bluuebunny/crossref_metadata_2025 huggingface dataset:
360. Evaluation of Cycle Threshold Values in Patients with Symptomatic COVID-19 Infection
Authors: Dixon Danielle , Madrid-Morales Julieta , Cadena-Zuluaga Jose , Frei Christopher R
Published: December 2021

Background

One of the tests used to identify COVID-19 infections is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) test. There is a measure known as the cycle threshold (Ct) value, which provides an indirect measure of viral load. It has been proposed that the Ct value could help with clinical decisions regarding duration of isolation. We hypothesize that Ct values will correlate with symptom duration in a population of veterans with COVID-19 infection.

Methods

We reviewed the records of patients presenting to the emergency department (ED) or admitted to Audie L. Murphy VA Medical Center in San Antonio, Texas with positive SARS-CoV-2 PCR tests. We looked at patients who received multiple SARS-CoV-2 RT-qPCR tests. We compared date of onset of symptoms and cycle threshold values from their initial test to another test ordered after 7, 10, and 20 days from symptom onset. We recorded the Ct value for the N2 and E genes. Patients were classified into mild, severe and critical based on Center for Disease Control and Prevention (CDC) criteria. A Ct value of >30 as threshold for transmissible disease was used based on previously published studies.

Results

We identified 49 patients with more than two SARS-CoV-2 RT-qPCR tests. Patients with mild disease with tests less than or equal to ten days from symptom onset (n=10) had a mean Ct value 23.2 (±5.6) and 26.0 (±5.8) for the E and N2 genes. Patients with mild disease with tests greater than ten days from symptom onset (n=4) had mean Ct values of 26.0 (±6.5) and 27.8 (±6.8). When we stratified the patient population by disease severity, patients with severe and critical disease with tests less than ten days from symptom onset (n=24) had mean Ct values of 20.1 (±7.3) and 23.4 (±7.5). Patients with severe and critical disease greater than twenty days (n=6) had Ct values of 29.0 (±5.1) and 31.1 (±5.4).

Conclusion

We found that Ct values increased with longer symptom duration. We currently use the CDC criteria to discontinue isolation at ten days for mild disease and twenty days for severe and critical disease. The findings of this study suggest that our current practice for duration of isolation correlates with increasing Ct values near or above the threshold for transmissible disease.

Disclosures

All Authors: No reported disclosures
361. Aseptic Meningitis Associated to SARS Cov2 Infection and MIS-C: Pediatric Presentation of Covid-19
Authors: Quintero Mónica J Olguín , Pellegrini Sergio RenÉ Bonilla , JuÁrez Rodolfo N JimÉnez , Casillas María Citlalli Casillas
Published: December 2021

Background

Novel SARS CoV2 may target the central nervous system and several neurological symptoms have been reported in patients with Coronavirus disease (COVID-19). Mucocutaneous and inflammatory symptoms are important in pediatric population associated to immune dysregulation. There are few reports of clinical manifestations in children and less frequently the isolation and affection of Central Nervous System.

Methods

A previously healthy four months female infant with familiar contact to SARS-CoV2 four weeks ago. Start with fever of 104°F, vomiting, maculopapular rash on the anterior thorax and upper extremities involving the palms and soles associated with edema. On physical examination, irritable, bulging anterior fontanelle, non-purulent bilateral conjunctival injection, cheilitis and rash was confirmed.

Results

Laboratory findings: thrombocytopenia, elevated D-Dimer, fibrinogen, PCT, CRP, ferritin and ESR with hypoalbuminemia. MIS-C is integrated with cutaneous, gastrointestinal and neurological affections. Empirically ceftriaxone, vancomycin and acyclovir are started due to suspicion of meningoencephalitis. RT-PCR for SARS-CoV-2 positive. CSF: transparent appearance, slightly xanthochromic color, coagulation and negative film. Proteins 105 mg / dl, glucose 45 mg / dl, leukocytes 121 mm3, erythrocytes 66 mm3, PMN 8% and MNN 92%. Negative culture,PCR Herpes Virus negative,Viral load for SARS CoV2 in CSF 3,400 cop / ml and plasma 118,900 cop / ml, Aseptic meningitis is confirmed by SARS-CoV-2. Antiviral and antibiotics are discontinued and Gamma globulin and methylprednisolone are administered. Evolving favorably and egress at 6th day to complete oral steroid treatment for 3 more day.

Conclusion

The mechanism by which SARS-CoV2 affects the CNS is still unknown.This findings suggests direct infection can be possible. Although it is also described vascular affection has been found that the Spike protein of the virus binds to ACE-2 receptor present in the cerebral vascular endothelium. Neurological manifestations have been described even without respiratory symptoms. A novel pediatric case with viral load for SARS-CoV-2 in CSF is demonstrated. Importance of detecting SARS-CoV-2 in children with encephalitis, which can progress satisfactorily.

Disclosures

All Authors: No reported disclosures
363. Characteristics of Envelope and Nuclear Gene Expression Patterns in Asymptomatic SARS-CoV-2 Patients: A Single Center Retrospective Observational Study
Authors: Mizuno Keiko , Komatu Takayuki , Usuda Daisuke , Hocchi Shiori , Ashizawa Karin , Aoki Takashi , Ogura Kanako , Takami Hiroki , Nomura Tomohisa , Sugita Manabu
Published: December 2021

Background

Reverse transcription-polymerase chain reaction (RT-PCR) is used for the diagnosis of COVID-19, caused by SARS-CoV-2. RT-PCR is a method that detects the virus by amplifying two regions of the target viral genome, namely the nuclear (N) and envelope (E) encoding sequences. However, no reports have shown a relationship between the symptoms and the gene expression patterns, especially in asymptomatic patients. Herein, we validated the characteristics of E and N gene expression patterns using RT-PCR on samples obtained from asymptomatic COVID-19-positive patients.

