Seroepidemiology of SARS-CoV-2 in healthcare personnel working at the largest tertiary COVID-19 referral hospitals in Mexico City.

INTRODUCTION: We performed a longitudinal SARS-CoV-2 seroepidemiological study in healthcare personnel of the two largest tertiary COVID-19 referral hospitals in Mexico City. METHODS: All healthcare personnel, including staff physicians, physicians in training, nurses, laboratory technicians, researchers, students, housekeeping, maintenance, security, and administrative staff were invited to voluntarily participate, after written informed consent. Participants answered a computer-assisted self-administered interview and donated blood samples for antibody testing every three weeks from October 2020 to June 2021. RESULTS: A total of 883 participants (out of 3639 registered employees) contributed with at least one blood sample. The median age was 36 years (interquartile range: 28-46) and 70% were women. The most common occupations were nurse (28%), physician (24%), and administrative staff (22%). Two hundred and ninety participants (32.8%) had a positive-test result in any of the visits, yielding an overall adjusted prevalence of 33.5% for the whole study-period. Two hundred and thirty-five positive tests were identified at the baseline visit (prevalent cases), the remaining 55 positive tests were incident cases. Prevalent cases showed associations with both occupational (institution 2 vs. 1: adjusted odds ratio [aOR] = 2.24, 95% confidence interval [CI]: 1.54-3.25; laboratory technician vs. physician: aOR = 4.38, 95% CI: 1.75-10.93) and community (municipality of residence Xochimilco vs. Tlalpan: aOR = 2.03, 95% CI: 1.09-3.79) risk-factors. The incidence rate was 3.0 cases per 100 person-months. Incident cases were associated with community-acquired risk, due to contact with suspect/confirmed COVID-19 cases (HR = 2.45, 95% CI: 1.21-5.00). CONCLUSIONS: We observed that between October 2020 and June 2021, healthcare workers of the two largest tertiary COVID-19 referral centers in Mexico City had similar level of exposure to SARS-CoV-2 than the general population. Most variables associated with exposure in this setting pointed toward community rather than occupational risk. Our observations are consistent with successful occupational medicine programs for SARS-CoV-2 infection control in the participating institutions but suggest the need to strengthen mitigation strategies in the community.

SerumCovid database: Description and preliminary analysis of serological COVID-19 diagnosis in healthcare workers.

Serological databases represent an important source of information to perceive COVID-19 impact on health professionals involved in combating the disease. This paper describes SerumCovid, a COVID-19 serological database focused on the diagnosis of health professionals, providing a preliminary analysis to contribute to the understanding of the antibody response to the SARS-CoV-2. The study population comprises 321 samples from 236 healthcare and frontline workers fighting COVID-19 in Vitória de Santo Antão, Brazil. Samples were collected from at least six days of symptoms to more than 100 days. The used immunoenzymatic assays were Euroimmun Anti-SARS-CoV-2 ELISA IgG and IgA. The most common gender in SerumCovid is female, while the most common age group is between 30 and 39 years old. However, no statistical differences were observed in either genders or age categories. The most reported symptoms were fatigue, headaches, and myalgia. Still, some subjects presented positive results for IgA after 130 days. Based on a temporal analysis, we have not identified general patterns as subjects presented high and low values of IgA and IgG with different evolution trends. Unexpectedly, for subjects with both serological tests, the outcome of IgA and IgG tests were the same (either positive or negative) for more than 80% of the samples. Therefore, SerumCovid helps better understand how COVID-19 affected healthcare and frontline workers, which increases knowledge about the infection and enables direct prevention actions.

Large-Scale Implementation of a Daily Rapid Antigen Testing Program in California for Detecting SARS-CoV-2.

Objectives. To evaluate a daily antigen testing program for health care personnel. Methods. We examined antigen testing results between December 13, 2020, and April 30, 2021, from 5 forensic psychiatric inpatient hospitals throughout California. Results. Among 471 023 antigen tests administered, 449 positives (0.0036% false positives) were detected. Conclusions. Antigen tests had low false-positive rates, high positive predictive value, and high levels of acceptability, important characteristics when considering their application in the community. Public Health Implications. Daily antigen testing was feasible and should be considered to reduce COVID-19 transmission. (Am J Public Health. 2022;112(3):467-471. https://doi.org/10.2105/AJPH.2021.306588).

