Prevalence of SARS-CoV-2 in hemoglobinopathies is modified by age and race.

Prior literature has established a positive association between sickle cell disease and risk of contracting SARS-CoV-2. Data from a cross-sectional study evaluating COVID-19 testing devices (n = 10,567) was used to examine the association between underlying health conditions and SARS-CoV-2 infection in an urban metropolis in the southern United States. Firth's logistic regression was used to fit the model predicting SARS-CoV-2 positivity using vaccine status and different medical conditions commonly associated with COVID-19. Another model using the same method was built using SARS-CoV-2 positivity as the outcome and hemoglobinopathy presence, age (<16 Years vs. ≥16 Years), race/ethnicity and comorbidities, including hemoglobinopathy, as the factors. Our first model showed a significant association between hemoglobinopathy and SARS-CoV-2 infection (OR: 2.28, 95 % CI: (1.17,4.35), P = 0.016). However, in the second model, this association was not maintained (OR: 1.35, 95 % CI: (0.72,2.50), P = 0.344). We conclude that the association between SARS-CoV-2 positivity and presence of hemoglobinopathies like sickle cell disease is confounded by race, age, and comorbidity status. Our results illuminate previous findings by identifying underlying clinical/demographic factors that confound the reported association between hemoglobinopathies and SARS-CoV-2. These findings demonstrate how social determinants of health may influence disease manifestations more than genetics alone.

Utilizing river and wastewater as a SARS-CoV-2 surveillance tool to predict trends and identify variants of concern in settings with limited formal sewage systems.

The COVID-19 pandemic continues to impact health systems globally and robust surveillance is critical for pandemic control, however not all countries can sustain community surveillance programs. Wastewater surveillance has proven valuable in high-income settings, but little is known about how river and informal sewage in low-income countries can be used for environmental surveillance of SARS-CoV-2. In Malawi, a country with limited community-based COVID-19 testing capacity, we explored the utility of rivers and wastewater for SARS-CoV-2 surveillance. From May 2020 â€" January 2022, we collected water from up to 112 river or informal sewage sites/month, detecting SARS-CoV-2 in 8.3% of samples. Peak SARS-CoV-2 detection in water samples predated peaks in clinical cases. Sequencing of water samples identified the Beta, Delta, and Omicron variants, with Delta and Omicron detected well in advance of detection in patients. Our work highlights wastewater can be used for detecting emerging waves, identifying variants of concern and function as an early warning system in settings with no formal sewage systems.

Outbreak.info genomic reports: scalable and dynamic surveillance of SARS-CoV-2 variants and mutations.

In response to the emergence of SARS-CoV-2 variants of concern, the global scientific community, through unprecedented effort, has sequenced and shared over 11 million genomes through GISAID, as of May 2022. This extraordinarily high sampling rate provides a unique opportunity to track the evolution of the virus in near real-time. Here, we present outbreak.info , a platform that currently tracks over 40 million combinations of Pango lineages and individual mutations, across over 7,000 locations, to provide insights for researchers, public health officials and the general public. We describe the interpretable visualizations available in our web application, the pipelines that enable the scalable ingestion of heterogeneous sources of SARS-CoV-2 variant data and the server infrastructure that enables widespread data dissemination via a high-performance API that can be accessed using an R package. We show how outbreak.info can be used for genomic surveillance and as a hypothesis-generation tool to understand the ongoing pandemic at varying geographic and temporal scales.

Severe acute respiratory syndrome coronavirus 2 vaccine breakthrough infections: A single metro-based testing network experience.