Methods

In this retrospective cohort study, conducted at Juntendo University Nerima Hospital, Tokyo, Japan, SARS-Cov-2 RT-PCR positive patients whose specimens had been obtained and analyzed by our laboratory technicians from September 1, 2020 to December 31, 2020 were enrolled. For RT-PCR, the LightMix Modular SARS-CoV-2 reagent (TIB MOLBIOL company) was used. After excluding patients who had symptoms, background, demographic, laboratory, and gene expression pattern data were collected from RT-PCR-positive asymptomatic patients. We also investigated patients who met the release criteria of the Center for Disease Control and prevention. Continuous and categorical variables were analyzed, with p< 0.05 set as statistical significance using the student-t test, chi-square test, or Fisher’s exact test, respectively.

Results

Of 92 RT-PCR-positive asymptomatic patients, 57 comprised the expression E only group (Group E) and 35 comprised the E+N group (Group E+N). Significantly more patients in Group E met the release criteria compared to those in Group E+N [41 (71%) vs 10 (28%), p< 0.001]. Among patients who met the release criteria, those in Group E+N had significantly more immunosuppression [7 (70%) vs 8 (30%), p=0.004].

Moreover, among the patients who underwent RT-PCR screening, no patients in Group E developed symptoms [0 vs 6 (42%), p=0.02].

Conclusion

The results of this study suggest that RT-PCR-positive asymptomatic patients can be divided into three patterns: pre-symptomatic, gene E+N-positive patients; post-symptomatic covid-19-recovered patients, regardless of gene E and N expression patterns; and false positive, gene E-positive patients.

Disclosures

All Authors: No reported disclosures
364. Individualized Prognostics in COVID-19 Facilitated by Computer Recognition of Blood Leukocyte Subsets
Authors: Libertin Claudia R , Kempaiah Prakash , Durvasula Ravindra , Rivas Ariel
Published: December 2021

Background

To determine whether CBC differentials of COVID+ inpatients can predict, at admission, both maximum oxygen requirements (MOR) and 30-day mortality.

Methods

Based on an approved IRB protocol, CBC differentials from the first 3 days of hospitalization of 12 SARS CoV-2 infected patients were retrospectively extracted from hospital records and analyzed with a privately owned Pattern Recognition Software (PRS, US Patent 10,429,389 B2) previously validated in sepsis, HIV, and hantavirus infections. PRS partitions the data into subsets immunologically dissimilar from one another, although internally similar.

Results

Regardless of the angle considered, the classic analysis −which measured the percentages of lymphocytes, monocytes, and neutrophils− did not distinguish outcomes (A). In contrast, non-overlapping patterns generated by the PRS differentiated 3 (left, vertical, and right) groups of patients (B). One subset was only composed of survivors (B). The remaining subsets included the highest oxygenation requirements (B). At least two immunologically interpretable, multi-cellular indicators distinguished the 3 data subsets with statistically significant differences (C, p≤ 0.05). Survivors (the left subset) showed lower N/L and/or higher M/L ratios than non-survivors (the vertical subset, C).Therefore, PRS partitioned the data into subsets that displayed both biological and significant differences. Because it offers visually explicit information, clinicians do not require a specialized training to interpret PRS-generated results.

CBCs vs. outcomes - Software-analyzed CBCs vs. outcomes

Conclusion

(1) Analysis of blood leukocyte data predicts MOR and 30-d mortality. (2) Real time PRS analysis facilitates personalized medical decisions. (3) PRS measures two dimensions rarely assessed: multi-cellularity and dynamics. (4) Even with very small datasets, PRS may achieve statistical significance. (5) Larger COVID+ infected cohort is being analyzed for potential commercialization.

Disclosures

Claudia R. Libertin, MD, Gilead (Grant/Research Support)
366. Abbott BinaxNOW Rapid Antigen Test Performance in Detecting SARS-CoV-2 Infections in a COVID-19 Outbreak Among Horse Racetrack Workers
Authors: Surasi Krishna , Cummings Kristin J , Hanson Carl V , Morris Mary Kate , Salas Maria , Seftel David , Ortiz Liza M , Thilakaratne Ruwan , Stainken Cameron , Wadford Debra
Published: December 2021

Background

Rapid antigen tests (e.g., Abbott’s BinaxNOW) are cheaper and faster than nucleic acid amplification tests (e.g., real-time reverse transcription polymerase chain reaction [RT-PCR]) for SARS-CoV-2 infection, with variable reported sensitivity. A horse racetrack in California experienced a COVID-19 outbreak among staff and used BinaxNOW to supplement RT-PCR. Utility of BinaxNOW in detecting SARS-CoV-2 infection in a workplace outbreak was assessed.

Methods

Between November 25–December 22, 2020, anterior nasal swabs were collected from racetrack staff for six rounds of paired BinaxNOW and RT-PCR tests. BinaxNOW tests were interpreted according to manufacturer instructions. RT-PCR was performed at the state public health lab using the ThermoFisher TaqPath COVID-19 Combo Kit. Staff with positive results on either test were isolated and removed from subsequent testing. Viral cultures were attempted on specimens with cycle threshold (Ct) < 30.

