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1.
Mmwr-Morbidity and Mortality Weekly Report ; 71(36):1151-1154, 2022.
Article in English | Web of Science | ID: covidwho-2068408

ABSTRACT

What is already known about this topic? Before emergence of the SARS-CoV-2 B.1.1.529 (Omicron) variant, infectious SARS-CoV-2 was unlikely to be cultured at high cycle threshold (Ct) values. Based on this, low Ct values, which are suggestive of high RNA levels, are sometimes used as surrogate markers for infectiousness. What is added by this report? In a longitudinal study including daily nasal swabbing, although Omicron BA.1 sublineage infections exhibited higher Ct values than did pre-Omicron infections, culturable Omicron virus was still detected. Among virus-positive specimens, Ct values were higher for Omicron than for pre-Omicron specimens, especially during the first week of illness. What are the implications for public health practice? Supporting CDC guidance, these data show that Ct values likely do not provide a consistent proxy for infectiousness across SARS-CoV-2 variants.

2.
Neurol Neuroimmunol Neuroinflamm ; 9(5)2022 09.
Article in English | MEDLINE | ID: covidwho-1892254

ABSTRACT

BACKGROUND AND OBJECTIVES: The biologic mechanisms underlying neurologic postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) are incompletely understood. METHODS: We measured markers of neurologic injury (glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) and soluble markers of inflammation among a cohort of people with prior confirmed SARS-CoV-2 infection at early and late recovery after the initial illness (defined as less than and greater than 90 days, respectively). The primary clinical outcome was the presence of self-reported CNS PASC symptoms during the late recovery time point. We compared fold changes in marker values between those with and without CNS PASC symptoms using linear mixed-effects models and examined relationships between neurologic and immunologic markers using rank linear correlations. RESULTS: Of 121 individuals, 52 reported CNS PASC symptoms. During early recovery, those who went on to report CNS PASC symptoms had elevations in GFAP (1.3-fold higher mean ratio, 95% CI 1.04-1.63, p = 0.02), but not NfL (1.06-fold higher mean ratio, 95% CI 0.89-1.26, p = 0.54). During late recovery, neither GFAP nor NfL levels were elevated among those with CNS PASC symptoms. Although absolute levels of NfL did not differ, those who reported CNS PASC symptoms demonstrated a stronger downward trend over time in comparison with those who did not report CNS PASC symptoms (p = 0.041). Those who went on to report CNS PASC also exhibited elevations in interleukin 6 (48% higher during early recovery and 38% higher during late recovery), monocyte chemoattractant protein 1 (19% higher during early recovery), and tumor necrosis factor α (19% higher during early recovery and 13% higher during late recovery). GFAP and NfL correlated with levels of several immune activation markers during early recovery; these correlations were attenuated during late recovery. DISCUSSION: Self-reported neurologic symptoms present approximately 4 months after SARS-CoV-2 infection are associated with elevations in markers of neurologic injury and inflammation at earlier time points. Some inflammatory pathways seem to be involved months after acute infection. Additional work will be needed to better characterize these processes and to identify interventions to prevent or treat this condition.


Subject(s)
COVID-19 , Biomarkers , COVID-19/complications , Humans , Inflammation , SARS-CoV-2 , Self Report
3.
Topics in Antiviral Medicine ; 30(1 SUPPL):247-248, 2022.
Article in English | EMBASE | ID: covidwho-1880706

ABSTRACT

Background: The biologic mechanisms underlying neurologic post-acute-sequelae of SARS-CoV-2 infection (PASC) are incompletely understood. We measured plasma markers of neuronal injury (glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) and inflammation among a cohort of people with prior confirmed SARS-CoV-2 infection at early and late recovery following the initial illness (defined as < and > 90 days since COVID-19 onset, respectively). We hypothesized that those experiencing persistent neurologic symptoms would have elevations in these markers. Methods: The primary clinical outcome was the presence of self-reported central nervous system (CNS) PASC symptoms during the late recovery timepoint. We compared fold-changes in marker values between those with and without CNS PASC symptoms using linear mixed effects models and examined relationships between neurologic and immunologic markers using rank linear correlations. Results: Of 121 individuals, 52 reported CNS PASC symptoms. During early recovery, those who went on to report CNS PASC symptoms had elevations in GFAP (1.3-fold higher mean ratio, 95% CI 1.04-1.63, p=0.02), but not NfL (1.06-fold higher mean ratio, 95% CI 0.89-1.26, p=0.54). During late recovery, neither GFAP nor NfL levels were elevated among those with CNS PASC symptoms. Although absolute levels of NfL did not differ, those who reported CNS PASC symptoms demonstrated a stronger downward trend over time in comparison to those who did not report CNS PASC symptoms (p=0.041). Those who went on to report CNS PASC also exhibited elevations in IL-6 (48% higher during early recovery and 38% higher during late recovery), MCP-1 (19% higher during early recovery), and TNF-alpha (19% higher during early recovery and 13% higher during late recovery). GFAP and NfL correlated with levels of several immune markers during early recovery (MCP-1, IL-6, TNF-a, IFN-g);these correlations were attenuated during late recovery. Conclusion: Self-reported neurologic symptoms present approximately four months following SARS-CoV-2 infection are associated with elevations in markers of neurologic injury and inflammation at early recovery timepoints, suggesting that early injury can result in long-term disease. The correlation of GFAP and NfL with markers of systemic immune activation suggests one possible mechanism that might contribute to these symptoms. Additional work will be needed to better characterize these processes and to identify interventions to prevent or treat this condition.