Objectives: Understanding the incidence and characteristics that influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infections (VBIs) is imperative for developing public health policies to mitigate the coronavirus disease of 2019 (COVID-19) pandemic. We examined these factors and post-vaccination mitigation practices in individuals partially and fully vaccinated against SARS-CoV-2. Materials and methods: Adults >18 years old were voluntarily enrolled from a single metro-based SARS-CoV-2 testing network from January to July 2021. Participants were categorized as asymptomatic or symptomatic, and as unvaccinated, partially vaccinated, or fully vaccinated. All participants had confirmed SARS-CoV-2 infection based on standard of care (SOC) testing with nasopharyngeal swabs. Variant analysis by rRT-PCR was performed in a subset of time-matched vaccinated and unvaccinated individuals. A subgroup of partially and fully vaccinated individuals with a positive SARS-CoV-2 rRT-PCR was contacted to assess disease severity and post-vaccination mitigation practices. Results: Participants (n = 1,317) voluntarily underwent testing for SARS-CoV-2 during the enrollment period. A total of 29.5% of the population received at least one SARS-CoV-2 vaccine (n = 389), 12.8% partially vaccinated (n = 169); 16.1% fully vaccinated (n = 213). A total of 21.3% of partially vaccinated individuals tested positive (n = 36) and 9.4% of fully vaccinated individuals tested positive (n = 20) for SARS-CoV-2. Pfizer/BioNTech mRNA-1273 was the predominant vaccine received (1st dose = 66.8%, 2nd dose = 67.9%). Chronic liver disease and immunosuppression were more prevalent in the vaccinated (partially/fully) group compared to the unvaccinated group (p = 0.003, p = 0.021, respectively). There were more asymptomatic individuals in the vaccinated group compared to the unvaccinated group [n = 6 (10.7%), n = 16 (4.1%), p = 0.045]. CT values were lower for the unvaccinated group (median 24.3, IQR 19.1-30.5) compared to the vaccinated group (29.4, 22.0-33.7, p = 0.004). In the vaccinated group (n = 56), 18 participants were successfully contacted, 7 were lost to follow-up, and 2 were deceased. A total of 50% (n = 9) required hospitalization due to COVID-19 illness. Adherence to nationally endorsed mitigation strategies varied post-vaccination. Conclusion: The incidence of SARS-CoV-2 infection at this center was 21.3% in the partially vaccinated group and 9.4% in the fully vaccinated group. Chronic liver disease and immunosuppression were more prevalent in the vaccinated SARS-CoV-2 positive group, suggesting that these may be risk factors for VBIs. Partially and fully vaccinated individuals had a higher incidence of asymptomatic SARS-CoV-2 and higher CT values compared to unvaccinated SARS-CoV-2 positive individuals.

Wastewater surveillance for public health.

Wastewater contains information on pathogen spread, evolution, and outbreak risk.

Severe acute respiratory syndrome coronavirus 2 vaccine breakthrough infections: A single metro-based testing network experience

Objectives Understanding the incidence and characteristics that influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infections (VBIs) is imperative for developing public health policies to mitigate the coronavirus disease of 2019 (COVID-19) pandemic. We examined these factors and post-vaccination mitigation practices in individuals partially and fully vaccinated against SARS-CoV-2. Materials and methods Adults >18 years old were voluntarily enrolled from a single metro-based SARS-CoV-2 testing network from January to July 2021. Participants were categorized as asymptomatic or symptomatic, and as unvaccinated, partially vaccinated, or fully vaccinated. All participants had confirmed SARS-CoV-2 infection based on standard of care (SOC) testing with nasopharyngeal swabs. Variant analysis by rRT-PCR was performed in a subset of time-matched vaccinated and unvaccinated individuals. A subgroup of partially and fully vaccinated individuals with a positive SARS-CoV-2 rRT-PCR was contacted to assess disease severity and post-vaccination mitigation practices. Results Participants (n = 1,317) voluntarily underwent testing for SARS-CoV-2 during the enrollment period. A total of 29.5% of the population received at least one SARS-CoV-2 vaccine (n = 389), 12.8% partially vaccinated (n = 169);16.1% fully vaccinated (n = 213). A total of 21.3% of partially vaccinated individuals tested positive (n = 36) and 9.4% of fully vaccinated individuals tested positive (n = 20) for SARS-CoV-2. Pfizer/BioNTech mRNA-1273 was the predominant vaccine received (1st dose = 66.8%, 2nd dose = 67.9%). Chronic liver disease and immunosuppression were more prevalent in the vaccinated (partially/fully) group compared to the unvaccinated group (p = 0.003, p = 0.021, respectively). There were more asymptomatic individuals in the vaccinated group compared to the unvaccinated group [n = 6 (10.7%), n = 16 (4.1%), p = 0.045]. CT values were lower for the unvaccinated group (median 24.3, IQR 19.1–30.5) compared to the vaccinated group (29.4, 22.0–33.7, p = 0.004). In the vaccinated group (n = 56), 18 participants were successfully contacted, 7 were lost to follow-up, and 2 were deceased. A total of 50% (n = 9) required hospitalization due to COVID-19 illness. Adherence to nationally endorsed mitigation strategies varied post-vaccination. Conclusion The incidence of SARS-CoV-2 infection at this center was 21.3% in the partially vaccinated group and 9.4% in the fully vaccinated group. Chronic liver disease and immunosuppression were more prevalent in the vaccinated SARS-CoV-2 positive group, suggesting that these may be risk factors for VBIs. Partially and fully vaccinated individuals had a higher incidence of asymptomatic SARS-CoV-2 and higher CT values compared to unvaccinated SARS-CoV-2 positive individuals.