Results

Overall, 769 paired results from 342 staff were analyzed. Most were of Hispanic ethnicity (62.0%) and ages ranged from 18 to 92 years (median 52). BinaxNOW performance compared to RT-PCR (95% CI) was as follows: positive percent agreement (PPA) 43.3% (34.6%–52.4%); negative percent agreement (NPA) 100% (99.4%–100%); positive predictive value (PPV) 100% (93.5%–100%); negative predictive value 89.9% (87.5%–92.0%). Among 127 RT-PCR-positive specimens, those with paired BinaxNOW-positive results (n = 55) had a lower mean Ct value than those with paired BinaxNOW-negative results (n = 72) (17.8 vs. 28.5) (p < 0.001). In dual positive pairs, median time from specimen collected to RT-PCR result reported was 4 days (range 1-6), compared to the 15-minute BinaxNOW reporting time. Of 100 Ct < 30 specimens, 51 resulted in positive virus isolation, 45 (88.2%) of which were BinaxNOW-positive.

Conclusion

High NPA and PPV support immediate isolation of BinaxNOW-positive individuals, while low PPA supports confirmatory testing following BinaxNOW-negative results. BinaxNOW performed better in paired specimens with lower Ct value and positive viral cultures, which could suggest that among RT-PCR-positive specimens, those that are BinaxNOW-negative may be less likely to contain infectious virus than those that are BinaxNOW-positive.

Disclosures

David Seftel, M.D., M.D., M.B.A., Enable Biosciences, Inc (Board Member, Employee, Scientific Research Study Investigator, Shareholder)
367. Role of Conventional Biomarker for Prediction of Chest CT-confirmed COVID-19 Pneumonia
Authors: Harnphadungkit Monprach , Siripongboonsitti Taweegrit
Published: December 2021

Background

The coronavirus disease 2019 (COVID-19) has a wide range of severity. Chest computed tomography (CT) had high sensitivity and specificity to identify COVID-19 pneumonia. However, chest CT was not available in almost all hospitals in pandemic settings, including developed countries. This study is to evaluate the potential role of conventional inflammatory biomarkers to predict COVID-19 pneumonia.

Methods

All 155 RT-PCR-confirmed COVID-19 patients were evaluated for pneumonia by chest CT from April 10, 2021 to May 3, 2021 in the outpatient unit, a Thai university hospital. The inflammatory biomarkers were evaluated the sensitivity, specificity, LR+, LR-, and ROC to predict COVID-19 pneumonia.

Results

Of all 155 patients, pneumonia was diagnosed by chest CT in 117 patients. The pneumonia patients had a median (IQR) age of 38 (30, 55) years old. The BMI was higher in pneumonia than mild illness in 25.5 (22.0, 29.5) and 22.9 (19.4, 26.9) kg/m2, respectively (p=0.031). In univariate analysis, serum high-sensitivity C-reactive protein (hsCRP), lactate dehydrogenase (LDH), ferritin, total lymphocyte count (TLC), and albumin were associated with pneumonia, but the only hsCRP demonstrated association by multivariate analysis. The area under the ROC curves (AUC) was 0.82, 0.74, 0.68, 0.38, and 0.37 in hsCRP, LDH, ferritin, TLC, and albumin, respectively. The optimal cut-off level for CRP to diagnose COVID-19 pneumonia was 2.00 mg/L given sensitivity, specificity, LR+, LR- of 81.9%, 70.3%, 2.75, and 0.26 respectively (Figure 1 and Table 1).

ROC Curve of hsCRP to Diagnose of COVID-19 Pneumonia

This figure shows ROC curve for hsCRP to diagnose of chest CT-confirmed COVID-19 pneumonia. The area under the ROC curve is 0.82. The optimal cut-off value for hsCRP is 2.00 given sensitivity of 81.9% and specificity of 70.3%.

Conclusion

The hsCRP was the conventional biomarker that had an excellent performance in predicting COVID-19 pneumonia lead to early anti-SARS-CoV-2 treatment. This study demonstrated the potential role of hsCRP combined with clinical assessment in negative chest X-rays to replace chest CT in a high burden COVID-19 country during pandemic situations.

Disclosures

All Authors: No reported disclosures
370. Examining the Relationship Between SARS-CoV-2 PCR Cycle Threshold, Disease Severity and Epidemiologic Trends
Authors: Penney Jessica , Jung Amanda , Koethe Benjamin , Doron Shira
Published: December 2021

Background

Real-time reverse transcriptase PCR (rRT-PCR) has become the primary method for detection of SARS-CoV-2. Specific measurements of cycle threshold (Ct) values can give an estimate of viral load. Previous studies have shown temporal trends in Ct values, which could be used to predict the phase of the pandemic. This study’s goal was to examine the relationship between Ct and disease severity, as well as Ct trends.

Methods

Testing was performed using the Abbott M2000 SARS-CoV-2 assay. Data was collected for 262 SARS-CoV-2 positive patients from March-May 2020. Kruskal-Wallis testing was performed to determine differences in median Ct based on age, gender, race and ethnicity. To determine relationship between symptom onset and clinical severity with Ct, linear and logistic regression were performed.

Results

The majority of the patients had mild to moderate disease. Average time since symptom onset was 5.9 days, and 92% were symptomatic. Figure 1 demonstrates the distribution of Ct by disease severity at time of testing. There was no significant difference in cycle threshold by sex, age, race or ethnicity. Figure 2 shows weekly mean cycle threshold by total new cases in Massachusetts to reflect temporal trend of Ct and cases. In the multivariable linear regression model, Ct increased with days since symptom onset (P< 0.001). Cycle threshold was inversely associated with disease severity in multivariable logistic regression though (OR 1.06, 95%CI 1.01-1.11, p=0.03), even when controlling for time since symptom onset.

Figure 1. Distribution of Ct by disease severity at time of SARS-CoV-2 testing

Boxplot demonstrating distribution of Ct by disease severity at time of testing. There was no significant difference between groups.

Figure 2. Weekly Mean Cycle Threshold by Total New MA Cases

Line represents mean Ct over time period included in this study overlaid on total new cases in Massachusetts. Lower Ct were seen in the course as cases were increasing which peaked as cases stabilized.

