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1.
JAMA Netw Open ; 5(4): e227038, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1787607

ABSTRACT

Importance: Recent reports on waning of COVID-19 vaccine-induced immunity have led to the approval and rollout of additional doses and booster vaccinations. Individuals at increased risk of SARS-CoV-2 infection are receiving additional vaccine doses in addition to the regimen that was tested in clinical trials. Risks and adverse event profiles associated with additional vaccine doses are currently not well understood. Objective: To evaluate the safety of third-dose vaccination with US Food and Drug Administration (FDA)-approved COVID-19 mRNA vaccines. Design, Setting, and Participants: This cohort study was conducted using electronic health record (EHR) data from December 2020 to October 2021 from the multistate Mayo Clinic Enterprise. Participants included all 47 999 individuals receiving 3-dose COVID-19 mRNA vaccines within the study setting who met study inclusion criteria. Participants were divided into 2 cohorts by vaccine brand administered and served as their own control groups, with no comparison made between cohorts. Data were analyzed from September through November 2021. Exposures: Three doses of an FDA-authorized COVID-19 mRNA vaccine, BNT162b2 or mRNA-1273. Main Outcomes and Measures: Vaccine-associated adverse events were assessed via EHR report. Adverse event risk was quantified using the percentage of study participants who reported the adverse event within 14 days after each vaccine dose and during a 14-day control period, immediately preceding the first vaccine dose. Results: Among 47 999 individuals who received 3-dose COVID-19 mRNA vaccines, 38 094 individuals (21 835 [57.3%] women; median [IQR] age, 67.4 [52.5-76.5] years) received BNT162b2 (79.4%) and 9905 individuals (5099 [51.5%] women; median [IQR] age, 67.7 [59.5-73.9] years) received mRNA-1273 (20.6%). Reporting of severe adverse events remained low after the third vaccine dose, with rates of pericarditis (0.01%; 95% CI, 0%-0.02%), anaphylaxis (0%; 95% CI, 0%-0.01%), myocarditis (0%; 95% CI, 0%-0.01%), and cerebral venous sinus thrombosis (no individuals) consistent with results from earlier studies. Significantly more individuals reported low-severity adverse events after the third dose compared with after the second dose, including fatigue (2360 individuals [4.92%] vs 1665 individuals [3.47%]; P < .001), lymphadenopathy (1387 individuals [2.89%] vs 995 individuals [2.07%]; P < .001), nausea (1259 individuals [2.62%] vs 979 individuals [2.04%]; P < .001), headache (1185 individuals [2.47%] vs 992 individuals [2.07%]; P < .001), arthralgia (1019 individuals [2.12%] vs 816 individuals [1.70%]; P < .001), myalgia (956 individuals [1.99%] vs 784 individuals [1.63%]; P < .001), diarrhea (817 individuals [1.70%] vs 595 individuals [1.24%]; P < .001), fever (533 individuals [1.11%] vs 391 individuals [0.81%]; P < .001), vomiting (528 individuals [1.10%] vs 385 individuals [0.80%]; P < .001), and chills (224 individuals [0.47%] vs 175 individuals [0.36%]; P = .01). Conclusions and Relevance: This study found that although third-dose vaccination against SARS-CoV-2 infection was associated with increased reporting of low-severity adverse events, risk of severe adverse events remained comparable with risk associated with the standard 2-dose regime. These findings suggest the safety of third vaccination doses in individuals who were eligible for booster vaccination at the time of this study.