Clinical evaluation of the Diagnostic Analyzer for Selective Hybridization (DASH): A point-of-care PCR test for rapid detection of SARS-CoV-2 infection.

BACKGROUND: An ideal test for COVID-19 would combine the sensitivity of laboratory-based PCR with the speed and ease of use of point-of-care (POC) or home-based rapid antigen testing. We evaluated clinical performance of the Diagnostic Analyzer for Selective Hybridization (DASH) SARS-CoV-2 POC rapid PCR test. METHODS: We conducted a cross-sectional study of adults with and without symptoms of COVID-19 at four clinical sites where we collected two bilateral anterior nasal swabs and information on COVID-19 symptoms, vaccination, and exposure. One swab was tested with the DASH SARS-CoV-2 POC PCR and the second in a central laboratory using Cepheid Xpert Xpress SARS-CoV-2 PCR. We assessed test concordance and calculated sensitivity, specificity, negative and positive predictive values using Xpert as the "gold standard". RESULTS: We enrolled 315 and analyzed 313 participants with median age 42 years; 65% were female, 62% symptomatic, 75% had received ≥2 doses of mRNA COVID-19 vaccine, and 16% currently SARS-CoV-2 positive. There were concordant results for 307 tests indicating an overall agreement for DASH of 0.98 [95% CI 0.96, 0.99] compared to Xpert. DASH performed at 0.96 [95% CI 0.86, 1.00] sensitivity and 0.98 [95% CI 0.96, 1.00] specificity, with a positive predictive value of 0.85 [95% CI 0.73, 0.96] and negative predictive value of 0.996 [95% CI 0.99, 1.00]. The six discordant tests between DASH and Xpert all had high Ct values (>30) on the respective positive assay. DASH and Xpert Ct values were highly correlated (R = 0.89 [95% CI 0.81, 0.94]). CONCLUSIONS: DASH POC SARS-CoV-2 PCR was accurate, easy to use, and provided fast results (approximately 15 minutes) in real-life clinical settings with an overall performance similar to an EUA-approved laboratory-based PCR.

SARS-CoV-2 reliably detected in frozen saliva samples stored up to one year.

Viability of saliva samples stored for longer than 28 days has not been reported in the literature. The COVID-19 pandemic has spawned new research evaluating various sample types, thus large biobanks have been started. Residual saliva samples from university student surveillance testing were retested on SalivaDirect and compared with original RT-PCR (cycle threshold values) and quantitative antigen values for each month in storage. We conclude that saliva samples stored at -80°C are still viable in detecting SARS-CoV-2 after 12 months of storage, establishing the validity of these samples for future testing.

The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic.

Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 is critical to preventing future zoonotic outbreaks before they become the next pandemic. The Huanan Seafood Wholesale Market in Wuhan, China, was identified as a likely source of cases in early reports, but later this conclusion became controversial. We show here that the earliest known COVID-19 cases from December 2019, including those without reported direct links, were geographically centered on this market. We report that live SARS-CoV-2-susceptible mammals were sold at the market in late 2019 and that within the market, SARS-CoV-2-positive environmental samples were spatially associated with vendors selling live mammals. Although there is insufficient evidence to define upstream events, and exact circumstances remain obscure, our analyses indicate that the emergence of SARS-CoV-2 occurred through the live wildlife trade in China and show that the Huanan market was the epicenter of the COVID-19 pandemic.

The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2.

Understanding the circumstances that lead to pandemics is important for their prevention. We analyzed the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic. We show that SARS-CoV-2 genomic diversity before February 2020 likely comprised only two distinct viral lineages, denoted "A" and "B." Phylodynamic rooting methods, coupled with epidemic simulations, reveal that these lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October to 8 December), and the separate introduction of lineage A likely occurred within weeks of this event. These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans before November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events.

Passive order auditing associated with reductions in red blood cell utilization: National blood shortage experience.