Conclusion

Cycle threshold increased with time since symptom onset, consistent with prior data showing increasing Ct from time since infection due to decreasing viral replication. This study showed an inverse relationship between cycle threshold and disease severity, which differs from previous studies which demonstrated higher odds of progression to severe disease and mortality with lower Ct. This finding may reflect the disease severity associated with the secondary inflammatory phase of SARS-CoV-2 seen later in the disease course, although there was only moderate correlation between Ct and time since symptom onset. Further research is needed to better understand the role of Ct in predicting clinical severity of SARS-CoV-2 infections.

Disclosures

All Authors: No reported disclosures
372. Detection of SARS-CoV-2 RNAemia in Deceased Tissue Donors
Authors: Greenwald Melissa , Grebe Eduard , Green Valerie , Jones Alyce Linthurst , Williamson Philip , Busch Michael , Kuehnert Matthew
Published: December 2021

Background

Tissue donors are evaluated for communicable disease in order to minimize the risk of transmission to recipients. Although there are data suggesting SARS-CoV-2 viremia across a wide spectrum of illness, prevalence in deceased tissue donors and the potential for transplant transmission are unknown.

Methods

Eight tissue banks participated in a retrospective analysis of samples from eligible deceased tissue donors from Oct 2019 through June 2020, one participant in Canada and the remainder located in the United States. All four Census regions of the continental US and all major racial-ethnic groups were represented. EDTA or sodium citrate plasma aliquots were tested in singlicate with the Research Use Only Procleix SARS-CoV-2 Assay on the Procleix Panther System, which uses transcription-mediated nucleic acid amplification (TMA) technology for detection of the SARS-CoV-2 RNA. Plasma (or if unavailable, serum) aliquots were sent to Grifols for an alternate SARS-CoV-2 nucleic acid amplification (NAT) test to verify reactivity and also sent for antibody testing using the emergency use authorization Ortho VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test. The VITROS assay uses immunometric technology for qualitative measurement of total antibody (IgG, IgA and IgM) to SARS-CoV-2. The proportion of donors with confirmed RNAemia (i.e., presence of SARS-CoV-2 RNA in plasma or serum) and 95% confidence intervals were computed.

Results

Of 3,455 donor samples with valid final results, 26 (0.76%) were initially positive for SARS-CoV-2 RNA; of these, 3 were confirmed by alternate NAT. Of donor samples collected in 2019 0.00% (95% CI: 0.00%,0.43%) were confirmed RNAemic, while of those collected in 2020, 0.12% (0.04%,0.34%) were confirmed RNAemic. One of 26 initial positive, and none of the three samples confirmed by alternate NAT, tested positive for anti-SARS-CoV-2 Spike antibodies by serology. Infectivity studies are pending on one sample with sufficient available volume.

Conclusion

The rate of SARS-CoV-2 RNAemia in deceased tissue donors is approximately 1 per 1,000, and it is unknown whether this RNAemia reflects the presence of infectious virus. Given these results, the risk of transmission through tissue is most likely to be low.

Disclosures

Melissa Greenwald, MD, Alamo Biologics (Consultant)Eurofins VRL Laboratories (Consultant)Right Cell Biologics (Consultant, Consultant Medical Director) Eduard Grebe, PhD, Gilead Sciences (Consultant)Sedia Biosciences Corporation (Consultant, Grant/Research Support)Vitalant (Employee) Alyce Linthurst Jones, PhD, LifeNet Health (Employee) Matthew Kuehnert, MD, American Association of Tissue Banks (Board Member)ICCBBA (Board Member)Musculoskeletal Transplant Foundation (Employee)
373. Household transmission of SARS-CoV-2 B.1.1.7 lineage –2 U.S. States, 2021
Authors: Soto Raymond , Hsu Christoper , Chuey Meagan , Donnelly Marisa , Chu Victoria T , Schwartz Noah G , Tong Suxiang , Thornburg Natalie J , Killerby Marie E , Staples J Erin , Kirking Hannah L , Tate Jacqueline , Matanock Almea , Stringer Ginger , Albanese Bernadette , Beatty Mark , Hughes Laura J
Published: December 2021

Background

In December 2020, B.1.1.7 lineage of SARS-CoV-2 was first detected in the United States and has since become the dominant lineage. Previous investigations involving B.1.1.7 suggested higher rates of transmission relative to non-B.1.1.7 lineages. We conducted a household transmission investigation to determine the secondary infection rates (SIR) of B.1.1.7 and non-B.1.1.7 SARS-CoV-2 lineages.

Methods

From January–April 2021, we enrolled members of households in San Diego County, CA, and Denver, CO metropolitan area (Tri-County), with a confirmed SARS-CoV-2 infection in a household member with illness onset date in the previous 10 days. CDC investigators visited households at enrollment and 14 days later at closeout to obtain demographic and clinical data and nasopharyngeal (NP) samples on all consenting household members. Interim visits, with collection of NP swabs, occurred if a participant became symptomatic during follow-up. NP samples were tested for SARS-CoV-2 using TaqPath™ RT-PCR test, where failure to amplify the spike protein results in S-Gene target failure (SGTF) may indicate B.1.1.7 lineage. Demographic characteristics and SIR were compared among SGTF and non-SGTF households using two-sided p-values with chi-square tests; 95% confidence intervals (CI) were calculated with Wilson score intervals.

