SARS-CoV-2 testing and detection during peripartum hospitalizations among a multi-center cohort of pregnant persons, March 2020-February 2021.

BACKGROUND: Identifying SARS-CoV-2 infections during peripartum hospitalizations is important to guide care, implement prevention measures, and understand infection burden. METHODS: This cross-sectional analysis used electronic health record data from hospitalizations during which pregnancies ended (peripartum hospitalizations) among a cohort of pregnant persons at 3 U.S. integrated healthcare networks (Sites 1-3). Maternal demographic, medical encounter, SARS-CoV-2 testing, and pregnancy and neonatal outcome information was extracted for persons with estimated delivery and pregnancy end dates during March 2020-February 2021 and ≥1 prenatal care record. Site-stratified multivariable logistic regression was used to identify factors associated with testing and compare pregnancy and neonatal outcomes among persons tested. RESULTS: Among 17,858 pregnant persons, 10,863 (60.8%) had peripartum SARS-CoV-2 testing; 222/10,683 (2.0%) had positive results. Testing prevalence varied by site and was lower during March-May 2020. Factors associated with higher peripartum SARS-CoV-2 testing odds were Asian race (adjusted odds ratio [aOR]: 1.36; 95% CI: 1.03-1.79; referent: White) (Site 1), Hispanic or Latina ethnicity (aOR: 1.33; 95% CI: 1.08-1.64) (Site 2), peripartum Medicaid coverage (aOR: 1.33; 95% CI: 1.06-1.66) (Site 1), and preterm hospitalization (aOR: 1.69; 95% CI: 1.19-2.39 [Site 1]; aOR: 1.39; 95% CI: 1.03-1.88 [Site 2]). CONCLUSIONS: Findings highlight potential disparities in SARS-CoV-2 peripartum testing by demographic and pregnancy characteristics. Testing practice variations should be considered when interpreting studies relying on convenience samples of pregnant persons testing positive for SARS-CoV-2. Efforts to address testing differences between groups could improve equitable testing practices and care for pregnant persons with SARS-CoV-2 infections.

Incidence Rates of Medically Attended COVID-19 in Infants Less Than 6 Months of Age.

BACKGROUND: Studies suggest infants may be at increased risk of severe coronavirus disease 2019 (COVID-19) relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age. METHODS: We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from 3 health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses and severe acute respiratory syndrome coronavirus syndrome 2 (SARS-CoV-2) test results. Medically attended COVID-19 episodes were defined by positive SARS-CoV-2 clinical tests and/or COVID-19 diagnosis codes during medical care visits. Unadjusted and site-adjusted incidence rates by infant month of age, low and high SARS-CoV-2 circulation periods and maternal COVID-19 diagnosis were calculated. RESULTS: Among 18,192 infants <6 months of age whose mothers received prenatal care within the 3 systems, 173 (1.0%) had medically attended COVID-19 episodes. Incidence rates were highest among infants under 1 month of age (2.0 per 1000 person-weeks) and 1 month (2.0 per 1000 person-weeks) compared with older infants. Incidence rates were also higher for infants born to women with postpartum COVID-19 compared with women without known COVID-19 and women diagnosed with COVID-19 during pregnancy. CONCLUSIONS: Infants of women with postpartum COVID-19 had a higher risk of medically attended COVID-19 than infants born to mothers who were diagnosed during pregnancy or never diagnosed underscoring the importance of COVID-19 prevention measures for their household members and caregivers to prevent infections in infants.

Medically Attended Influenza During Pregnancy in the 2019-2020 and 2020-2021 Influenza Seasons.

Influenza testing and case-confirmation rates in pregnant populations have not been reported during the coronavirus disease 2019 (COVID-19) pandemic. Using electronic medical record data from a cohort of nearly 20,000 pregnancies in the United States, this retrospective cohort study examines the frequency of acute respiratory or febrile illness encounters, influenza testing, and influenza positivity during the 2020-2021 influenza season, which occurred during the COVID-19 pandemic, compared with the 2019-2020 influenza season, which largely did not. The ratios of influenza tests to acute respiratory or febrile illness visits were similar in the 2019-2020 and 2020-2021 influenza seasons (approximately 1:8 and 1:9, respectively) but were low and varied by study site. Although influenza testing in pregnant patients continued in the 2020-2021 season, when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) circulation was widespread in the United States, no cases of influenza were identified in our study cohort.

Abnormalities in cardiac and inflammatory biomarkers in ambulatory subjects after COVID-19 infection.