3.
Mayo Clin Proc ; 97(3): 454-464, 2022 03.
Article in English | MEDLINE | ID: covidwho-1665266

ABSTRACT

OBJECTIVE: To describe the clinical data from the first 108 patients seen in the Mayo Clinic post-COVID-19 care clinic (PCOCC). METHODS: After Institutional Review Board approval, we reviewed the charts of the first 108 patients seen between January 19, 2021, and April 29, 2021, in the PCOCC and abstracted from the electronic medical record into a standardized database to facilitate analysis. Patients were grouped into phenotypes by expert review. RESULTS: Most of the patients seen in our clinic were female (75%; 81/108), and the median age at presentation was 46 years (interquartile range, 37 to 55 years). All had post-acute sequelae of SARS-CoV-2 infection, with 6 clinical phenotypes being identified: fatigue predominant (n=69), dyspnea predominant (n=23), myalgia predominant (n=6), orthostasis predominant (n=6), chest pain predominant (n=3), and headache predominant (n=1). The fatigue-predominant phenotype was more common in women, and the dyspnea-predominant phenotype was more common in men. Interleukin 6 (IL-6) was elevated in 61% of patients (69% of women; P=.0046), which was more common than elevation in C-reactive protein and erythrocyte sedimentation rate, identified in 17% and 20% of cases, respectively. CONCLUSION: In our PCOCC, we observed several distinct clinical phenotypes. Fatigue predominance was the most common presentation and was associated with elevated IL-6 levels and female sex. Dyspnea predominance was more common in men and was not associated with elevated IL-6 levels. IL-6 levels were more likely than erythrocyte sedimentation rate and C-reactive protein to be elevated in patients with post-acute sequelae of SARS-CoV-2 infection.


Subject(s)
COVID-19/complications , Adult , COVID-19/immunology , Female , Humans , Male , Middle Aged , Prospective Studies , Sex Distribution
4.
Med (N Y) ; 3(1): 28-41.e8, 2022 Jan 14.
Article in English | MEDLINE | ID: covidwho-1559964

ABSTRACT

Background: mRNA coronavirus disease 2019 (COVID-19) vaccines are safe and effective, but increasing reports of breakthrough infections highlight the need to vigilantly monitor and compare the effectiveness of these vaccines. Methods: We retrospectively compared protection against symptomatic infection conferred by mRNA-1273 and BNT162b2 at Mayo Clinic sites from December 2020 to September 2021. We used a test-negative case-control design to estimate vaccine effectiveness (VE) and to compare the odds of symptomatic infection after full vaccination with mRNA-1273 versus BNT162b2, while adjusting for age, sex, race, ethnicity, geography, comorbidities, and calendar time of vaccination and testing. Findings: Both vaccines were highly effective over the study duration (VEmRNA-1273: 84.1%, 95% confidence interval [CI]: 81.6%-86.2%; VEBNT162b2: 75.6%, 95% CI: 72.2%-78.7%), but their effectiveness was reduced during July-September (VEmRNA-1273: 75.6%, 95% CI: 70.1%-80%; VEBNT162b2: 63.5%, 95% CI: 55.8%-69.9%) as compared to December-May (VEmRNA-1273: 93.7%, 95% CI: 90.4%-95.9%; VEBNT162b2: 85.7%, 95% CI: 81.4%-88.9%). Adjusted for demographic characteristics, clinical comorbidities, time of vaccination, and time of testing, the odds of experiencing a symptomatic breakthrough infection were lower after full vaccination with mRNA-1273 than with BNT162b2 (odds ratio: 0.60; 95% CI: 0.55-0.67). Conclusions: Both mRNA-1273 and BNT162b2 strongly protect against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It is imperative to continue monitoring and comparing available vaccines over time and with respect to emerging variants to inform public and global health decisions. Funding: This study was funded by nference.