Results

552 persons from 151 households were enrolled. 91 (60%) households were classified as SGTF, 57 (38%) non-SGTF, and 3 (2%) indeterminant. SGTF and non-SGTF households had similar sex distribution (49% female and 52% female, respectively; P=0.54) and age (median 30 years, interquartile range (IQR 14–47) and 31 years (IQR 15–45), respectively). Hispanic people accounted for 24% and 32% of enrolled members of SGTF and non-SGTF households, respectively (p=0.04). At least one secondary case occurred in 61% of SGTF and 58% of non-SGTF households (P=0.66). SIR was 52% (95%[CI] 46%-59%) for SGTF and 45% (95% CI 37%-53%) for non-SGTF households (P=0.18).

Conclusion

SIRs were high in both SGTF and non-SGTF households; our findings did not support an increase in SIR for SGTF relative to non-SGTF households in this setting. Sequence confirmed SARS-CoV-2 samples will provide further information on lineage specific SIRs.

Disclosures

All Authors: No reported disclosures
374. Need to Improve Minority Representation through COVID-19 Community Research Partnership
Authors: Dantuluri Keerti , Rossman Whitney , Lu Lauren C , Dunn Connell O , Harris Anna M , Hetherington Timothy , Priem Jennifer , Ahmed Amina , Ahmed Amina
Published: December 2021

Background

Minorities are often unrepresented in research, which limits equity in healthcare advances. The racial and ethnic disparities in outcomes of individuals infected with COVID-19 highlight the importance of inclusivity in research to improve public health measures.

Methods

We performed a descriptive analysis of the racial and ethnic distribution of children enrolled in our COVID-19 Community Research Partnership (CRP) study, a syndromic and serological surveillance study of children aged 2 – 17 years receiving care at three healthcare systems spanning North and South Carolina. Syndromic surveillance involved daily symptom reporting using a web-based monitoring application. Participants consenting to serological surveillance were mailed at-home tests sampling finger prick capillary blood. In-person and electronic recruitment efforts were conducted in English and Spanish. At one of the study sites, we compared the racial/ethnic distribution of enrolled children to the racial/ethnic distribution of all children who received care at the same site during the same timeframe. We compared the racial/ethnic distribution of participants who ultimately submitted samples for serological testing compared to those who consented to serologic testing.

Results

At total of1630 children were enrolled from April 2, 2021 – June 8, 2021. Most children were > 5 years old, 50.2% were female, and 88.5% were from mostly urban counties (Table 1). Of enrolled children, 4.2% were Hispanic, 8.2% were black, and 81.6% were white (Table 2). Among 135,355 unique children who received care at the institution during the same time, 12.4% were Hispanic, 23.0% were black, and 63.1% were white. Of 1552 participants who consented to serologic testing, 4.4% were Hispanic, 8.1% were black, and 81.8% were white (Table 3). To date, 242 children submitted serologic samples; 4.1% were Hispanic, 5.0% were black, and 85.5% were white.

Table 1. Characteristics of enrolled children in COVID-19 surveillance study

Table 2. Racial and Ethnic distribution of children enrolled in the study compared to target population

Table 3. Racial and ethnic distribution of children who participated in serology testing

Conclusion

Despite efforts to recruit a diverse group of children, the proportion of minorities enrolled in our COVID-19 surveillance study underrepresents the targeted population. Ongoing efforts will work to identify barriers and facilitators to research participation among minority families.

Disclosures

Amina Ahmed, MD, Nothing to disclose
375. High Laboratory-confirmed SARS-CoV-2 Attack Rate in Lima Health Care Personnel During August 2020-March 2021 Suggests Role for Improved Infection Control
Authors: Westercamp Matthew , Soto Giselle , Smith Rachel , Azziz-Baumgartner Eduardo , Bollinger Susan , Castillo Roger , Cuentas Alejandro Llanos , Grogl Max , Olson Natalie , Prouty Mike , Matos Eduardo , Romero Candice , Silva Marita , Lessa Fernanda C , Lessa Fernanda C , Arriola Carmen S
Published: December 2021

Background

Peru has one of the highest per capita SARS-CoV-2 death rates in Latin America. Healthcare workers (HCW) are a critical workforce during the COVID-19 pandemic but are themselves often at increased risk of infection. We evaluated SARS-CoV-2 attack rate and risk factors among frontline HCWs.

Methods

We performed a prospective cohort study of HCW serving two acute care hospitals in Lima, Peru from Aug 2020 to Mar 2021. Participants had baseline SARS-CoV-2 serology using the CDC ELISA, active symptom monitoring, and weekly respiratory specimen collection with COVID-19 exposure/risk assessment for 16-weeks regardless of symptoms. Respiratory specimens were tested by real-time reverse transcriptase PCR (rRT-PCR).

Results

Of 783 eligible, 667 (85%) HCW were enrolled (33% nurse assistants, 29% non-clinical staff, 26% nurses, 7% physicians, and 6% other). At baseline and prior to COVID-19 vaccine introduction, 214 (32.1%; 214/667) were reactive for SARS-CoV-2 antibodies. In total, 72 (10.8%; 72/667) HCWs were found to be rRT-PCR positive during weekly follow-up. Of the rRT-PCR positive HCWs, 37.5% (27/72) did not report symptoms within 1-week of specimen collection. During follow up, HCW without detectable SARS-CoV-2 antibodies at baseline were significantly more likely to be rRT-PCR positive (65/453, 14.3%) compared to those with SARS-CoV-2 antibodies at baseline (4/214, 1.9%) (p-value: < 0.001). Three HCW were both serologically reactive and rRT-PCR positive at baseline. Looking only at HCW without SARS-CoV-2 antibodies, nurse assistants (rRT-PCR positive: 18.6%; 27/141) and non-clinical healthcare workers (16.5%; 21/127) were at greater risk of infection compared to nurses (8.5%; 10/118), physicians (7.9%; 3/38), and other staff (10.3%; 4/29) (RR 1.95;95%CI 1.2,3.3; p-value: 0.01).

