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Kathleen Tompkins

Bio: Kathleen Tompkins is an academic researcher from University of North Carolina at Chapel Hill. The author has contributed to research in topics: Achromobacter xylosoxidans & Pneumonia. The author has an hindex of 5, co-authored 10 publications receiving 42 citations.

Papers
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Journal ArticleDOI
TL;DR: The CO-HOST prospective cohort study as mentioned in this paper showed that household crowding in the context of high-inoculum infections may amplify the spread of COVID-19, potentially contributing to disproportionate impact on communities of color.
Abstract: BACKGROUND: Households are hotspots for SARS-CoV-2 transmission. In the US, the COVID-19 pandemic has had a disproportionate impact on communities of color. METHODS: Between April-October 2020, the CO-HOST prospective cohort study enrolled 100 COVID-19 cases and 208 of their household members in North Carolina, including 44% who identified as Hispanic or non-white. Households were enrolled a median of 6 days from symptom onset in the index case. Incident secondary cases within the household were detected by quantitative PCR of weekly nasal swabs (days 7, 14, 21) or by seroconversion at day 28. RESULTS: Excluding 73 household contacts who were PCR-positive at baseline, the secondary attack rate among household contacts was 32% (33/103, 95% CI 22%-44%). The majority of cases occurred by day 7, with later cases confirmed as household-acquired by viral sequencing. Infected persons in the same household had similar nasopharyngeal viral loads (ICC=0.45, 95% CI 0.23-0.62). Households with secondary transmission had index cases with a median viral load that was 1.4 log10 higher than households without transmission (p=0.03) as well as higher living density (>3 persons occupying <6 rooms) (OR 3.3, 95% CI 1.02-10.9). Minority households were more likely to experience high living density and had a higher risk of incident infection than did white households (SAR 51% vs. 19%, p=0.01). CONCLUSIONS: Household crowding in the context of high-inoculum infections may amplify the spread of COVID-19, potentially contributing to disproportionate impact on communities of color.