5.
Lancet Respir Med ; 10(3): 237-246, 2022 03.
Article in English | MEDLINE | ID: covidwho-1550165

ABSTRACT

BACKGROUND: The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes. Lenzilumab, a GM-CSF neutralising monoclonal antibody, was investigated in the LIVE-AIR trial to assess its efficacy and safety in treating COVID-19 beyond available treatments. METHODS: In LIVE-AIR, a phase 3, randomised, double-blind, placebo-controlled trial, hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (600 mg per dose) or placebo delivered 8 h apart. All patients received standard supportive care, including the use of remdesivir and corticosteroids. Patients were stratified at randomisation by age and disease severity. The primary endpoint was survival without invasive mechanical ventilation to day 28 in the modified intention-to-treat population (mITT), comprising all randomised participants who received at least one dose of study drug under the documented supervision of the principal investigator or sub-investigator. Adverse events were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04351152, and is completed. FINDINGS: Patients were enrolled from May 5, 2020, until Jan 27, 2021. 528 patients were screened, of whom 520 were randomly assigned and included in the intention-to-treat population. 479 of these patients (n=236, lenzilumab; n=243, placebo) were included in the mITT analysis for the primary outcome. Baseline demographics were similar between groups. 311 (65%) participants were males, mean age was 61 (SD 14) years at baseline, and median C-reactive protein concentration was 79 (IQR 41-137) mg/L. Steroids were administered to 449 (94%) patients and remdesivir to 347 (72%) patients; 331 (69%) patients received both treatments. Survival without invasive mechanical ventilation to day 28 was achieved in 198 (84%; 95% CI 79-89) participants in the lenzilumab group and in 190 (78%; 72-83) patients in the placebo group, and the likelihood of survival was greater with lenzilumab than placebo (hazard ratio 1·54; 95% CI 1·02-2·32; p=0·040). 68 (27%) of 255 patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group experienced at least one adverse event that was at least grade 3 in severity based on CTCAE criteria. The most common treatment-emergent adverse events of grade 3 or higher were related to respiratory disorders (26%) and cardiac disorders (6%) and none led to death. INTERPRETATION: Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with COVID-19, with a safety profile similar to that of placebo. The added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains unknown. FUNDING: Humanigen.


Subject(s)
COVID-19 , Adult , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/drug therapy , Double-Blind Method , Humans , Male , Middle Aged , SARS-CoV-2 , Treatment Outcome
6.
Mayo Clin Proc ; 96(10): 2561-2575, 2021 10.
Article in English | MEDLINE | ID: covidwho-1521396

ABSTRACT

OBJECTIVE: To compare coronavirus disease 2019 (COVID-19) acute kidney injury (AKI) to sepsis-AKI (S-AKI). The morphology and transcriptomic and proteomic characteristics of autopsy kidneys were analyzed. PATIENTS AND METHODS: Individuals 18 years of age and older who died from COVID-19 and had an autopsy performed at Mayo Clinic between April 2020 to October 2020 were included. Morphological evaluation of the kidneys of 17 individuals with COVID-19 was performed. In a subset of seven COVID-19 cases with postmortem interval of less than or equal to 20 hours, ultrastructural and molecular characteristics (targeted transcriptome and proteomics analyses of tubulointerstitium) were evaluated. Molecular characteristics were compared with archived cases of S-AKI and nonsepsis causes of AKI. RESULTS: The spectrum of COVID-19 renal pathology included macrophage-dominant microvascular inflammation (glomerulitis and peritubular capillaritis), vascular dysfunction (peritubular capillary congestion and endothelial injury), and tubular injury with ultrastructural evidence of mitochondrial damage. Investigation of the spatial architecture using a novel imaging mass cytometry revealed enrichment of CD3+CD4+ T cells in close proximity to antigen-presenting cells, and macrophage-enriched glomerular and interstitial infiltrates, suggesting an innate and adaptive immune tissue response. Coronavirus disease 2019 AKI and S-AKI, as compared to nonseptic AKI, had an enrichment of transcriptional pathways involved in inflammation (apoptosis, autophagy, major histocompatibility complex class I and II, and type 1 T helper cell differentiation). Proteomic pathway analysis showed that COVID-19 AKI and to a lesser extent S-AKI were enriched in necroptosis and sirtuin-signaling pathways, both involved in regulatory response to inflammation. Upregulation of the ceramide-signaling pathway and downregulation of oxidative phosphorylation in COVID-19 AKI were noted. CONCLUSION: This data highlights the similarities between S-AKI and COVID-19 AKI and suggests that mitochondrial dysfunction may play a pivotal role in COVID-19 AKI. This data may allow the development of novel diagnostic and therapeutic targets.