Factors influencing the performance of rapid SARS-CoV-2 antigen tests under field condition.

BACKGROUND: Globally, real-time reverse transcription-polymerase chain reaction (rRT-PCR) is the reference detection technique for SARS-CoV-2, which is expensive, time consuming, and requires trained laboratory personnel. Thus, a cost-effective, rapid antigen test is urgently needed. This study evaluated the performance of the rapid antigen tests (RATs) for SARS-CoV-2 compared with rRT-PCR, considering different influencing factors. METHODS: We enrolled a total of 214 symptomatic individuals with known COVID-19 status using rRT-PCR. We collected and tested paired nasopharyngeal (NP) and nasal swab (NS) specimens (collected from same individual) using rRT-PCR and RATs (InTec and SD Biosensor). We assessed the performance of RATs considering specimen types, viral load, the onset of symptoms, and presenting symptoms. RESULTS: We included 214 paired specimens (112 NP and 100 NS SARS-CoV-2 rRT-PCR positive) to the analysis. For NP specimens, the average sensitivity, specificity, and accuracy of the RATs were 87.5%, 98.6%, and 92.8%, respectively, when compared with rRT-PCR. While for NS, the overall kit performance was slightly lower than that of NP (sensitivity 79.0%, specificity 96.1%, and accuracy 88.3%). We observed a progressive decline in the performance of RATs with increased Ct values (decreased viral load). Moreover, the RAT sensitivity using NP specimens decreased over the time of the onset of symptoms. CONCLUSION: The RATs showed strong performance under field conditions and fulfilled the minimum performance limit for rapid antigen detection kits recommended by World Health Organization. The best performance of the RATs can be achieved within the first week of the onset of symptoms with high viral load.

Modeling serological testing to inform relaxation of social distancing for COVID-19 control.

Serological testing remains a passive component of the public health response to the COVID-19 pandemic. Using a transmission model, we examine how serological testing could have enabled seropositive individuals to increase their relative levels of social interaction while offsetting transmission risks. We simulate widespread serological testing in New York City, South Florida, and Washington Puget Sound and assume seropositive individuals partially restore their social contacts. Compared to no intervention, our model suggests that widespread serological testing starting in late 2020 would have averted approximately 3300 deaths in New York City, 1400 deaths in South Florida and 11,000 deaths in Washington State by June 2021. In all sites, serological testing blunted subsequent waves of transmission. Findings demonstrate the potential benefit of widespread serological testing, had it been implemented in the pre-vaccine era, and remain relevant now amid the potential for emergence of new variants.

Prevalence and correlates of SARS-CoV-2 seropositivity among people who inject drugs in the San Diego-Tijuana border region.

BACKGROUND: People who inject drugs may be at elevated SARS-CoV-2 risk due to their living conditions and/or exposures when seeking or using drugs. No study to date has reported upon risk factors for SARS-CoV-2 infection among people who inject drugs. METHODS AND FINDINGS: Between October, 2020 and June, 2021, participants aged ≥18 years from San Diego, California, USA and Tijuana, Baja California, Mexico who injected drugs within the last month underwent interviews and testing for SARS-CoV-2 RNA and antibodies. Binomial regressions identified correlates of SARS-CoV-2 seropositivity. RESULTS: Of 386 participants, SARS-CoV-2 seroprevalence was 36.3% (95% CI: 31.5%-41.1%); 92.1% had detectable IgM antibodies. Only 37.5% had previously been tested. Seroprevalence did not differ by country of residence. None tested RNA-positive. Most (89.5%) reported engaging in ≥1 protective behavior [e.g., facemasks (73.5%), social distancing (46.5%), or increasing handwashing/sanitizers (22.8%)]. In a multivariate model controlling for sex, older age, and Hispanic/Latinx/Mexican ethnicity were independently associated with SARS-CoV-2 seropositivity, as was engaging in sex work (AdjRR: 1.63; 95% CI: 1.18-2.27) and having been incarcerated in the past six months (AdjRR: 1.49; 95% CI: 0.97-2.27). Comorbidities and substance using behaviors were not associated with SARS-CoV-2 seropositivity. CONCLUSIONS: In this community-based study of people who inject drugs in the San Diego-Tijuana border region, over one third were SARS-CoV-2 seropositive, exceeding estimates from the general population in either city. We found no evidence that substance use behaviors were associated with an elevated risk of SARS-CoV-2 infection, but observed that circumstances in the risk environment, notably sex work and incarceration, were independently associated with higher SARS-CoV-2 seroprevalence. Our findings suggest that a binational policy response to COVID-19 mitigation is warranted beyond the closure of the U.S.-Mexico border. Furthermore, decriminalizing sex work and drug use could reduce the burden of COVID-19 among people who inject drugs.