37 citations

Posted ContentDOI
12 Mar 2021-medRxiv
TL;DR: In this paper, a prospective observational study of SARS-CoV-2 transmission within households has been reported from the United States, where COVID-19 cases are the highest in the world and the pandemic has had disproportionate impact on communities of color.
Abstract: BackgroundFew prospective studies of SARS-CoV-2 transmission within households have been reported from the United States, where COVID-19 cases are the highest in the world and the pandemic has had disproportionate impact on communities of color. Methods and FindingsThis is a prospective observational study. Between April-October 2020, the UNC CO-HOST study enrolled 102 COVID-positive persons and 213 of their household members across the Piedmont region of North Carolina, including 45% who identified as Hispanic/Latinx or non-white. Households were enrolled a median of 6 days from onset of symptoms in the index case. Secondary cases within the household were detected either by PCR of a nasopharyngeal (NP) swab on study day 1 and weekly nasal swabs (days 7, 14, 21) thereafter, or based on seroconversion by day 28. After excluding household contacts exposed at the same time as the index case, the secondary attack rate (SAR) among susceptible household contacts was 60% (106/176, 95% CI 53%-67%). The majority of secondary cases were already infected at study enrollment (73/106), while 33 were observed during study follow-up. Despite the potential for continuous exposure and sequential transmission over time, 93% (84/90, 95% CI 86%-97%) of PCR-positive secondary cases were detected within 14 days of symptom onset in the index case, while 83% were detected within 10 days. Index cases with high NP viral load (>10^6 viral copies/ul) at enrollment were more likely to transmit virus to household contacts during the study (OR 4.9, 95% CI 1.3-18 p=0.02). Furthermore, NP viral load was correlated within families (ICC=0.44, 95% CI 0.26-0.60), meaning persons in the same household were more likely to have similar viral loads, suggesting an inoculum effect. High household living density was associated with a higher risk of secondary household transmission (OR 5.8, 95% CI 1.3-55) for households with >3 persons occupying <6 rooms (SAR=91%, 95% CI 71-98%). Index cases who self-identified as Hispanic/Latinx or non-white were more likely to experience a high living density and transmit virus to a household member, translating into an SAR in minority households of 70%, versus 52% in white households (p=0.05). ConclusionsSARS-CoV-2 transmits early and often among household members. Risk for spread and subsequent disease is elevated in high-inoculum households with limited living space. Very high infection rates due to household crowding likely contribute to the increased incidence of SARS-CoV-2 infection and morbidity observed among racial and ethnic minorities in the US. Quarantine for 14 days from symptom onset of the first case in the household is appropriate to prevent onward transmission from the household. Ultimately, primary prevention through equitable distribution of effective vaccines is of paramount importance. AUTHORS SUMMARYO_ST_ABSWhy was this study done?C_ST_ABSO_LIUnderstanding the secondary attack rate and the timing of transmission of SARS-CoV-2 within households is important to determine the role of household transmission in the larger pandemic and to guide public health policies about quarantine. C_LIO_LIProspective studies looking at the determinants of household transmission are sparse, particularly studies including substantial racial and ethnic minorities in the United States and studies with adequate follow-up to detect sequential transmission events. C_LIO_LIIdentifying individuals at high risk of transmitting and acquiring SARS-CoV-2 will inform strategies for reducing transmission in the household, or reducing disease in those exposed. C_LI What did the researchers do and find?O_LIBetween April-November 2020, the UNC CO-HOST study enrolled 102 households across the Piedmont region of North Carolina, including 45% with an index case who identified as racial or ethnic minorities. C_LIO_LIOverall secondary attack rate was 60% with two-thirds of cases already infected at study enrollment. C_LIO_LIDespite the potential for sequential transmission in the household, the majority of secondary cases were detected within 10 days of symptom onset of the index case. C_LIO_LIViral loads were correlated within families, suggesting an inoculum effect. C_LIO_LIHigh viral load in the index case was associated with a greater likelihood of household transmission. C_LIO_LISpouses/partners of the COVID-positive index case and household members with obesity were at higher risk of becoming infected. C_LIO_LIHigh household living density contributed to an increased risk of household transmission. C_LIO_LIRacial/ethnic minorities had an increased risk of acquiring SARS-CoV-2 in their households in comparison to members of the majority (white) racial group. C_LI What do these findings mean?O_LIHousehold transmission often occurs quickly after a household member is infected. C_LIO_LIHigh viral load increases the risk of transmission. C_LIO_LIHigh viral load cases cluster within households - suggesting high viral inoculum in the index case may put the whole household at risk for more severe disease. C_LIO_LIIncreased household density may promote transmission within racial and ethnic minority households. C_LIO_LIEarly at-home point-of-care testing, and ultimately vaccination, is necessary to effectively decrease household transmission. C_LI

29 citations

Journal ArticleDOI
TL;DR: The potential for the development of resistance to these therapies remains high, and enhanced antimicrobial stewardship is imperative both to reduce the spread of CRE worldwide and to ensure continued access to efficacious treatment options.
Abstract: Carbapenem-resistant Enterobacterales (CRE) are a growing threat to human health worldwide. CRE often carry multiple resistance genes that limit treatment options and require longer durations of therapy, are more costly to treat, and necessitate therapies with increased toxicities when compared with carbapenem-susceptible strains. Here, we provide an overview of the mechanisms of resistance in CRE, the epidemiology of CRE infections worldwide, and available treatment options for CRE. We review recentlyapproved agents for the treatment of CRE, including ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and novel aminoglycosides and tetracyclines. We also discuss recent advances in phage therapy and antibiotics that are currently in development targeted to CRE. The potential for the development of resistance to these therapies remains high, and enhanced antimicrobial stewardship is imperative both to reduce the spread of CRE worldwide and to ensure continued access to efficacious treatment options.

25 citations

Journal ArticleDOI
TL;DR: In this article, a critically ill patient with coronavirus disease 2019 (COVID-19) was found to have acquired immune deficiency syndrome and Pneumocystis jirovecii pneumonia (PCP).
Abstract: We present a case of a critically ill patient with coronavirus disease 2019 (COVID-19) found to have acquired immune deficiency syndrome and Pneumocystis jirovecii pneumonia (PCP). Coronavirus disease 2019 and PCP co-occurrence is increasingly reported and may complicate diagnostic and therapeutic strategies. Patients with severe COVID-19 should be screened for underlying immunocompromise and coinfections should be considered.