Conclusion

Baseline SARS-CoV-2 prevalence and 16-week cumulative incidence were substantial in this pre-vaccination Peruvian HCW cohort. Almost 40% of new infections occurred in HCW without complaint of symptoms illustrating a limitation of symptom-based HCW screening for COVID-19 prevention. Nurse assistants and non-clinical healthcare workers were at greater risk of infection indicating a role for focused infection prevention and risk reduction strategies for some groups of HCW.

Disclosures

Fernanda C. Lessa, MD, MPH, Nothing to disclose
376. Sensitivity and Specificity of the WHO Probable SARS-CoV-2 Case Definition Among Symptomatic Healthcare Personnel
Authors: Nguyen Han , Weber Sarah , Kataria Yachana , Cole Manisha , Duffy Elizabeth , Ragan Elizabeth , Turcinovic Jacquelyn , Miller Nancy , Hanage William P , Connor John , Pierre Cassandra , Jacobson Karen , Lodi Sara , Bouton Tara
Published: December 2021

Background

SARS-CoV-2 continues to spread globally, including in limited resource settings. It is therefore important to derive general case definitions that can be useful and accurate in the absence of timely test results. We aim to validate the World Health Organization (WHO) case definition, a symptom-screening tool currently used to identify SARS-CoV-2 cases in a cohort of symptomatic health care providers (HCP) who completed a symptom survey interview and received a PCR test at Boston Medical Center (BMC) between March 13, 2020 and May 5, 2020.

Methods

We classified each HCP as a probable or not probable case of SARS-CoV-2 based on the WHO case definition. Using PCR test as gold standard, we computed the sensitivity and specificity of the WHO case definition. We used a stepwise logistic regression model on all PCR-tested HCP to identify symptoms predictive of PCR positivity.

Results

Of 328 included HCP, 109 (33.2%) were PCR positive, 213 (64.9%) negative, and 6 (1.8%) had indeterminate test result. The sensitivity and specificity of the WHO case definition were 65.1% and 74.6%, respectively. The positive predictive value was 56.8% and the negative predictive value was 80.7%. Symptoms found to be predictive of PCR positivity were fever, headache, loss of smell and/or loss of taste, and muscle ache/joint pain. Sore throat was found to be predictive of PCR negativity. The area under the curve using the final model was 0.8412. All statistically significant symptoms included in the final model, were also included in the WHO case definition.

Conclusion

In our largely symptomatic HCP cohort, our model yielded similar symptoms to those identified in the WHO probable case definition. As seen in similar studies, it is unlikely that further adjustment will improve the performance of a SARS-CoV-2 case definition. However, it is concerning that 35% (38/109) of PCR positive SARS-CoV-2 HCP would have been classified as not probable cases by the WHO definition, given that this definition does not even include asymptomatic cases. This is further evidence for global building of laboratory capacity and development of affordable diagnostics to improve global pandemic control.

Disclosures

All Authors: No reported disclosures
377. SARS-CoV-2 Genomic Surveillance Reveals Little Spread Between a Large University Campus and the Surrounding Community
Authors: Valesano Andrew , Fitzsimmons William , Blair Christopher , Woods Robert , Gilbert Julie , Rudnik Dawn , Mortenson Lindsey , Petrie Joshua G , Martin Emily T , Lauring Adam
Published: December 2021

Background

Understanding SARS-CoV-2 transmission dynamics is critical for controlling and preventing outbreaks. The genomic epidemiology of SARS-CoV-2 on college campuses has not been comprehensively studied, and the extent to which campus-associated outbreaks lead to transmission in nearby communities is unclear. We used high-density genomic surveillance to track SARS-CoV-2 transmission across the University of Michigan-Ann Arbor campus and Washtenaw County during the Fall 2020 semester.

Methods

We retrieved all available residual diagnostic specimens from the Michigan Medicine Clinical Microbiology Laboratory and University Health Service that were positive for SARS-CoV-2 from August 16th – November 25th, 2020 (n = 2245). We extracted viral RNA, amplified the SARS-CoV-2 genome by multiplex RT-PCR, and sequenced these amplicons on an Illumina MiSeq. We applied maximum likelihood phylogenetic analysis to whole genome sequences to define and characterize transmission lineages.

Results

We assembled complete viral genomes from 1659 individual infections, representing roughly 25% of confirmed cases in Washtenaw County across the fall semester. Of these cases, 468 were University of Michigan students. Phylogenetic analysis revealed 203 genetically distinct introductions of SARS-CoV-2 into the student population, most of which were singletons (n = 171) or small clusters of 2 – 8 students. We identified two large SARS-CoV-2 transmission lineages (115 and 73 students, respectively), including individuals from multiple on-campus residences. Viral descendants of these student outbreaks were rare, constituting less than 4% of cases in the community.

Conclusion

We identified many SARS-CoV-2 transmission introductions into the University of Michigan campus in Fall 2020. While there was widespread transmission among students, there is little evidence that these outbreaks significantly contributed to the rise in COVID-19 cases that Washtenaw County experienced in November 2020.

Disclosures

Adam Lauring, MD, PhD, Roche (Advisor or Review Panel member) Sanofi (Consultant)
378. Descriptive Analysis of SARS-CoV-2 Infections Among Health System and University Employees
Authors: Seidelman Jessica , Akinboyo Ibukunoluwa , Rinehart Maya , Moehring Rebekah W , Anderson Deverick J , Said Kristen , Epling Carol A , Lewis Sarah S , Smith Becky , Stiegel Matthew
Published: December 2021

Background

We aimed to describe SARS-CoV-2 (COVID-19) infections among employees in a large, academic institution.

