Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 46 Records) |
Query Trace: Abedi GR[original query] |
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Viral determinants of acute COVID-19 symptoms in a nonhospitalized adult population in the pre-Omicron era
Goldberg SA , Lu S , Garcia-Knight M , Davidson MC , Tassetto M , Anglin K , Pineda-Ramirez J , Chen JY , Rugart PR , Mathur S , Forman CA , Donohue KC , Abedi GR , Saydah S , Briggs-Hagen M , Midgley CM , Andino R , Peluso MJ , Glidden DV , Martin JN , Kelly JD . Open Forum Infect Dis 2023 10 (8) ofad396 BACKGROUND: The influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA level and presence of infectious virus on symptom occurrence is poorly understood, particularly among nonhospitalized individuals. METHODS: The study included 85 nonhospitalized, symptomatic adults, who were enrolled from September 2020 to November 2021. Data from a longitudinal cohort studied over 28 days was used to analyze the association of individual symptoms with SARS-CoV-2 viral RNA load, or the presence or level of infectious (culturable) virus. Presence of infectious virus and viral RNA load were assessed daily, depending on specimen availability, and amount of infectious virus was assessed on the day of maximum RNA load. Participants were surveyed for the start and end dates of 31 symptoms at enrollment and at days 9, 14, 21, and 28; daily symptom presence was determined analytically. We describe symptoms and investigate their possible association with viral determinants through a series of single or pooled (multiple days across acute period) cross-sectional analyses. RESULTS: There was an association between viral RNA load and the same-day presence of many individual symptoms. Additionally, individuals with infectious virus were more than three times as likely to have a concurrent fever than individuals without infectious virus, and more than two times as likely to have concurrent myalgia, chills, headache, or sore throat. CONCLUSIONS: We found evidence to support the association of viral RNA load and infectious virus on some, but not all symptoms. Fever was most strongly associated with the presence of infectious virus; this may support the potential for symptom-based isolation guidance for COVID-19. |
Longitudinal and Quantitative Fecal Shedding Dynamics of SARS-CoV-2, Pepper Mild Mottle Virus and CrAssphage (preprint)
Arts PJ , Kelly JD , Midgley CM , Anglin K , Lu S , Abedi GR , Andino R , Bakker KM , Banman B , Boehm AB , Briggs-Hagen M , Brouwer AF , Davidson MC , Eisenberg MC , Garcia-Knight M , Knight S , Peluso MJ , Pineda-Ramirez J , Sanchez RD , Saydah S , Tassetto M , Martin JN , Wigginton KR . medRxiv 2023 07 e0013223 Wastewater-based epidemiology (WBE) emerged during the COVID-19 pandemic as a scalable and broadly applicable method for community-level monitoring of infectious disease burden, though the lack of high-quality, longitudinal fecal shedding data of SARS-CoV-2 and other viruses limits the interpretation and applicability of wastewater measurements. In this study, we present longitudinal, quantitative fecal shedding data for SARS-CoV-2 RNA, as well as the commonly used fecal indicators Pepper Mild Mottle Virus (PMMoV) RNA and crAss-like phage (crAssphage) DNA. The shedding trajectories from 48 SARS-CoV-2 infected individuals suggest a highly individualized, dynamic course of SARS-CoV-2 RNA fecal shedding, with individual measurements varying from below limit of detection to 2.79x106 gene copies/mg - dry mass of stool (gc/mg-dw). Of individuals that contributed at least 3 samples covering a range of at least 15 of the first 30 days after initial acute symptom onset, 77.4% had at least one positive SARS-CoV-2 RNA stool sample measurement. We detected PMMoV RNA in at least one sample from all individuals and in 96% (352/367) of samples overall; and measured crAssphage DNA above detection limits in 80% (38/48) of individuals and 48% (179/371) of samples. Median shedding values for PMMoV and crAssphage nucleic acids were 1x105 gc/mg-dw and 1.86x103 gc/mgdw, respectively. These results can be used to inform and build mechanistic models to significantly broaden the potential of WBE modeling and to provide more accurate insight into SARS-CoV-2 prevalence estimates. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Presence of Symptoms 6 Weeks After COVID-19 Among Vaccinated and Unvaccinated U.S. Healthcare Personnel (preprint)
Mohr NM , Plumb ID , Harland KK , Pilishvili T , Fleming-Dutra KE , Krishnadasan A , Hoth KF , Saydah SH , Mankoff Z , Haran JP , Leon ES , Talan DA , Smithline HA , Hou PC , Lee LC , Lim SC , Moran GJ , Steele MT , Beiser DG , Faine B , Nandi U , Schrading WA , Chinnock B , Chipman A , Fuentes M , LoVecchio F , Clinansmith B , Landers S , Horcher A , Wallace K , Uribe L , Pathmarajah K , Poronsky KE , Hashimoto DM , Bahamon M , Romain MSt , Kean E , Krebs E , Stubbs A , Roy S , Volturo G , Higgins A , Galbraith J , Crosby JC , Mulrow M , Gonzalez E , Gierke R , Farrar JL , Xing W , Chung Y , Yousaf A , Okaro JO , Briggs-Hagen M , Abedi GR , Nyanseor S , Watts CK . medRxiv 2022 25 Importance: Although COVID-19 vaccines protect against infection and severe disease, the role of vaccination in preventing prolonged symptoms in those with subsequent infection is unclear. Objective(s): To determine differences in symptoms stratified by prior vaccination reported by healthcare personnel (HCP) 6 weeks after onset of COVID-19, and whether there were differences in timing of return to work. Design(s): Nested cohort study within a multicenter vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset. Setting(s): Health systems in 12 U.S. states. Participant(s): HCP participating in a vaccine effectiveness study were eligible for inclusion if they had confirmed COVID-19 with either verified mRNA vaccination (symptom onset =14 days after two doses) or no prior COVID-19 vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey approximately 6 weeks after illness onset. Exposures: Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine. Main Outcomes and Measures: Presence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work after COVID-19 illness. Result(s): Among 419 HCP with confirmed COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants (60.6%) compared with unvaccinated participants (60.6% vs. 79.1%; aRR 0.70, 95% CI 0.58-0.84). Vaccinated HCP returned to work a median 2.0 days (95% CI 1.0-3.0) sooner than unvaccinated HCP (aHR 1.37; 95% CI, 1.04-1.79). Conclusion(s): A history of two doses of COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased risk of COVID-like symptoms at 6 weeks and earlier to return to work. Vaccination is associated with improved recovery from COVID-19, in addition to preventing symptomatic infection. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Infectious viral shedding of SARS-CoV-2 Delta following vaccination: a longitudinal cohort study (preprint)