Background: Coronavirus-2019 (COVID-19) is known to affect the heart and is associated with a pro-inflammatory state. Most studies to date have focused on clinically sick subjects. Here, we report cardiac and proinflammatory biomarkers levels in ambulatory young adults with asymptomatic or mild COVID-19 infection compared to those without infection 4-8 weeks after severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) testing. Methods: 131 asymptomatic or mildly symptomatic subjects were enrolled following testing for SARS-COV-2. Fifty subjects tested negative, and 81 subjects tested positive. Serum samples were collected for measurement of C-reactive protein, ferritin, interleukin-6, NT-pro-B-type natriuretic peptide, and cardiac troponin 28-55 days after SARS-COV-2 RT-PCR testing. Results: Biomarker levels trended higher in SARS-COV-2-positive vs negative subjects, but differences in biomarker levels or proportion of subjects with elevated biomarkers were not statistically significant with respect to SARS-COV-2 status. Among individuals with ≥ 1 comorbidity, odds of elevated CRP were greater compared to individuals without any comorbidities (odds ratio [OR] = 2.90); this effect size was increased 1.4-fold among SARS-COV-2-positive subjects (OR = 4.03). Similarly, NT-pro-BNP was associated with CVD, with the strongest association in COVID-positive individuals (OR = 16.9). Conclusions: In a relatively young, healthy adult population, mild COVID-19 infection was associated with mild elevations in cardiac and proinflammatory biomarkers within 4-8 weeks of mild or asymptomatic COVID-19 infection in individuals with preexisting comorbidities, but not among individuals without comorbidities. For the general population of young adults, we did not find evidence of elevation of cardiac or proinflammatory biomarkers 4-8 weeks after COVID-19 infection.Clinical Perspective: This is a characterization of cardiac and proinflammatory biomarkers in ambulatory subjects following asymptomatic or mild COVID-19 infection. Young, ambulatory individuals did not have cardiac and proinflammatory biomarker elevation 4-8 weeks after mild COVID-19 infection. However, COVID-19 infection was associated with biomarker elevations in select individuals with comorbidities.Clinical study number: H-47423.

Factors Associated with Hospitalization with Symptomatic COVID-19 Illness Among Pregnant Individuals: A Multi-Center Retrospective Cohort Study

Background Pregnant individuals are at increased risk of COVID-19 hospitalization and death, and primary and booster COVID-19 vaccination is recommended for this population. Methods Among a cohort of pregnant individuals who received prenatal care at three healthcare systems in the United States, we estimated the cumulative incidence of hospitalization with symptomatic COVID-19 illness. We also identified factors associated with COVID-19 hospitalization using a multivariable Cox proportional-hazards model with pregnancy weeks as the timescale and a time-varying adjustor that accounted for SARS-CoV-2 circulation;model covariates included site, age, race, ethnicity, insurance status, pre-pregnancy weight status, and selected underlying medical conditions. Data were collected primarily through medical record extraction. Results Among 19,456 pregnant individuals with an estimated due date March 1, 2020-February 28, 2021, 75 (0.4%) were hospitalized with symptomatic COVID-19. Factors associated with hospitalization for symptomatic COVID-19 were Hispanic ethnicity (aHR: 2.7;95% CI: 1.3,5.5), native Hawaiian or Pacific Islander race (aHR: 12;95% CI: 3.2,45.5), age <25 years (aHR: 3.1;95% CI: 1.3,7.6), pre-pregnancy obesity (aHR: 2.1;95% CI: 1.1,3.9), diagnosis of a metabolic disorder (aHR: 2.2;95% CI: 1.2,3.8), lung disease excluding asthma (aHR: 49;95% CI: 28,84) and cardiovascular disease (aHR: 2.6;95% CI: 1.5,4.7). Conclusion Although hospitalization with symptomatic COVID-19 was uncommon, pregnant individuals should be aware of risk factors associated with severe illness when considering COVID-19 vaccination.

