Temporal Trend in Mortality from COVID-19 Associated with Cardiovascular Disease (preprint)

Background: The COVID-19 pandemic has endured for over three years with over twelve variants afflicting humans worldwide. The impact and longevity of the pandemic has driven the medical community and researchers to identify high-risk populations, yet few studies have explored temporal trends during the pandemic. The objective of this study is to investigate trends in all-cause mortality associated with co-morbid cardiovascular disease (CVD) throughout the consecutive waves of the COVID-19 pandemic. Methods: A retrospective cohort study was conducted on patients with COVID-19 infection who received care at a tertiary care center in Chicago between March 2020 and September 2022. Multivariable logistic regression was used to investigate associations between co-existing CVD (defined as congestive heart failure, myocardial infarction, cerebrovascular disease, peripheral vascular disease) and mortality, adjusting for age, sex, race, and comorbidities defined in the Charlson comorbidity index. Results: The study included 38651 participants (mean age 45 years, 57.6% female, 11.4% with co-existing CVD). All-cause mortality in COVID-19 patients was highest during the Delta wave and remained elevated until the late Omicron wave. Mortality associated with co-existing CVD increased during the early pandemic waves, decreased in the later waves, but remained elevated relative to the overall population. When adjusted for age, sex, and race, all-cause mortality was 2.3-fold higher in patients with co-existing CVD compared to those with non-CVD comorbidities (OR = 2.30, 95% CI 1.95 - 2.62; p < 0.001). Conclusions: While overall mortality rates declined toward the later waves of the pandemic, all-cause mortality associated with CVD remained elevated compared to individuals without CVD.

Prevalence of SARS-CoV-2 Antibodies after the Omicron Surge, Kingston, Jamaica, 2022 (preprint)

A cross-sectional SARS-CoV-2 serosurvey was conducted after the Omicron surge in Jamaica using 1,540 samples collected during March - May 2022 from persons attending antenatal, STI and non-communicable diseases clinics in Kingston, Jamaica. SARS-CoV-2 spike receptor binding domain (RBD) and/or nucleocapsid IgG antibodies were detected for 88.4% of the study population, with 77.0% showing evidence of previous SARS-CoV-2 infection. Of persons previously infected with SARS-CoV-2 and/or with COVID-19 vaccination, 9.6% were negative for spike RBD IgG, most of which were unvaccinated previously infected persons. Amongst unvaccinated previously infected people, age was associated with testing spike RBD IgG negative. When considering all samples, median spike RBD IgG levels were 131.6 BAU/mL for unvaccinated persons with serological evidence of past infection, 90.3 BAU/mL for vaccinated persons without serological evidence of past infection, and 896.1 BAU/mL for vaccinated persons with serological evidence of past infection. Our study of the first reported SARS-CoV-2 serosurvey in Jamaica shows extensive SARS-CoV-2 population immunity, identifies a substantial portion of the population lacking spike RBD IgG, and provides additional evidence for increasing COVID-19 vaccine coverage in Jamaica.

A mixture model to estimate SARS-CoV-2 seroprevalence in Chennai, India (preprint)

Serological assays used to estimate SARS-CoV-2 seroprevalence rely on manufacturer cut-offs established based on more severe early cases who tended to be older. We conducted a household-based serosurvey of 4,677 individuals from 2,619 households in Chennai, India from January to May, 2021. Samples were tested for SARS-CoV-2 IgG antibodies to the spike (S) and nucelocapsid (N) proteins. We calculated seroprevalence using manufacturer cut-offs and using a mixture model in which individuals were assigned a probability of being seropositive based on their measured IgG, accounting for heterogeneous antibody response across individuals. The SARS-CoV-2 seroprevalence to anti-S and anti-N IgG was 62.0% (95% confidence interval [CI], 60.6 to 63.4) and 13.5% (95% CI, 12.6 to 14.5), respectively applying the manufacturer's cut-offs, with low inter-assay agreement (Cohen's kappa 0.15). With the mixture model, estimated anti-S IgG and anti-N IgG seroprevalence was 64.9% (95% Credible Interval [CrI], 63.8 to 66.0) and 51.5% (95% CrI, 50.2 to 52.9) respectively, with high inter-assay agreement (Cohen's kappa 0.66). Age and socioeconomic factors showed inconsistent relationships with anti-S IgG and anti-N IgG seropositivity using manufacturer's cut-offs, but the mixture model reconciled these differences. In the mixture model, age was not associated with seropositivity, and improved household ventilation was associated with lower seropositivity odds. With global vaccine scale-up, the utility of the more stable anti-S IgG assay may be limited due to the inclusion of the S protein in several vaccines. SARS-CoV-2 seroprevalence estimates using alternative targets must consider heterogeneity in seroresponse to ensure seroprevalence is not underestimated and correlates not misinterpreted.

