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Viruses ; 14(9):1872, 2022.
Article in English | MDPI | ID: covidwho-2006215


Beyond their pulmonary disease, many COVID-19 patients experience a complex constellation of characteristics, including hyperinflammatory responses, autoimmune disorders, and coagulopathies. However, the pathogenesis of these aspects of COVID-19 is obscure. More than 90% of people are latently infected with the lymphotropic herpesviruses Epstein–Barr Virus (EBV) and/or Human Herpesvirus-6 (HHV-6). Some of the inflammatory features of COVID-19 resemble clinical syndromes seen during EBV and HHV-6 infection, and these latent viruses can be reactivated by inflammatory mediators. We hypothesized that EBV and HHV-6 reactivation might be a common feature of early COVID-19, particularly in patients with more inflammation. We tested for EBV and HHV-6 reactivation in 67 patients acutely hospitalized with COVID-19 using previously validated quantitative PCR assays on the plasma. In our cohort, we found that 15/67 (22.4%) patients had detectable EBV and 3/67 (4.5%) had detectable HHV-6. This frequency of activation is somewhat more than the frequency reported for some healthy cohorts, such as blood donors and other healthy control cohorts. There was no association between EBV or HHV-6 and markers indicative of more inflammatory disease. We conclude that EBV and HHV-6 activation at about day 7 of hospitalization occurred in a modest fraction of our cohort of COVID-19 patients and was not associated with high levels of inflammation. In the modest fraction of patients, EBV and HHV-6 reactivation could contribute to some features of acute disease and pre-disposition to post-acute sequelae in a subset of patients.

J Thorac Cardiovasc Surg ; 2022 Mar 14.
Article in English | MEDLINE | ID: covidwho-1796408


OBJECTIVE: We sought to determine the influence of venovenous extracorporeal membrane oxygenation (ECMO) on outcomes of mechanically ventilated patients with COVID-19 during the first 120 days after hospital discharge. METHODS: Five academic centers conducted a retrospective analysis of mechanically ventilated patients with COVID-19 admitted during March through May 2020. Survivors had access to a multidisciplinary postintensive care recovery clinic. Physical, psychological, and cognitive deficits were measured using validated instruments and compared based on ECMO status. RESULTS: Two hundred sixty two mechanically ventilated patients were compared with 46 patients cannulated for venovenous ECMO. Patients receiving ECMO were younger and traveled farther but there was no significant difference in gender, race, or body mass index. ECMO patients were mechanically ventilated for longer durations (median, 26 days [interquartile range, 19.5-41 days] vs 13 days [interquartile range, 7-20 days]) and were more likely to receive inhaled pulmonary vasodilators, neuromuscular blockade, investigational COVID-19 therapies, blood transfusions, and inotropes. Patients receiving ECMO experienced greater bleeding and clotting events (P < .01). However, survival at discharge was similar (69.6% vs 70.6%). Of the 217 survivors, 65.0% had documented follow-up within 120 days. Overall, 95.5% were residing at home, 25.7% had returned to work or usual activity, and 23.1% were still using supplemental oxygen; these rates did not differ significantly based on ECMO status. Rates of physical, psychological, and cognitive deficits were similar. CONCLUSIONS: Our data suggest that COVID-19 survivors experience significant physical, psychological, and cognitive deficits following intensive care unit admission. Despite a more complex critical illness course, longer average duration of mechanical ventilation, and longer average length of stay, patients treated with venovenous ECMO had similar survival at discharge and outcomes within 120 days of discharge.

Front Immunol ; 13: 850987, 2022.
Article in English | MEDLINE | ID: covidwho-1779942


Three COVID-19 vaccines have received FDA-authorization and are in use in the United States, but there is limited head-to-head data on the durability of the immune response elicited by these vaccines. Using a quantitative assay we studied binding IgG antibodies elicited by BNT162b2, mRNA-1273 or Ad26.COV2.S in an employee cohort over a span out to 10 months. Age and sex were explored as response modifiers. Of 234 subjects in the vaccine cohort, 114 received BNT162b2, 114 received mRNA-1273 and six received Ad26.COV2.S. IgG levels measured between seven to 20 days after the second vaccination were similar in recipients of BNT162b2 and mRNA-127 and were ~50-fold higher than in recipients of Ad26.COV2.S. However, by day 21 and at later time points IgG levels elicited by BNT162b2 were lower than mRNA-1273. Accordingly, the IgG decay curve was steeper for BNT162b2 than mRNA-1273. Age was a significant modifier of IgG levels in recipients of BNT162b2, but not mRNA-1273. After six months, IgG levels elicited by BNT162b2, but not mRNA-1273, were lower than IgG levels in patients who had been hospitalized with COVID-19 six months earlier. Similar findings were observed when comparing vaccine-elicited antibodies with steady-state IgG targeting seasonal human coronaviruses. Differential IgG decay could contribute to differences observed in clinical protection over time between BNT162b2 and mRNA-1273.

