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1.
Cureus ; 14(8):e27653, 2022.
Article in English | MEDLINE | ID: covidwho-2025412

ABSTRACT

This case report presents the management of a 69-year-old gentleman with acute coronary syndrome in the setting of an incidentally detected hepatocellular carcinoma with intra-tumoral bleed. Initially, the patient presented with fever, cough, and sudden onset of dyspnea on rest accompanied by angina, after which he was diagnosed with non-ST segment elevated myocardial infarction complicated with congestive cardiac failure. His laboratory and radiological investigations were suggestive of a possible infective etiology which, in an era of COVID-19, was investigated further with a high-resolution CT scan of the chest, which was suggestive of features of pulmonary edema along with an incidental discovery of liver lesions on the abdominal cuts. A further workup with a dedicated triple-phase computed tomography scan abdomen demonstrated features of undiagnosed hepatocellular cancer with intra-tumoral bleeding. Therefore, a mesenteric celiac angiogram followed by trans arterial bland embolization of the bleeding vessel was performed. In the same setting, for the simultaneous management of the acute coronary syndrome, coronary angiography performed revealed a triple vessel disease which was immediately followed by a percutaneous transluminal coronary angioplasty.

2.
Frontiers in Psychology ; 13:903044, 2022.
Article in English | MEDLINE | ID: covidwho-2022864

ABSTRACT

Background: Students were confined to their homes due to the national closure of educational institutions during the COVID 19 pandemic, thus presenting an unprecedented risk to children's education, protection, and wellbeing. Aim: This study aimed to understand the determinants of subjective wellbeing of adolescents and youth (aged 11-21 years) during the COVID-19 pandemic in India. Materials and methods: A cross-sectional web-based survey was adapted, pre-tested, and finalized to obtain the participant's responses from schools and colleges. Participants aged 11-17 years were engaged through schools. Consent procedures were followed. The survey link was disseminated through social media for the participants aged 18-21 years. The survey was made available in English and Hindi. The data was collected from March-June, 2021. Results: Overall, 1,596 students completed the survey. Out of 1,596 students, 1252 (78%) were below 18 years and 344 (21.5%) participants were 18 years and above. Results suggest a statistically significant (p < 0.01) difference in the level of student's life satisfaction before and during the COVID-19 pandemic. Of the students who were dissatisfied with their general life during the pandemic, nearly 63.4% felt sadness followed by other feelings, i.e., boredom (around 60.5%), loneliness (63.7%), and anxiety (62.2%). Conclusion: This study highlights the need for innovative strategies for adolescents and parents to adopt and promote overall subjective wellbeing, especially during public health crises such as the COVID-19 pandemic.

3.
Critical Care Explorations ; 4(9):e0755, 2022.
Article in English | MEDLINE | ID: covidwho-2018216

ABSTRACT

Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death. DESIGN: Multicenter cohort study. SETTING: ICUs at 68 hospitals across the United States. PATIENTS: A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association between age and death. Effect modification by the number of risk factors was assessed through a multiplicative interaction term in the logistic regression model. Among the 5,037 patients included (mean age, 60.9 yr [+/- 14.7], 3,179 [63.1%] male), 1,786 (35.4%) died within 28 days. Age had a nonlinear association with 28-day mortality (p for nonlinearity <0.001) after adjustment for covariates that included demographics, preexisting comorbidities, acute physiologic ICU factors, number of ICU beds, and treatments for COVID-19. The number of preexisting comorbidities and acute physiologic ICU factors modified the association between age and 28-day mortality (p for interaction <0.001), but this effect modification was modest as age still had an exponential relationship with death in subgroups stratified by the number of risk factors. CONCLUSIONS: In a large population of critically ill patients with COVID-19, age had an independent exponential association with death. The number of preexisting comorbidities and acute physiologic ICU factors modified the association between age and death, but age still had an exponential association with death in subgroups according to the number of risk factors present. Additional studies are needed to identify the mechanisms underpinning why older age confers an increased risk of death in critically ill patients with COVID-19.