Seroprevalence of SARS-CoV-2 Antibodies Among Children in School and Day Care in Montreal, Canada.

Importance: Quebec prioritized in-person learning after the first wave of the COVID-19 pandemic, with school closures being implemented temporarily in selected schools or in hot-spot areas. Quebec's decision to keep most schools open was controversial, especially in Montreal, which was the epicenter of Canada's first and second waves; therefore, understanding the extent to which children were infected with SARS-CoV-2 provides important information for decisions about school closures. Objective: To estimate the seroprevalence of SARS-CoV-2 antibodies in children and teenagers in 4 neighborhoods of Montreal, Canada. Design, Setting, and Participants: This cohort study (the Enfants et COVID-19: Étude de séroprévalence [EnCORE] study) enrolled a convenience sample of children aged 2 to 17 years between October 22, 2020, and March 22, 2021, in Montreal, Canada. Exposures: Potential exposure to SARS-CoV-2. Main Outcomes and Measures: The main outcome was seroprevalence of SARS-CoV-2 antibodies, collected using dried blood spots (DBSs) and analyzed with a research-based enzyme-linked immunosorbent assay (ELISA). Parents also completed an online questionnaire that included questions on self-reported COVID-19 symptoms and tests, along with sociodemographic questions. Results: This study included 1632 participants who provided a DBS sample from 30 day cares, 22 primary schools, and 11 secondary schools. The mean (SD) age of the children who provided a DBS sample was 9.0 (4.4) years; 801 (49%) were female individuals, with 354 participants (22%) from day cares, 725 (44%) from primary schools, and 553 (34%) from secondary schools. Most parents had at least a bachelor's degree (1228 [75%]), and 210 (13%) self-identified as being a racial or ethnic minority. The mean seroprevalence was 5.8% (95% CI, 4.6%-7.0%) but increased over time from 3.2% (95% CI, 0.7%-5.8%) in October to November 2020 to 8.4% (95% CI, 4.4%-12.4%) in March to April 2021. Of the 95 children with positive SARS-CoV-2 antibody results, 78 (82%) were not tested or tested negative with reverse transcription-polymerase chain reaction (RT-PCR) testing, and all experienced mild (49 [52%]) or no clinical symptoms (46 [48%]). The children of parents who self-identified as belonging to a racial and ethnic minority group were more likely to be seropositive compared with children of White parents (adjusted seroprevalence ratio, 1.9; 95% CI, 1.1-2.6). Conclusions and Relevance: These results provide a benchmark of the seroprevalence status in Canadian children. The findings suggest that there was more transmission occurring in children compared with what was being detected by RT-PCR, although children experienced few or mild symptoms. It will be important to continue monitoring the serological status of children, particularly in the context of new COVID-19 variants of concern and in the absence of mass vaccination campaigns targeting young children.

The burden of SARS-CoV-2 among healthcare workers across 16 hospitals of Kashmir, India-A seroepidemiological study.