Garcia-Knight M , Anglin K , Tassetto M , Lu S , Zhang A , Goldberg SA , Catching A , Davidson MC , Shak JR , Romero M , Pineda-Ramirez J , Sanchez RD , Rugart P , Donohue K , Massachi J , Sans HM , Djomaleu M , Mathur S , Servellita V , McIlwain D , Gaudiliere B , Chen J , Martinez EO , Tavs JM , Bronstone G , Weiss J , Watson JT , Briggs-Hagen M , Abedi GR , Rutherford GW , Deeks SG , Chiu C , Saydah S , Peluso MJ , Midgley CM , Martin JN , Andino R , Kelly JD . medRxiv 2022 19 (9) e1010802 The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P=0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Longitudinal and quantitative fecal shedding dynamics of SARS-CoV-2, pepper mild mottle virus, and crAssphage
Arts PJ , Kelly JD , Midgley CM , Anglin K , Lu S , Abedi GR , Andino R , Bakker KM , Banman B , Boehm AB , Briggs-Hagen M , Brouwer AF , Davidson MC , Eisenberg MC , Garcia-Knight M , Knight S , Peluso MJ , Pineda-Ramirez J , Diaz Sanchez R , Saydah S , Tassetto M , Martin JN , Wigginton KR . mSphere 2023 8 (4) e0013223 Wastewater-based epidemiology (WBE) emerged during the coronavirus disease 2019 (COVID-19) pandemic as a scalable and broadly applicable method for community-level monitoring of infectious disease burden. The lack of high-resolution fecal shedding data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) limits our ability to link WBE measurements to disease burden. In this study, we present longitudinal, quantitative fecal shedding data for SARS-CoV-2 RNA, as well as for the commonly used fecal indicators pepper mild mottle virus (PMMoV) RNA and crAss-like phage (crAssphage) DNA. The shedding trajectories from 48 SARS-CoV-2-infected individuals suggest a highly individualized, dynamic course of SARS-CoV-2 RNA fecal shedding. Of the individuals that provided at least three stool samples spanning more than 14 days, 77% had one or more samples that tested positive for SARS-CoV-2 RNA. We detected PMMoV RNA in at least one sample from all individuals and in 96% (352/367) of samples overall. CrAssphage DNA was detected in at least one sample from 80% (38/48) of individuals and was detected in 48% (179/371) of all samples. The geometric mean concentrations of PMMoV and crAssphage in stool across all individuals were 8.7 × 10(4) and 1.4 × 10(4) gene copies/milligram-dry weight, respectively, and crAssphage shedding was more consistent for individuals than PMMoV shedding. These results provide us with a missing link needed to connect laboratory WBE results with mechanistic models, and this will aid in more accurate estimates of COVID-19 burden in sewersheds. Additionally, the PMMoV and crAssphage data are critical for evaluating their utility as fecal strength normalizing measures and for source-tracking applications. IMPORTANCE This research represents a critical step in the advancement of wastewater monitoring for public health. To date, mechanistic materials balance modeling of wastewater-based epidemiology has relied on SARS-CoV-2 fecal shedding estimates from small-scale clinical reports or meta-analyses of research using a wide range of analytical methodologies. Additionally, previous SARS-CoV-2 fecal shedding data have not contained sufficient methodological information for building accurate materials balance models. Like SARS-CoV-2, fecal shedding of PMMoV and crAssphage has been understudied to date. The data presented here provide externally valid and longitudinal fecal shedding data for SARS-CoV-2, PMMoV, and crAssphage which can be directly applied to WBE models and ultimately increase the utility of WBE. |
Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, 2017-2018
Hakawi A , Rose EB , Biggs HM , Lu X , Mohammed M , Abdalla O , Abedi GR , Alsharef AA , Alamri AA , Bereagesh SA , Al Dosari KM , Ashehri SA , Fakhouri WG , Alzaid SZ , Lindstrom S , Gerber SI , Asiri A , Jokhdar H , Watson JT . Emerg Infect Dis 2019 25 (11) 2149-2151 We characterized exposures and demographics of Middle East respiratory syndrome coronavirus cases reported to the Saudi Arabia Ministry of Health during July 1-October 31, 2017, and June 1-September 16, 2018. Molecular characterization of available specimens showed that circulating viruses during these periods continued to cluster within lineage 5. |
Association of culturable-virus detection and household transmission of SARS-CoV-2 - California and Tennessee, 2020-2022
Deyoe JE , Kelly JD , Grijalva CG , Bonenfant G , Lu S , Anglin K , Garcia-Knight M , Pineda-Ramirez J , Briggs Hagen M , Saydah S , Abedi GR , Goldberg SA , Tassetto M , Zhang A , Donohue KC , Davidson MC , Diaz Sanchez R , Djomaleu M , Mathur S , Shak JR , Deeks SG , Peluso MJ , Chiu CY , Zhu Y , Halasa NB , Chappell JD , Mellis A , Reed C , Andino R , Martin JN , Zhou B , Talbot HK , Midgley CM , Rolfes MA . J Infect Dis 2023 From two SARS-CoV-2 household transmission studies (enrolling April 2020 - January 2022) with rapid enrollment and specimen collection for 14 days, 61% (43/70) of primary cases had culturable-virus detected ≥6 days post-onset. Risk of secondary infection among household contacts tended to be greater when primary cases had culturable-virus detected after onset. Regardless of duration of culturable-virus, most secondary infections [70% (28/40)] had serial intervals <6 days, suggesting early transmission. These data examine viral culture as a proxy for infectiousness, reaffirm the need for rapid control measures after infection and highlight the potential for prolonged infectiousness (≥6 days) in many individuals. |
Infectious viral shedding of SARS-CoV-2 Delta following vaccination: A longitudinal cohort study.
Garcia-Knight M , Anglin K , Tassetto M , Lu S , Zhang A , Goldberg SA , Catching A , Davidson MC , Shak JR , Romero M , Pineda-Ramirez J , Diaz-Sanchez R , Rugart P , Donohue K , Massachi J , Sans HM , Djomaleu M , Mathur S , Servellita V , McIlwain D , Gaudiliere B , Chen J , Martinez EO , Tavs JM , Bronstone G , Weiss J , Watson JT , Briggs-Hagen M , Abedi GR , Rutherford GW , Deeks SG , Chiu C , Saydah S , Peluso MJ , Midgley CM , Martin JN , Andino R , Kelly JD . PLoS Pathog 2022 18 (9) e1010802 The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P = 0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset. |
Magnitude and determinants of SARS-CoV-2 household transmission: a longitudinal cohort study.