Table 1. COVID-19 Attribution Definitions

Table 2. Description of 3,140 COVID 19 Infections in Employees from 3/2020 to 4/2021

Methods

We prospectively tracked and traced COVID-19 infections among employees across our health system and university. Each employee with a confirmed positive test and 3 presumed positive cases were interviewed with a standard contact tracing template that included descriptive variables such as high-risk behaviors and contacts, dates worked while infectious, and initial symptoms. Using this information, the most likely location of infection acquisition was adjudicated (Table 1). We compared behavior frequency between community and unknown, likely community and community and unknown cases using descriptive statistics.

Table 3. Risk Factors for Community, Likely Community, and Unknown Cases

Number of SARS-CoV-2 cases among employees between 3/2020 and 4/2021 by month and stratified according to clinical employee working in the healthcare system, non-clinical employee employed by the healthcare system, and university employee

Results

From 3/2020 to 4/2021 we identified 3,140 COVID-19 infections in 3,119 employees out of a total of 34,562 employees (9.0%) (Figure 1). Of those 3,119 employees 1,685 (54.0%) were clinical employees working in the health system, 916 (29.4%) were non-clinical employees working in the health system, and 518 (16.6%) were university employees. Descriptive characteristics for the COVID-19 infections and adjudications are outlined in Table 2. Severe disease among employees was significantly less frequent compared to patients in the health system (15.3% vs 2.2%, p< 0.01). The frequency of travel within 14 days, masked gatherings and unmasked gatherings/activities was not significantly different between the community and unknown, likely community groups or the community and unknown groups (Table 3).

Conclusion

The majority of COVID-19 infections were linked to acquisition in the community, and few were attributed to workplace exposures. Employees with unknown sources of COVID-19 participated in higher-risk activities at approximately the same frequency as employees with community sources of COVID-19. The most frequently reported initial symptoms were mild and non-specific and rarely included fever. Despite a comprehensive testing and benefit program, a large proportion of COVID-positive employees worked with symptoms, highlighting ongoing challenges with presenteeism in healthcare.

Disclosures

Rebekah W. Moehring, MD, MPH, UpToDate, Inc. (Other Financial or Material Support, Author Royalties)
379. Abstract For Comparison of Mandatory vs Non-Mandatory Compliance Rates For SARS-CoV-2 Testing in Grades K-12
Authors: Veltman Jennifer , Papayanis Philip , Dubov Alex
Published: December 2021

Background

Rapid testing to identify asymptomatically infected students with SARS-CoV-2 in elementary schools has been suggested as a possible method to reduce risk for in person instruction. As of August 3, 2020 (updated on January 25, 2021), California schools who obtained a waiver to conduct in-person instruction are not required to have mandatory testing for asymptomatic students, except for high contact sports which are required to undergo weekly testing. We explored the uptake of voluntary vs mandatory testing in a private waivered school.

Methods

Between the dates January 25, 2021 to April 16, 2021, the K-12 school superintendent sent an email to all parents outlining the voluntary testing program with a link to the on-line sign up and consent form. All students were offered weekly self-collected anterior nares BinaxNOW Rapid Antigen Test. Signed parental consent was required and tests were performed at the school. Students participating in contact sports were required to undergo testing the week a varsity game was played as a condition of participation. Data was gathered from the school administration and de-identified.

Results

K-5 Lower school had a school population of 448 students. Testing was offered on 8 weeks during the period of 2/15-2/19 to 4/5-4/9. 2 students (0.45%) receive screening on the week of 3/22-3/26. The other seven weeks when screening was offered 0 students received screening. 6-12 Upper school had a school population of 360 enrolled students. Testing was offered 3/8-3/12 and 3/15-3/19. The upper school had 22 students (6.11%) receive testing on the week of 3/8-3/12 and 21 students (5.83%) on the week of 3/15-3/19. Contact sports teams had 67 students on their roster. Weekly testing was offered from 3/22-3/26 to 4/12-4/16. Contact sports teams had 10 students (14.93%) receive testing on the week of 3/22-3/26, 33 students (52.24%) on the week of 4/5-4/9, and 32 students (49.25%) on the week of 4/12-4/16.

Figure 1. Percent of students from each campus and sports team screened per week offered.

Conclusion

Voluntary SARS-CoV-2 screening was not a feasible approach for detection of asymptomatically infected individuals due to low uptake, however in the same school, mandatory testing had high uptake and would be a feasible strategy.

Disclosures

All Authors: No reported disclosures
380. Environmental Contamination with SARS-CoV-2 in Nursing Homes
Authors: Mody Lona , Gibson Kristen , Bautista Liza , Neeb Karen , Montoya Ana , Jenq Grace , Mills John , Min Lillian , Mantey Julia , Kabeto Mohammed , Galecki Andrzej , Cassone Marco , Martin Emily T
Published: December 2021

Background

The COVID-19 pandemic has disproportionately affected nursing home (NH) patients, accounting for 5% of all cases and 32% of all COVID-19 deaths nationwide. Little is known about the frequency and persistence of SARS-CoV-2 environmental contamination in NHs. We characterize SARS-CoV-2 contamination in the rooms of COVID-19 patients and common areas in and around COVID-19 units.

Methods

A prospective cohort study was conducted at four NHs in Michigan between October 2020 and January 2021. Clinical research personnel obtained swab specimens from high-touch room surfaces of COVID-19 infected patients, up to three times per patient. Weekly swab specimens from six high-touch surfaces in common areas were also obtained. Demographic and clinical data were collected from patient clinical records. Our primary outcome of interest was the probability of SARS-CoV-2 detection from specific environmental surfaces in COVID-19 patient rooms.

