppressive effect of MV-infected DCs. Infected DCs responded aberrantly to secondary maturation stimuli such as CD40L or TLR4 stimulation. MV infection resulted in apoptosis in DC/T-cell cocultures, which may contribute to a reduced T-cell response. Additionally, the immunological synapse between infected DCs and T cells was compromised resulting in reduced T-cell interaction times and activation signaling. The mechanisms of MV contribution to DC dysfunction appear multifaceted and central to MV-induced immunosuppression.

Multiplex Bead Assay for the Serological Surveillance of Measles and Rubella.

There is increasing interest in evaluating antibody responses to multiple antigen targets in a single assay. Immunity to measles and rubella are often evaluated together because immunity is provided through combined vaccines and because routine immunization efforts and surveillance for measles and rubella pathogens are combined in many countries. The multiplex bead assay (MBA) also known as the multiplex immunoassay (MIA) described here combines the measurement of measles- and rubella-specific IgG antibodies in serum quantitatively according to international serum standards and has been successfully utilized in integrated serological surveillance.

shinyMBA: a novel R shiny application for quality control of the multiplex bead assay for serosurveillance studies.

The multiplex bead assay (MBA) based on Luminex xMAP technology can be used as a tool to measure seroprevalence as part of population immunity evaluations to multiple antigens in large-scale serosurveys. However, multiplexing several antigens presents challenges for quality control (QC) assessments of the data because multiple parameters must be evaluated for each antigen. MBA QC parameters include monitoring bead counts and median fluorescence intensity (MFI) for each antigen in plate wells, and performance of assay controls included on each plate. Analyzing these large datasets to identify plates failing QC standards presents challenges for many laboratories. We developed a novel R Shiny application, shinyMBA, to expedite the MBA QC processes and reduce the risk of user error. The app allows users to rapidly merge multi-plate assay outputs to evaluate bead count, MFI, and performance of assay controls using statistical process control charts for all antigen targets simultaneously. The utility of the shinyMBA application and its various outputs are demonstrated using data from 32 synthetic xPONENT files with 3 multiplex antigens and two population serosurveillance studies that evaluated 1200 and 3871 samples, respectively, for 20 multiplexed antigens. The shinyMBA open-source code is available for download and modification at https://github.com/CDCgov/shinyMBA . Incorporation of shinyMBA into Luminex serosurveillance workflows can vastly improve the speed and accuracy of QC processes.

The impact of sub-national heterogeneities in demography and epidemiology on the introduction of rubella vaccination programs in Nigeria.

Rubella infection during pregnancy can result in miscarriage or infants with a constellation of birth defects known as congenital rubella syndrome (CRS). When coverage is inadequate, rubella vaccination can increase CRS cases by increasing the average age of infection. Thus, the World Health Organisation recommends that countries introducing rubella vaccine be able to vaccinate at least 80% of each birth cohort. Previous studies have focused on national-level analyses and have overlooked sub-national variation in introduction risk. We characterised the sub-national heterogeneity in rubella transmission within Nigeria and modelled local rubella vaccine introduction under different scenarios to refine the set of conditions and strategies required for safe rubella vaccine use. Across Nigeria, the basic reproduction number ranged from 2.6 to 6.2. Consequently, the conditions for safe vaccination varied across states with low-risk areas requiring coverage levels well below 80 %. In high-risk settings, inadequate routine coverage needed to be supplemented by campaigns that allowed for gradual improvements in vaccination coverage over time. Understanding local heterogeneities in both short-term and long-term epidemic dynamics can permit earlier nationwide introduction of rubella vaccination and identify sub-national areas suitable for program monitoring, program improvement and campaign support.

Antigenic Characterization of Circulating and Emerging SARS-CoV-2 Variants in the U.S. throughout the Delta to Omicron Waves.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates.

Neutralizing human monoclonal antibodies to severe acute respiratory syndrome coronavirus: target, mechanism of action, and therapeutic potential.