BACKGROUND: Decreased blood collection during the Coronavirus Disease 2019 (COVID-19) pandemic resulted in long-term red blood cell (RBC) shortages in the United States. In an effort to conserve RBCs, the existing passive alert system for auditing inpatient transfusions was modified to activate at a lower hemoglobin threshold (6.5 g/dL instead of 7.0 g/dL for stable, nonbleeding inpatients) during a 9-month shortage at an academic medical center. Hemoglobin levels prior to RBC transfusions were compared for inpatients receiving RBC transfusions to determine whether RBC utilization changed during the intervention. STUDY DESIGN AND METHODS: This retrospective study compared the number of single-unit RBC transfusions and hemoglobin levels prior to RBC transfusion among inpatients during the 9 months of the intervention (Period 2, 06/01/2021-2/28/2022) to the same period of the previous year (Period 1, 06/01/2020-2/28/2021). RESULTS: Overall full unit RBC transfusions to inpatients decreased by 15% from 5182 to 4421. Of all transfusions, 50.3% and 49.8% were single-unit RBC transfusions in Period 1 and Period 2, respectively. The incidence rate difference and incidence rate ratio of single RBC units transfused per 1000 patient days were significantly decreased (p = 0.0007). The average pre-transfusion hemoglobin level significantly decreased from 7.18 g/dL to 7.05 g/dL (p = 0.0002), largely due to significant decreases in hemoglobin transfusion triggers for adult inpatient ward transfusions. DISCUSSION: Modification of the passive alert system was associated with significantly decreased RBC utilization during a long-term RBC shortage. Modification of transfusion criteria recommended by passive alerts may be a feasible option to decrease RBC utilization at centers during long-term RBC shortages.

Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission.

As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing and/or sequencing capacity, which can also introduce biases1-3. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing4,5. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We developed and deployed improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detected emerging variants of concern up to 14 days earlier in wastewater samples, and identified multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

Predictive Value of Isolated Symptoms for Diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children Tested During Peak Circulation of the Delta Variant.

BACKGROUND: Coronavirus disease 2019 (COVID-19) testing policies for symptomatic children attending US schools or daycare vary, and whether isolated symptoms should prompt testing is unclear. We evaluated children presenting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to determine if the likelihood of having a positive SARS-CoV-2 test differed between participants with 1 symptom vs ≥2 symptoms, and to examine the predictive capability of isolated symptoms. METHODS: Participants aged <18 years presenting for clinical SARS-CoV-2 molecular testing in 6 sites in urban/suburban/rural Georgia (July-October, 2021; Delta variant predominant) were queried about individual symptoms. Participants were classified into 3 groups: asymptomatic, 1 symptom only, or ≥2 symptoms. SARS-CoV-2 test results and clinical characteristics of the 3 groups were compared. Sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) for isolated symptoms were calculated by fitting a saturated Poisson model. RESULTS: Of 602 participants, 21.8% tested positive and 48.7% had a known or suspected close contact. Children reporting 1 symptom (n = 82; odds ratio [OR], 6.00 [95% confidence interval {CI}, 2.70-13.33]) and children reporting ≥2 symptoms (n = 365; OR, 5.25 [95% CI, 2.66-10.38]) were significantly more likely to have a positive COVID-19 test than asymptomatic children (n = 155), but they were not significantly different from each other (OR, 0.88 [95% CI, .52-1.49]). Sensitivity and PPV were highest for isolated fever (33% and 57%, respectively), cough (25% and 32%), and sore throat (21% and 45%); headache had low sensitivity (8%) but higher PPV (33%). Sensitivity and PPV of isolated congestion/rhinorrhea were 8% and 9%, respectively. CONCLUSIONS: With high Delta variant prevalence, children with isolated symptoms were as likely as those with multiple symptoms to test positive for COVID-19. Isolated fever, cough, sore throat, or headache, but not congestion/rhinorrhea, offered the highest predictive value.

Don't forget about human factors: Lessons learned from COVID-19 point-of-care testing.

During the COVID-19 pandemic, the development of point-of-care (POC) diagnostic testing accelerated in an unparalleled fashion. As a result, there has been an increased need for accurate, robust, and easy-to-use POC testing in a variety of non-traditional settings (i.e., pharmacies, drive-thru sites, schools). While stakeholders often express the desire for POC technologies that are "as simple as digital pregnancy tests," there is little discussion of what this means in regards to device design, development, and assessment. The design of POC technologies and systems should take into account the capabilities and limitations of the users and their environments. Such "human factors" are important tenets that can help technology developers create POC technologies that are effective for end-users in a multitude of settings. Here, we review the core principles of human factors and discuss lessons learned during the evaluation process of SARS-CoV-2 POC testing.

