Severe acute infection and chronic pulmonary disease are risk factors for developing post-COVID-19 conditions

Post-COVID-19 conditions, also known as "long COVID", has significantly impacted the lives of many individuals, but the risk factors for this condition are poorly understood. In this study, we performed a retrospective EHR analysis of 89,843 individuals at a multi-state health system in the United States with PCR-confirmed COVID-19, including 1,086 patients diagnosed with long COVID and 1,086 matched controls not diagnosed with long COVID. For these two cohorts, we evaluated a wide range of clinical covariates, including laboratory tests, medication orders, phenotypes recorded in the clinical notes, and outcomes. We found that chronic pulmonary disease (CPD) was significantly more common as a pre-existing condition for the long COVID cohort than the control cohort (odds ratio: 1.9, 95% CI: [1.5, 2.6]). Additionally, long-COVID patients were more likely to have a history of migraine (odds ratio: 2.2, 95% CI: [1.6, 3.1]) and fibromyalgia (odds ratio: 2.3, 95% CI: [1.3, 3.8]). During the acute infection phase, the following lab measurements were abnormal in the long COVID cohort: high triglycerides (meanlongCOVID: 278.5 mg/dL vs. meancontrol: 141.4 mg/dL), low HDL cholesterol levels (meanlongCOVID: 38.4 mg/dL vs. meancontrol: 52.5 mg/dL), and high neutrophil-lymphocyte ratio (meanlongCOVID: 10.7 vs. meancontrol: 7.2). The hospitalization rate during the acute infection phase was also higher in the long COVID cohort compared to the control cohort (ratelongCOVID: 5% vs. ratecontrol: 1%). Overall, this study suggests that the severity of acute infection and a history of CPD, migraine, CFS, or fibromyalgia may be risk factors for long COVID symptoms. Our findings motivate clinical studies to evaluate whether suppressing acute disease severity proactively, especially in patients at high risk, can reduce incidence of long COVID.

Genomic epidemiology and phylodynamics for county-to-county transmission of SARS-CoV-2 in Minnesota, from 19A to Omicron

SARS-CoV-2 has had an unprecedented impact on human health and highlights the need for genomic epidemiology studies to increase our understanding of the evolution and spread of pathogens and to inform policy decisions. Most efforts have focused on international or country-wide transmission, which are unable to highlight state-wide trends. We sequenced virus genomes from over 22,000 patients tested at Mayo Clinic Laboratories between 2020-2022 and leveraged detailed patient metadata to describe county-to-county spread in Minnesota. Our findings indicate that spread in the state was mostly dominated by viruses from Hennepin County, which contains the largest metropolis. For many counties, we found that state government restrictions eventually led to a decrease in the diversity of circulating viruses from other counties and that their complete removal in May of 2021 saw a drastic revert to levels at or greater than those observed during the months before. We also linked over 14,000 genomes with patient risk characteristics and infection-related phenotypes from the Mayo Clinic electronic health record. We found that the genetic relationship of Omicron viruses was structured by clinical outcomes when stratifying by patient risk factor and variant of concern. However, we were unable to identify nucleotide variants that drove this association.

SARS-CoV-2 and influenza co-infection throughout the COVID-19 pandemic: An assessment of co-infection rates and cohort characterization