SARS-CoV-2 Vaccinated Breakthrough Infections With Fatal and Critical Outcomes in the Department of Antioquia, Colombia (preprint)

The introduction of variants of concern and interest in the Departamento of Antioquia, Colombia, was concomitant with the beginning of the COVID-19 immunization program. Genomic surveillance indicates that none of the emerging variants –alpha, gamma, lambda, mu or delta– were dominant between January and August 2021. The immunization includes CoronaVac, BNT162b2, Ad26.COV2.S and ChAdOx1-S vaccines. By September 10 th , 34.43% inhabitants were fully vaccinated. We characterized, SARS-CoV-2 breakthrough infections in 96 patients, 30 with fatal outcomes, 13 with ICU hospitalization and 53 with mild or asymptomatic disease. Even though gamma and mu variants co-circulated at similar levels, the latter was found to be predominant in patients with fatal outcomes and in those with ICU hospitalizations. We found a significant occurrence of the B.1.625 variant in these patients. Genetic substitutions of therapeutic and immunological concern, E484K and N501Y, are consistently observed in 90.1% and 79.5% of these variants, respectively. Evidence suggests that it is less probable to become infected after 60 days post-treatment with BNT162b2 than with CoronaVac. Importantly, we found that advanced age and comorbidities foster conditions for fatal and ICU outcomes in vaccinated patients. Our observations demonstrate the effectiveness of vaccination and identify patients with higher risks of subsequent breakthrough infections.

Severe Acute Respiratory Syndrome Coronavirus-2 Seropositivity in South-Central Uganda, During 2019 - 2021 (preprint)

Background: Globally, key subpopulations such as healthcare workers (HCWs) have a higher risk of contracting SARS-CoV-2. In Uganda, limited access to personal protective equipment amidst lack of clarity on the extent and pattern of the community disease burden may exacerbate this situation. We assessed SARS-CoV-2 antibody seroprevalence among high-risk sub-populations in South-central Uganda, including HCWs, persons within the general population previously reporting experiencing key COVID-19 like symptoms (fever, cough, loss of taste and smell) and archived plasma specimens collected between October 2019 – 18 th March 2020, prior to confirmation of COVID-19 in Uganda. Methods: : From November 2020 - January 2021, we collected venous blood from HCWs at selected health facilities in South-Central Uganda and from population-cohort participants who reported specific COVID-19 like symptoms in a prior phone-based survey conducted (between May to August 2020) during the first national lockdown. Pre-lockdown plasma collected (between October 2019 and March 18 th , 2020) from individuals considered high risk for SARS-CoV-2 infection was retrieved. Specimens were tested for antibodies to SARS-CoV-2 using the CoronaChek TM rapid COVID-19 IgM/IgG lateral flow test assay. IgM only positive samples were confirmed using a chemiluminescent microparticle immunoassay (CMIA) (Architect AdviseDx SARS-CoV-2 IgM) which targets the spike protein. SARS-CoV-2 exposure was defined as either confirmed IgM, both IgM and IgG or sole IgG positivity. Results: : The seroprevalence of antibodies to SARS-CoV-2 in HCWs was 21.1% [95%CI: 18.2-24.2]. Of the phone-based survey participants, 11.9% [95%CI: 8.0-16.8] had antibodies to SARS-CoV-2. Among 636 pre-lockdown plasma specimens, 1.7% [95%CI: 0.9-3.1] were reactive. Conclusions: : Findings suggest a high seroprevalence of antibodies to SARS-CoV-2 among HCWs and substantial exposure in persons presenting with specific COVID-19 like symptoms in the general population of South-central Uganda. Based on current limitations in serological test confirmation, it remains unclear whether pre-lockdown seropositivity implies prior SARS-CoV-2 exposure in Uganda.