4.
PubMed; 2022.
Preprint in English | PubMed | ID: ppcovidwho-338328

ABSTRACT

BACKGROUND: Mechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 "PASC" or "Long COVID") remain unclear. The purpose of this study was to elucidate the pathophysiology of cardiopulmonary PASC using multimodality cardiovascular imaging including cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring. METHODS: We performed CMR, CPET, and ambulatory rhythm monitoring among adults > 1 year after PCR-confirmed SARS-CoV-2 infection in the UCSF Long-Term Impact of Infection with Novel Coronavirus cohort (LIINC;NCT04362150 ) and correlated findings with previously measured biomarkers. We used logistic regression to estimate associations with PASC symptoms (dyspnea, chest pain, palpitations, and fatigue) adjusted for confounders and linear regression to estimate differences between those with and without symptoms adjusted for confounders. RESULTS: Out of 120 participants in the cohort, 46 participants (unselected for symptom status) had at least one advanced cardiac test performed at median 17 months following initial SARS-CoV-2 infection. Median age was 52 (IQR 42-61), 18 (39%) were female, and 6 (13%) were hospitalized for severe acute infection. On CMR (n=39), higher extracellular volume was associated with symptoms, but no evidence of late-gadolinium enhancement or differences in T1 or T2 mapping were demonstrated. We did not find arrhythmias on ambulatory monitoring. In contrast, on CPET (n=39), 13/23 (57%) with cardiopulmonary symptoms or fatigue had reduced exercise capacity (peak VO 2 <85% predicted) compared to 2/16 (13%) without symptoms (p=0.008). The adjusted difference in peak VO 2 was 5.9 ml/kg/min lower (-9.6 to -2.3;p=0.002) or -21% predicted (-35 to -7;p=0.006) among those with symptoms. Chronotropic incompetence was the primary abnormality among 9/15 (60%) with reduced peak VO 2 . Adjusted heart rate reserve <80% was associated with reduced exercise capacity (OR 15.6, 95%CI 1.30-187;p=0.03). Inflammatory markers (hsCRP, IL-6, TNF-alpha) and SARS-CoV-2 antibody levels measured early in PASC were negatively correlated with peak VO 2 more than 1 year later. CONCLUSIONS: Cardiopulmonary symptoms and elevated inflammatory markers present early in PASC are associated with objectively reduced exercise capacity measured on cardiopulmonary exercise testing more than 1 year following COVID-19. Chronotropic incompetence may explain reduced exercise capacity among some individuals with PASC. Clinical Perspective: What is New?Elevated inflammatory markers in early post-acute COVID-19 are associated with reduced exercise capacity more than 1 year later.Impaired chronotropic response to exercise is associated with reduced exercise capacity and cardiopulmonary symptoms more than 1 year after SARS-CoV-2 infection.Findings on ambulatory rhythm monitoring point to perturbed autonomic function, while cardiac MRI findings argue against myocardial dysfunction and myocarditis. Clinical Implications: Cardiopulmonary testing to identify etiologies of persistent symptoms in post-acute sequalae of COVID-19 or "Long COVID" should be performed in a manner that allows for assessment of heart rate response to exercise. Therapeutic trials of anti-inflammatory and exercise strategies in PASC are urgently needed and should include assessment of symptoms and objective testing with cardiopulmonary exercise testing.