SARS-CoV-2 pandemic has greatly affected healthcare workers because of the high risk of getting infected. The present cross-sectional study measured SARS-CoV-2 antibody in healthcare workers of Kashmir, India. METHODS: Serological testing to detect antibodies against nucleocapsid protein of SARS-CoV-2 was performed in 2003 healthcare workers who voluntarily participated in the study. RESULTS: We report relatively high seropositivity of 26.8% (95% CI 24.8-28.8) for SARS-CoV-2in healthcare workers, nine months after the first case was detected in Kashmir. Most of the healthcare workers (71.7%) attributed infection to the workplace environment. Among healthcare workers who neither reported any prior symptom nor were they ever tested for infection by nasopharyngeal swab test, 25.5% were seropositive. CONCLUSION: We advocate interval testing by nasopharyngeal swab test of all healthcare workers regardless of symptoms to limit the transmission of infection within healthcare settings.

Prevalence of COVID-19 antibodies among operating room and critical care staff at a tertiary teaching hospital: A cross-sectional study.

OBJECTIVES: To identify the prevalence of COVID-19 antibodies among operating room and critical care staff. METHODS: In this cross-sectional study, we recruited 319 Healthcare workers employed in the operation theater and intensive care unit of King Abdulaziz University Hospital (KAUH), a tertiary teaching hospital in Jeddah, Saudi Arabia between August 9, 2020 and November 2, 2020. All participants completed a 20-item questionnaire on demographic data and COVID-19 risk factors and provided blood samples. Antibody testing was performed using an in-house enzyme immunoassay and microneutralization test. RESULTS: Of the 319 participants, 39 had detectable COVID-19 antibodies. Five of them had never experienced any symptoms suggestive of COVID-19, and only 19 were previously diagnosed with COVID-19. The odds of developing COVID-19 or having corresponding antibodies increased if participants experienced COVID-19 symptoms (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.2-7.5) or reported contact with an infected family member (OR, 5.3; 95% CI, 2.5-11.2). Disease acquisition was not associated with employment in the ICU and involvement in the intubation of or close contact with COVID-19 patients. Of the 19 previously diagnosed participants, 6 did not possess any detectable COVID-19 antibodies. CONCLUSIONS: Healthcare workers may have undiagnosed COVID-19, and those previously infected may not have long-lasting immunity. Therefore, hospitals must continue to uphold strict infection control during the COVID-19 pandemic.

Association of Self-reported COVID-19 Infection and SARS-CoV-2 Serology Test Results With Persistent Physical Symptoms Among French Adults During the COVID-19 Pandemic.

Importance: After an infection by SARS-CoV-2, many patients present with persistent physical symptoms that may impair their quality of life. Beliefs regarding the causes of these symptoms may influence their perception and promote maladaptive health behaviors. Objective: To examine the associations of self-reported COVID-19 infection and SARS-CoV-2 serology test results with persistent physical symptoms (eg, fatigue, breathlessness, or impaired attention) in the general population during the COVID-19 pandemic. Design, Setting, and Participants: Participants in this cross-sectional analysis were 26 823 individuals from the French population-based CONSTANCES cohort, included between 2012 and 2019, who took part in the nested SAPRIS and SAPRIS-SERO surveys. Between May and November 2020, an enzyme-linked immunosorbent assay was used to detect anti-SARS-CoV-2 antibodies. Between December 2020 and January 2021, the participants reported whether they believed they had experienced COVID-19 infection and had physical symptoms during the previous 4 weeks that had persisted for at least 8 weeks. Participants who reported having an initial COVID-19 infection only after completing the serology test were excluded. Main Outcomes and Measures: Logistic regressions for each persistent symptom as the outcome were computed in models including both self-reported COVID-19 infection and serology test results and adjusting for age, sex, income, and educational level. Results: Of 35 852 volunteers invited to participate in the study, 26 823 (74.8%) with complete data were included in the present study (mean [SD] age, 49.4 [12.9] years; 13 731 women [51.2%]). Self-reported infection was positively associated with persistent physical symptoms, with odds ratios ranging from 1.39 (95% CI, 1.03-1.86) to 16.37 (95% CI, 10.21-26.24) except for hearing impairment (odds ratio, 1.45; 95% CI, 0.82-2.55) and sleep problems (odds ratio, 1.14; 95% CI, 0.89-1.46). A serology test result positive for SARS-COV-2 was positively associated only with persistent anosmia (odds ratio, 2.72; 95% CI, 1.66-4.46), even when restricting the analyses to participants who attributed their symptoms to COVID-19 infection. Further adjusting for self-rated health or depressive symptoms yielded similar results. There was no significant interaction between belief and serology test results. Conclusions and Relevance: The findings of this cross-sectional analysis of a large, population-based French cohort suggest that persistent physical symptoms after COVID-19 infection may be associated more with the belief in having been infected with SARS-CoV-2 than with having laboratory-confirmed COVID-19 infection. Further research in this area should consider underlying mechanisms that may not be specific to the SARS-CoV-2 virus. A medical evaluation of these patients may be needed to prevent symptoms due to another disease being erroneously attributed to "long COVID."