Daniel Kelly J , Lu S , Anglin K , Garcia-Knight M , Pineda-Ramirez J , Goldberg SA , Tassetto M , Zhang A , Donohue K , Davidson MC , Romero M , Sanchez RD , Djomaleu M , Mathur S , Chen JY , Forman CA , Servellita V , Montejano RD , Shak JR , Rutherford GW , Deeks SG , Abedi GR , Rolfes MA , Saydah S , Briggs-Hagen M , Peluso MJ , Chiu C , Midgley CM , Andino R , Martin JN . Clin Infect Dis 2022 75 S193-S204 BACKGROUND: Households have emerged as important venues for SARS-CoV-2 transmission. Little is known, however, regarding the magnitude and determinants of household transmission in increasingly vaccinated populations. METHODS: From September 2020 to January 2022, symptomatic non-hospitalized individuals with SARS-CoV-2 infection by RNA detection were identified within 5 days of symptom onset; all individuals resided with at least one other SARS-CoV-2-uninfected household member. These infected persons (cases) and their household members (contacts) were subsequently followed with questionnaire-based measurement and serial nasal specimen collection. The primary outcome was SARS-CoV-2 infection among contacts. RESULTS: We evaluated 42 cases and their 74 household contacts. Among the contacts, 32 (43%) became infected, of whom 5/32 (16%) were asymptomatic; 81% of transmissions occurred by 5 days after the case's symptom onset. From 21 unvaccinated cases, 14-day cumulative incidence of SARS-CoV-2 infection among contacts was 18/40 (45%; 95% CI: 29, 62), most of whom were unvaccinated. From 21 vaccinated cases, 14-day cumulative incidence of SARS-CoV-2 infection was 14/34 (41%; 95% CI: 25, 59) among all contacts and 12/29 (41%; 95% CI: 24, 61) among vaccinated contacts. At least one co-morbid condition among cases and 10 or more days of RNA detection in cases were associated with increased risk of infection among contacts. CONCLUSIONS: Among households including individuals with symptomatic SARS-CoV-2 infection, both vaccinated-to-vaccinated and unvaccinated-to-unvaccinated transmission of SARS-CoV-2 to household contacts was common. Because vaccination alone did not notably reduce risk of infection, household contacts will need to employ additional interventions to avoid infection. |
Behaviors and attitudes of college students during an academic semester at two Wisconsin universities during the COVID-19 pandemic.
Rosenblum HG , Segaloff HE , Cole D , Lee CC , Currie DW , Abedi GR , Remington PL , Kelly GP , Pitts C , Langolf K , Kahrs J , Leibold K , Westergaard RP , Hsu CH , Kirking HL , Tate JE . J Am Coll Health 2022 1-8 OBJECTIVE: Characterize college student COVID-19 behaviors and attitudes during the early pandemic. Participants: Students on two university campuses in Wisconsin. METHODS: Surveys administered in September and November 2020. RESULTS: Few students (3-19%) participated in most in-person activities during the semester, with eating at restaurants as the exception (72-80%) and attending work (35%) and parties (33%) also reported more frequently. The majority wore masks in public (94-99%), but comparatively fewer (42%) did so at parties. Mask-wearing at parties decreased from September to November (p<0.05). Students attending parties, or consuming more alcohol, were less concerned and more likely to take COVID-19-associated risks. CONCLUSIONS: Students were motivated to adhere to COVID-19 prevention measures but gathered socially. Though there was frequent public masking, mask-wearing at parties declined in November and may represent pandemic fatigue. High-yield strategies for decreasing viral spread may include changing masking social norms and engaging with students about creative risk-reduction strategies. |
A cohort study measuring SARS-CoV-2 seroconversion and serial viral testing in university students.
Lee CC , Segaloff HE , Cole D , Rosenblum HG , Morgan CN , Somers T , Desamu-Thorpe R , Foster MA , Currie D , Ruff J , Payne D , Whyte TJ , Abedi GR , Bigouette JP , Kahrs J , Langolf K , Remington P , Sterkel A , Kelly P , Westergaard RP , Bateman AC , Hsu CH , Tate JE , Kirking HL . BMC Infect Dis 2022 22 (1) 314 BACKGROUND: To improve understanding of the antibody response to SARS-CoV-2 infection, we examined seroprevalence, incidence of infection, and seroconversion among a cohort of young adults living on university campuses during the fall of 2020. METHODS: At the beginning (semester start) and end (semester end) of an 11-week period, serum collected from 107 students was tested using the qualitative Abbott Architect SARS-CoV-2 IgG and AdviseDx SARS-CoV-2 IgG II assays. Results were matched to interim weekly surveillance viral testing and symptom data. RESULTS: With the SARS-CoV-2 IgG assay, 15 (14.0%) students were seropositive at semester start; 29 (27.1%) students were seropositive at semester end; 10 (9.3%) were seropositive at both times. With the AdviseDx SARS-CoV-2 IgG II assay, 17 (16.3%) students were seropositive at semester start, 37 (35.6%) were seropositive at semester end, and 16 (15.3%) were seropositive at both times. Overall, 23 students (21.5%) had positive viral tests during the semester. Infection was identified by serial testing in a large majority of individuals who seroconverted using both assays. Those seropositive at semester end more frequently reported symptomatic infections (56.5%) than asymptomatic infections (30.4%). CONCLUSION: Differences between antibody targets were observed, with more declines in antibody index values below the threshold of positivity with the anti-nucleocapsid assay compared to the anti-spike assay. Serology testing, combined with serial viral testing, can detect seroconversions, and help understand the potential correlates of protection provided by antibodies to SARS-CoV-2. |
Twelve-Month Follow-up of Early COVID-19 Cases in the United States: Cellular and Humoral Immune Longevity.
Shah MM , Rasheed MAU , Harcourt JL , Abedi GR , Stumpf MM , Kirking HL , Tamin A , Mills L , Armstrong M , Salvatore PP , Surasi K , Scott SE , Killerby ME , Briggs-Hagen M , Saydah S , Tate JE , Fry AM , Hall AJ , Thornburg NJ , Midgley CM . Open Forum Infect Dis 2022 9 (3) ofab664 We quantify antibody and memory B-cell responses to severe acute respiratory syndrome coronavirus 2 at 6 and 12 months postinfection among 7 unvaccinated US coronavirus disease 2019 cases. All had detectable S-specific memory B cells and immunoglobulin G at both time points, with geometric mean titers of 117.2 BAU/mL and 84.0 BAU/mL at 6 and 12 months, respectively. |
Risk Factors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Presence of Anti-SARS-CoV-2 Antibodies Among University Student Dormitory Residents, September-November 2020.