BackgroundCase reports of patients infected with COVID-19 and influenza virus ("flurona") have raised questions around the prevalence and clinical significance of these reports. MethodsEpidemiological data from the HHS Protect Public Data Hub was analyzed to show trends in SARS-CoV-2 and influenza co-infection-related hospitalizations in the United States in relation to SARS-CoV-2 and influenza strain data from NCBI Virus and FluView. In addition, we retrospectively analyzed all cases of PCR-confirmed SARS-CoV-2 across the Mayo Clinic Enterprise from January 2020 to January 2022 and identified cases of influenza co-infections within two weeks of PCR-positive diagnosis date. Using a cohort from the Mayo Clinic with joint PCR testing data, we estimated the expected number of co-infection cases given the background prevalences of COVID-19 and influenza during the Wuhan (Original), Alpha, Delta, and Omicron waves of the pandemic. FindingsConsidering data from all states of the United States using HHS Protect Public Data Hub, hospitalizations due to influenza co-infection with SARS-CoV-2 were seen to be highest in January 2022 compared to all previous months during the COVID-19 pandemic. Among 171,639 SARS-CoV-2-positive cases analyzed at Mayo Clinic between January 2020 and January 2022, only 73 cases of influenza co-infection were observed. Identified coinfected patients were relatively young (mean age: 28.4 years), predominantly male, and had few comorbidities. During the Delta era (June 16, 2021 to December 13, 2021), there were 9 lab-confirmed co-infection cases observed compared to 13.9 expected cases (95% CI: [12.7, 15.2]), and during the Omicron era (December 14, 2021 to January 17, 2022), there were 54 lab-confirmed co-infection cases compared to 80.9 expected cases (95% CI: [76.6, 85.1]). ConclusionsReported co-infections of SARS-CoV-2 and influenza are rare. These co-infections have occurred throughout the COVID-19 pandemic and their prevalence can be explained by background rates of COVID-19 and influenza infection. Preliminary assessment of longitudinal EHR data suggests that most co-infections so far have been observed among relatively young and healthy patients. Further analysis is needed to assess the outcomes of "flurona" among subpopulations with risk factors for severe COVID-19 such as older age, obesity, and immunocompromised status. Significance StatementReports of COVID-19 and influenza co-infections ("flurona") have raised concern in recent months as both COVID-19 and influenza cases have increased to significant levels in the US. Here, we analyze trends in co-infection cases over the course of the pandemic to show that these co-infection cases are expected given the background prevalences of COVID-19 and influenza independently. In addition, from an initial analysis of these co-infection cases which have been observed at the Mayo Clinic, we find that these co-infection cases are extremely rare and have mostly been observed in relatively young, healthy patients.

Three doses of COVID-19 mRNA vaccination are safe based on adverse events reported in electronic health records

Recent reports on waning of COVID-19 vaccine induced immunity have led to the approval and roll-out of additional dose and booster vaccinations. At risk individuals are receiving additional vaccine dose(s), in addition to the regimen that was tested in clinical trials. The risks and the adverse event profiles associated with these additional vaccine doses are currently not well understood. Here, we performed a retrospective study analyzing vaccine-associated adverse events using electronic health records (EHRs) of individuals that have received three doses of mRNA-based COVID-19 vaccines (n = 47,999). By comparing symptoms reported in 2-week time periods after each vaccine dose and in a 2-week period before the 1st vaccine dose, we assessed the risk associated with 3rd dose vaccination, for both BNT162b2 and mRNA-1273. Reporting of severe adverse events remained low after the 3rd vaccine dose, with rates of pericarditis (0.01%, 0%-0.02% 95% CI), anaphylaxis (0.00%, 0%-0.01% 95% CI), myocarditis (0.00%, 0%-0.01% 95% CI), and cerebral venous sinus thrombosis (no cases), consistent with earlier studies. Significantly more individuals (p-value < 0.05) report low-severity adverse events after their 3rd dose compared with after their 2nd dose, including fatigue (4.92% after 3rd dose vs 3.47% after 2nd dose), lymphadenopathy (2.89% vs 2.07%), nausea (2.62% vs 2.04%), headache (2.47% vs 2.07%), arthralgia (2.12% vs 1.70%), myalgia (1.99% vs 1.63%), diarrhea (1.70% vs 1.24%), fever (1.11% vs 0.81%), vomiting (1.10% vs 0.80%), and chills (0.47% vs 0.36%). Our results show that although 3rd dose vaccination against SARS-CoV-2 infection led to increased reporting of low-severity adverse events, risk of severe adverse events remained comparable to the standard 2-dose regime. This study provides support for the safety of 3rd vaccination doses of individuals that are at high-risk of severe COVID-19 and breakthrough infection.

