Assessing Vulnerability to COVID-19 in High-Risk Populations: The Role of SARS-CoV-2 Spike-Targeted Serology.

Individuals at increased risk for severe coronavirus disease-2019 (COVID-19) outcomes, due to compromised immunity or other risk factors, would benefit from objective measures of vulnerability to infection based on vaccination or prior infection. The authors reviewed published data to identify a specific role and interpretation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike-targeted serology testing. Specific recommendations are provided for an evidence-based and clinically-useful interpretation of SARS-CoV-2 spike-targeted serology to identify vulnerability to infection and potential subsequent adverse outcomes. Decreased vaccine effectiveness among immunocompromised individuals is linked to correspondingly high rates of breakthrough infections. Negative results on SARS-CoV-2 antibody tests are associated with increased risk for subsequent infection. "Low-positive" results on semiquantitative SARS-CoV-2 spike-targeted antibody tests may help identify persons at increased risk as well. Standardized SARS-CoV-2 spike-targeted antibody tests may provide objective information on the risk of SARS-CoV-2 infection and associated adverse outcomes. This holds especially for high-risk populations that demonstrate a relatively high rate of seronegativity. The widespread availability of such tests presents an opportunity to refine risk assessment for individuals with suboptimal SARS-CoV-2 antibody levels and to promote effective interventions. Interim federal guidance would support physicians and patients while additional investigations are pursued.

Risk of and duration of protection from SARS-CoV-2 reinfection assessed with real-world data.

This retrospective observational study aimed to gain a better understanding of the protective duration of prior SARS-CoV-2 infection against reinfection. The objectives were two-fold: to assess the durability of immunity to SARS-CoV-2 reinfection among initially unvaccinated individuals with previous SARS-CoV-2 infection, and to evaluate the crude SARS-CoV-2 reinfection rate and associated risk factors. During the pandemic era time period from February 29, 2020, through April 30, 2021, 144,678,382 individuals with SARS-CoV-2 molecular diagnostic or antibody test results were studied. 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. Consistent with prior findings, the risk of reinfection among index-positive individuals was 87% lower than the risk of infection among index-negative individuals. 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. This large US population-based study suggests that infection induced immunity is durable for variants circulating pre-Delta predominance.

Changes in ganglioside antibody positivity rates during the COVID-19 pandemic.

Reports suggested an association between SARS-CoV-2 infection and GBS, but subsequent studies produced conflicting results regarding the incidence of GBS during the pandemic. This study assessed positivity rates for GQ1b, GM-1, GD1a, and GD1b for tests performed January 2016, through March 2021, at a national laboratory. Relative to pre-pandemic levels, positivity rates during the pandemic declined by 61% for GQ1b and 24% for GM-1, while unchanged for GD1a and GD1b. These findings suggest heterogeneity with positivity rates of GBS-associated ganglioside antibodies during the COVID-19 pandemic. Mitigation strategies during the pandemic may have reduced the frequency of certain forms of GBS.

Patterns of Prostate-Specific Antigen Testing and Prostate Biopsies During the COVID-19 Pandemic.

PURPOSE: This study examined changes in prostate disease screening (prostatic-specific antigen [PSA] testing), prostate biopsy testing, and prostate cancer diagnoses during the COVID-19 pandemic through December 2020. MATERIALS AND METHODS: This analysis included test results from men ≥ 40 years, without prior International Classification of Diseases-10 record of prostate cancer since January 2016, who received PSA or prostate biopsy testing at Quest Diagnostics during January 2018-December 2020. Monthly trends were evaluated for three periods: prepandemic (January 2018-February 2020), early-pandemic (March-May 2020), and late-pandemic (June-December 2020). RESULTS: Meeting inclusion criteria were 16,365,833 PSA and 48,819 prostate biopsy results. The average monthly number of PSA tests declined from 465,187 prepandemic to 295,786 early-pandemic (36.4% decrease; P = .01) before rebounding to 483,374 (3.9% increase; P = .23) late-pandemic. The monthly average number of PSA results ≥ 50 ng/mL (23,356; 0.14% of all PSA results) dipped from 659 prepandemic to 506 early-pandemic (23.2% decrease; P = .02) and rebounded to 674 late-pandemic (2.3% increase; P = .65). The average monthly number of prostate biopsy results decreased from 1,453 prepandemic to 903 early-pandemic (37.9% decrease; P = .01) before rebounding to 1,190 late-pandemic (18.1% decrease; P = .01). The average monthly number for Gleason score ≥ 8 (6,241; 12.8% of all prostate biopsies) declined from 182 prepandemic to 130 early-pandemic (28.6% decrease; P = .02) and decreased to 161 late-pandemic (11.5% decrease; P = .02). CONCLUSION: The findings suggest that a substantial number of prostate screening opportunities and cancer diagnoses have been missed. Efforts are needed to bring such patients back for screening and diagnostic testing and to restore appropriate care for non-COVID-19-related medical conditions.