24 citations

Journal ArticleDOI
TL;DR: Eight cystic fibrosis patients with A. xylosoxidans were treated with 12 cefiderocol courses, and microbiologic relapse was observed after 11/12 treatment courses, notably without emergence of resistance.
Abstract: Treatment options for Achromobacter xylosoxidans are limited. Eight cystic fibrosis patients with A. xylosoxidans were treated with 12 cefiderocol courses. Pre-treatment in vitro resistance was seen in 3/8 cases. Clinical response occurred after 11/12 treatment courses. However, microbiologic relapse was observed after 11/12 treatment courses, notably without emergence of resistance.

22 citations


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Journal ArticleDOI
TL;DR: The ability of MSCs to modulate liver, kidney, heart and intestinal repair is examined, and their opposing qualities of being less immunogenic and therefore tolerated in a transplant situation, yet being able to contribute to xenograft models of human tumour formation in other contexts are updated.
Abstract: There is currently much interest in adult mesenchymal stem cells (MSCs) and their ability to differentiate into other cell types, and to partake in the anatomy and physiology of remote organs. It is now clear these cells may be purified from several organs in the body besides bone marrow. MSCs take part in wound healing by contributing to myofibroblast and possibly fibroblast populations, and may be involved in epithelial tissue regeneration in certain organs, although this remains more controversial. In this review, we examine the ability of MSCs to modulate liver, kidney, heart and intestinal repair, and we update their opposing qualities of being less immunogenic and therefore tolerated in a transplant situation, yet being able to contribute to xenograft models of human tumour formation in other contexts. However, such observations have not been replicated in the clinic. Recent studies showing the clinical safety of MSC in several pathologies are discussed. The possible opposing powers of MSC need careful understanding and control if their clinical potential is to be realised with long-term safety for patients.

119 citations

Journal ArticleDOI
TL;DR: The results suggest that emerging SARS-CoV-2 variants of concern have increased transmissibility and the changes in estimated vaccine effectiveness underscore the challenges of developing effective vaccines concomitant with viral evolution.
Abstract: This systematic reviewe and meta-analysis evaluates household secondary attack rates of SARS-CoV-2 by variant and vaccination status.

100 citations

Journal ArticleDOI
02 Aug 2021
TL;DR: A previous systematic review and meta-analysis of household transmission of SARS-CoV-2 that summarized 54 published studies through October 19, 2020, found an overall secondary attack rate (SAR) of 16.6% (95% CI, 14.0%-19.3%).
Abstract: Importance A previous systematic review and meta-analysis of household transmission of SARS-CoV-2 that summarized 54 published studies through October 19, 2020, found an overall secondary attack rate (SAR) of 16.6% (95% CI, 14.0%-19.3%). However, the understanding of household secondary attack rates for SARS-CoV-2 is still evolving, and updated analysis is needed. Objective To use newly published data to further the understanding of SARS-CoV-2 transmission in the household. Data sources PubMed and reference lists of eligible articles were used to search for records published between October 20, 2020, and June 17, 2021. No restrictions on language, study design, time, or place of publication were applied. Studies published as preprints were included. Study selection Articles with original data that reported at least 2 of the following factors were included: number of household contacts with infection, total number of household contacts, and secondary attack rates among household contacts. Studies that reported household infection prevalence (which includes index cases), that tested contacts using antibody tests only, and that included populations overlapping with another included study were excluded. Search terms were SARS-CoV-2 or COVID-19 with secondary attack rate, household, close contacts, contact transmission, contact attack rate, or family transmission. Data extraction and synthesis Meta-analyses were performed using generalized linear mixed models to obtain SAR estimates and 95% CIs. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Main outcomes and measures Overall household SAR for SARS-CoV-2, SAR by covariates (contact age, sex, ethnicity, comorbidities, and relationship; index case age, sex, symptom status, presence of fever, and presence of cough; number of contacts; study location; and variant), and SAR by index case identification period. Results A total of 2722 records (2710 records from database searches and 12 records from the reference lists of eligible articles) published between October 20, 2020, and June 17, 2021, were identified. Of those, 93 full-text articles reporting household transmission of SARS-CoV-2 were assessed for eligibility, and 37 studies were included. These 37 new studies were combined with 50 of the 54 studies (published through October 19, 2020) from our previous review (4 studies from Wuhan, China, were excluded because their study populations overlapped with another recent study), resulting in a total of 87 studies representing 1 249 163 household contacts from 30 countries. The estimated household SAR for all 87 studies was 18.9% (95% CI, 16.2%-22.0%). Compared with studies from January to February 2020, the SAR for studies from July 2020 to March 2021 was higher (13.4% [95% CI, 10.7%-16.7%] vs 31.1% [95% CI, 22.6%-41.1%], respectively). Results from subgroup analyses were similar to those reported in a previous systematic review and meta-analysis; however, the SAR was higher to contacts with comorbidities (3 studies; 50.0% [95% CI, 41.4%-58.6%]) compared with previous findings, and the estimated household SAR for the B.1.1.7 (α) variant was 24.5% (3 studies; 95% CI, 10.9%-46.2%). Conclusions and relevance The findings of this study suggest that the household remains an important site of SARS-CoV-2 transmission, and recent studies have higher household SAR estimates compared with the earliest reports. More transmissible variants and vaccines may be associated with further changes.