Segaloff HE , Cole D , Rosenblum HG , Lee CC , Morgan CN , Remington P , Pitts C , Kelly P , Baggott J , Bateman A , Somers T , Ruff J , Payne D , Desamu-Thorpe R , Foster MA , Currie DW , Abedi GR , Westergaard R , Hsu CH , Tate JE , Kirking HL . Open Forum Infect Dis 2021 8 (9) ofab405 BACKGROUND: Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks occurred at universities during Fall 2020, but little is known about risk factors for campus-associated infections or immunity provided by anti-SARS-CoV-2 antibodies in young adults. METHODS: We conducted surveys and serology tests among students living in dormitories in September and November to examine infection risk factors and antibody presence. Using campus weekly reverse-transcription polymerase chain reaction (RT-PCR) test results, the relationship between survey responses, SARS-CoV-2 antibodies, and infections was assessed. RESULTS: Of 6136 students, 1197 completed the survey and 572 also completed serologic testing in September compared with 517 and 414 in November, respectively. Participation in fraternity or sorority events (adjusted risk ratio [aRR], 1.9 [95% confidence interval {CI}, 1.4-2.5]) and frequent alcohol consumption (aRR, 1.6 [95% CI, 1.2-2.2]) were associated with SARS-CoV-2 infection. Mask wearing during social events (aRR, 0.6 [95% CI, .6-1.0]) was associated with decreased risk. None of the 20 students with antibodies in September tested positive for SARS-CoV-2 during the semester, while 27.8% of students who tested RT-PCR positive tested negative for antibodies in November. CONCLUSIONS: Frequent drinking and attending social events were associated with SARS-CoV-2 infection. Antibody presence in September appeared to be protective from reinfection, but this finding was not statistically significant. |
Outbreak of Acute Respiratory Illness Associated with Human Adenovirus Type 4 at the U.S. Coast Guard Academy, 2019.
Chu VT , Simon E , Lu X , Rockwell P , Abedi GR , Gardner C , Kujawski SA , Schneider E , Gentile M , Ramsey LA , Liu R , Jones S , Janik C , Siniscalchi A , Landry ML , Christopher J , Lindstrom S , Steiner S , Thomas D , Gerber SI , Biggs HM . J Infect Dis 2021 225 (1) 55-64 BACKGROUND: Although a human adenovirus (HAdV) vaccine is available for military use, officers-in-training are not routinely vaccinated. We describe an HAdV-associated respiratory outbreak among unvaccinated cadets at the U.S. Coast Guard Academy and its impact on cadet training. METHODS: We defined a case as a cadet with new onset cough or sore throat during August 1-October 4, 2019. We reviewed medical records and distributed a questionnaire to identify cases and to estimate impact on cadet training. We performed real-time PCR testing on patient and environmental samples and whole genome sequencing on a subset of positive patient samples. RESULTS: Among the 1,072 cadets, 378 (35%) cases were identified by medical records (n=230) or additionally by the questionnaire (n=148). Of the 230 cases identified from medical records, 138 (60%) were male and 226 (98%) had no underlying conditions. From questionnaire responses, 113/228 (50%) cases reported duty restrictions. Of cases with respiratory specimens, 36/50 (72%) were HAdV positive; all 14 sequenced specimens were HAdV-4a1. Sixteen (89%) of 18 environmental specimens from the cadet dormitory were HAdV-positive. CONCLUSIONS: The HAdV-4-associated outbreak infected a substantial number of cadets and significantly impacted cadet training. Routine vaccination could prevent HAdV respiratory outbreaks in this population. |
Epidemiologic characteristics associated with SARS-CoV-2 antigen-based test results, rRT-PCR cycle threshold values, subgenomic RNA, and viral culture results from university testing.
Ford L , Lee C , Pray IW , Cole D , Bigouette JP , Abedi GR , Bushman D , Delahoy MJ , Currie DW , Cherney B , Kirby M , Fajardo G , Caudill M , Langolf K , Kahrs J , Zochert T , Kelly P , Pitts C , Lim A , Aulik N , Tamin A , Harcourt JL , Queen K , Zhang J , Whitaker B , Browne H , Medrzycki M , Shewmaker P , Bonenfant G , Zhou B , Folster J , Bankamp B , Bowen MD , Thornburg NJ , Goffard K , Limbago B , Bateman A , Tate JE , Gieryn D , Kirking HL , Westergaard R , Killerby M . Clin Infect Dis 2021 73 (6) e1348-e1355 BACKGROUND: Real-time reverse transcription polymerase chain reaction (rRT-PCR) and antigen tests are important diagnostics for SARS-CoV-2. Sensitivity of antigen tests has been shown to be lower than that of rRT-PCR; however, data to evaluate epidemiologic characteristics that affect test performance are limited. METHODS: Paired mid-turbinate nasal swabs were collected from university students and staff and tested for SARS-CoV-2 using both Quidel Sofia SARS Antigen Fluorescent Immunoassay (FIA) and rRT-PCR assay. Specimens positive by either rRT-PCR or antigen FIA were placed in viral culture and tested for subgenomic RNA (sgRNA). Logistic regression models were used to evaluate characteristics associated with antigen results, rRT-PCR cycle threshold (Ct) values, sgRNA, and viral culture. RESULTS: Antigen FIA sensitivity was 78.9% and 43.8% among symptomatic and asymptomatic participants respectively. Among rRT-PCR positive participants, negative antigen results were more likely among asymptomatic participants (OR 4.6, CI:1.3-15.4) and less likely among participants reporting nasal congestion (OR 0.1, CI:0.03-0.8). rRT-PCR-positive specimens with higher Ct values (OR 0.5, CI:0.4-0.8) were less likely, and specimens positive for sgRNA (OR 10.2, CI:1.6-65.0) more likely, to yield positive virus isolation. Antigen testing was >90% positive in specimens with Ct values <29. Positive predictive value of antigen test for positive viral culture (57.7%) was similar to that of rRT-PCR (59.3%). CONCLUSIONS: SARS-CoV-2 antigen test advantages include low cost, wide availability and rapid turnaround time, making them important screening tests. The performance of antigen tests may vary with patient characteristics, so performance characteristics should be accounted for when designing testing strategies and interpreting results. |
Shedding of culturable virus, seroconversion, and 6-month follow-up antibody responses in the first 14 confirmed cases of COVID-19 in the United States.