Results of the RENAISSANCE Study: REsponse to BNT162b2 COVID-19 vacciNe-short- And long-term Immune reSponSe evAluatioN in health Care workErs.

OBJECTIVE: To evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike (S) IgG antibody production after vaccination with BNT162b2 and the protection from symptomatic breakthrough infections in health care workers. METHODS: This prospective observational study (RENAISSANCE) had as a primary end point the evaluation of serologic response to BNT162b2 14 days after a second dose. SARS-CoV-2 anti-S IgG antibodies were evaluated with LIAISON SARS-CoV-2 TrimericS IgG assay (DiaSorin S.p.A.), which is able to detect the presence of both binding and neutralizing antibodies for trimeric spike glycoprotein. Participants were recruited from February 1, 2021, to February 22, 2021. Occurrence of vaccine breakthrough infections was assessed by reverse transcription-polymerase chain reaction on symptomatic and contact cases up to June 6, 2021. RESULTS: Of 2569 staff evaluated, only 4 were nonresponders (0.16%; 95% CI, 0.04% to 0.41%). All 4 nonresponders were severely immunosuppressed and receiving treatment with mycophenolate mofetil or mycophenolic acid. At 14 days after the second dose, 67.5% (1733) of staff had anti-S IgG titers of 2000 BAU/mL or higher; 19.2% (494), between 1500 and 2000 BAU/mL; 9.8% (251), between 1000 and 1500 BAU/mL; and 3.4% (87), 1000 BAU/mL or lower. Women had a higher probability of having higher titers than men (64.5% [1044/1618] vs 58.3% [410/703]; P=.005). This was confirmed after adjustment for age group (odds ratio, 1.275; 95% CI, 1.062 to 1.531; P=.009). Four months after the end of the vaccination program, only 13 participants (0.26%) had experienced a breakthrough SARS-CoV-2 infection, including 1 nonresponder. This was the only participant requiring hospitalization for severe COVID-19. CONCLUSION: The vaccination campaign among health care workers at the ASST GOM Niguarda has resulted in a marked serologic response and reduction of incident COVID-19 cases. Yet, the lack of protection should not be overlooked in immunocompromised individuals.

SARS-CoV-2 infection in central North Carolina: Protocol for a population-based longitudinal cohort study and preliminary participant results.

Public health surveillance systems likely underestimate the true prevalence and incidence of SARS-CoV-2 infection due to limited access to testing and the high proportion of subclinical infections in community-based settings. This ongoing prospective, observational study aimed to generate accurate estimates of the prevalence and incidence of, and risk factors for, SARS-CoV-2 infection among residents of a central North Carolina county. From this cohort, we collected survey data and nasal swabs every two weeks and venous blood specimens every month. Nasal swabs were tested for the presence of SARS-CoV-2 virus (evidence of active infection), and serum specimens for SARS-CoV-2-specific antibodies (evidence of prior infection). As of June 23, 2021, we have enrolled a total of 153 participants from a county with an estimated 76,285 total residents. The anticipated study duration is at least 24 months, pending the evolution of the pandemic. Study data are being shared on a monthly basis with North Carolina state health authorities and future analyses aim to compare study data to state-wide metrics over time. Overall, the use of a probability-based sampling design and a well-characterized cohort will enable collection of critical data that can be used in planning and policy decisions for North Carolina and may be informative for other states with similar demographic characteristics.

SARS-CoV-2 mucosal antibody development and persistence and their relation to viral load and COVID-19 symptoms.