The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) led to a rapid response not only to contain the outbreak but also to identify possible therapeutic interventions, including the generation of human monoclonal antibodies (hmAbs). hmAbs may be used therapeutically without the drawbacks of chimeric or animal Abs. Several different methods have been used to generate SARS-CoV specific neutralizing hmAbs including the immunization of transgenic mice, cloning of small chain variable regions from naïve and convalescent patients, and the immortalization of convalescent B cells. Irrespective of the techniques used, the majority of hmAbs specifically reacted with the receptor binding domain (RBD) of the spike (S) protein and likely prevented receptor binding. However, several hmAbs that can bind to epitopes either within the RBD, located N terminal of the RBD or in the S2 domain, and neutralize the virus with or without inhibiting receptor binding have been identified. Therapeutic utility of hmAbs has been further elucidated through the identification of potential combinations of hmAbs that could neutralize viral variants including escape mutants selected using hmAbs. These results suggest that a cocktail of hmAbs that can bind to unique epitopes and have different mechanisms of action might be of clinical utility against SARS-CoV infection, and indicate that a similar approach may be applied to treat other viral infections.

Characterizing infection of B cells with wild-type and vaccine strains of measles virus.

Acute infection with measles virus (MeV) causes transient immunosuppression often leading to secondary infections. MeV infection of B lymphocytes results in changes in the antibody repertoire and memory B cell populations for which the mechanism is unknown. In this study, we characterize the infection of primary B cells with wild-type and vaccine strains of MeV. Vaccine-infected B cells were characterized by a higher percentage of cells positive for viral protein, a higher level of viral transcription and reduced cell death compared to wild-type infected cells, regardless of B cell subtype. Vaccine-infected cells showed more production of TNF-α and IL-10 but less production of IL-8 compared to wild-type infected cells. IL-4 and IL-6 levels detected were increased during both vaccine and wild-type infection. Despite evidence of replication, measles-infected B cells did not produce detectable viral progeny. This study furthers our understanding of the outcomes of MeV infection of human B cells.

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

Background: We assessed the association between antibody concentration ≤5 days of symptom onset and COVID-19 illness among patients enrolled in a test-negative study. Methods: From October 2021-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)×100, adjusting for COVID-19 vaccination status, age, site, and high-risk exposure. Results: A 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:690-981) among COVID-19 case-patients versus 1,189 BAU/mL (95%CI:1,050-1,347) 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. Conclusion: Higher anti-RBD antibodies in patients were associated with protection against symptomatic COVID-19 during emergence of SARS-CoV-2 Delta and Omicron variants.

Performance of SARS-CoV-2 Antigens in a Multiplex Bead Assay for Integrated Serological Surveillance of Neglected Tropical and Other Diseases.

Serosurveillance can provide estimates of population-level exposure to infectious pathogens and has been used extensively during the COVID-19 pandemic. Simultaneous, serological testing for multiple pathogens can be done using bead-based immunoassays to add value to disease-specific serosurveys. We conducted a validation of four SARS-CoV-2 antigens-full-length spike protein, two receptor binding domain proteins, and the nucleocapsid protein-on our existing multiplex bead assay (MBA) for enteric diseases, malaria, and vaccine preventable diseases. After determining the optimal conditions for coupling the antigens to microsphere beads, the sensitivity and specificity of the assay were determined on two instruments (Luminex-200 and MAGPIX) when testing singly (monoplex) versus combined (multiplex). Sensitivity was assessed using plasma from 87 real-time reverse transcription polymerase chain reaction (rRT-PCR) positive persons collected in March-May of 2020 and ranged from 94.3% to 96.6% for the different testing conditions. Specificity was assessed using 98 plasma specimens collected prior to December 2019 and plasma from 19 rRT-PCR negative persons and ranged from 97.4% to 100%. The positive percent agreement was 93.8% to 97.9% using 48 specimens collected > 21 days post-symptom onset, while the negative percent agreement was ≥ 99% for all antigens. Test performance was similar using monoplex or multiplex testing. Integrating SARS-CoV-2 serology with other diseases of public health interest could add significant value to public health programs that have suffered severe programmatic setbacks during the COVID-19 pandemic.