Killerby ME , Ata Ur Rasheed M , Tamin A , Harcourt JL , Abedi GR , Lu X , Kujawski S , Shah MM , Kirking HL , Gold JAW , Salvatore PP , Coughlin MM , Whitaker B , Tate JE , Watson JT , Lindstrom S , Hall AJ , Fry AM , Gerber SI , Midgley CM , Thornburg NJ . J Infect Dis 2021 224 (5) 771-776 We aimed to characterize presence of culturable virus in clinical specimens during acute illness, and antibody kinetics up to six months post-onset, among 14 early US COVID-19 patients. We isolated viable SARS-CoV-2 from rRT-PCR-positive respiratory specimens collected during days 0-8 post-onset, but not after. All 13 patients with two or more serum specimens developed anti-spike antibodies; 12 developed detectable neutralizing antibodies. We did not isolate virus after detection of neutralizing antibodies. Eight participants provided serum at six months post-onset; all retained detectable anti-spike IgG, and half had detectable neutralizing antibodies. Two participants reported not feeling fully recovered at six months. |
Performance of an Antigen-Based Test for Asymptomatic and Symptomatic SARS-CoV-2 Testing at Two University Campuses - Wisconsin, September-October 2020.
Pray IW , Ford L , Cole D , Lee C , Bigouette JP , Abedi GR , Bushman D , Delahoy MJ , Currie D , Cherney B , Kirby M , Fajardo G , Caudill M , Langolf K , Kahrs J , Kelly P , Pitts C , Lim A , Aulik N , Tamin A , Harcourt JL , Queen K , Zhang J , Whitaker B , Browne H , Medrzycki M , Shewmaker P , Folster J , Bankamp B , Bowen MD , Thornburg NJ , Goffard K , Limbago B , Bateman A , Tate JE , Gieryn D , Kirking HL , Westergaard R , Killerby M . MMWR Morb Mortal Wkly Rep 2021 69 (5152) 1642-1647 Antigen-based tests for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), are inexpensive and can return results within 15 minutes (1). Antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in asymptomatic and symptomatic persons within the first 5-12 days after symptom onset (2). These tests have been used at U.S. colleges and universities and other congregate settings (e.g., nursing homes and correctional and detention facilities), where serial testing of asymptomatic persons might facilitate early case identification (3-5). However, test performance data from symptomatic and asymptomatic persons are limited. This investigation evaluated performance of the Sofia SARS Antigen Fluorescent Immunoassay (FIA) (Quidel Corporation) compared with real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection among asymptomatic and symptomatic persons at two universities in Wisconsin. During September 28-October 9, a total of 1,098 paired nasal swabs were tested using the Sofia SARS Antigen FIA and real-time RT-PCR. Virus culture was attempted on all antigen-positive or real-time RT-PCR-positive specimens. Among 871 (79%) paired swabs from asymptomatic participants, the antigen test sensitivity was 41.2%, specificity was 98.4%, and in this population the estimated positive predictive value (PPV) was 33.3%, and negative predictive value (NPV) was 98.8%. Antigen test performance was improved among 227 (21%) paired swabs from participants who reported one or more symptoms at specimen collection (sensitivity = 80.0%; specificity = 98.9%; PPV = 94.1%; NPV = 95.9%). Virus was isolated from 34 (46.6%) of 73 antigen-positive or real-time RT-PCR-positive nasal swab specimens, including two of 18 that were antigen-negative and real-time RT-PCR-positive (false-negatives). The advantages of antigen tests such as low cost and rapid turnaround might allow for rapid identification of infectious persons. However, these advantages need to be balanced against lower sensitivity and lower PPV, especially among asymptomatic persons. Confirmatory testing with an FDA-authorized nucleic acid amplification test (NAAT), such as RT-PCR, should be considered after negative antigen test results in symptomatic persons, and after positive antigen test results in asymptomatic persons (1). |
Severe Acute Respiratory Syndrome Coronavirus 2 Prevalence, Seroprevalence, and Exposure among Evacuees from Wuhan, China, 2020.
Hallowell BD , Carlson CM , Jacobs JR , Pomeroy M , Steinberg J , Tenforde MW , McDonald E , Foster L , Feldstein LR , Rolfes MA , Haynes A , Abedi GR , Odongo GS , Saruwatari K , Rider EC , Douville G , Bhakta N , Maniatis P , Lindstrom S , Thornburg NJ , Lu X , Whitaker BL , Kamili S , Sakthivel SK , Wang L , Malapati L , Murray JR , Lynch B , Cetron M , Brown C , Roohi S , Rotz L , Borntrager D , Ishii K , Moser K , Rasheed M , Freeman B , Lester S , Corbett KS , Abiona OM , Hutchinson GB , Graham BS , Pesik N , Mahon B , Braden C , Behravesh CB , Stewart R , Knight N , Hall AJ , Killerby ME . Emerg Infect Dis 2020 26 (9) 1998-2004 To determine prevalence of, seroprevalence of, and potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a cohort of evacuees returning to the United States from Wuhan, China, in January 2020, we conducted a cross-sectional study of quarantined evacuees from 1 repatriation flight. Overall, 193 of 195 evacuees completed exposure surveys and submitted upper respiratory or serum specimens or both at arrival in the United States. Nearly all evacuees had taken preventive measures to limit potential exposure while in Wuhan, and none had detectable SARS-CoV-2 in upper respiratory tract specimens, suggesting the absence of asymptomatic respiratory shedding among this group at the time of testing. Evidence of antibodies to SARS-CoV-2 was detected in 1 evacuee, who reported experiencing no symptoms or high-risk exposures in the previous 2 months. These findings demonstrated that this group of evacuees posed a low risk of introducing SARS-CoV-2 to the United States. |
Surveillance and testing for Middle East respiratory syndrome coronavirus, Saudi Arabia, March 2016-March 2019
Alzahrani A , Kujawski SA , Abedi GR , Tunkar S , Biggs HM , Alghawi N , Jokhdar H , Assiri AM , Watson JT . Emerg Infect Dis 2020 26 (7) 1571-1574 During March 2016-March 2019, a total of 200,936 suspected cases of Middle East respiratory syndrome coronavirus infection were identified in Saudi Arabia; infections were confirmed in 698 cases (0.3% [0.7/100,000 population per year]). Continued surveillance is necessary for early case detection and timely infection control response. |
Estimated Community Seroprevalence of SARS-CoV-2 Antibodies - Two Georgia Counties, April 28-May 3, 2020.