Durability analysis of the highly effective BNT162b2 vaccine against COVID-19

SARS-CoV-2 breakthrough infections have been increasingly reported in fully vaccinated individuals. We conducted a test-negative case-control study to assess the durability of protection after full vaccination with BNT162b2, defined as 14 days after the second dose, against polymerase chain reaction (PCR)-confirmed symptomatic SARS-CoV-2 infection, in a national medical practice between February 1, 2021 and August 22, 2021. We fit conditional logistic regression (CLR) models stratified on residential county and calendar time of testing to assess the association between time elapsed since vaccination and the odds of symptomatic infection or non-COVID-19 hospitalization (negative control), adjusted for several covariates. The primary population included 652 individuals who had a positive symptomatic test after full vaccination with BNT162b2 (cases) and 5,946 individuals with at least one negative symptomatic test after full vaccination (controls). The adjusted odds of symptomatic infection were higher 120 days after full vaccination versus at the date of full vaccination (Odds Ratio [OR]: 3.21, 95% confidence interval [CI]: 1.33-7.74). Importantly, the odds of infection were still lower 150 days after the first BNT162b2 dose as compared to 4 days after the first dose (OR: 0.3, 95% CI: 0.19-0.45), when immune protection approximates the unvaccinated status. Low rates of COVID-19 associated hospitalization or death in this cohort precluded analyses of these severe outcomes. The odds of experiencing a non-COVID-19 hospitalization decreased with time since vaccination, suggesting a possible underestimation of waning protection by this approach due to confounding factors. Taken together, these data constitute an early signal for waning protection against symptomatic illness while also providing reassurance that BNT162b2 continues to protect against symptomatic SARS-CoV-2 infection several months after full vaccination. Continued surveillance of COVID-19 vaccine durability, particularly against severe disease, is critical to guide effective and equitable strategies to respond to the pandemic, including distribution of booster doses, development of new vaccines, and implementation of both pharmaceutical and nonpharmaceutical interventions.

Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence

Although clinical trials and real-world studies have affirmed the effectiveness and safety of the FDA-authorized COVID-19 vaccines, reports of breakthrough infections and persistent emergence of new variants highlight the need to vigilantly monitor the effectiveness of these vaccines. Here we compare the effectiveness of two full-length Spike protein-encoding mRNA vaccines from Moderna (mRNA-1273) and Pfizer/BioNTech (BNT162b2) in the Mayo Clinic Health System over time from January to July 2021, during which either the Alpha or Delta variant was highly prevalent. We defined cohorts of vaccinated and unvaccinated individuals from Minnesota (n = 25,589 each) matched on age, sex, race, history of prior SARS-CoV-2 PCR testing, and date of full vaccination. Both vaccines were highly effective during this study period against SARS-CoV-2 infection (mRNA-1273: 86%, 95%CI: 81-90.6%; BNT162b2: 76%, 95%CI: 69-81%) and COVID-19 associated hospitalization (mRNA-1273: 91.6%, 95% CI: 81-97%; BNT162b2: 85%, 95% CI: 73-93%). In July, vaccine effectiveness against hospitalization has remained high (mRNA-1273: 81%, 95% CI: 33-96.3%; BNT162b2: 75%, 95% CI: 24-93.9%), but effectiveness against infection was lower for both vaccines (mRNA-1273: 76%, 95% CI: 58-87%; BNT162b2: 42%, 95% CI: 13-62%), with a more pronounced reduction for BNT162b2. Notably, the Delta variant prevalence in Minnesota increased from 0.7% in May to over 70% in July whereas the Alpha variant prevalence decreased from 85% to 13% over the same time period. Comparing rates of infection between matched individuals fully vaccinated with mRNA-1273 versus BNT162b2 across Mayo Clinic Health System sites in multiple states (Minnesota, Wisconsin, Arizona, Florida, and Iowa), mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). Our observational study highlights that while both mRNA COVID-19 vaccines strongly protect against infection and severe disease, further evaluation of mechanisms underlying differences in their effectiveness such as dosing regimens and vaccine composition are warranted.

Association of Intravenous Bamlanivimab Use with Reduced Hospitalization, Intensive Care Unit Admission, and Mortality in Patients with Mild to Moderate COVID-19

BackgroundClinical data to support the use of bamlanivimab for the treatment of outpatients with mild to moderate coronavirus disease-19 (COVID-19) is needed. Methods2,335 patients who received single-dose bamlanivimab infusion between November 12, 2020 to February 17, 2021 were compared with a propensity-matched control of 2,335 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; 47.3% of the bamlanivimab-treated cohort were [≥]65 years; 49.3% were female. High-risk characteristics included hypertension (54.2%), body mass index [≥]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%; Odds Ratio [OR], 0.38), 21 (1.9% vs 3.9%; OR, 0.46), and 28 (2.5% vs 3.9%; OR, 0.61). Secondary exploratory outcomes included lower intensive care unit admission rates at days 14 (0.14% vs 1%; OR, 0.12), 21 (0.25% vs 1%; OR: 0.24) and 28 (0.56% vs 1.1%; OR: 0.52), and lower all-cause mortality at days 14 (0% vs 0.33%), 21 (0.05% vs 0.4%; OR,0.08) and 28 (0.11% vs 0.44%; OR, 0.01). Adverse events were uncommon with bamlanivimab, occurring in 19/2355, 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 compared with usual care. FundingMayo Clinic.

