Abstract Background and objectivesThe optimal iron hypothesis (OIH) posits that risk for infection is lowest at a mild level of iron deficiency. The extent to which this protection results from arms race dynamics in the evolution of iron acquisition and sequestration mechanisms is unclear. We evaluated the OIH with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an emerging infectious agent. MethodologyWe tested 304 healthcare workers at baseline for iron deficiency (zinc protoporphyrin:heme), anemia (hemoglobin), and SARS-CoV-2 (salivary PCR), and followed them for ~3 months with biweekly SARS-CoV-2 tests. We fit logistic regression models based on Akaike Information Criterion. ResultsAdequate data were available for 199 participants. Iron replete (OR: 2.87, 95% CI: 0.85, 9.75) and anemia (OR: 2.48; 95% CI: 0.82, 7.85) were associated with higher risk for SARS-CoV-2 infection after control for covariates. Logistic regression and Cox proportional hazards models of the SARS-CoV-2 outcome were similar. Anemia (OR: 1.81; 95% CI: 0.88, 3.71) was associated with respiratory symptoms regardless of SARS-CoV-2 infection. Conclusions and implicationsThese findings provide partial support for the OIH: SARS-CoV-2 infection risk was elevated at the high end of the range of iron availability; however, the elevated risk among those with anemia was not, as expected, specific to severe iron deficiency. Narrowly, for COVID-19 epidemiology, these findings accord with evidence that SARS-CoV-2’s ability to establish infection is enhanced by access to iron. More broadly, these findings suggest that the OIH does not hinge on a long history of evolutionary arms race dynamics in access to host iron. 
                        more » 
                        « less   
                    
                            
                            Overestimation of Severe Acute Respiratory Syndrome Coronavirus 2 Household Transmission in Settings of High Community Transmission: Insights From an Informal Settlement Community in Salvador, Brazil
                        
                    
    
            Abstract BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has spread globally. However, the contribution of community versus household transmission to the overall risk of infection remains unclear. MethodsBetween November 2021 and March 2022, we conducted an active case-finding study in an urban informal settlement with biweekly visits across 1174 households with 3364 residents. Individuals displaying coronavirus disease 2019 (COVID-19)–related symptoms were identified, interviewed along with household contacts, and defined as index and secondary cases based on reverse-transcription polymerase chain reaction (RT-PCR) and symptom onset. ResultsIn 61 households, we detected a total of 94 RT-PCR–positive cases. Of 69 sequenced samples, 67 cases (97.1%) were attributed to the Omicron BA.1* variant. Among 35 of their households, the secondary attack rate was 50.0% (95% confidence interval [CI], 37.0%–63.0%). Women (relative risk [RR], 1.6 [95% CI, .9–2.7]), older individuals (median difference, 15 [95% CI, 2–21] years), and those reporting symptoms (RR, 1.73 [95% CI, 1.0–3.0]) had a significantly increased risk for SARS-CoV-2 secondary infection. Genomic analysis revealed substantial acquisition of viruses from the community even among households with other SARS-CoV-2 infections. After excluding community acquisition, we estimated a household secondary attack rate of 24.2% (95% CI, 11.9%–40.9%). ConclusionsThese findings underscore the ongoing risk of community acquisition of SARS-CoV-2 among households with current infections. The observed high attack rate necessitates swift booster vaccination, rapid testing availability, and therapeutic options to mitigate the severe outcomes of COVID-19. 
        more » 
        « less   
        
    
                            - Award ID(s):
- 2223843
- PAR ID:
- 10533565
- Publisher / Repository:
- Oxford Academic
- Date Published:
- Journal Name:
- Open Forum Infectious Diseases
- Volume:
- 11
- Issue:
- 3
- ISSN:
- 2328-8957
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
- 
            