5.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-334273

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS) but it is unknown whether prone positioning improves outcomes in mechanically ventilated patients with moderate to severe ARDS due to COVID-19. METHODS: A cohort study at a New York City hospital at the peak of the early pandemic in the United States, under crisis conditions. The aim was to determine the benefit of prone positioning in mechanically ventilated patients with ARDS due to COVID-19. The primary outcome was in-hospital death. Secondary outcomes included changes in physiologic parameters. Fine-Gray competing risks models with stabilized inverse probability treatment weighting (sIPTW) were used to determine the effect of prone positioning on outcomes. In addition, linear mixed effects models (LMM) were used to assess changes in physiology with prone positioning. RESULTS: Out of 335 participants who were intubated and mechanically ventilated, 62 underwent prone positioning, 199 met prone positioning criteria and served as controls and 74 were excluded. The intervention and control groups were similar at baseline. In multivariate-adjusted competing risks models with sIPTW, prone positioning was significantly associated with reduced mortality (SHR 0.61, 95% CI 0.46-0.80, P < 0.005). Using LMM to evaluate the impact of positioning maneuvers on physiological parameters, the oxygenation-saturation index was significantly improved during days 1-3 ( P < 0.01) whereas oxygenation-saturation index (OSI), oxygenation-index (OI) and arterial oxygen partial pressure to fractional inspired oxygen (P a O 2 :FiO 2 ) were significantly improved during days 4-7 ( P < 0.05 for all). CONCLUSIONS: Prone positioning in patients with moderate to severe ARDS due to COVID-19 is associated with reduced mortality and improved physiologic parameters. One in-hospital death could be averted for every eight patients treated. Replicating results and scaling the intervention are important, but prone positioning may represented an additional therapeutic option in patients with ARDS due to COVID-19.

6.
MEDLINE;
Preprint in English | MEDLINE | ID: ppcovidwho-326622

ABSTRACT

The biological determinants of the wide spectrum of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 single-cell immune features comprising cell phenotype, basal signaling activity, and signaling responses to inflammatory ligands were assessed in peripheral blood from patients with mild, moderate, and severe COVID-19, at the time of diagnosis. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identified and independently validated a multivariate model classifying COVID-19 severity (multi-class AUCtraining = 0.799, p-value = 4.2e-6;multi-class AUCvalidation = 0.773, p-value = 7.7e-6). Features of this high-dimensional model recapitulated recent COVID-19 related observations of immune perturbations, and revealed novel biological signatures of severity, including the mobilization of elements of the renin-angiotensin system and primary hemostasis, as well as dysregulation of JAK/STAT, MAPK/mTOR, and NF-kappaB immune signaling networks. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for the prevention of COVID-19 progression.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316251

ABSTRACT

This paper provides the first quantitative investigation of the receipt of funds from the Paycheck Protection Program (PPP) among Veterans between April and June. We find that Veterans received 3.5% more loans and 6.8% larger loans than their counterparts (p<0.01), controlling for a wide array of zipcode characteristics and exploits within-zipcode variation in further robustness. We subsequently use machine learning to predict PPP loan receipt among Veterans, finding that characteristics about quality of the local Department of Veterans Affairs medical centers are predictive. We develop models to predict the number of PPP loans awarded to Veteran-owned, finding that the inclusion of local VA medical center characteristics adds almost as much explanatory power as the industry and occupational composition in an area and even more than the education, race, and age distribution combined. Our results suggest that VA medical centers can play an important role in helping Veterans thrive even beyond addressing their direct medical needs.

9.
PUBMED; 2021.
Preprint in English | PUBMED | ID: ppcovidwho-293448

ABSTRACT

Serosurveys are a key resource for measuring SARS-CoV-2 cumulative incidence. A growing body of evidence suggests that asymptomatic and mild infections (together making up over 95% of all infections) are associated with lower antibody titers than severe infections. Antibody levels also peak a few weeks after infection and decay gradually. We developed a statistical approach to produce adjusted estimates of seroprevalence from raw serosurvey results that account for these sources of spectrum bias. We incorporate data on antibody responses on multiple assays from a post-infection longitudinal cohort, along with epidemic time series to account for the timing of a serosurvey relative to how recently individuals may have been infected. We applied this method to produce adjusted seroprevalence estimates from five large-scale SARS-CoV-2 serosurveys across different settings and study designs. We identify substantial differences between reported and adjusted estimates of over two-fold in the results of some surveys, and provide a tool for practitioners to generate adjusted estimates with pre-set or custom parameter values. While unprecedented efforts have been launched to generate SARS-CoV-2 seroprevalence estimates over this past year, interpretation of results from these studies requires properly accounting for both population-level epidemiologic context and individual-level immune dynamics.