Results

One hundred four patients with COVID-19 were enrolled and followed for 241 visits. Patient characteristics included: 61.5% over the age of 80; 67.3% female; 89.4% non-Hispanic white; 50.1% short-stay. The study population had significant disabilities in activities of daily living (ADL; 81.7% dependent in four or more ADLs) and comorbidities including dementia (55.8%), diabetes (40.4%) and heart failure (32.7) (Table 1). Over the 3-month study period, 2087 swab specimens were collected (1896 COVID-19 patient room surfaces, 191 common area swabs). Figure 1 shows contamination rates at sites proximate and distant to the patient bed. SARS-CoV-2 positivity was 28.4% (538/1896 swabs) on patient room surfaces and 3.7% (7/191 swabs) on common area surfaces. Over the course of follow-up, 89.4% (93/104) of patients had SARS-CoV-2 contamination in their room at least once (Figure 2). Environmental contamination detected on enrollment correlated with contamination of the same site during follow-up. Functional independence increased the odds of proximate contamination.

Table 1. Clinical and Demographic Characteristics of the Study Population Including Short- and Long-stay Patients

Figure 1. Contamination of Environmental Surfaces Relative to Distance from Patient Bed

Figure 2. SARS-CoV-2 on Swab Specimens Collected – Patient-level, Visit-level, and Swab-level

Conclusion

We conclude that environmental contamination of surfaces in the rooms of COVID-19 patients is nearly universal and persistent. Patients with greater independence are more likely than fully dependent patients to contaminate their immediate environment.

Disclosures

All Authors: No reported disclosures
382. Vitamin D Supplementation and Covid 19: Results from the U.S. N3C Data Enclave
Authors: Murray Kim , Fairfield Kathleen M , Rosen Clifford james , Hodder Sally L , Harper Jeremy
Published: December 2021

Background

It is estimated that 18% of adults in the U.S. take Vitamin D supplements. Some observational studies suggest that vitamin D supplementation activates the innate immune system and reduces the incidence and severity of viral infections. During the SARS-CoV-2 pandemic, vitamin D supplements were touted as a potential therapy to prevent the disease and/or complications. However, supportive evidence is lacking.

Methods

The National COVID Cohort Collaborative (N3C) enclave is the largest COVID-19 data base with nearly 1.4 million positive patients at 56 sites in the U.S. We performed a retrospective analysis of vitamin D supplementation, either prescribed before or during hospitalization for SARS-CoV-2.

Results

137,399 people took vitamin D supplements out of 1.4 million. Females prescribed vitamin D outnumbered males by almost 2:1, whereas in non-users there were no sex differences. Most supplement users were older than 50. African Americans constituted 13% of the non-users, but 23% of those prescribed vitamin D. Infected individuals with any vitamin D supplementation, pre-Covid, post-Covid or both, had a 6.66% mortality rate vs 2% mortality in non-users. Similarly, nearly a third of the supplement users were hospitalized compared to 11% in the non-users. The Charlson Co-Morbidity Index was 3.0±3 (SD) in users vs 1.0±2 (SD) in non-users.

Conclusion

10% of SARS-CoV-2 infected patients were taking vitamin D. They tended to be older, more likely to be African American and have significant co-morbidities. Hospitalization and mortality were higher among those taking Vitamin D in this cohort. Vitamin D is widely used to prevent and treat SARS-CoV-2 but without evidence of efficacy.

Disclosures

Sally L. Hodder, M.D., Gilead (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Viiv Healthcare (Grant/Research Support, Advisor or Review Panel member)
383. Feasibility of Specimen Self-collection in Young Children Undergoing SARS-CoV-2 Surveillance for In-person Learning
Authors: Altamirano Jonathan , Tam Grace , Lopez Marcela , Robinson India , Chun Leanne , Shaikh Nuzhat , Leary Sean , Carrington Yuan J , Jani Shilpa , Pulendran Uma , Ma Jasmin , Toomarian Elizabeth , Wang C Jason , Govindarajan Prasanthi , Blomkalns Andra , Robinson Makeda , Maldonado Yvonne A
Published: December 2021

Background

While pediatric cases of COVID-19 are at low risk for adverse events, schoolchildren should be considered for surveillance as they can become infected at school and serve as sources of household or community transmission. Our team assessed the feasibility of young children self-collecting SARS-CoV-2 samples for surveillance testing in an educational setting.

Methods

Students at a K-8 school were tested weekly for SARS-CoV-2 from September 2020 - June 2021. Error rates were collected from September 2020 - January 2021. Clinical staff provided all students with instructions for anterior nares specimen self-collection and then observed them to ensure proper technique. Instructions included holding the sterile swab while making sure not to touch the tip, inserting the swab into their nostril until they start to feel resistance, and rubbing the swab in four circles before repeating the process in their other nostril. An independent observer timed random sample self-collections from April - June 2021.

Results

2,590 samples were collected from 209 students during the study period when data on error rates were collected. Errors occurred in 3.3% of all student encounters (n=87). Error rates over time are shown in Figure 1, with the highest rate occurring on the first day of testing (n=20/197, 10.2%) and the lowest in January 2021 (n=1/202, 0.5%). 2,574 visits for sample self-collection occurred during the study period when independent timing data was collected (April - June 2021). Of those visits, 7.5% (n=193) were timed. The average duration of each visit was 70 seconds.

Figure 1. Swab Error Rates Over Time

Conclusion

Pediatric self-collected lower nasal swabs are a viable and easily tolerated specimen collection method for SARS-CoV-2 surveillance in school settings, as evidenced by the low error rate and short time window of sample self-collection during testing. School administrators should expect errors to drop quickly after implementing testing.

Disclosures

All Authors: No reported disclosures