The Public Health Impact of Delaying a Second Dose of the BNT162b2 or mRNA-1273 COVID-19 Vaccine

ObjectivesTo estimate population health outcomes under delayedsecond dose versus standard schedule SARS-CoV-2 mRNA vaccination. DesignAgent-based modeling on a simulated population of 100,000 based on a real-world US county. The simulation runs were replicated 10 times. To test the robustness of these findings, simulations were performed under different estimates for single-dose efficacy and vaccine administration rates, and under the possibility that a vaccine prevents only symptoms but not asymptomatic spread. Settingpopulation level simulation. Participants100,000 agents are included in the simulation, with a representative distribution of demographics and occupations. Networks of contacts are established to simulate potentially infectious interactions though occupation, household, and random interactions Interventionswe simulate standard Covid-19 vaccination, versus delayed-second-dose vaccination prioritizing first dose. Sensitivity analyses include first-dose vaccine efficacy of 70%, 80% and 90% after day 12 post-vaccination; vaccination rate of 0.1%, 0.3%, and 1% of population per day; assuming the vaccine prevents only symptoms but not asymptomatic spread; and an alternative vaccination strategy that implements delayed-second-dose only for those under 65 years of age. Main outcome measurescumulative Covid-19 mortality over 180 days, cumulative infections and hospitalizations. ResultsOver all simulation replications, the median cumulative mortality per 100,000 for standard versus delayed second dose was 226 vs 179; 233 vs 207; and 235 vs 236; for 90%, 80% and 70% first-dose efficacy, respectively. The delayed-second-dose strategy was optimal for vaccine efficacies at or above 80%, and vaccination rates at or below 0.3% population per day, both under sterilizing and non-sterilizing vaccine assumptions, resulting in absolute cumulative mortality reductions between 26 and 47 per 100,000. The delayed-second-dose for those under 65 performed consistently well under all vaccination rates tested. ConclusionsA delayed-second-dose vaccination strategy, at least for those under 65, could result in reduced cumulative mortality under certain conditions.

FDA-authorized COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system

Large Phase 3 clinical trials of the two FDA-authorized COVID-19 vaccines, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech), have demonstrated efficacies of 94.1% (n = 30,420, 95% CI: 89.3-96.8) and 95% (n = 43,448, 95% CI: 90.3-97.6) in preventing symptomatic COVID-19, respectively. Given the ongoing vaccine rollout to healthcare personnel and residents of long-term care facilities, here we provide a preliminary assessment of real-world vaccination efficacy in 62,138 individuals from the Mayo Clinic and associated health system (Arizona, Florida, Minnesota, Wisconsin) between December 1st 2020 and February 8th 2021. Our retrospective analysis contrasts 31,069 individuals receiving at least one dose of either vaccine with 31,069 unvaccinated individuals who are propensity-matched based on demographics, location (zip code), and number of prior SARS-CoV-2 PCR tests. 8,041 individuals received two doses of a COVID-19 vaccine and were at risk for infection at least 36 days after their first dose. Administration of two COVID-19 vaccine doses was 88.7% effective in preventing SARS-CoV-2 infection (95% CI: 68.4-97.1%) with onset at least 36 days after the first dose. Furthermore, vaccinated patients who were subsequently diagnosed with COVID-19 had significantly lower 14-day hospital admission rates than propensity-matched unvaccinated COVID-19 patients (3.7% vs. 9.2%; Relative Risk: 0.4; p-value: 0.007). Building upon the previous randomized trials of these vaccines, this study demonstrates their real-world effectiveness in reducing the rates of SARS-CoV-2 infection and COVID-19 severity among individuals at highest risk for infection.