99 citations

Journal ArticleDOI
TL;DR: A concise review of the published scientific data on the radiobiological features of MSCs is presented, the involvement of different DNA damage recognition and repair pathways in the creation of a radioresistant MSC phenotype is outlined, and the roles of apoptosis, senescence and autophagy regarding the reported radioresistance are summarized.
Abstract: Mesenchymal stem cells (MSCs) comprise a heterogeneous population of multipotent stromal cells and can be isolated from various tissues and organs. Due to their regenerative potential, they have been subject to intense research efforts, and they may provide an efficient means for treating radiation-induced tissue damage. MSCs are relatively resistant to ionizing radiation and retain their stem cell characteristics even after high radiation doses. The underlying mechanisms for the observed MSC radioresistance have been extensively studied and may involve efficient DNA damage recognition, double strand break repair and evasion of apoptosis. Here, we present a concise review of the published scientific data on the radiobiological features of MSCs. The involvement of different DNA damage recognition and repair pathways in the creation of a radioresistant MSC phenotype is outlined, and the roles of apoptosis, senescence and autophagy regarding the reported radioresistance are summarized. Finally, potential influences of the radioresistant MSCs for the clinic are discussed with respect to the repair and radioprotection of irradiated tissues.

75 citations

Posted ContentDOI
11 Jan 2022-medRxiv
TL;DR: To examine how emerging variants and increased vaccination have affected transmission rates, PubMed was searched from June 18, 2021, through January 7, 2022 to obtain SAR estimates and 95%CI, disaggregated by several covariates.
Abstract: We previously reported a household secondary attack rate (SAR) for SARS-CoV-2 of 18.9% through June 17, 2021. To examine how emerging variants and increased vaccination have affected transmission rates, we searched PubMed from June 18, 2021, through January 7, 2022. Meta-analyses used generalized linear mixed models to obtain SAR estimates and 95%CI, disaggregated by several covariates. SARs were used to estimate vaccine effectiveness based on the transmission probability for susceptibility (VE_S,p), infectiousness (VE_I,p), and total vaccine effectiveness (VE_T,p). Household SAR for 27 studies with midpoints in 2021 was 35.8% (95%CI, 30.6%-41.3%), compared to 15.7% (95%CI, 13.3%-18.4%) for 62 studies with midpoints through April 2020. Household SARs were 38.0% (95%CI, 36.0%-40.0%), 30.8% (95%CI, 23.5%-39.3%), and 22.5% (95%CI, 18.6%-26.8%) for Alpha, Delta, and Beta, respectively. VE_I,p, VE_S,p, and VE_T,p were 56.6% (95%CI, 28.7%-73.6%), 70.3% (95%CI, 59.3%-78.4%), and 86.8% (95%CI, 76.7%-92.5%) for full vaccination, and 27.5% (95%CI, -6.4%-50.7%), 43.9% (95%CI, 21.8%-59.7%), and 59.9% (95%CI, 34.4%-75.5%) for partial vaccination, respectively. Household contacts exposed to Alpha or Delta are at increased risk of infection compared to the original wild-type strain. Vaccination reduced susceptibility to infection and transmission to others.

66 citations