Duration of Protection Against SARS-CoV-2 Reinfection and Associated Risk of Reinfection Assessed with Real-World Data

ImportanceBetter understanding of the protective duration of prior SARS-CoV-2 infection against reinfection is needed. ObjectivePrimary: To assess the durability of immunity to SARS-CoV-2 reinfection among initially unvaccinated individuals with previous SARS-CoV-2 infection. Secondary: Evaluate the crude SARS-CoV-2 reinfection rate and associated characteristics. Design and SettingRetrospective observational study of HealthVerity data among 144,678,382 individuals, during the pandemic era through April 2021. ParticipantsIndividuals studied had SARS-CoV-2 molecular diagnostic or antibody index test results from February 29 through December 9, 2020, with [≥]365 days of pre-index continuous closed medical enrollment, claims, or electronic health record activity. Main Outcome(s) and Measure(s)Rates of reinfection among index-positive individuals were compared to rates of infection among index-negative individuals. Factors associated with reinfection were evaluated using multivariable logistic regression. For both objectives, the outcome was a subsequent positive molecular diagnostic test result. ResultsAmong 22,786,982 individuals with index SARS-CoV-2 laboratory test data (2,023,341 index positive), the crude rate of reinfection during follow-up was significantly lower (9.89/1,000-person years) than that of primary infection (78.39/1,000 person years). Consistent with prior findings, the risk of reinfection among index-positive individuals was 87% lower than the risk of infection among index-negative individuals (hazard ratio, 0.13; 95% CI, 0.13, 0.13). The cumulative incidence of reinfection among index-positive individuals and infection among index-negative individuals was 0.85% (95% CI: 0.82%, 0.88%) and 6.2% (95% CI: 6.1%, 6.3%), respectively, over follow-up of 375 days. The duration of protection against reinfection was stable over the median 5 months and up to 1-year follow-up interval. Factors associated with an increased reinfection risk included older age, comorbid immunologic conditions, and living in congregate care settings; healthcare workers had a decreased reinfection risk. Conclusions and RelevanceThis large US population-based study demonstrates that SARS-CoV-2 reinfection is uncommon among individuals with laboratory evidence of a previous infection. Protection from SARS-CoV-2 reinfection is stable up to one year. Reinfection risk was primarily associated with age 85+ years, comorbid immunologic conditions and living in congregate care settings; healthcare workers demonstrated a decreased reinfection risk. These findings suggest that infection induced immunity is durable for variants circulating prior to Delta. Key PointsO_ST_ABSQuestionC_ST_ABSHow long does prior SARS-CoV-2 infection provide protection against SARS-CoV-2 reinfection? FindingAmong >22 million individuals tested February 2020 through April 2021, the relative risk of reinfection among those with prior infection was 87% lower than the risk of infection among individuals without prior infection. This protection was durable for up to a year. Factors associated with increased likelihood of reinfection included older age (85+ years), comorbid immunologic conditions, and living in congregate care settings; healthcare workers had lower risk. MeaningPrior SARS-CoV-2 infection provides a durable, high relative degree of protection against reinfection.

Use of an EHR to inform an administrative data algorithm to categorize inpatient COVID-19 severity