Augmented curation of clinical notes of COVID-19 and influenza patients reveals that long-term neuropsychiatric and coagulopathic symptoms are more associated with COVID-19

After one year of the COVID-19 pandemic, over 130 million individuals worldwide have been infected with the novel coronavirus, yet the post-acute sequelae of COVID-19 (PASC), also referred to as the long COVID syndrome, remains mostly uncharacterized. We leveraged machine-augmented curation of the physician notes from electronic health records (EHRs) across the multi-state Mayo Clinic health system to retrospectively contrast the occurrence of symptoms and diseases in COVID-19 patients in the post-COVID period relative to the pre-COVID period (n=6,413). Through comparison of the frequency of 10,039 signs and symptoms before and after diagnosis, we identified an increase in hypertensive chronic kidney disease (OR 47.3, 95% CI 23.9-93.6, p=3.50x10-9), thromboembolism (OR 3.84, 95% CI 3.22-4.57, p=1.18x10-4), and hair loss (OR 2.44, 95% CI 2.15-2.76, p=8.46x10-3) in COVID-19 patients three to six months after diagnosis. The sequelae associated with long COVID were notably different among male vs female patients and patients above vs under 55 years old, with the hair loss enrichment found primarily in females and the thromboembolism enrichment in males. These findings compel targeted investigations into what may be persistent dermatologic, cardiovascular, and coagulopathic phenotypes following SARS-CoV-2 infection.

Healthcare disparities among anticoagulation therapies for severe COVID-19 patients in the multi-site VIRUS registry

COVID-19 patients are at an increased risk of thrombosis and various anticoagulants are being used in patient management without an established standard-of-care. Here, we analyze hospitalized and ICU patient outcomes from the Viral Infection and Respiratory illness Universal Study (VIRUS) registry. We find that severe COVID patients administered unfractionated heparin but not enoxaparin have a higher mortality-rate (311 deceased patients out of 760 total patients = 41%) compared to patients administered enoxaparin but not unfractionated heparin (214 deceased patients out of 1,432 total patients = 15%), presenting a risk ratio of 2.74 (95% C.I.: [2.35, 3.18]; p-value: 1.4e-41). This difference persists even after balancing on a number of covariates including: demographics, comorbidities, admission diagnoses, and method of oxygenation, with an amplified mortality rate of 39% (215 of 555) for unfractionated heparin vs. 23% (119 of 522) for enoxaparin, presenting a risk ratio of 1.70 (95% C.I.: [1.40, 2.05]; p-value: 2.5e-7). In these balanced cohorts, a number of complications occurred at an elevated rate for patients administered unfractionated heparin compared to those administered enoxaparin, including acute kidney injury (227 of 642 [35%] vs. 156 of 608 [26%] respectively, adjusted p-value 0.0019), acute cardiac injury (40 of 642 [6.2%] vs. 15 of 608 [2.5%] respectively, adjusted p-value 0.01), septic shock (118 of 642 [18%] vs. 73 of 608 [12%] respectively, adjusted p-value 0.01), and anemia (81 of 642 [13%] vs. 46 of 608 [7.6%] respectively, adjusted p-value 0.02). Furthermore, a higher percentage of Black/African American COVID patients (375 of 1,203 [31%]) were noted to receive unfractionated heparin compared to White/Caucasian COVID patients (595 of 2,488 [24%]), for a risk ratio of 1.3 (95% C.I.: [1.17, 1.45], adjusted p-value: 1.6e-5). After balancing upon available clinical covariates, this difference in anticoagulant use remained statistically significant (272 of 959 [28%] for Black/African American vs. 213 of 959 [22%] for White/Caucasian, adjusted p-value: 0.01, relative risk: 1.28, 95% C.I.: [1.09, 1.49]). While retrospective studies cannot suggest any causality, these findings motivate the need for follow-up prospective research in order to elucidate potential socioeconomic, racial, or other disparities underlying the use of anticoagulants to treat severe COVID patients.

Pre-existing conditions are associated with long-COVID patients hospitalization, despite confirmed clearance of SARS-CoV-2 virus