Biggs HM , Harris JB , Breakwell L , Dahlgren FS , Abedi GR , Szablewski CM , Drobeniuc J , Bustamante ND , Almendares O , Schnall AH , Gilani Z , Smith T , Gieraltowski L , Johnson JA , Bajema KL , McDavid K , Schafer IJ , Sullivan V , Punkova L , Tejada-Strop A , Amiling R , Mattison CP , Cortese MM , Ford SE , Paxton LA , Drenzek C , Tate JE , CDC Field Surveyor Team , Brown Nicole , Chang Karen T , Deputy Nicholas P , Desamu-Thorpe Rodel , Gorishek Chase , Hanchey Arianna , Melgar Michael , Monroe Benjamin P , Nielsen Carrie F , Pellegrini Gerald JJr , Shamout Mays , Tison Laura I , Vagi Sara , Zacks Rachael . MMWR Morb Mortal Wkly Rep 2020 69 (29) 965-970 Transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is ongoing in many communities throughout the United States. Although case-based and syndromic surveillance are critical for monitoring the pandemic, these systems rely on persons obtaining testing or reporting a COVID-19-like illness. Using serologic tests to detect the presence of SARS-CoV-2 antibodies is an adjunctive strategy that estimates the prevalence of past infection in a population. During April 28-May 3, 2020, coinciding with the end of a statewide shelter-in-place order, CDC and the Georgia Department of Public Health conducted a serologic survey in DeKalb and Fulton counties in metropolitan Atlanta to estimate SARS-CoV-2 seroprevalence in the population. A two-stage cluster sampling design was used to randomly select 30 census blocks in each county, with a target of seven participating households per census block. Weighted estimates were calculated to account for the probability of selection and adjusted for age group, sex, and race/ethnicity. A total of 394 households and 696 persons participated and had a serology result; 19 (2.7%) of 696 persons had SARS-CoV-2 antibodies detected. The estimated weighted seroprevalence across these two metropolitan Atlanta counties was 2.5% (95% confidence interval [CI] = 1.4-4.5). Non-Hispanic black participants more commonly had SARS-CoV-2 antibodies than did participants of other racial/ethnic groups (p<0.01). Among persons with SARS-CoV-2 antibodies, 13 (weighted % = 49.9; 95% CI = 24.4-75.5) reported a COVID-19-compatible illness,* six (weighted % = 28.2; 95% CI = 11.9-53.3) sought medical care for a COVID-19-compatible illness, and five (weighted % = 15.7; 95% CI = 5.1-39.4) had been tested for SARS-CoV-2 infection, demonstrating that many of these infections would not have been identified through case-based or syndromic surveillance. The relatively low seroprevalence estimate in this report indicates that most persons in the catchment area had not been infected with SARS-CoV-2 at the time of the survey. Continued preventive measures, including social distancing, consistent and correct use of face coverings, and hand hygiene, remain critical in controlling community spread of SARS-CoV-2. |
Clinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States.
Kujawski SA , Wong KK , Collins JP , Epstein L , Killerby ME , Midgley CM , Abedi GR , Ahmed NS , Almendares O , Alvarez FN , Anderson KN , Balter S , Barry V , Bartlett K , Beer K , Ben-Aderet MA , Benowitz I , Biggs HM , Binder AM , Black SR , Bonin B , Bozio CH , Brown CM , Bruce H , Bryant-Genevier J , Budd A , Buell D , Bystritsky R , Cates J , Charles EM , Chatham-Stephens K , Chea N , Chiou H , Christiansen D , Chu V , Cody S , Cohen M , Conners EE , Curns AT , Dasari V , Dawson P , DeSalvo T , Diaz G , Donahue M , Donovan S , Duca LM , Erickson K , Esona MD , Evans S , Falk J , Feldstein LR , Fenstersheib M , Fischer M , Fisher R , Foo C , Fricchione MJ , Friedman O , Fry A , Galang RR , Garcia MM , Gerber SI , Gerrard G , Ghinai I , Gounder P , Grein J , Grigg C , Gunzenhauser JD , Gutkin GI , Haddix M , Hall AJ , Han GS , Harcourt J , Harriman K , Haupt T , Haynes AK , Holshue M , Hoover C , Hunter JC , Jacobs MW , Jarashow C , Joshi K , Kamali T , Kamili S , Kim L , Kim M , King J , Kirking HL , Kita-Yarbro A , Klos R , Kobayashi M , Kocharian A , Komatsu KK , Koppaka R , Layden JE , Li Y , Lindquist S , Lindstrom S , Link-Gelles R , Lively J , Livingston M , Lo K , Lo J , Lu X , Lynch B , Madoff L , Malapati L , Marks G , Marlow M , Mathisen GE , McClung N , McGovern O , McPherson TD , Mehta M , Meier A , Mello L , Moon SS , Morgan M , Moro RN , Murray J , Murthy R , Novosad S , Oliver SE , O’Shea J , Pacilli M , Paden CR , Pallansch MA , Patel M , Patel S , Pedraza I , Pillai SK , Pindyck T , Pray I , Queen K , Quick N , Reese H , Reporter R , Rha B , Rhodes H , Robinson S , Robinson P , Rolfes MA , Routh JA , Rubin R , Rudman SL , Sakthivel SK , Scott S , Shepherd C , Shetty V , Smith EA , Smith S , Stierman B , Stoecker W , Sunenshine R , Sy-Santos R , Tamin A , Tao Y , Terashita D , Thornburg NJ , Tong S , Traub E , Tural A , Uehara A , Uyeki TM , Vahey G , Verani JR , Villarino E , Wallace M , Wang L , Watson JT , Westercamp M , Whitaker B , Wilkerson S , Woodruff RC , Wortham JM , Wu T , Xie A , Yousaf A , Zahn M , Zhang J . Nat Med 2020 26 (6) 861-868 Data on the detailed clinical progression of COVID-19 in conjunction with epidemiological and virological characteristics are limited. In this case series, we describe the first 12 US patients confirmed to have COVID-19 from 20 January to 5 February 2020, including 4 patients described previously(1-3). Respiratory, stool, serum and urine specimens were submitted for SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing, viral culture and whole genome sequencing. Median age was 53 years (range: 21-68); 8 patients were male. Common symptoms at illness onset were cough (n = 8) and fever (n = 7). Patients had mild to moderately severe illness; seven were hospitalized and demonstrated clinical or laboratory signs of worsening during the second week of illness. No patients required mechanical ventilation and all recovered. All had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset. Lowest real-time PCR with reverse transcription cycle threshold values in the upper respiratory tract were often detected in the first week and SARS-CoV-2 was cultured from early respiratory specimens. These data provide insight into the natural history of SARS-CoV-2. Although infectiousness is unclear, highest viral RNA levels were identified in the first week of illness. Clinicians should anticipate that some patients may worsen in the second week of illness. |