STRUCTURED ABSTRACTO_ST_ABSImportanceC_ST_ABSAlgorithms for classification of inpatient COVID-19 severity are necessary for confounding control in studies using real-world data (RWD). ObjectiveTo explore use of electronic health record (EHR) data to inform an administrative data algorithm for classification of supplemental oxygen or noninvasive ventilation (O2/NIV) and invasive mechanical ventilation (IMV) to assess disease severity in hospitalized COVID-19 patients. DesignIn this retrospective cohort study, we developed an initial procedure-based algorithm to identify O2/NIV, IMV, and NEITHER O2/NIV nor IMV in two inpatient RWD sources. We then expanded the algorithm to explore the impact of adding diagnoses indicative of clinical need for O2/NIV (hypoxia, hypoxemia) or IMV (acute respiratory distress syndrome) and O2-related patient vitals available in the EHR. Observed changes in severity categorization were used to augment the administrative algorithm. SettingOptum de-identified COVID-19 EHR data and HealthVerity claims and chargemaster data (March - August 2020). ParticipantsAmong patients hospitalized with COVID-19 in each RWD source, our motivating example selected dexamethasone (DEX+) initiators and a random selection of patients who were non-initiators of a corticosteroid of interest (CSI-) matched on date of DEX initiation, age, sex, baseline comorbidity score, days since admission, and COVID-19 severity level (NEITHER, O2/NIV, IMV) on treatment index. Main Outcome and MeasuresInpatient COVID-19 severity was defined using the algorithms developed to classify respiratory support requirements among hospitalized COVID-19 patients (NEITHER, O2/NIV, IMV). Measures were reported as the treatment-specific distributions of patients in each severity level, and as observed changes in severity categorization between the initial procedure-based and expanded algorithms. ResultsIn the administrative data cohort with 5,524 DEX+ and CSI- patient pairs matched using the initial procedure-based algorithm, 30% were categorized as O2/NIV, 5% as IMV, and 65% as NEITHER. Among patients assigned NEITHER via the initial algorithm, use of an expanded algorithm informed by the EHR-based algorithm shifted 54% DEX+ and 28% CSI- to O2/NIV, and 2% DEX+ and 1% CSI- to IMV. Among patients initially assigned O2/NIV, 7% DEX+ and 3% CSI- shifted to IMV. Conclusions and RelevanceApplication of learnings from an EHR-based exploration to our administrative algorithm minimized treatment-differential misclassification of COVID-19 severity.

Real-world data suggest antibody positivity to SARS-CoV-2 is associated with a decreased risk of future infection

ImportanceThere is limited evidence regarding whether the presence of serum antibodies to SARS-CoV-2 is associated with a decreased risk of future infection. Understanding susceptibility to infection and the role of immune memory is important for identifying at-risk populations and could have implications for vaccine deployment. ObjectiveThe purpose of this study was to evaluate subsequent evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among individuals who are antibody-positive compared with those who are antibody-negative, using real-world data. DesignThis was an observational descriptive cohort study. ParticipantsThe study utilized a national sample to create cohorts from a de-identified dataset composed of commercial laboratory test results, open and closed medical and pharmacy claims, electronic health records, hospital billing (chargemaster) data, and payer enrollment files from the United States. Patients were indexed as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test recorded in the database. Patients with more than 1 antibody test on the index date where results were discordant were excluded. Main Outcomes/MeasuresPrimary endpoints were index antibody test results and post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, as measured in 30-day intervals (0-30, 31-60, 61-90, >90 days). Additional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, such as recorded signs and symptoms or prior evidence of COVID-19 (diagnoses or NAAT+) and recorded comorbidities. ResultsWe included 3,257,478 unique patients with an index antibody test. Of these, 2,876,773 (88.3%) had a negative index antibody result, 378,606 (11.6%) had a positive index antibody result, and 2,099 (0.1%) had an inconclusive index antibody result. Patients with a negative antibody test were somewhat older at index than those with a positive result (mean of 48 versus 44 years). A fraction (18.4%) of individuals who were initially seropositive converted to seronegative over the follow up period. During the follow-up periods, the ratio (CI) of positive NAAT results among individuals who had a positive antibody test at index versus those with a negative antibody test at index was 2.85 (2.73 - 2.97) at 0-30 days, 0.67 (0.6 - 0.74) at 31-60 days, 0.29 (0.24 - 0.35) at 61-90 days), and 0.10 (0.05 - 0.19) at >90 days. ConclusionsPatients who display positive antibody tests are initially more likely to have a positive NAAT, consistent with prolonged RNA shedding, but over time become markedly less likely to have a positive NAAT. This result suggests seropositivity using commercially available assays is associated with protection from infection. The duration of protection is unknown and may wane over time; this parameter will need to be addressed in a study with extended duration of follow up. Key PointsO_ST_ABSQuestionC_ST_ABSCan real-world data be used to evaluate the comparative risk of SARS-CoV-2 infection for individuals who are antibody-positive versus antibody-negative? FindingOf patients indexed on a positive antibody test, 10 of 3,226 with a NAAT (0.3%) had evidence of a positive NAAT > 90 days after index, compared with 491 of 16,157 (3.0%) indexed on a negative antibody test. MeaningIndividuals who are seropositive for SARS-CoV-2 based on commercial assays may be at decreased future risk of SARS-CoV-2 infection.