The current diagnostic gold-standard for SARS-CoV-2 clearance from infected patients is two consecutive negative PCR test results. However, there are anecdotal reports of hospitalization from protracted COVID complications despite such confirmed viral clearance, presenting a clinical conundrum. We conducted a retrospective analysis of 266 COVID patients to compare those that were admitted/re-admitted post-viral clearance (hospitalized post-clearance cohort, n=93) with those that were hospitalized pre-clearance but were not re-admitted post-viral clearance (non-hospitalized post-clearance cohort, n=173). In order to differentiate these two cohorts, we used neural network models for the augmented curation of comorbidities and complications with positive sentiment in the EHR physician notes. In the year preceding COVID onset, acute kidney injury (n=15 (16.1%), p-value: 0.03), anemia (n=20 (21.5%), p-value: 0.02), and cardiac arrhythmia (n=21 (22.6%), p-value: 0.05) were significantly enriched in the physician notes of the hospitalized post-clearance cohort. This study highlights that these specific pre-existing conditions are associated with amplified hospitalization risk in COVID patients, despite their successful SARS-CoV-2 viral clearance. Our finding that pre-COVID anemia amplifies risk of post-COVID hospitalization is particularly concerning given the high prevalence and endemic nature of anemia in many low- and middle-income countries (per the World Bank definition; e.g. India, Brazil), which are unfortunately also seeing high rates of SARS-CoV-2 infection and COVID-induced mortality. This study motivates follow-up prospective research into the specific risk factors we have identified that appear to predispose some patients towards the after effects of COVID-19. Article summary - Strengths and limitations of this studyO_LIThis is the first study at a major healthcare center analyzing risk factors for post-viral clearance hospitalization of COVID-19 patients. C_LIO_LIThis analysis uses augmented curation methods to identify complications and comorbidities from the physician notes, rather than relying upon ICD codes. C_LIO_LIThe statistical analysis identifies specific comorbidities in the year preceding PCR diagnosis of SARS-CoV-2 which are associated with increased rates of post-viral clearance hospitalization. C_LIO_LIThe dataset used for this study is limited to a single healthcare system, so the underlying clinical characteristics of the study population are biased to reflect the clinical characteristics of individuals that receive medical treatment in certain regions of the United States (Arizona, Florida, Minnesota). C_LIO_LIIn this study, we use the first of two consecutive negative PCR tests to estimate the viral clearance date for each patient, however the true viral clearance date for each patient is unknown. C_LI

Enoxaparin is associated with lower rates of thrombosis, kidney injury, and mortality than Unfractionated Heparin in hospitalized COVID patients

Although anticoagulants such as unfractionated heparin and low molecular weight heparin (LMWH, e.g. enoxaparin) are both being used for therapeutic mitigation of COVID associated coagulopathy (CAC), differences in their clinical outcomes remain to be investigated. Here, we employ automated neural networks supplemented with expert curation ( augmented curation) for retrospectively analyzing the complete electronic health records (EHRs) of 671 hospitalized COVID-19 patients administered either enoxaparin or unfractionated heparin, but not both. We find that COVID-19 patients administered unfractionated heparin but not enoxaparin have higher rates of mortality (risk ratio: 2.6; 95% C.I.: [1.2-5.4]; p-value: 0.02; BH adjusted p-value: 0.09), thrombotic events (risk ratio: 5.7, 95% C.I.: [2.1, 33.9], p-value: 0.024), acute kidney injury (risk ratio: 5.5; 95% C.I.: [1.2-17.7]; p-value: 0.02; BH adjusted p-value: 0.10), and bacterial pneumonia (risk ratio undefined; 95% C.I.: [1.0, 292]; p-value:0.02; BH adjusted p-value:0.10), compared to patients administered enoxaparin but not unfractionated heparin. Notably, even after controlling for potential confounding factors such as demographics, comorbidities, admission diagnosis, initial ICU status, and initial level of oxygen support, the above differences between the enoxaparin and unfractionated heparin patient cohorts remain statistically significant. This study emphasizes the need for mechanistically investigating differential modulation of the COVID-associated coagulation cascades by enoxaparin versus unfractionated heparin.

Exploratory analysis of immunization records highlights decreased SARS-CoV-2 rates in individuals with recent non-COVID-19 vaccinations

Multiple clinical studies are ongoing to assess whether existing vaccines may afford protection against SARS-CoV-2 infection through trained immunity. In this exploratory study, we analyze immunization records from 137,037 individuals who received SARS-CoV-2 PCR tests. We find that polio, Hemophilus influenzae type-B (HIB), measles-mumps-rubella (MMR), varicella, pneumococcal conjugate (PCV13), geriatric flu, and hepatitis A / hepatitis B (HepA-HepB) vaccines administered in the past 1, 2, and 5 years are associated with decreased SARS-CoV-2 infection rates, even after adjusting for geographic SARS-CoV-2 incidence and testing rates, demographics, comorbidities, and number of other vaccinations. Furthermore, age, race/ethnicity, and blood group stratified analyses reveal significantly lower SARS-CoV-2 rate among black individuals who have taken the PCV13 vaccine, with relative risk of 0.45 at the 5 year time horizon (n: 653, 95% CI: (0.32, 0.64), p-value: 6.9e-05). These findings suggest that additional pre-clinical and clinical studies are warranted to assess the protective effects of existing non-COVID-19 vaccines and explore underlying immunologic mechanisms. We note that the findings in this study are preliminary and are subject to change as more data becomes available and as further analysis is conducted.