Decreases in Hepatitis C Testing and Treatment During the COVID-19 Pandemic.

INTRODUCTION: The COVID-19 pandemic has disrupted healthcare services, reducing opportunities to conduct routine hepatitis C virus antibody screening, clinical care, and treatment. Therefore, people living with undiagnosed hepatitis C virus during the pandemic may later become identified at more advanced stages of the disease, leading to higher morbidity and mortality rates. Further, unidentified hepatitis C virus-infected individuals may continue to unknowingly transmit the virus to others. METHODS: To assess the impact of the COVID-19 pandemic, data were evaluated from a large national reference clinical laboratory and from national estimates of dispensed prescriptions for hepatitis C virus treatment. Investigators estimated the average number of hepatitis C virus antibody tests, hepatitis C virus antibody-positive test results, and hepatitis C virus RNA-positive test results by month in January-July for 2018 and 2019, compared with the same months in 2020. To assess the impact of hepatitis C virus treatment, dispensed hepatitis C virus direct-acting antiretroviral medications were examined for the same time periods. Statistical analyses of trends were performed using negative binomial models. RESULTS: Compared with the 2018 and 2019 months, hepatitis C virus antibody testing volume decreased 59% during April 2020 and rebounded to a 6% reduction in July 2020. The number of hepatitis C virus RNA-positive results fell by 62% in March 2020 and remained 39% below the baseline by July 2020. For hepatitis C virus treatment, prescriptions decreased 43% in May, 37% in June, and 38% in July relative to the corresponding months in 2018 and 2019. CONCLUSIONS: During the COVID-19 pandemic, continued public health messaging, interventions and outreach programs to restore hepatitis C virus testing and treatment to prepandemic levels, and maintenance of public health efforts to eliminate hepatitis C infections remain important.

Insights from Patterns of SARS-CoV-2 Immunoglobulin G Serology Test Results from a National Clinical Laboratory, United States, March-July 2020.

Serologic tests for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provide information on past infection and immune response. To better understand the persistence of immune response and the proportion of the population who can develop one, the authors assessed patterns of immunoglobulin G (IgG) positivity over time in individuals tested for SARS-CoV-2 RNA or IgG at a large national reference laboratory. More than 2.4 million SARS-CoV-2 IgG serology (initiated April 21, 2020) and 6.6 million nucleic acid amplification testing (NAAT) (initiated March 9, 2020) results on persons from across the United States as of July 10, 2020 were analyzed. Additional IgG serology results through August 11, 2020 were used for one household analysis. SARS-CoV-2 IgG positivity was observed in 91% (19,434/21,452) of individuals tested after a positive NAAT result and in 10% (7,831/80,968) after a negative NAAT result. Factors associated with seropositivity include age, region of patient residence, and interval between NAAT and IgG serology. The probability of persistent IgG seropositivity declined from 98.6% after 1 week to 74.3% after 2 months, less so in individuals ages ≥55 years than in younger groups. Specimens within 2 days from pairs of same-household members showed 92% IgG antibody concordance. Household adults were more frequently IgG positive prior to household children testing positive (36% versus 8%). IgG serology testing can identify an immune response to SARS-CoV-2 that varies based on age, sex, and duration since exposure. Loss of detectable IgG seropositivity occurs, in some patients, over weeks or months. Adults may be infecting household children.

The Opioid Epidemic Within the COVID-19 Pandemic: Drug Testing in 2020.

The convergence of the opioid epidemic and the coronavirus disease 2019 (COVID-19) pandemic has created new health care challenges. The authors analyzed changes in clinical drug testing patterns and results at a national clinical laboratory, comparing data obtained before and during the pandemic. Testing for prescription and illicit drugs declined rapidly during the pandemic, with weekly test volumes falling by approximately 70% from the baseline period to the trough (the week beginning March 29) before rising in subsequent weeks. Among individuals tested, positivity increased by 35% for non-prescribed fentanyl and 44% for heroin during the pandemic. Positivity for non-prescribed fentanyl increased significantly among patients positive for other drugs: by 89% for specimens positive for amphetamines; 48% for benzodiazepines; 34% for cocaine; and 39% for opiates (P < 0.01 for all comparisons). These findings suggest significant increases in dangerous drug combinations. Positivity for non-prescribed use of many other drugs remained consistent or declined for some drugs, relative to pre-pandemic patterns. Models adjusting for potential confounding variables, including medication-assisted treatment and treatment at a substance use disorder facility indicated that the risk for non-prescribed fentanyl positivity rose by more than 50% during the pandemic. In summary, these findings demonstrate decreased drug testing overall, with increased positivity for high-risk drugs and dangerous drug combinations. The convergence of the drug abuse epidemic and COVID-19 pandemic has led to an increased need for health care and public health resources dedicated to supporting vulnerable patients and addressing the underlying causes of these disturbing trends.