10.
PUBMED; 2021.
Preprint in English | PUBMED | ID: ppcovidwho-292848

ABSTRACT

Background As of 26 March 2021, the Africa CDC had reported 4,159,055 cases of COVID-19 and 111,357 deaths among the 55 African Union Member States;however, no country has published a nationally representative serosurvey as of May 2021. Such data are vital for understanding the pandemic's progression on the continent, evaluating containment measures, and policy planning. Methods We conducted a cross-sectional, nationally representative, age-stratified serosurvey in Sierra Leone in March 2021 by randomly selecting 120 Enumeration Areas throughout the country and 10 randomly selected households in each of these. One to two persons per selected household were interviewed to collect information on socio-demographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. Capillary blood was collected by fingerstick, and blood samples were tested using the Hangzhou Biotest Biotech RightSign COVID-19 IgG/IgM Rapid Test Cassette. Total seroprevalence was was estimated after applying sampling weights. Findings The overall weighted seroprevalence was 2.6% (95% CI 1.9-3.4). This is 43 times higher than the reported number of cases. Rural seropositivity was 1.8% (95% CI 1.0-2.5), and urban seropositivity was 4.2% (95% CI 2.6-5.7). Interpretation Although overall seroprevalence was low compared to countries in Europe and the Americas (suggesting relatively successful containment in Sierra Leone), our findings indicate enormous underreporting of active cases. This has ramifications for the country's third wave (which started in June 2021), where the average number of daily reported cases was 87 by the end of the month: this could potentially be on the order of 3,700 actual infections, calling for stronger containment measures in a country with only 0.2% of people fully vaccinated. It may also reflect significant underreporting of incidence and mortality across the continent.

11.
Computer Aided Chemical Engineering ; 50:2057-2063, 2021.
Article in English | Scopus | ID: covidwho-1328685

ABSTRACT

Academia is an arena where practitioners from industry are integrated to theoreticians. Such alliance has been intensified by the industry 4.0 (I4) age from which these counterparts are seeking to merge efforts towards society 5.0 (S5), enabling next generations to easily accept novelties and changes in well-established operations, process-of-work, behaviours, etc. In educational centres, such a pace into the I4-S5 state pushes new ways of adopting (or adapting current) sharing of work among peers since this may potentially become a tool for an efficient process-of-research. Thus, we particularly cover postgraduate centres with part-time (PT) and full-time (FT) students in the fields of process system engineering (PSE) and we are widely relying on computer aided process engineering (CAPE) tools, algorithms, software, packages, etc. A collaborative research and development of PSE-CAPE systems may a) involve PT and FT postgraduates in multi-disciplinary fields of science and engineering and b) go across physics, math, and technologies to include social sciences, public policies, and beyond. The proposition is to analyse PT-FT synergies considering their experiences, accessibility of data to validate models, viability to handle CAPE tools, etc. An example of collaboration between PT and FT students, involving a university, a research center, a consulting company, and a medical corporation, is highlighted to optimise healthcare treatment systems for social progress and sustainable development amid COVID-19. © 2021 Elsevier B.V.

12.
Journal of Clinical Urology ; 2020.
Article in English | EMBASE | ID: covidwho-917905

ABSTRACT

Objective: Delivery of a safe cystectomy service is a multidisciplinary exercise. In this article, we detail the measures implemented at our institution to deliver a cystectomy service for bladder cancer patients during coronavirus disease 2019 (COVID-19). Methods: A ‘one-stop’ enhanced recovery clinic had been established at our hospital, consisting of an anaesthetist, an exercise testing service, urinary diversion nurses, clinical nurse specialists and surgeons. During COVID-19, we modified these processes in order to continue to provide urgent cystectomy safely for bladder cancer. We collected patients’ outcomes prospectively measuring demographic characteristics, oncological and perioperative outcomes, the presence of COVID-19 symptoms and confirmed COVID-19 test results. Results: From March to May 2020, 25 patients underwent radical cystectomy for bladder cancer. Twenty-four procedures were performed with robotic assistance and one open as part of a research trial. We instituted modifications at various multidisciplinary steps, including patient selection, preoperative optimisation, enhanced recovery protocols, patient counselling and perioperative protocols. Thirty-day mortality was 0%. The 30-day rate of Clavien ⩾3 complications was 8%. Postoperatively, none of the patients developed COVID-19 based on World Health Organization criteria and testing. Conclusion: We safely delivered a complex cystectomy service during the peak of the COVID-19 pandemic without any COVID-19-related morbidity or mortality. Level of evidence: Level 2b.

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