Quantifying the prevalence of SARS-CoV-2 long-term shedding among non-hospitalized COVID-19 patients

Analysis of 851 COVID-19 patients with a SARS-CoV-2-positive PCR at follow-up shows 99 patients remained SARS-CoV-2-positive after four weeks from initial diagnosis. Surprisingly, a majority of these long-term viral RNA shedders were not hospitalized (61 of 99), with variable PCR Crossing point values over the month post diagnosis. For the 851-patient cohort, the mean lower bound of viral RNA shedding was 17.3 days (SD: 7.8), and the mean upper bound of viral RNA shedding from 668 patients transitioning to confirmed PCR-negative status was 22.7 days (SD: 11.8). Among 104 patients with an IgG test result, 90 patients were seropositive to date, with mean upper bound of time to seropositivity from initial diagnosis being 37.8 days (95%CI: 34.3-41.3). Juxtaposing IgG/PCR tests revealed that 14 of 90 patients are non-hospitalized and seropositive yet shed viral RNA. This study emphasizes the need for monitoring viral loads and neutralizing antibody titers in long-term shedders.

Longitudinal laboratory testing tied to PCR diagnostics in COVID-19 patients reveals temporal evolution of distinctive coagulopathy signatures

Temporal inference from laboratory testing results and their triangulation with clinical outcomes as described in the associated unstructured text from the providers notes in the Electronic Health Record (EHR) is integral to advancing precision medicine. Here, we studied 181 COVIDpos and 7,775 COVIDneg patients subjected to 1.3 million laboratory tests across 194 assays during a two-month observation period centered around their SARS-CoV-2 PCR testing dates. We found that compared to COVIDneg at the time of clinical presentation and diagnostic testing, COVIDpos patients tended to have higher plasma fibrinogen levels and similarly low platelet counts, with approximately 25% of patients in both cohorts showing outright thrombocytopenia. However, these measures show opposite longitudinal trends as the infection evolves, with declining fibrinogen and increasing platelet counts to levels that are lower and higher compared to the COVIDneg cohort, respectively. Our EHR augmented curation efforts suggest a minority of patients develop thromboembolic events after the PCR testing date, including rare cases with disseminated intravascular coagulopathy (DIC), with most patients lacking the platelet reductions typically observed in consumptive coagulopathies. These temporal trends present, for the first time, fine-grained resolution of COVID-19 associated coagulopathy (CAC), via a digital framework that synthesizes longitudinal lab measurements with structured medication data and neural network-powered extraction of outcomes from the unstructured EHR. This study demonstrates how a precision medicine platform can help contextualize each patients specific coagulation profile over time, towards the goal of informing better personalization of thromboprophylaxis regimen.

Augmented Curation of Unstructured Clinical Notes from a Massive EHR System Reveals Specific Phenotypic Signature of Impending COVID-19 Diagnosis

Understanding temporal dynamics of COVID-19 patient symptoms could provide fine-grained resolution to guide clinical decision-making. Here, we use deep neural networks over an institution-wide platform for the augmented curation of clinical notes from 77,167 patients subjected to COVID-19 PCR testing. By contrasting Electronic Health Record (EHR)-derived symptoms of COVID-19-positive (COVIDpos; n=2,317) versus COVID-19-negative (COVIDneg; n=74,850) patients for the week preceding the PCR testing date, we identify anosmia/dysgeusia (27.1-fold), fever/chills (2.6-fold), respiratory difficulty (2.2-fold), cough (2.2-fold), myalgia/arthralgia (2-fold), and diarrhea (1.4-fold) as significantly amplified in COVIDpos over COVIDneg patients. The combination of cough and fever/chills has 4.2-fold amplification in COVIDpos patients during the week prior to PCR testing, and along with anosmia/dysgeusia, constitutes the earliest EHR-derived signature of COVID-19. This study introduces an Augmented Intelligence platform for the real-time synthesis of institutional biomedical knowledge. The platform holds tremendous potential for scaling up curation throughput, thus enabling EHR-powered early disease diagnosis.

Pregnancy outcome in unbooked mothers at a tertiary health institution, South-South, Nigeria.