- 
            Objectives: The SARS-CoV-2 BQ.1* variant rapidly spread globally in late 2022, posing a challenge due to its increased immune evasion. Methods: We conducted a prevalence survey in Brazil from November 16 to December 22, 2022, as part of a cohort study. We conducted interviews and collected nasal samples for reverse transcription-polymerase chain reaction (RT-PCR) testing and whole-genome sequencing. Cumulative incidence was estimated using RT-PCR positivity, cycle threshold values, and external data on the dynamics of RT-PCR positivity following infection. Results: Among 535 participants, 54% had documented SARS-CoV-2 exposure before this outbreak and 74% had received COVID-19 vaccination. In this study, 14.8% tested positive for SARS-CoV-2, with BQ.1* identified in 90.7% of cases. Using case data and cycle threshold values, cumulative incidence was estimated at 56% (95% confidence interval, 36-88%). Of the 79 positive participants, 48.1% had a symptomatic illness, with a lower proportion fulfilling the World Health Organization COVID-19 case definition compared to prior Omicron waves. No participants required medical attention. Conclusions: Despite high population-level hybrid immunity, the BQ.1* variant attacked 56% of our population. Lower disease severity was associated with BQ.1* compared to prior Omicron variants. Hybrid immunity may provide protection against future SARS-CoV-2 variants but in this case was not able to prevent widespread transmission.more » « less
- 
            Abstract Objective: Current guidance states that asymptomatic screening for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) prior to admission to an acute-care setting is at the facility’s discretion. This study’s objective was to estimate the number of undetected cases of SARS-CoV-2 admitted as inpatients under 4 testing approaches and varying assumptions. Design and setting: Individual-based microsimulation of 104 North Carolina acute-care hospitals Patients: All simulated inpatient admissions to acute-care hospitals from December 15, 2021, to January 13, 2022 [ie, during the SARS-COV-2 ο (omicron) variant surge]. Interventions: We simulated (1) only testing symptomatic patients, (2) 1-stage antigen testing with no confirmatory polymerase chain reaction (PCR) test, (3) 1-stage antigen testing with a confirmatory PCR for negative results, and (4) serial antigen screening (ie, repeat antigen test 2 days after a negative result). Results: Over 1 month, there were 77,980 admissions: 13.7% for COVID-19, 4.3% with but not for COVID-19, and 82.0% for non–COVID-19 indications without current infection. Without asymptomatic screening, 1,089 (credible interval [CI], 946–1,253) total SARS-CoV-2 infections (7.72%) went undetected. With 1-stage antigen screening, 734 (CI, 638–845) asymptomatic infections (67.4%) were detected, with 1,277 false positives. With combined antigen and PCR screening, 1,007 (CI, 875–1,159) asymptomatic infections (92.5%) were detected, with 5,578 false positives. A serial antigen testing policy detected 973 (CI, 845–1,120) asymptomatic infections (89.4%), with 2,529 false positives. Conclusions: Serial antigen testing identified >85% of asymptomatic infections and resulted in fewer false positives with less cost per identified infection compared to combined antigen plus PCR testing.more » « less
- 
            Low, Nicola (Ed.)Background While booster vaccinations clearly reduce the risk of severe Coronavirus Disease 2019 (COVID-19) and death, the impact of boosters on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections has not been fully characterized: Doing so requires understanding their impact on asymptomatic and mildly symptomatic infections that often go unreported but nevertheless play an important role in spreading SARS-CoV-2. We sought to estimate the impact of COVID-19 booster doses on SARS-CoV-2 infections in a vaccinated population of young adults during an Omicron BA.1-predominant period. Methods and findings We implemented a cohort study of young adults in a college environment (Cornell University’s Ithaca campus) from a period when Omicron BA.1 was the predominant SARS-CoV-2 variant on campus (December 5 to December 31, 2021). Participants included 15,800 university students who completed initial vaccination series with vaccines approved by the World Health Organization for emergency use, were enrolled in mandatory at-least-weekly surveillance polymerase chain reaction (PCR) testing, and had no positive SARS-CoV-2 PCR test within 90 days before the start of the study period. Robust multivariable Poisson regression with the main outcome of a positive SARS-CoV-2 PCR test was performed to compare those who completed their initial vaccination series and a booster dose to those without a booster dose. A total of 1,926 unique SARS-CoV-2 infections were identified in the study population. Controlling for sex, student group membership, date of completion of initial vaccination series, initial vaccine type, and temporal effect during the study period, our analysis estimates that receiving a booster dose further reduces the rate of having a PCR-detected SARS-CoV-2 infection relative to an initial vaccination series by 56% (95% confidence interval [42%, 67%], P < 0.001). While most individuals had recent booster administration before or during the study period (a limitation of our study), this result is robust to the assumed delay over which a booster dose becomes effective (varied from 1 day to 14 days). The mandatory active surveillance approach used in this study, under which 86% of the person-days in the study occurred, reduces the likelihood of outcome misclassification. Key limitations of our methodology are that we did not have an a priori protocol or statistical analysis plan because the analysis was initially done for institutional research purposes, and some analysis choices were made after observing the data. Conclusions We observed that boosters are effective, relative to completion of initial vaccination series, in further reducing the rate of SARS-CoV-2 infections in a college student population during a period when Omicron BA.1 was predominant; booster vaccinations for this age group may play an important role in reducing incidence of COVID-19.more » « less
- 
            Abstract BackgroundFour severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants predominated in the United States since 2021. Understanding disease severity related to different SARS-CoV-2 variants remains limited. MethodViral genome analysis was performed on SARS-CoV-2 clinical isolates circulating March 2021 through March 2022 in Cleveland, Ohio. Major variants were correlated with disease severity and patient outcomes. ResultsIn total 2779 patients identified with either Alpha (n = 1153), Gamma (n = 122), Delta (n = 808), or Omicron variants (n = 696) were selected for analysis. No difference in frequency of hospitalization, intensive care unit (ICU) admission, and death were found among Alpha, Gamma, and Delta variants. However, patients with Omicron infection were significantly less likely to be admitted to the hospital, require oxygen, or admission to the ICU (χ2 = 12.8, P < .001; χ2 = 21.6, P < .002; χ2 = 9.6, P = .01, respectively). In patients whose vaccination status was known, a substantial number had breakthrough infections with Delta or Omicron variants (218/808 [26.9%] and 513/696 [73.7%], respectively). In breakthrough infections, hospitalization rate was similar regardless of variant by multivariate analysis. No difference in disease severity was identified between Omicron subvariants BA.1 and BA.2. ConclusionsDisease severity associated with Alpha, Gamma, and Delta variants is comparable while Omicron infections are significantly less severe. Breakthrough disease is significantly more common in patients with Omicron infection.more » « less
 An official website of the United States government
An official website of the United States government 
				
			 
					 
					
 
                                    