Treatment strategies for postviral olfactory dysfunction: A systematic review.

Background: The coronavirus disease 2019 (COVID-19) pandemic has been associated with a dramatic increase in postviral olfactory dysfunction (PVOD) among patients who are infected. A contemporary evidence-based review of current treatment options for PVOD is both timely and relevant to improve patient care. Objective: This review seeks to impact patient care by qualitatively reviewing available evidence in support of medical and procedural treatment options for PVOD. Systematic evaluation of data quality and of the level of evidence was completed to generate current treatment recommendations. Methods: A systematic review was conducted to identify primary studies that evaluated treatment outcomes for PVOD. A number of medical literature data bases were queried from January 1998 to May 2020, with completion of subsequent reference searches of retrieved articles to identify all relevant studies. Validated tools for the assessment of bias among both interventional and observational studies were used to complete quality assessment. The summary level of evidence and associated outcomes were used to generate treatment recommendations. Results: Twenty-two publications were identified for qualitative review. Outcomes of alpha-lipoic acid, intranasal and systemic corticosteroids, minocycline, zinc sulfate, vitamin A, sodium citrate, caroverine, intranasal insulin, theophylline, and Gingko biloba are reported. In addition, outcomes of traditional Chinese acupuncture and olfactory training are reviewed. Conclusion: Several medical and procedural treatments may expedite the return of olfactory function after PVOD. Current evidence supports olfactory training as a first-line intervention. Additional study is required to define specific treatment recommendations and expected outcomes for PVOD in the setting of COVID-19.

Comparison of Symptoms and Antibody Response Following Administration of Moderna or Pfizer SARS-CoV-2 Vaccines.

CONTEXT.­: Moderna (mRNA-1272) and Pfizer (BNT162b2) SARS-CoV-2 vaccines demonstrate favorable safety and efficacy profiles, but direct comparison data are lacking. OBJECTIVE.­: To determine the vaccines' side effect profiles and expected antibody responses. These data may help personalize vaccine selection and identify individuals with a suboptimal vaccine response. DESIGN.­: One hundred forty-nine healthy, largely seronegative adults were assigned Moderna (n = 79) or Pfizer (n = 70). Following the second dose, participants completed a survey documenting their side effects. Serum was collected 0 to 4 days prior to dose 2, and 14 ± 4 days, 30 ± 4 days, 90 ± 10 days, and 180 ± 20 days after dose 2. Convalescent serum specimens were collected 32 to 54 days from donors after a polymerase chain reaction-confirmed SARS-CoV-2 infection (n = 20). Anti-spike antibodies were measured using the Roche Diagnostics Elecys Anti-SARS-CoV-2 S assay on a Roche cobas e801 instrument. RESULTS.­: Participants receiving the Moderna vaccine experienced side effects with greater frequency and severity. Both vaccines elicited a robust antibody response, but median signal was higher in Moderna recipients. Symptom severity decreased with age. Antibody response in Pfizer recipients negatively correlated with age. Antibody response decreased after 6 months (84% reduction in Moderna, 79% Pfizer), but values remained greater than for convalescent donors. Antibody response did not correlate with gender or symptom severity. CONCLUSIONS.­: Moderna may be preferred in individuals in need of greater immune stimulation (eg, older individuals), whereas Pfizer may be preferred in those concerned about vaccine reactions. Anti-spike antibody signal varies by vaccine, so specific reference intervals will be needed to identify individuals with a suboptimal response.

The RADx Tech Test Verification Core and the ACME POCT in the Evaluation of COVID-19 Testing Devices: A Model for Progress and Change.

Faced with the COVID-19 pandemic, the US system for developing and testing technologies was challenged in unparalleled ways. This article describes the multi-institutional, transdisciplinary team of the "RADxSM Tech Test Verification Core" and its role in expediting evaluations of COVID-19 testing devices. Expertise related to aspects of diagnostic testing was coordinated to evaluate testing devices with the goal of significantly expanding the ability to mass screen Americans to preserve lives and facilitate the safe return to work and school. Focal points included: laboratory and clinical device evaluation of the limit of viral detection, sensitivity, and specificity of devices in controlled and community settings; regulatory expertise to provide focused attention to barriers to device approval and distribution; usability testing from the perspective of patients and those using the tests to identify and overcome device limitations, and engineering assessment to evaluate robustness of design including human factors, manufacturability, and scalability.