Subject(s)
Acute Kidney Injury/pathology , COVID-19/pathology , Kidney/pathology , Sepsis/pathology , Acute Kidney Injury/virology , Adult , Autopsy , Humans , Kidney Tubules, Proximal/pathology , Male , Middle Aged , Sepsis/virology
7.
JAMA Netw Open ; 4(11): e2132540, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1490645

ABSTRACT

Importance: Continuous assessment of the effectiveness and safety of the US Food and Drug Administration-authorized SARS-CoV-2 vaccines is critical to amplify transparency, build public trust, and ultimately improve overall health outcomes. Objective: To evaluate the effectiveness of the Johnson & Johnson Ad26.COV2.S vaccine for preventing SARS-CoV-2 infection. Design, Setting, and Participants: This comparative effectiveness research study used large-scale longitudinal curation of electronic health records from the multistate Mayo Clinic Health System (Minnesota, Arizona, Florida, Wisconsin, and Iowa) to identify vaccinated and unvaccinated adults between February 27 and July 22, 2021. The unvaccinated cohort was matched on a propensity score derived from age, sex, zip code, race, ethnicity, and previous number of SARS-CoV-2 polymerase chain reaction tests. The final study cohort consisted of 8889 patients in the vaccinated group and 88 898 unvaccinated matched patients. Exposure: Single dose of the Ad26.COV2.S vaccine. Main Outcomes and Measures: The incidence rate ratio of SARS-CoV-2 infection in the vaccinated vs unvaccinated control cohorts, measured by SARS-CoV-2 polymerase chain reaction testing. Results: The study was composed of 8889 vaccinated patients (4491 men [50.5%]; mean [SD] age, 52.4 [16.9] years) and 88 898 unvaccinated patients (44 748 men [50.3%]; mean [SD] age, 51.7 [16.7] years). The incidence rate ratio of SARS-CoV-2 infection in the vaccinated vs unvaccinated control cohorts was 0.26 (95% CI, 0.20-0.34) (60 of 8889 vaccinated patients vs 2236 of 88 898 unvaccinated individuals), which corresponds to an effectiveness of 73.6% (95% CI, 65.9%-79.9%) and a 3.73-fold reduction in SARS-CoV-2 infections. Conclusions and Relevance: This study's findings are consistent with the clinical trial-reported efficacy of Ad26.COV2.S and the first retrospective analysis, suggesting that the vaccine is effective at reducing SARS-CoV-2 infection, even with the spread of variants such as Alpha or Delta that were not present in the original studies, and reaffirm the urgent need to continue mass vaccination efforts globally.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Adolescent , Adult , Aged , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Nucleic Acid Testing , COVID-19 Vaccines/administration & dosage , Drug Evaluation , Female , Humans , Incidence , Male , Middle Aged , Pandemics , Propensity Score , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Time Factors , United States/epidemiology , Vaccination/statistics & numerical data , Young Adult
8.
J Clin Invest ; 131(19)2021 10 01.
Article in English | MEDLINE | ID: covidwho-1448085