Serum IgG anti-SARS-CoV-2 Binding Antibody Level Is Strongly Associated With IgA and Functional Antibody Levels in Adults Infected With SARS-CoV-2.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019 in Wuhan, China, and then rapidly spread causing an unprecedented pandemic. A robust serological assay is needed to evaluate vaccine candidates and better understand the epidemiology of coronavirus disease (COVID-19). Methods: We used the full-length spike (S) protein of SARS-CoV-2 for the development of qualitative and quantitative IgG and IgA anti-S enzyme linked immunosorbent assays (ELISA). A total of 320 sera used for assay development were comprised of pandemic sera from SARS-CoV-2 infected adults (n=51) and pre-pandemic sera (n=269) including sera from endemic human coronavirus infected adults. Reverse cumulative curves and diagnostic test statistics were evaluated to define the optimal serum dilution and OD cutoff value for IgG anti-S and IgA anti-S ELISAs. The IgG and IgA anti-S, and three functional antibodies (ACE-2 receptor blocking antibody, lentipseudovirus-S neutralizing antibody, and SARS-CoV-2 neutralizing antibody) were measured using additional SARS-CoV-2 PCR positive sera (n=76) and surveillance sera (n=25). Lastly, the IgG and IgA anti-S levels were compared in different demographic groups. Results: The optimal serum dilution for the qualitative IgG anti-S ELISA was at 1:1024 yielding a 99.6% specificity, 92.2% sensitivity, 92.9% positive predictive value (PPV), and 99.6% negative predictive value (NPV) at a SARS-CoV-2 seroprevalence of 5%. The optimal serum dilution for the qualitative IgA anti-S ELISA was at 1:128 yielding a 98.9% specificity, 76.5% sensitivity, 78.3% PPV, and 98.8% NPV at the same seroprevalence. Significant correlations were demonstrated between the IgG and IgA (r=0.833 for concentrations, r=0.840 for titers) as well as between IgG and three functional antibodies (r=0.811-0.924 for concentrations, r=0.795-0.917 for titers). The IgG and IgA anti-S levels were significantly higher in males than females (p<0.05), and in adults with moderate/severe symptoms than in adults with mild/moderate symptoms (p<0.001). Conclusion: We developed a highly specific and sensitive IgG anti-S ELISA assay to SARS-CoV-2 using full length S protein. The IgG anti-S antibody level was strongly associated with IgA and functional antibody levels in adults with SARS-CoV-2 infection. Gender and disease severity, rather than age, play an important role in antibody levels.

Oligonucleotide capture sequencing of the SARS-CoV-2 genome and subgenomic fragments from COVID-19 individuals.

The newly emerged and rapidly spreading SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). To facilitate a deeper understanding of the viral biology we developed a capture sequencing methodology to generate SARS-CoV-2 genomic and transcriptome sequences from infected patients. We utilized an oligonucleotide probe-set representing the full-length genome to obtain both genomic and transcriptome (subgenomic open reading frames [ORFs]) sequences from 45 SARS-CoV-2 clinical samples with varying viral titers. For samples with higher viral loads (cycle threshold value under 33, based on the CDC qPCR assay) complete genomes were generated. Analysis of junction reads revealed regions of differential transcriptional activity among samples. Mixed allelic frequencies along the 20kb ORF1ab gene in one sample, suggested the presence of a defective viral RNA species subpopulation maintained in mixture with functional RNA in one sample. The associated workflow is straightforward, and hybridization-based capture offers an effective and scalable approach for sequencing SARS-CoV-2 from patient samples.

SARS-CoV-2 re-infection versus prolonged shedding: A case series.

Since the start of the SARS-CoV-2 pandemic, it has been difficult to differentiate between SARS-CoV-2 re-infection and prolonged RNA shedding. In this report, we identified patients with positive RT-PCR results for SARS-CoV-2 ≥70 days apart. Clinical and laboratory data were collected and criteria were applied to discern whether the presentation was consistent with SARS-CoV-2 re-infection or prolonged viral RNA shedding. Eleven individuals met the initial testing criteria, of which, seven met at least one criteria for re-infection and four were consistent with prolonged RNA shedding. These data demonstrate the need for criteria to differentiate SARS-CoV-2 re-infection from prolonged RNA shedding.

Viral Load of Severe Acute Respiratory Syndrome Coronavirus 2 in Adults During the First and Second Wave of Coronavirus Disease 2019 Pandemic in Houston, Texas: The Potential of the Superspreader.

BACKGROUND: During the coronavirus disease 2019 pandemic, a minority of index cases are associated with a majority of secondary cases suggesting that superspreaders could drive the pandemic. We identified a phenotype in individuals with extremely high viral load who could act as superspreaders. METHODS: Data were analyzed from individuals tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 18 March through 15 August 2020. Outcomes were compared using contingency table and quantile regression to test the equality of medians between the pandemic waves and by viral load groups. RESULTS: Of the 11 564 samples tested, 1319 (11.4%) were positive for SARS-CoV-2. An increase in weekly median viral load occurred in the second wave of the SARS-CoV2 pandemic. This population was more likely to be women, outpatients, and symptomatic and to have an extremely high or high viral load. In patients with multiple reverse-transcription polymerase chain reaction-positive test results, the durations of viral shedding were comparable between individuals with asymptomatic/mild and mild/moderate illness severity. CONCLUSIONS: We detected a small group of individuals with extremely high SARS-CoV-2 viral loads and mild illness. We believe that these individuals' characteristics could be consistent with the superspreader phenomenon and that greater awareness of the social dynamics of these individuals is needed to understand the spread of SARS-CoV-2.