Although serological studies have shown that antibodies against SARS-CoV-2 play an important role in protection against (re)infection, the dynamics of mucosal antibodies during primary infection and their potential impact on viral load and the resolution of disease symptoms remain unclear. During the first pandemic wave, we assessed the longitudinal nasal antibody response in index cases with mild COVID-19 and their household contacts. Nasal and serum antibody responses were analysed for up to nine months. Higher nasal receptor binding domain and spike protein-specific antibody levels at study inclusion were associated with lower viral load. Older age was correlated with more frequent COVID-19 related symptoms. Receptor binding domain and spike protein-specific mucosal antibodies were associated with the resolution of systemic, but not respiratory symptoms. Finally, receptor binding domain and spike protein-specific mucosal antibodies remained elevated up to nine months after symptom onset.

Serological Testing Reveals the Hidden COVID-19 Burden among Health Care Workers Experiencing a SARS-CoV-2 Nosocomial Outbreak.

We describe the results of testing health care workers, from a tertiary care hospital in Japan that had experienced a coronavirus disease 2019 (COVID-19) outbreak during the first peak of the pandemic, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody seroconversion. Using two chemiluminescent immunoassays and a confirmatory surrogate virus neutralization test, serological testing revealed that a surprising 42% of overlooked COVID-19 diagnoses (27/64 cases) occurred when case detection relied solely on SARS-CoV-2 nucleic acid amplification testing (NAAT). Our results suggest that the NAAT-positive population is only the tip of the iceberg and the portion left undetected might potentially have led to silent transmissions and triggered the spread. A questionnaire-based risk assessment was further indicative of exposures to specific aerosol-generating procedures (i.e., noninvasive ventilation and airway suctioning) having mediated transmission and served as the origins of the outbreak. Our observations are supportive of a multitiered testing approach, including the use of serological diagnostics, in order to accomplish exhaustive case detection along the whole COVID-19 spectrum. IMPORTANCE We describe the results of testing frontline health care workers, from a hospital in Japan that had experienced a COVID-19 outbreak, for SARS-CoV-2-specific antibodies. Antibody testing revealed that a surprising 42% of overlooked COVID-19 diagnoses occurred when case detection relied solely on PCR-based viral detection. COVID-19 clusters have been continuously striking the health care system around the globe. Our findings illustrate that such clusters are lined with hidden infections eluding detection with diagnostic PCR and that the cluster burden in total is more immense than actually recognized. The mainstays of diagnosing infectious diseases, including COVID-19, generally consist of two approaches, one aiming to detect molecular fragments of the invading pathogen and the other to measure immune responses of the host. Considering antibody testing as one trustworthy option to test our way through the pandemic can aid in the exhaustive case detection of COVID-19 patients with variable presentations.

Tensor-structured decomposition improves systems serology analysis.

Systems serology provides a broad view of humoral immunity by profiling both the antigen-binding and Fc properties of antibodies. These studies contain structured biophysical profiling across disease-relevant antigen targets, alongside additional measurements made for single antigens or in an antigen-generic manner. Identifying patterns in these measurements helps guide vaccine and therapeutic antibody development, improve our understanding of diseases, and discover conserved regulatory mechanisms. Here, we report that coupled matrix-tensor factorization (CMTF) can reduce these data into consistent patterns by recognizing the intrinsic structure of these data. We use measurements from two previous studies of HIV- and SARS-CoV-2-infected subjects as examples. CMTF outperforms standard methods like principal components analysis in the extent of data reduction while maintaining equivalent prediction of immune functional responses and disease status. Under CMTF, model interpretation improves through effective data reduction, separation of the Fc and antigen-binding effects, and recognition of consistent patterns across individual measurements. Data reduction also helps make prediction models more replicable. Therefore, we propose that CMTF is an effective general strategy for data exploration in systems serology.

Use of Rapid Antigen Testing for SARS-CoV-2 in Remote Communities - Yukon-Kuskokwim Delta Region, Alaska, September 15, 2020-March 1, 2021.