ABSTRACT

BACKGROUNDClinical data to support the use of bamlanivimab for the treatment of outpatients with mild to moderate coronavirus disease-19 (COVID-19) are needed.METHODS2335 Patients who received single-dose bamlanivimab infusion between November 12, 2020, and February 17, 2021, were compared with a propensity-matched control of 2335 untreated patients with mild to moderate COVID-19 at Mayo Clinic facilities across 4 states. The primary outcome was the rate of hospitalization at days 14, 21, and 28.RESULTSThe median age of the population was 63 years; 47.3% of the bamlanivimab-treated cohort were 65 years or more; 49.3% were female and 50.7% were male. High-risk characteristics included hypertension (54.2%), BMI greater than or equal to 35 (32.4%), diabetes mellitus (26.5%), chronic lung disease (25.1%), malignancy (16.6%), and renal disease (14.5%). Patients who received bamlanivimab had lower all-cause hospitalization rates at days 14 (1.5% vs. 3.5%; risk ratio [RR], 0.41), 21 (1.9% vs. 3.9%; RR, 0.49), and 28 (2.5% vs. 3.9%; RR, 0.63). Secondary exploratory outcomes included lower intensive care unit (ICU) admission rates at days 14 (0.14% vs. 1%; RR, 0.14), 21 (0.25% vs.1%; RR, 0.25), and 28 (0.56% vs.1.1%; RR. 0.51) and lower all-cause mortality at days 14 (0% vs. 0.33%), 21 (0.05% vs. 0.4%; RR,0.13), and 28 (0.11% vs. 0.44%; RR, 0.26). Adverse events were uncommon with bamlanivimab, occurring in 19 of 2355 patients, and were most commonly fever (n = 6), nausea (n = 5), and lightheadedness (n = 3).CONCLUSIONSAmong high-risk patients with mild to moderate COVID-19, treatment with bamlanivimab was associated with a statistically significant lower rate of hospitalization, ICU admission, and mortality compared with usual care.FUNDINGMayo Clinic.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19 , Hospitalization , SARS-CoV-2/metabolism , Administration, Intravenous , Adult , Aged , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/mortality , Disease-Free Survival , Female , Humans , Intensive Care Units , Male , Middle Aged , Risk Factors , Survival Rate
10.
EClinicalMedicine ; 40: 101102, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1377701

ABSTRACT

BACKGROUND: Real-world clinical data to support the use of casirivimab-imdevimab for the treatment of outpatients with mild to moderate coronavirus disease-19 (COVID-19) is needed. This study aimed to assess the outcomes of casirivimab-imdevimab treatment of mild to moderate COVID-19. METHODS: A retrospective cohort of 696 patients who received casirivimab-imdevimab between December 4, 2020 and April 9, 2021 was compared to a propensity-matched control of 696 untreated patients with mild to moderate COVID-19 at Mayo Clinic sites in Arizona, Florida, Minnesota, and Wisconsin. Primary outcome was rate of hospitalization at days 14, 21 and 28 after infusion. FINDINGS: The median age of the antibody-treated cohort was 63 years (interquartile range, 52-71); 45·5% were ≥65 years old; 51.4% were female. High-risk characteristics were hypertension (52.4%), body mass index ≥35 (31.0%), diabetes mellitus (24.6%), chronic lung disease (22.1%), chronic renal disease (11.4%), congestive heart failure (6.6%), and compromised immune function (6.7%). Compared to the propensity-matched untreated control, patients who received casirivimab-imdevimab had significantly lower all-cause hospitalization rates at day 14 (1.3% vs 3.3%; Absolute Difference: 2.0%; 95% confidence interval (CI): 0.5-3.7%), day 21 (1.3% vs 4.2%; Absolute Difference: 2.9%; 95% CI: 1.2-4.7%), and day 28 (1.6% vs 4.8%; Absolute Difference: 3.2%; 95% CI: 1.4-5.1%). Rates of intensive care unit admission and mortality at days 14, 21 and 28 were similarly low for antibody-treated and untreated groups. INTERPRETATION: Among high-risk patients with mild to moderate COVID-19, casirivimab-imdevimab treatment was associated with a significantly lower rate of hospitalization. FUNDING: Mayo Clinic.