Impact of the COVID-19 Pandemic on Chlamydia and Gonorrhea Screening in the U.S.

INTRODUCTION: This study evaluates the impact of the COVID-19 pandemic on testing for common sexually transmitted infections. Specifically, changes are measured in chlamydia and gonorrhea testing and case detection among patients aged 14-49 years during the COVID-19 pandemic. METHODS: U.S. chlamydia and gonorrhea testing and positivity were analyzed on the basis of >18.6 million tests (13.6 million tests for female patients and 4.7 million tests for male patients) performed by a national reference clinical laboratory from January 2019 through June 2020. RESULTS: Chlamydia and gonorrhea testing reached a nadir in early April 2020, with decreases (relative to the baseline level) of 59% for female patients and 63% for male patients. Declines in testing were strongly associated with increases in weekly positivity rates for chlamydia (R2=0.96) and gonorrhea (R2=0.85). From March 2020 through June 2020, an expected 27,659 (26.4%) chlamydia and 5,577 (16.5%) gonorrhea cases were potentially missed. CONCLUSIONS: The COVID-19 pandemic impacted routine sexually transmitted infection services, suggesting an increase in syndromic sexually transmitted infection testing and missed asymptomatic cases. Follow-up analyses will be needed to assess the long-term implications of missed screening opportunities. These findings should serve as a warning for the potential sexual and reproductive health implications that can be expected from the overall decline in testing and potential missed cases.

Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection.

Importance: Understanding the effect of serum antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on susceptibility to infection is important for identifying at-risk populations and could have implications for vaccine deployment. Objective: The study purpose was to evaluate evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among patients with positive vs negative test results for antibodies in an observational descriptive cohort study of clinical laboratory and linked claims data. Design, Setting, and Participants: The study created cohorts from a deidentified data set composed of commercial laboratory tests, medical and pharmacy claims, electronic health records, and hospital chargemaster data. Patients were categorized as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test in the database. Main Outcomes and Measures: Primary end points were post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, 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, including recorded signs and symptoms or prior evidence of coronavirus 2019 (COVID) diagnoses or positive NAAT results and recorded comorbidities. Results: The cohort included 3 257 478 unique patients with an index antibody test; 56% were female with a median (SD) age of 48 (20) years. Of these, 2 876 773 (88.3%) had a negative index antibody result, and 378 606 (11.6%) had a positive index antibody result. Patients with a negative antibody test result were older than those with a positive result (mean age 48 vs 44 years). Of index-positive patients, 18.4% converted to seronegative over the follow-up period. During the follow-up periods, the ratio (95% CI) of positive NAAT results among individuals who had a positive antibody test at index vs those with a negative antibody test at index was 2.85 (95% CI, 2.73-2.97) at 0 to 30 days, 0.67 (95% CI, 0.6-0.74) at 31 to 60 days, 0.29 (95% CI, 0.24-0.35) at 61 to 90 days, and 0.10 (95% CI, 0.05-0.19) at more than 90 days. Conclusions and Relevance: In this cohort study, patients with positive antibody test results were initially more likely to have positive NAAT results, consistent with prolonged RNA shedding, but became markedly less likely to have positive NAAT results over time, suggesting that seropositivity is associated with protection from infection. The duration of protection is unknown, and protection may wane over time.

Pooling of Upper Respiratory Specimens Using a SARS-CoV-2 Real-time RT-PCR Assay Authorized for Emergency Use in Low-Prevalence Populations for High-Throughput Testing.