Severe Acute Respiratory Syndrome Coronavirus-2 seropositivity in South-central Uganda, during 2019 - 2021 (preprint)

Globally, key subpopulations have a high risk of contracting SARS-CoV-2. In Uganda, limited access to personal protective equipment amidst lack of clarity on the extent of the community disease burden may exacerbate this situation. We assessed SARS-CoV-2 antibody seroprevalence among high-risk sub-populations, including healthcare workers, persons within the general population previously reporting experiencing key COVID-19 like symptoms and archived plasma specimens collected prior to confirmation of COVID-19 in Uganda. We collected venous blood from HCWs at selected health facilities and from population-cohort participants who reported specific COVID-19 like symptoms in a prior phone-based survey conducted during the first national lockdown (May-August 2020). Pre-lockdown plasma collected from individuals considered high risk for SARS-CoV-2 infection was retrieved. Specimens were tested for antibodies to SARS-CoV-2 using the CoronaChek rapid COVID-19 IgM/IgG lateral flow test assay. IgM only positive samples were confirmed using a chemiluminescent microparticle immunoassay (ARCHITECT AdviseDx SARS-CoV-2 IgM) which targets the spike. SARS-CoV-2 exposure was defined as either confirmed IgM, both IgM and IgG or sole IgG positivity. The seroprevalence of antibodies to SARS-CoV-2 in HCWs was 21.1% [95%CI: 18.2-24.2]. Of the phone-based survey participants, 11.9% [95%CI: 8.0-16.8] had antibodies to SARS-CoV-2. Among 636 pre-lockdown plasma specimens, 1.7% [95%CI: 0.9-3.1] were reactive. Findings suggest a high seroprevalence of antibodies to SARS-CoV-2 among HCWs and substantial exposure in persons presenting with specific COVID-19 like symptoms in the general population of South-central Uganda. Based on current limitations in serological test confirmation, it remains unclear whether pre-lockdown seropositivity implies prior SARS-CoV-2 exposure in Uganda.

Emergence of Novel Combinations of SARS-CoV-2 Spike Receptor Binding Domain Variants in Senegal (preprint)

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages that carry mutations in the spike gene are of concern for potential impact to treatment and prevention efforts. To monitor for new SARS-CoV-2 mutations, a panel of specimens were sequenced from both wave one (N=96), and wave two (N=117) of the pandemic in Senegal by whole genome next generation sequencing. Amongst these genomes, new combinations of SARS-CoV-2 spike mutations were identified, with E484K+N501T, L452R+N501Y, and L452M+S477N exclusively found in second wave specimens. These sequences are evidence of local diversification over the course of the pandemic and parallel evolution of escape mutations in different lineages.

A Targeted Geospatial Approach to COVID-19 Vaccine Delivery: Findings from the Johns Hopkins Hospital Emergency Department (preprint)

While COVID-19 vaccines have been shown to significantly decrease morbidity and mortality, there is still much debate about optimal strategies of vaccine rollout. We tested identity-unlinked stored remnant blood specimens of patients at least 18 years presenting to the Johns Hopkins Hospital emergency department (ED) between May to November 2020 for IgG to SARS-CoV-2. Data on SARS-CoV-2 RT PCR were available for patients who were tested due to suspected infection. SARS-CoV-2 infections was defined as either a positive IgG and/or RT-PCR. SARS-CoV-2 infection clustering by zipcode was analyzed by spatial analysis using the Bernoulli model (SaTScan software, Version 9.7). Median age of the 7,461 unique patients visiting the ED was 47 years and 50.8% were female; overall, 740 (9.9%) unique patients had evidence of SARS-CoV-2 infection. Prevalence of infection in ED patients by ZIP code ranged from 4.1% to 22.3%. The observed number of cases in ZIP code C was nearly double the expected (observed/expected ratio = 1.99; 95% CI: 1.62, 2.42). These data suggest a targeted geospatial approach to COVID vaccination should be considered to maximize vaccine rollout efficiency and include high-risk populations that may otherwise be subjected to delays, or missed.