11.
NPJ Digit Med ; 4(1): 117, 2021 Jul 27.
Article in English | MEDLINE | ID: covidwho-1328860

ABSTRACT

Understanding the relationships between pre-existing conditions and complications of COVID-19 infection is critical to identifying which patients will develop severe disease. Here, we leverage ~1.1 million clinical notes from 1803 hospitalized COVID-19 patients and deep neural network models to characterize associations between 21 pre-existing conditions and the development of 20 complications (e.g. respiratory, cardiovascular, renal, and hematologic) of COVID-19 infection throughout the course of infection (i.e. 0-30 days, 31-60 days, and 61-90 days). Pleural effusion was the most frequent complication of early COVID-19 infection (89/1803 patients, 4.9%) followed by cardiac arrhythmia (45/1803 patients, 2.5%). Notably, hypertension was the most significant risk factor associated with 10 different complications including acute respiratory distress syndrome, cardiac arrhythmia, and anemia. The onset of new complications after 30 days is rare and most commonly involves pleural effusion (31-60 days: 11 patients, 61-90 days: 9 patients). Lastly, comparing the rates of complications with a propensity-matched COVID-negative hospitalized population confirmed the importance of hypertension as a risk factor for early-onset complications. Overall, the associations between pre-COVID conditions and COVID-associated complications presented here may form the basis for the development of risk assessment scores to guide clinical care pathways.

12.
Open Forum Infect Dis ; 8(7): ofab284, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1309623

ABSTRACT

BACKGROUND: Statins up-regulate angiotensin-converting enzyme 2, the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while also exhibiting pleiotropic antiviral, antithrombotic, and anti-inflammatory properties. Uncertainties exist about their effect on the course of SARS-CoV-2 infection. We sought to systematically review the literature and perform a meta-analysis to examine the association between prior statin use and outcomes of patients with coronavirus disease 2019 (COVID-19). METHODS: We searched Ovid Medline, Web of Science, Scopus, and the preprint server medRxiv from inception to December 2020. We assessed the quality of eligible studies with the Newcastle-Ottawa quality scale. We pooled adjusted relative risk (aRRs) of the association between prior statin use and outcomes of patients with COVID-19 using the DerSimonian-Laird random-effects model and assessed heterogeneity using the I 2 index. RESULTS: Overall, 19 (16 cohorts and 3 case-control) studies were eligible, with a total of 395 513 patients. Sixteen of 19 studies had low or moderate risk of bias. Among 109 080 patients enrolled in 13 separate studies, prior statin use was associated with a lower risk of mortality (pooled aRR, 0.65 [95% confidence interval {CI}, .56-.77], I 2 = 84.1%) and a reduced risk of severe COVID-19 was also observed in 48 110 patients enrolled in 9 studies (pooled aRR, 0.73 [95% CI, .57-.94], I 2 = 82.8%), with no evidence of publication bias. CONCLUSIONS: Cumulative evidence suggests that prior statin use is associated with lower risks of mortality or severe disease in patients with COVID-19. These data support the continued use of statins medications in patients with an indication for lipid-lowering therapy during the COVID-19 pandemic.

13.
J Stroke Cerebrovasc Dis ; 30(10): 105923, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1300924

ABSTRACT

OBJECTIVE: To assess the association of COVID-19 vaccines and non-COVID-19 vaccines with cerebral venous sinus thrombosis (CVST). MATERIALS AND METHOD: We retrospectively analyzed a cohort of 771,805 vaccination events across 266,094 patients in the Mayo Clinic Health System between 01/01/2017 and 03/15/2021. The primary outcome was a positive diagnosis of CVST, identified either by the presence of a corresponding ICD code or by an NLP algorithm which detected positive diagnosis of CVST within free-text clinical notes. For each vaccine we calculated the relative risk by dividing the incidence of CVST in the 30 days following vaccination to that in the 30 days preceding vaccination. RESULTS: We identified vaccination events for all FDA-approved COVID-19 vaccines including Pfizer-BioNTech (n = 94,818 doses), Moderna (n = 36,350 doses) and Johnson & Johnson - J&J (n = 1,745 doses). We also identified vaccinations events for 10 common FDA-approved non-COVID-19 vaccines (n = 771,805 doses). There was no statistically significant difference in the incidence rate of CVST in 30-days before and after vaccination for any vaccine in this population. We further found the baseline CVST incidence in the study population between 2017 and 2021 to be 45 to 98 per million patient years. CONCLUSIONS: This real-world evidence-based study finds that CVST is rare and is not significantly associated with COVID-19 vaccination in our patient cohort. Limitations include the rarity of CVST in our dataset, a relatively small number of J&J COVID-19 vaccination events, and the use of a population drawn from recipients of a SARS-CoV-2 PCR test in a single health system.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Sinus Thrombosis, Intracranial/epidemiology , Vaccination/adverse effects , COVID-19/immunology , COVID-19/virology , Electronic Health Records , Humans , Incidence , Retrospective Studies , Risk Assessment , Risk Factors , Sinus Thrombosis, Intracranial/diagnosis , Time Factors , United States/epidemiology
14.
Am J Transplant ; 21(8): 2890-2894, 2021 08.
Article in English | MEDLINE | ID: covidwho-1297494

ABSTRACT

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.