Diabetes mellitus, hypertension, and death among 32 patients with MERS-CoV infection, Saudi Arabia
Alanazi KH , Abedi GR , Midgley CM , Alkhamis A , Alsaqer T , Almoaddi A , Algwizani A , Ghazal SS , Assiri AM , Jokhdar H , Gerber SI , Alabdely H , Watson JT . Emerg Infect Dis 2020 26 (1) 166-168 Diabetes mellitus and hypertension are recognized risk factors for severe clinical outcomes, including death, associated with Middle East respiratory syndrome coronavirus infection. Among 32 virus-infected patients in Saudi Arabia, severity of illness and frequency of death corresponded closely with presence of multiple and more severe underlying conditions. |
Middle East respiratory syndrome coronavirus infection dynamics and antibody responses among clinically diverse patients, Saudi Arabia
Al-Abdely HM , Midgley CM , Alkhamis AM , Abedi GR , Lu X , Binder AM , Alanazi KH , Tamin A , Banjar WM , Lester S , Abdalla O , Dahl RM , Mohammed M , Trivedi S , Algarni HS , Sakthivel SK , Algwizani A , Bafaqeeh F , Alzahrani A , Alsharef AA , Alhakeem RF , Jokhdar HAA , Ghazal SS , Thornburg NJ , Erdman DD , Assiri AM , Watson JT , Gerber SI . Emerg Infect Dis 2019 25 (4) 753-766 Middle East respiratory syndrome coronavirus (MERS-CoV) shedding and antibody responses are not fully understood, particularly in relation to underlying medical conditions, clinical manifestations, and mortality. We enrolled MERS-CoV-positive patients at a hospital in Saudi Arabia and periodically collected specimens from multiple sites for real-time reverse transcription PCR and serologic testing. We conducted interviews and chart abstractions to collect clinical, epidemiologic, and laboratory information. We found that diabetes mellitus among survivors was associated with prolonged MERS-CoV RNA detection in the respiratory tract. Among case-patients who died, development of robust neutralizing serum antibody responses during the second and third week of illness was not sufficient for patient recovery or virus clearance. Fever and cough among mildly ill patients typically aligned with RNA detection in the upper respiratory tract; RNA levels peaked during the first week of illness. These findings should be considered in the development of infection control policies, vaccines, and antibody therapeutics. |
Picornavirus etiology of acute infections among hospitalized infants.
Abedi GR , Messacar K , Luong W , Nix WA , Rogers S , Queen K , Tong S , Oberste MS , Watt J , Rothrock G , Dominguez S , Gerber SI , Watson JT . J Clin Virol 2019 116 39-43 BACKGROUND: Enteroviruses (EV) and parechoviruses (PeV) are ubiquitous viruses that cause a range of illness, including acute illness in children aged <1 year. OBJECTIVES: We describe EV and PeV infections among children from 2 US study sites aged <1 year and hospitalized with acute infections. For EV- and PeV-negative case-patients, we explored other viral etiologies. METHODS: Participants were aged <1 year, hospitalized during 2016, and had cerebrospinal fluid (CSF) collected for routine diagnostic testing. Demographic and clinical data were abstracted from medical charts, and residual specimens were sent to CDC for confirmatory testing and typing. RESULTS: Of 472 eligible case-patients, CSF specimen was available for 319 (67.6%). Among those, 13 (4.1%) were positive for EV and 11 (3.4%) for PeV. Most case-patients (86.8%, n = 277) were aged <2 months, as were all EV- or PeV-positive case-patients. None of the positive case-patients had underlying conditions, and the chief complaint for 91.7% (n = 22) was fever. Twelve positive case-patients were admitted to intensive care (ICU) and had brief hospital stays (median 2 days). Sequencing revealed a variety of EV types and the predominance of PeV-A3 among the PeV-positive case-patients. CONCLUSIONS: A range of EV and PeV types were associated with acute febrile illnesses leading to hospitalization in children aged <2 months. Approximately half of EV and PeV case-patients were admitted to ICU, but length of hospital stay was brief and illnesses were generally self-limiting. Clinicians should consider EV and PeV infections in infants presenting with febrile illness. |
Scope and extent of healthcare-associated Middle East respiratory syndrome coronavirus transmission during two contemporaneous outbreaks in Riyadh, Saudi Arabia, 2017.
Alanazi KH , Killerby ME , Biggs HM , Abedi GR , Jokhdar H , Alsharef AA , Mohammed M , Abdalla O , Almari A , Bereagesh S , Tawfik S , Alresheedi H , Alhakeem RF , Hakawi A , Alfalah H , Amer H , Thornburg NJ , Tamin A , Trivedi S , Tong S , Lu X , Queen K , Li Y , Sakthivel SK , Tao Y , Zhang J , Paden CR , Al-Abdely HM , Assiri AM , Gerber SI , Watson JT . Infect Control Hosp Epidemiol 2019 40 (1) 79-88 OBJECTIVE: To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications. DESIGN: Outbreak investigation. SETTING: Cases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit. METHODS: Contact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases. RESULTS: In total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to >/=5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive. CONCLUSIONS: We describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission. |
Multihospital Outbreak of a Middle East Respiratory Syndrome Coronavirus Deletion Variant, Jordan: A Molecular, Serologic, and Epidemiologic Investigation.