Controlling the spread of SARS-CoV-2, the virus that causes COVID-19, in Alaska is challenging. Alaska includes many remote and isolated villages with small populations (ranging from 15 to >1,000 persons) that are accessible only by air from larger communities. Until rapid point-of-care testing became widely available, a primary challenge in the diagnosis of COVID-19 in rural Alaska was slow turnaround times for SARS-CoV-2 test results, attributable to the need to transport specimens to testing facilities. To provide more timely test results and isolation of cases, the Yukon Kuskokwim Health Corporation (YKHC) introduced Abbott BinaxNOW COVID-19 Ag rapid antigen test (BinaxNOW) on November 9, 2020, in the rural Yukon-Kuskokwim Delta region in southwestern Alaska. To evaluate the impact of implementing antigen testing, YKHC reviewed the results of 54,981 antigen and molecular tests for SARS-CoV-2 performed in the Yukon-Kuskokwim Delta during September 15, 2020-March 1, 2021. Introduction of rapid, point-of-care testing was followed by a more than threefold reduction in daily SARS-CoV-2 case rates during approximately 1 month before the introduction of COVID-19 vaccination. The median turnaround time for SARS-CoV-2 test results decreased by >30%, from 6.4 days during September 15-November 8, 2020, to 4.4 days during November 9, 2020-March 1, 2021 (p<0.001). Daily incidence decreased 65% after the introduction of BinaxNOW, from 342 cases per 100,000 population during the week of November 9 to 119 during the week of December 13 (p<0.001). These findings indicate that point-of-care rapid antigen testing can be a valuable tool in reducing turnaround times in rural communities where local access to laboratory-based nucleic acid amplification testing (NAAT) is not readily available and could thereby reduce transmission by facilitating rapid isolation of infected persons, contact tracing, and implementation of local mitigation strategies.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Qualitative Immunoglobulin G Assays: The Value of Numeric Reporting.

CONTEXT.­: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) testing is used for serosurveillance and will be important to evaluate vaccination status. Given the urgency to release coronavirus disease 2019 (COVID-19) serology tests, most manufacturers have developed qualitative tests. OBJECTIVE.­: To evaluate clinical performance of 6 different SARS-CoV-2 IgG assays and their quantitative results to better elucidate the clinical role of serology testing in COVID-19. DESIGN.­: Six SARS-CoV-2 IgG assays were tested using remnant specimens from 190 patients. Sensitivity and specificity were evaluated for each assay with the current manufacturer's cutoff and a lower cutoff. A numeric result analysis and discrepancy analysis were performed. RESULTS.­: Specificity was higher than 93% for all assays, and sensitivity was higher than 80% for all assays (≥7 days post-polymerase chain reaction testing). Inpatients with more severe disease had higher numeric values compared with health care workers with mild or moderate disease. Several discrepant serology results were those just below the manufacturers' cutoff. CONCLUSIONS.­: Severe acute respiratory syndrome coronavirus 2 IgG antibody testing can aid in the diagnosis of COVID-19, especially with negative polymerase chain reaction. Quantitative COVID-19 IgG results are important to better understand the immunologic response and disease course of this novel virus and to assess immunity as part of future vaccination programs.

Classification under uncertainty: data analysis for diagnostic antibody testing.

Formulating accurate and robust classification strategies is a key challenge of developing diagnostic and antibody tests. Methods that do not explicitly account for disease prevalence and uncertainty therein can lead to significant classification errors. We present a novel method that leverages optimal decision theory to address this problem. As a preliminary step, we develop an analysis that uses an assumed prevalence and conditional probability models of diagnostic measurement outcomes to define optimal (in the sense of minimizing rates of false positives and false negatives) classification domains. Critically, we demonstrate how this strategy can be generalized to a setting in which the prevalence is unknown by either (i) defining a third class of hold-out samples that require further testing or (ii) using an adaptive algorithm to estimate prevalence prior to defining classification domains. We also provide examples for a recently published SARS-CoV-2 serology test and discuss how measurement uncertainty (e.g. associated with instrumentation) can be incorporated into the analysis. We find that our new strategy decreases classification error by up to a decade relative to more traditional methods based on confidence intervals. Moreover, it establishes a theoretical foundation for generalizing techniques such as receiver operating characteristics by connecting them to the broader field of optimization.