Subject(s)
COVID-19 , Liver Failure, Acute , Liver Transplantation , Adolescent , Female , Humans , Liver Failure, Acute/etiology , Liver Failure, Acute/surgery , Liver Transplantation/adverse effects , Pandemics , Polymerase Chain Reaction , SARS-CoV-2
16.
Med (N Y) ; 2(8): 965-978.e5, 2021 08 13.
Article in English | MEDLINE | ID: covidwho-1294062

ABSTRACT

BACKGROUND: As the coronavirus disease 2019 (COVID-19) vaccination campaign unfolds, it is important to continuously assess the real-world safety of Food and Drug Administration (FDA)-authorized vaccines. Curation of large-scale electronic health records (EHRs) enables near-real-time safety evaluations that were not previously possible. METHODS: In this retrospective study, we deployed deep neural networks over a large EHR system to automatically curate the adverse effects mentioned by physicians in over 1.2 million clinical notes between December 1, 2020 and April 20, 2021. We compared notes from 68,266 individuals who received at least one dose of BNT162b2 (n = 51,795) or mRNA-1273 (n = 16,471) to notes from 68,266 unvaccinated individuals who were matched by demographic, geographic, and clinical features. FINDINGS: Individuals vaccinated with BNT162b2 or mRNA-1273 had a higher rate of return to the clinic, but not the emergency department, after both doses compared to unvaccinated controls. The most frequently documented adverse effects within 7 days of each vaccine dose included myalgia, headache, and fatigue, but the rates of EHR documentation for each side effect were remarkably low compared to those derived from active solicitation during clinical trials. Severe events, including anaphylaxis, facial paralysis, and cerebral venous sinus thrombosis, were rare and occurred at similar frequencies in vaccinated and unvaccinated individuals. CONCLUSIONS: This analysis of vaccine-related adverse effects from over 1.2 million EHR notes of more than 130,000 individuals reaffirms the safety and tolerability of the FDA-authorized mRNA COVID-19 vaccines in practice. FUNDING: This study was funded by nference.


Subject(s)
COVID-19 , Drug-Related Side Effects and Adverse Reactions , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Mass Vaccination , RNA, Messenger , Retrospective Studies , SARS-CoV-2 , United States , United States Food and Drug Administration
17.
Med (N Y) ; 2(8): 979-992.e8, 2021 08 13.
Article in English | MEDLINE | ID: covidwho-1284376