BNT162 Vaccine , COVID-19 , 2019-nCoV Vaccine mRNA-1273 , Ad26COVS1 , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunoglobulin G , SARS-CoV-2 , United States , Vaccination
Chest ; 160(1): 15-16, 2021 07.
Article in English | MEDLINE | ID: covidwho-1291525

COVID-19 , Humans , SARS-CoV-2
Physiol Rep ; 9(7): e14843, 2021 04.
Article in English | MEDLINE | ID: covidwho-1197692


Hypoadiponectinemia is speculated to play a key role in the relationship between obesity and COVID-19 respiratory failure. However, only one study has examined adiponectin levels in COVID-19 patients, and none have investigated adiponectin levels strictly in patients with acute respiratory failure. In this study, we performed a retrospective case-control study of adipokine levels in patients with acute respiratory failure caused by either COVID-19 or other viral/bacterial source. All patients with COVID-19 respiratory failure in the University of Virginia Biorepository and Tissue Research database were included. We also selected patients with non-COVID-19 infectious respiratory failure from the same biorepository to serve as a comparison cohort. Plasma adipokine levels were measured on three occasions during the first 72 hours of hospitalization. Twelve patients with COVID-19 respiratory failure and 17 patients with other infectious respiratory failure were studied. Adiponectin levels were significantly lower in patients with COVID-19 respiratory failure, even after adjustment for age, sex, BMI, and other covariates. In conclusion, adiponectin levels appear to be reduced in COVID-19 respiratory failure. Larger studies are needed to confirm this report.

Adiponectin/blood , COVID-19/blood , Aged , Biomarkers/blood , COVID-19/diagnosis , Databases, Factual , Down-Regulation , Female , Humans , Male , Middle Aged , Retrospective Studies , Time Factors
Int Arch Allergy Immunol ; 182(5): 417-424, 2021.
Article in English | MEDLINE | ID: covidwho-1097047


BACKGROUND: Detailed understanding of the immune response to severe acute respiratory syndrome coronavirus (SARS-CoV)-2, the cause of coronavirus disease 2019 (CO-VID-19) has been hampered by a lack of quantitative antibody assays. OBJECTIVE: The objective was to develop a quantitative assay for IgG to SARS-CoV-2 proteins that could be implemented in clinical and research laboratories. METHODS: The biotin-streptavidin technique was used to conjugate SARS-CoV-2 spike receptor-binding domain (RBD) or nucleocapsid protein to the solid phase of the ImmunoCAP. Plasma and serum samples from patients hospitalized with COVID-19 (n = 60) and samples from donors banked before the emergence of COVID-19 (n = 109) were used in the assay. SARS-CoV-2 IgG levels were followed longitudinally in a subset of samples and were related to total IgG and IgG to reference antigens using an ImmunoCAP 250 platform. RESULTS: At a cutoff of 2.5 µg/mL, the assay demonstrated sensitivity and specificity exceeding 95% for IgG to both SARS-CoV-2 proteins. Among 36 patients evaluated in a post-hospital follow-up clinic, median levels of IgG to spike-RBD and nucleocapsid were 34.7 µg/mL (IQR 18-52) and 24.5 µg/mL (IQR 9-59), respectively. Among 17 patients with longitudinal samples, there was a wide variation in the magnitude of IgG responses, but generally the response to spike-RBD and to nucleocapsid occurred in parallel, with peak levels approaching 100 µg/mL, or 1% of total IgG. CONCLUSIONS: We have described a quantitative assay to measure IgG to SARS-CoV-2 that could be used in clinical and research laboratories and implemented at scale. The assay can easily be adapted to measure IgG to mutated COVID-19 proteins, has good performance characteristics, and has a readout in standardized units.

Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , COVID-19/immunology , Immunoglobulin G/blood , SARS-CoV-2/immunology , Biomarkers/blood , COVID-19/virology , Humans , Longitudinal Studies , Sensitivity and Specificity