Detection of SARS-CoV-2 variants by Abbott molecular, antigen, and serological tests (preprint)

Background Viral diversity presents an ongoing challenge for diagnostic tests, which need to accurately detect all circulating variants. The Abbott Global Surveillance program monitors severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and their impact on diagnostic test performance. Objectives To evaluate the capacity of Abbott molecular, antigen, and serologic assays to detect the SARS-CoV-2 B.1.1.7, B.1.351 and the P.1 variants. Study design Virus variant culture stock dilutions (B.1.1.7, BEI NR-54011; B.1.351, BEI NR-54008 and 54009; P.1, BEI NR-54982) and clinical samples from patients with confirmed B.1.1.7 variant infection were run on the Abbott ID NOW COVID-19, m 2000 RealTi m e SARS-CoV-2, Alinity m SARS-CoV-2, and Alinity m Resp-4-Plex molecular assays; the BinaxNOW COVID-19 Ag Card and Panbio COVID-19 Ag Rapid Test Device; and the ARCHITECT/Alinity i SARS-CoV-2 IgG and AdviseDx IgM assays, Panbio COVID-19 IgG assay, and ARCHITECT/Alinity i AdviseDx SARS-CoV-2 IgG II assay. Results Cultured virus stocks and B.1.1.7 clinical samples were detected with molecular, antigen, and serologic assays in the expected ranges, confirming in silico predictions. The ratio between genome equivalents (GE) and calculated median tissue culture infectious dose (TCID 50 ) were 31-to 83-fold higher for B.1.1.7 cultures compared to B.1.351 and P.1 cultures, demonstrating that GE are more consistent units between cultures than TCID 50 . Conclusions Abbott molecular and antigen assays effectively detect B.1.1.7, B.1.351, and P.1 variant infections and Abbott serologic assays detect B.1.1.7 antibodies in patient sera. Future studies with SARS-CoV-2 virus cultures should use quantitative viral load values to compare detection of variants. Highlights Abbott SARS-CoV-2 molecular and antigen assays detect B.1.1.7, B.1.351, and P.1 variants Abbott SARS-CoV-2 antibody assays detect B.1.1.7 antibodies in recovered patient sera Quantitation of viral load in genome equivalents allows comparison of assay performance

Expanding access to SARS-CoV-2 IgG and IgM serologic testing using fingerstick whole blood, plasma, and rapid lateral flow assays (preprint)

Serologic testing for SARS-CoV-2 antibodies can be used to confirm diagnosis, estimate seroprevalence, screen convalescent plasma donors, and assess vaccine efficacy. Several logistical and infrastructure challenges limit access to SARS-CoV-2 serologic testing. Dried blood spot (DBS) samples have been used for serology testing of various diseases in resource-limited settings. We examined the use of DBS samples and capillary blood (fingerstick) plasma collected in Microtainer tubes for SARS-CoV-2 testing with the automated Abbott ARCHITECT SARS-CoV-2 IgG (List 6R86) and IgM assays and use of venous whole blood with a prototype PANBIO rapid point-of-care lateral flow SARS-CoV-2 IgG assay. The ARCHITECT SARS-CoV-2 IgG assay was initially optimized for use with DBS, venous and capillary plasma, and venous whole blood collected from patients with symptoms and PCR-confirmed COVID-19 and negative asymptomatic controls. Assay linearity and reproducibility was confirmed with 3 contrived DBS samples, with sample stability and signal recovery after 14 days at room temperature. ARCHITECT SARS-CoV-2 IgG and IgM assay results showed high concordance between fingerstick DBS and venous DBS samples, and between fingerstick DBS and venous whole blood samples (n=61). Discordant results were seen in 3 participants (2 IgG, 1 IgM) who were in the process of seroreversion at the time of sample collection and had results near the assay cutoff. Use of fingerstick plasma collected in Microtainer tubes (n=109) showed 100% concordant results (R2=0.997) with matched patient venous plasma on the ARCHITECT SARS-CoV-2 IgG assay. High concordance of assay results (92.9% positive, 100% negative) was also observed for the PANBIO SARS-CoV-2 IgG assay compared to the ARCHITECT SARS-CoV-2 IgG assay run with matched venous plasma (n=61). Fingerstick DBS and plasma samples are easy and inexpensive to collect and, along with the use of rapid point-of-care testing platforms, will expand access to SARS-CoV-2 serology testing, particularly in resource-limited areas.