ABSTRACT

BACKGROUND: Two US Food and Drug Administration (FDA)-authorized coronavirus disease 2019 (COVID-19) mRNA vaccines, BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna), have demonstrated high efficacy in large phase 3 randomized clinical trials. It is important to assess their effectiveness in a real-world setting. METHODS: This is a retrospective analysis of 136,532 individuals in the Mayo Clinic health system (Arizona, Florida, Iowa, Minnesota, and Wisconsin) with PCR testing data between December 1, 2020 and April 20, 2021. We compared clinical outcomes for a vaccinated cohort of 68,266 individuals who received at least one dose of either vaccine (nBNT162b2 = 51,795; nmRNA-1273 = 16,471) and an unvaccinated control cohort of 68,266 individuals propensity matched based on relevant demographic, clinical, and geographic features. We estimated real-world vaccine effectiveness by comparing incidence rates of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR testing and COVID-19-associated hospitalization and intensive care unit (ICU) admission starting 7 days after the second vaccine dose. FINDINGS: The real-world vaccine effectiveness of preventing SARS-CoV-2 infection was 86.1% (95% confidence interval [CI]: 82.4%-89.1%) for BNT162b2 and 93.3% (95% CI: 85.7%-97.4%) for mRNA-1273. BNT162b2 and mRNA-1273 were 88.8% (95% CI: 75.5%-95.7%) and 86.0% (95% CI: 71.6%-93.9%) effective in preventing COVID-19-associated hospitalization. Both vaccines were 100% effective (95% CIBNT162b2: 51.4%-100%; 95% CImRNA-1273: 43.3%-100%) in preventing COVID-19-associated ICU admission. CONCLUSIONS: BNT162b2 and mRNA-1273 are effective in a real-world setting and are associated with reduced rates of SARS-CoV-2 infection and decreased burden of COVID-19 on the healthcare system. FUNDING: This study was funded by nference.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/epidemiology , Humans , RNA, Messenger/genetics , Retrospective Studies , SARS-CoV-2/genetics , United States/epidemiology , United States Food and Drug Administration
18.
iScience ; 24(7): 102780, 2021 Jul 23.
Article in English | MEDLINE | ID: covidwho-1284160

ABSTRACT

Patients with COVID-19 can experience symptoms and complications after viral clearance. It is important to identify clinical features of patients who are likely to experience these prolonged effects. We conducted a retrospective study to compare longitudinal laboratory test measurements (hemoglobin, hematocrit, estimated glomerular filtration rate, serum creatinine, and blood urea nitrogen) in patients rehospitalized after PCR-confirmed SARS-CoV-2 clearance (n = 104) versus patients not rehospitalized after viral clearance (n = 278). Rehospitalized patients had lower median hemoglobin levels in the year prior to COVID-19 diagnosis (Cohen's D = -0.50; p = 1.2 × 10-3) and during their active SARS-CoV-2 infection (Cohen's D = -0.71; p = 4.6 × 10-8). Rehospitalized patients were also more likely to be diagnosed with moderate or severe anemia during their active infection (Odds Ratio = 4.07; p = 4.99 × 10-9). These findings suggest that anemia-related laboratory tests should be considered in risk stratification algorithms for patients with COVID-19.

19.
J Proteome Res ; 20(7): 3404-3413, 2021 07 02.
Article in English | MEDLINE | ID: covidwho-1253877

ABSTRACT

SARS-CoV-2 infection has become a major public health burden and affects many organs including lungs, kidneys, the liver, and the brain. Although the virus is readily detected and diagnosed using nasopharyngeal swabs by reverse transcriptase polymerase chain reaction (RT-PCR), detection of its presence in body fluids is fraught with difficulties. A number of published studies have failed to detect viral RNA by RT-PCR methods in urine. Although microbial identification in clinical microbiology using mass spectrometry is undertaken after culture, here we undertook a mass spectrometry-based approach that employed an enrichment step to capture and detect SARS-CoV-2 nucleocapsid protein directly from urine of COVID-19 patients without any culture. We detected SARS-CoV-2 nucleocapsid protein-derived peptides from 13 out of 39 urine samples. Further, a subset of COVID-19 positive and COVID-19 negative urine samples validated by mass spectrometry were used for the quantitative proteomics analysis. Proteins with increased abundance in urine of SARS-CoV-2 positive individuals were enriched in the acute phase response, regulation of complement system, and immune response. Notably, a number of renal proteins such as podocin (NPHS2), an amino acid transporter (SLC36A2), and sodium/glucose cotransporter 5 (SLC5A10), which are intimately involved in normal kidney function, were decreased in the urine of COVID-19 patients. Overall, the detection of viral antigens in urine using mass spectrometry and alterations of the urinary proteome could provide insights into understanding the pathogenesis of COVID-19.


Subject(s)
Body Fluids , COVID-19 , Antigens, Viral , Humans , Immunity , Mass Spectrometry , Phosphoproteins , RNA, Viral , SARS-CoV-2
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