BACKGROUND: Nucleic acid amplification testing is a critical tool for addressing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Specimen pooling can increase throughput and conserve testing resources but requires validation to ensure that reduced sensitivity does not increase the false-negative rate. We evaluated the performance of a real-time reverse transcription polymerase chain reaction (RT-PCR) test authorized by the US Food and Drug Administration (FDA) for emergency use for pooled testing of upper respiratory specimens. METHODS: Positive specimens were selected from 3 prevalence groups, 1%-3%, >3%-6%, and >6%-10%. Positive percent agreement (PPA) was assessed by pooling single-positive specimens with 3 negative specimens; performance was assessed using Passing-Bablok regression. Additionally, we assessed the distributions of RT-PCR cycle threshold (Ct) values for 3091 positive specimens. RESULTS: PPA was 100% for the 101 pooled specimens. There was a linear relationship between Ct values for pooled and single-tested specimens (r = 0.96-0.99; slope ≈ 1). The mean pooled Ct shifts at 40 cycles were 2.38 and 1.90, respectively, for the N1 and N3 targets. The median Cts for 3091 positive specimens were 25.9 (N1) and 24.7 (N3). The percentage of positive specimens with Cts between 40 and the shifted Ct was 1.42% (N1) and 0.0% (N3). CONCLUSIONS: Pooled and individual testing of specimens positive for SARS-CoV-2 demonstrated 100% agreement, which demonstrates the viability of pooled specimens for SARS-COV-2 testing using a dual-target RT-PCR system. Pooled specimen testing can help increase testing capacity for SARS-CoV-2 with a low risk of false-negative results.

Disparities in SARS-CoV-2 Positivity Rates: Associations with Race and Ethnicity.

Numerous reports indicate that African Americans and Latinos are being affected disproportionately by coronavirus disease 2019 (COVID-19). Positivity rates have not been analyzed on scale because only 4 states report race/ethnicity as part of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. Previous studies also have had little ability to control for many known risk factors to better identify the effects of COVID-19 on racial and ethnic communities. Using test results from a large national reference laboratory database that included patients from all 50 states and the District of Columbia, this study compared positivity rates for SARS-CoV-2 nucleic acid amplification tests (NAAT) among various race/ethnicity groups by linking zip code-based race/ethnicity proportions from US Census data. Analysis of 2,331,175 unique patients tested March-May 2020 demonstrated an increasing trend in SARS-CoV-2 NAAT positivity across Black non-Hispanic community progressive quintiles (from 7.8% to 17.2%, P < 0.0001) and Hispanic community progressive quintiles (from 8.4% to 15.5%, P < 0.0001) and a decreasing trend across White non-Hispanic community progressive quintiles (from 17.4% to 7.1%, P < 0.0001). These trends in viral ribonucleic acid positivity remained in stratified analyses and in multivariable models that controlled for known risk factors including sex, population density, and the states initially hardest hit by COVID-19. These findings indicate that communities with the highest proportions of Black non-Hispanic and Hispanic populations have the highest SARS-CoV-2 NAAT positivity rates, even after controlling for other risk factors. More efforts are needed to mitigate the increased impact of COVID-19 on both the African American and Hispanic communities.

SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels.

Until treatment and vaccine for coronavirus disease-2019 (COVID-19) becomes widely available, other methods of reducing infection rates should be explored. This study used a retrospective, observational analysis of deidentified tests performed at a national clinical laboratory to determine if circulating 25-hydroxyvitamin D (25(OH)D) levels are associated with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) positivity rates. Over 190,000 patients from all 50 states with SARS-CoV-2 results performed mid-March through mid-June, 2020 and matching 25(OH)D results from the preceding 12 months were included. Residential zip code data was required to match with US Census data and perform analyses of race/ethnicity proportions and latitude. A total of 191,779 patients were included (median age, 54 years [interquartile range 40.4-64.7]; 68% female. The SARS-CoV-2 positivity rate was 9.3% (95% C.I. 9.2-9.5%) and the mean seasonally adjusted 25(OH)D was 31.7 (SD 11.7). The SARS-CoV-2 positivity rate was higher in the 39,190 patients with "deficient" 25(OH)D values (<20 ng/mL) (12.5%, 95% C.I. 12.2-12.8%) than in the 27,870 patients with "adequate" values (30-34 ng/mL) (8.1%, 95% C.I. 7.8-8.4%) and the 12,321 patients with values ≥55 ng/mL (5.9%, 95% C.I. 5.5-6.4%). The association between 25(OH)D levels and SARS-CoV-2 positivity was best fitted by the weighted second-order polynomial regression, which indicated strong correlation in the total population (R2 = 0.96) and in analyses stratified by all studied demographic factors. The association between lower SARS-CoV-2 positivity rates and higher circulating 25(OH)D levels remained significant in a multivariable logistic model adjusting for all included demographic factors (adjusted odds ratio 0.984 per ng/mL increment, 95% C.I. 0.983-0.986; p<0.001). SARS-CoV-2 positivity is strongly and inversely associated with circulating 25(OH)D levels, a relationship that persists across latitudes, races/ethnicities, both sexes, and age ranges. Our findings provide impetus to explore the role of vitamin D supplementation in reducing the risk for SARS-CoV-2 infection and COVID-19 disease.