Descriptive evaluation of antibody responses to severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in plasma and gingival crevicular fluid in a nursing home cohort-Arkansas, June-August 2020.

OBJECTIVE: To characterize and compare severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-specific immune responses in plasma and gingival crevicular fluid (GCF) from nursing home residents during and after natural infection. DESIGN: Prospective cohort. SETTING: Nursing home. PARTICIPANTS: SARS-CoV-2-infected nursing home residents. METHODS: A convenience sample of 14 SARS-CoV-2-infected nursing home residents, enrolled 4-13 days after real-time reverse transcription polymerase chain reaction diagnosis, were followed for 42 days. After diagnosis, plasma SARS-CoV-2-specific pan-Immunoglobulin (Ig), IgG, IgA, IgM, and neutralizing antibodies were measured at 5 time points, and GCF SARS-CoV-2-specific IgG and IgA were measured at 4 time points. RESULTS: All participants demonstrated immune responses to SARS-CoV-2 infection. Among 12 phlebotomized participants, plasma was positive for pan-Ig and IgG in all 12 participants. Neutralizing antibodies were positive in 11 participants; IgM was positive in 10 participants, and IgA was positive in 9 participants. Among 14 participants with GCF specimens, GCF was positive for IgG in 13 participants and for IgA in 12 participants. Immunoglobulin responses in plasma and GCF had similar kinetics; median times to peak antibody response were similar across specimen types (4 weeks for IgG; 3 weeks for IgA). Participants with pan-Ig, IgG, and IgA detected in plasma and GCF IgG remained positive throughout this evaluation, 46-55 days after diagnosis. All participants were viral-culture negative by the first detection of antibodies. CONCLUSIONS: Nursing home residents had detectable SARS-CoV-2 antibodies in plasma and GCF after infection. Kinetics of antibodies detected in GCF mirrored those from plasma. Noninvasive GCF may be useful for detecting and monitoring immunologic responses in populations unable or unwilling to be phlebotomized.

Infectious Period of Severe Acute Respiratory Syndrome Coronavirus 2 in 17 Nursing Home Residents-Arkansas, June-August 2020.

BACKGROUND: To estimate the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adults with underlying conditions, we assessed duration of coronavirus disease 2019 (COVID-19) symptoms, reverse-transcription polymerase chain reaction (RT-PCR) positivity, and culture positivity among nursing home residents. METHODS: We enrolled residents within 15 days of their first positive SARS-CoV-2 test (diagnosis) at an Arkansas facility from July 7 to 15, 2020 and instead them for 42 days. Every 3 days for 21 days and then weekly, we assessed COVID-19 symptoms, collected specimens (oropharyngeal, anterior nares, and saliva), and reviewed medical charts. Blood for serology was collected on days 0, 6, 12, 21, and 42. Infectivity was defined by positive culture. Duration of culture positivity was compared with duration of COVID-19 symptoms and RT-PCR positivity. Data were summarized using measures of central tendency, frequencies, and proportions. RESULTS: We enrolled 17 of 39 (44%) eligible residents. Median participant age was 82 years (range, 58-97 years). All had ≥3 underlying conditions. Median duration of RT-PCR positivity was 22 days (interquartile range [IQR], 8-31 days) from diagnosis; median duration of symptoms was 42 days (IQR, 28-49 days). Of 9 (53%) participants with any culture-positive specimens, 1 (11%) severely immunocompromised participant remained culture-positive 19 days from diagnosis; 8 of 9 (89%) were culture-positive ≤8 days from diagnosis. Seroconversion occurred in 12 of 12 (100%) surviving participants with ≥1 blood specimen; all participants were culture-negative before seroconversion. CONCLUSIONS: Duration of infectivity was considerably shorter than duration of symptoms and RT-PCR positivity. Severe immunocompromise may prolong SARS-CoV-2 infectivity. Seroconversion indicated noninfectivity in this cohort.