Payne DC , Biggs HM , Al-Abdallat MM , Alqasrawi S , Lu X , Abedi GR , Haddadin A , Iblan I , Alsanouri T , Al Nsour M , Sheikh Ali S , Rha B , Trivedi SU , Rasheed MAU , Tamin A , Lamers MM , Haagmans BL , Erdman DD , Thornburg NJ , Gerber SI . Open Forum Infect Dis 2018 5 (5) ofy095 Background: An outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. We conducted a molecular and seroepidemiologic investigation to describe the deletion variant's transmission patterns and epidemiology. Methods: We reviewed epidemiologic and medical chart data and analyzed viral genome sequences from respiratory specimens of MERS-CoV cases. In early 2016, sera and standardized interviews were obtained from MERS-CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike protein enzyme immunoassays and microneutralization. Results: Among 16 cases, 11 (69%) had health care exposure and 5 (31%) were relatives of a known case; 13 (81%) were symptomatic, and 7 (44%) died. Genome sequencing of MERS-CoV from 13 cases revealed 3 transmissible deletions associated with clinical illness during the outbreak. Deletion variant sequences were epidemiologically clustered and linked to a common transmission chain. Interviews and sera were collected from 2 surviving cases, 23 household contacts, and 278 health care contacts; 1 (50%) case, 2 (9%) household contacts, and 3 (1%) health care contacts tested seropositive. Conclusions: The MERS-CoV deletion variants retained human-to-human transmissibility and caused clinical illness in infected persons despite accumulated mutations. Serology suggested limited transmission beyond that detected during the initial outbreak investigation. |
Infectious MERS-CoV isolated from a mildly ill patient, Saudi Arabia
Al-Abdely HM , Midgley CM , Alkhamis AM , Abedi GR , Tamin A , Binder AM , Alanazi K , Lu X , Abdalla O , Sakthivel SK , Mohammed M , Queen K , Algarni HS , Li Y , Trivedi S , Algwizani A , Alhakeem RF , Thornburg NJ , Tong S , Ghazal SS , Erdman DD , Assiri AM , Gerber SI , Watson JT . Open Forum Infect Dis 2018 5 (6) ofy111 Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with a wide range of clinical presentations, from asymptomatic or mildly ill to severe respiratory illness including death. We describe isolation of infectious MERS-CoV from the upper respiratory tract of a mildly ill 27-year-old female in Saudi Arabia 15 days after illness onset. |
Serologic follow-up of Middle East Respiratory Syndrome coronavirus cases and contacts - Abu Dhabi, United Arab Emirates
Al Hosani FI , Kim L , Khudhair A , Pham H , Al Mulla M , Al Bandar Z , Pradeep K , Elkheir KA , Weber S , Khoury M , Donnelly G , Younis N , El Saleh F , Abdalla M , Imambaccus H , Haynes LM , Thornburg NJ , Harcourt JL , Miao C , Tamin A , Hall AJ , Russell ES , Harris AM , Kiebler C , Mir RA , Pringle K , Alami NN , Abedi GR , Gerber SI . Clin Infect Dis 2018 68 (3) 409-418 Background: Although there is evidence of person-to-person transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in household and healthcare settings, more data are needed to describe and better understand the risk factors and transmission routes in both settings, as well as the extent that disease severity affects transmission. Methods: A sero-epidemiological investigation was conducted among Middle East Respiratory Syndrome Coronavirus (MERS-CoV) case-patients and their household contacts to investigate transmission risk in Abu Dhabi, United Arab Emirates. Cases diagnosed between January 1, 2013-May 9, 2014 and their household contacts were approached for enrollment. Demographic, clinical, and exposure history data were collected. Sera were screened by MERS-CoV nucleocapsid protein (N) ELISA and indirect immunofluorescence, with results confirmed by microneutralization assay. Results: Ninety-one percent (n=31/34) of case-patients were asymptomatic or mildly symptomatic and did not require oxygen during hospitalization. MERS-CoV antibodies were detected in 13 of 24 (54%) cases with available sera, including 3 asymptomatic, 9 mildly symptomatic, and 1 severely symptomatic case-patient. No serologic evidence of MERS-CoV transmission was found among 105 household contacts with available sera. Conclusions: Transmission of MERS-CoV was not documented in this investigation of mostly asymptomatic and mildly symptomatic cases and their household contacts. These results have implications for clinical management of cases and formulation of isolation policies to reduce the risk of transmission. |
Enterovirus and parechovirus surveillance - United States, 2014-2016
Abedi GR , Watson JT , Nix WA , Oberste MS , Gerber SI . MMWR Morb Mortal Wkly Rep 2018 67 (18) 515-518 Infections caused by enteroviruses (EV) and parechoviruses (PeV), members of the Picornaviridae family, are associated with various clinical manifestations, including hand, foot, and mouth disease; respiratory illness; myocarditis; meningitis; and sepsis; and can result in death. The genus Enterovirus includes four species of enterovirus (A-D) known to infect humans, and the genus Parechovirus includes one species (A) that infects humans. These species are further divided into types, some of which are associated with specific clinical manifestations. During 2014-2016, a total of 2,967 U.S. cases of EV and PeV infections were reported to the National Enterovirus Surveillance System (NESS). The largest number of reports during that time (2,051) occurred in 2014, when a large nationwide outbreak of enterovirus D68 (EV-D68) occurred, accounting for 68% of cases reported to NESS that year (1). Reports to the National Respiratory and Enteric Virus Surveillance System (NREVSS) during 2014-2016 indicated that circulation of EV peaks annually in the summer and early fall. Because the predominant types of EV and PeV circulating from year to year tend to vary, tracking these trends requires consistent and complete reports from laboratories with the capacity to perform typing. |
The seasonality of nonpolio enteroviruses in the United States: Patterns and drivers
Pons-Salort M , Oberste MS , Pallansch MA , Abedi GR , Takahashi S , Grenfell BT , Grassly NC . Proc Natl Acad Sci U S A 2018 115 (12) 3078-3083 Nonpolio enteroviruses are diverse and common viruses that can circulate year-round but tend to peak in summer. Although most infections are asymptomatic, they can result in a wide range of neurological and other diseases. Many serotypes circulate every year, and different serotypes predominate in different years, but the drivers of their geographical and temporal dynamics are not understood. We use national enterovirus surveillance data collected by the US Centers for Disease Control and Prevention during 1983-2013, as well as demographic and climatic data for the same period, to study the patterns and drivers of the seasonality of these infections. We find that the seasonal pattern of enterovirus cases is spatially structured in the United States and similar to that observed for historical prevaccination poliomyelitis (1931-1954). We identify latitudinal gradients for the amplitude and the timing of the peak of cases, meaning that those are more regularly distributed all year-round in the south and have a more pronounced peak that arrives later toward the north. The peak is estimated to occur between July and September across the United States, and 1 month earlier than that for historical poliomyelitis. Using mixed-effects models, we find that climate, but not demography, is likely to drive the seasonal pattern of enterovirus cases and that the dew point temperature alone explains approximately 30% of the variation in the intensity of transmission. Our study contributes to a better understanding of the epidemiology of enteroviruses, demonstrates important similarities in their circulation dynamics with polioviruses, and identifies potential drivers of their seasonality. |
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