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Clinical Immunology Communications ; 2022.
Article in English | ScienceDirect | ID: covidwho-1819455


From asymptomatic to severe, SARS-CoV-2, causative agent of COVID-19, elicits varying disease severities. Moreover, understanding innate and adaptive immune responses to SARS-CoV-2 is imperative since variants such as Omicron negatively impact adaptive antibody neutralization. Severe COVID-19 is, in part, associated with aberrant activation of complement and Factor XII (FXIIa), initiator of contact system activation. Paradoxically, a protein that inhibits the three known pathways of complement activation and FXIIa, C1 esterase inhibitor (C1-INH), is increased in COVID-19 patient plasma and is associated with disease severity. Here we review the role of C1-INH in the regulation of innate and adaptive immune responses. Additionally, we contextualize regulation of C1-INH and SERPING1, the gene encoding C1-INH, by other pathogens and SARS viruses and propose that viral proteins bind to C1-INH to inhibit its function in severe COVID-19. Finally, we review the current clinical trials and published results of exogenous C1-INH treatment in COVID-19 patients.

Trauma Surg Acute Care Open ; 6(1): e000640, 2021.
Article in English | MEDLINE | ID: covidwho-1183382


BACKGROUND: Increased unemployment during the COVID-19 pandemic has likely led to widespread loss of employer-provided health insurance. This study examined trends in health insurance coverage among trauma patients during the COVID-19 pandemic, including differences in demographics and clinical characteristics by insurance type. METHODS: This was a retrospective study on adult patients admitted to six level 1 trauma centers between January 1, 2018 and June 30, 2020. The primary exposure was hospital admission date: January 1, 2018 to December 31, 2018 (Period 1), January 1, 2019 to March 15, 2020 (Period 2), and March 16, 2020 to June 30, 2020 (Period 3). Covariates included demographic and clinical variables. χ² tests examined whether the rates of patients covered by each insurance type differed between the pandemic and earlier periods. Mann-Whiney U and χ² tests investigated whether patient demographics or clinical characteristics differed within each insurance type across the study periods. RESULTS: A total of 31 225 trauma patients admitted between January 1, 2018 and June 30, 2019 were included. Forty-one per cent (n=12 651) were admitted in Period 1, 49% (n=15 258) were from Period 2, and 11% (n=3288) were from Period 3. Percentages of uninsured patients increased significantly across the three periods (Periods 1 to 3: 15%, 16%, 21%) (ptrend=0.02); however, there was no accompanying decrease in the percentages of commercial/privately insured patients (Periods 1 to 3: 40%, 39%, 39%) (ptrend=0.27). There was a significant decrease in the percentage of patients on Medicare during the pandemic period (Periods 1 to 3: 39%, 39%, 34%) (p<0.01). DISCUSSION: This study found that job loss during the COVID-19 pandemic resulted in increases of uninsured trauma patients. However, there was not a corresponding decrease in commercial/privately insured patients, as may have been expected; rather, a decrease in Medicare patients was observed. These findings may be attributable to a growing workforce during the study period, in combination with a younger overall patient population during the pandemic. LEVEL OF EVIDENCE: Retrospective, level III study.

Trauma Surg Acute Care Open ; 6(1): e000692, 2021.
Article in English | MEDLINE | ID: covidwho-1133334


INTRODUCTION: The COVID-19 pandemic has had major effects on hospitals' ability to perform scientific research while providing patient care and minimizing virus exposure and spread. Many non-COVID-19 research has been halted, and funding has been diverted to COVID-19 research and away from other areas. METHODS: A 28-question survey was administered to all level 1 trauma centers in the USA that included questions about how the pandemic affected the trauma centers' ability to fulfill the volume and research requirements of level 1 verification by the American College of Surgeons (ACS). RESULTS: The survey had a 29% response rate (40/137 successful invitations). Over half of respondents (52%) reported reduced trauma admissions during the pandemic, and 7% reported that their admissions dropped below the volume required for level 1 verification. Many centers diverted resources from research during the pandemic (44%), halted ongoing consenting studies (33%), and had difficulty fulfilling research requirements because of competing clinical priorities (40%). DISCUSSION: Results of this study show a need for flexibility in the ACS verification process during the COVID-19 pandemic, potentially including reduction of the required admissions and/or research publication volumes. LEVEL OF EVIDENCE: Level IV, cross-sectional study.

Heliyon ; 7(1): e05877, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1002561


Inflammatory responses to the novel coronavirus SARS-CoV-2, which causes COVID-19, range from asymptomatic to severe. Here we present a follow-up analysis of a longitudinal study characterizing COVID-19 immune responses from a father and son with distinctly different clinical courses. The father required a lengthy hospital stay for severe symptoms, whereas his son had mild symptoms and no fever yet tested positive for SARS-CoV-2 for 29 days. Father and son, as well as another unrelated COVID-19 patient, displayed a robust increase of SERPING1, the transcript encoding C1 esterase inhibitor (C1-INH). We further bolstered this finding by incorporating a serum proteomics dataset and found that serum C1-INH was consistently increased in COVID-19 patients. C1-INH is a central regulator of the contact and complement systems, potentially linking COVID-19 to complement hyperactivation, fibrin clot formation, and immune depression. Furthermore, despite distinct clinical cases, significant parallels were observed in transcripts involved in interferon and B cell signaling. As symptoms were resolving, widespread decreases were seen in immune-related transcripts to levels below those of healthy controls. Our study provides insight into the immune responses of likely millions of people with extremely mild symptoms who may not be aware of their infection with SARS-CoV-2 and implies a potential for long-lasting consequences that could contribute to reinfection risk.