Background: Maternal complications and poor perinatal outcome are highly associated with non-utilisation of antenatal and delivery care services. The study aimed at determining the socio-demographical characteristics and feto-maternal outcome in unbooked mothers who delivered at a tertiary referral hospital. Materials and Methods: A retrospective study of all unbooked patients managed at the Obstetric unit of the University of Port Harcourt Teaching Hospital (UPTH), Nigeria from January 1, 2009 to December 31, 2013. Data obtained from the theatre records, delivery registers and case notes were analysed using the statistical package SPSS 20. Results: Unbooked mothers constituted 15.8% (2,490) of the deliveries. Majority (81.7%) of the women were aged 20-34 years with a mean age of 30.8 ± 4.5 years. More than half of the women were Para 1-4 (61.3%). Emergency caesarean section was the mode of delivery in 58.7% of the women. The commonest indication for caesarean section was cephalopelvic disproportion (40%) followed by Obstructed labour (26%). There were 149 maternal deaths, giving maternal mortality ratio of 4654.8/100,000. The perinatal mortality rate was 331.7/1000 births. Conclusion: The study showed a positive correlation between lack of proper antenatal care and adverse pregnancy outcome in unbooked patients. Improvement in the socioeconomic conditions of the populace especially women and the removal of fee for service in maternal care services will help to improve the availability and accessibility of good quality antenatal care.

Foeto-maternal outcome of diabetes in a tertiary health facility in Nigeria

Diabetes complicating pregnancy is associated with adverse maternal, foetal and neonatal outcomes. We have determined the prevalence of both pre-gestational (PGDM) and gestational diabetes mellitus (GDM), and their associated maternal and perinatal morbidities and mortalities at the University of Port-Harcourt Teaching Hospital, Nigeria. A retrospective study was carried out of all cases of diabetes in pregnancy between 2008 and 2012. The case notes of the next two non-diabetic patients, whose gestational ages and parities matched, were examined as case controls. There were 122 cases of diabetes from a total of 14, 521 deliveries (8.4 per 1000 deliveries), 21 cases of PGDM, and 101 cases of GDM (1.45 per 1000 deliveries and 6.96 per 1000 deliveries respectively). There were 60 cases of foetal macrosomia (49%). The mean birth weight was 3.75±0.76 kg. There were 11 perinatal deaths (perinatal mortality rate 90 per 1000 deliveries). The caesarean delivery rate was 89%. Sixty (60) babies (49%) required neonatal intensive care admission. There were no maternal deaths or congenitally malformed babies. We conclude that diabetes in pregnancy is associated with adverse maternal and neonatal outcomes. Patients at risk should be encouraged to attend preconception clinics and register early in well-equipped hospitals for antenatal care. Universal screening of all pregnant women at booking and patients with clinical risks characteristics at 24 and 28 weeks of gestation may be effective for the early identification and management of GDM

AN APPRAISAL OF RETAINED PLACENTA AT THE UNIVERSITY OF PORT HARCOURT TEACHING HOSPITAL: A FIVE-YEAR REVIEW.

BACKGROUND: Retained placenta is associated with an increased risk of maternal morbidity and mortality especially in developing countries. OBJECTIVE: To determine the incidence and evaluate the mode of presentation, risk factors and method of treatment of patients with retained placenta. METHODOLOGY: A retrospective review of retained placenta managed at the University of Port Harcourt Teaching Hospital (UPTH), Port Harcourt over a 5 year period (January 2009 to December 2013). Data obtained were analyzed using statistical software SPSS 17.0. RESULTS: There were 93 cases of retained placenta out of 15,789 deliveries, giving an incidence of 0.59%.85 patients' case records were available for analysis. Majority of the patients 69 (81.2%) were unbooked (had no antenatal care) with 60 (70.6%) having home deliveries. Previous history of dilatation and curettage and preterm deliveries, accounted for the major identifiable risk factors at 55 (64.7%) and 22 (25.9%) respectively. At presentation, 22(25.9%) were in hypovolemic shock. Manual removal of the placenta was the commonest treatment modality (87.1%).There was one maternal death giving rise to a case fatality rate of 1.18%. CONCLUSION: Retained placenta is a major cause of maternal morbidity and mortality from postpartum haemorrhage and other complications related to its removal. The incidence can be reduced by antenatal care, skilled birth attendance and provision of emergency obstetrics care services.