4.
Indian Journal of Critical Care Medicine ; 26:S105, 2022.
Article in English | EMBASE | ID: covidwho-2006395

ABSTRACT

Aim and background: Severe COVID-19 pneumonia can be lifethreatening with a high mortality, largely due to an uncontrolled systemic hyperinflammatory response, generally referred to as cytokine storm. Tempering the immune response with immunomodulators has been considered as a potential therapeutic option. Except for a few, data on the effectiveness of different immunomodulating drugs are scarce and are limited to a few case reports and retrospective observational-cohort studies. Additionally, in the pandemic due to shortages, various immunomodulators were used with limited data on their effectiveness. This study looks at various immunomodulators used in the 2nd wave of COVID-19, and their impact on outcomes. Materials and methods: Retrospective analysis of 124 patients with severe COVID-19 disease who were treated with immunomodulators. The study population included patients above 18 years of age with confirmed COVID-19 admitted to ICU with severe pneumonia. All patients received standard of care treatment at the time of hospital admission according to the hospital protocols and updated data on treatment of COVID-19. Patients were considered eligible for immunomodulatory treatment if they showed rapidly worsening hypoxia and elevated inflammatory markers, as per standard recommendations. Immunomodulators were administered depending on the availability of specific agents at time of treatment. The immunomodulators used were tocilizumab, itolizumab, bevacizumab, pulse dose steroid with methylprednisolone and baricitinib. Results: 124 patients were treated with immunomodulators, 45 (36.3%) of them survived, and 79 (63.7%) passed away. Mean age in survivors was 48.2, and in non-survivors was 54.8, which was statistically significant. Diabetes and hypertension were the most common comorbidities observed. 97/124 patients (78.2%) received immunomodulator therapy within 48 hours of ICU admission, out of which 41 (42.2%) recovered and 56 (57.7%) passed away. 21/124 (21.8%) patients received immunomodulators after 48 hours of admission, and had a high mortality with only 3 (14.2%) recovering and 18 (85.7%) dead. There was a significant reduction in CRP levels post immunomodulator therapy among survivors compared to nonsurvivors. The mean invasive ventilator days were 4.27 and there was a significant difference among survivors and non-survivors. Among survivors (45) in our study, we found that immunomodulator therapy was seen to avoid mechanical ventilation in severe COVID patients (33) who received immunomodulator therapy early within 48 hours of ICU admission as seen by the improvement on a 7-point ordinal scale. The mean ventilator days for patients who received immunomodulator therapy after intubation were also reduced. Most common adverse events were found with itolizumab administration. Secondary infections were more in non-survivors and secondary bacterial pneumonia was the commonest. Conclusion: Our descriptive study showed that the early administration(<48 hours) of various immunomodulators reduced the need for ventilation and the number of ventilator days, compared to administration after 48 hours. There was an increased incidence of secondary bacterial infections among the non-survivors.

5.
Indian Journal of Critical Care Medicine ; 26:S98, 2022.
Article in English | EMBASE | ID: covidwho-2006387

ABSTRACT

Introduction: The 1st wave of COVID-19 spread rapidly affecting most countries globally in a short duration. Many countries suffered the 2nd wave of COVID-19 infection, months after the 1st wave, largely driven by viral mutants with high transmissibility and reduced susceptibility to neutralising antibodies (1-3). Despite COVID-19 being the common etiology, the two waves have significant differences impacting both current understanding and future planning of the impact of COVID-19. This study from a tertiary ICU is a comparative analysis focusing on the cardinal differences in COVID-19 ICU patients between the two waves, with respect to baseline demographics, clinical features, disease severity, and outcomes. Materials and methods: Retrospective data was collected from the medical records of all patients with COVID-19 disease admitted to the intensive care unit (ICU) in the 1st and 2nd wave of the pandemic. COVID-19 disease was confirmed by means of a positive RT-PCR or a rapid antigen test (RAT) on a nasopharyngeal swab or respiratory sample. Baseline demographic and clinical data, disease severity, and outcomes were analysed. Results: 419 patients (74.9% males) were admitted to the ICU between July and December 2020 and 206 (65% males) patients between April and June 2021. The mean age of patients admitted in the 1st wave was 59.84 ± 13.7 (mean ± SD) years and the 2nd wave was 55.31 ± 14.9 years (p = 0.038). The duration from symptom onset to admission (Median, IQR) was 5 days (3, 7) for the 1st wave and 5 days (3, 8) for the 2nd wave. 74.5% (312/419) of the patients in the 1st wave and 64.5% (129/206) in the 2nd wave had one or more comorbidities (p = 0.05). The median CRP values were 83.0 mg% (IQR 31.45, 159.7) for the 1st wave and 93.0 mg% (IQR 48.0, 141.0) for the 2nd wave, respectively, statistically not significant. 31.8% (131/412) of the ICU patients in the 1st wave and 52.3% (103/196) in the 2nd wave required mechanical ventilator support (p < 0.05). The overall ICU mortality was 32.1% (134/418) for the 1st and 52.5% (104/198) for the 2nd wave (p value?). Conclusion: There is a significant difference between the 2 waves in age, comorbidities, and mortality, likely related to viral mutants, vaccination policies, and social mobility dynamics.

6.
Indian Journal of Critical Care Medicine ; 26:S97, 2022.
Article in English | EMBASE | ID: covidwho-2006386

ABSTRACT

Aim and background: The COVID-19 pandemic has raised significant concerns over secondary infections because of the widespread use of steroids, immunomodulators, and empiric antimicrobials as part of the recommended treatment protocol. Various studies have shown that COVID-19 infection by itself predisposes to secondary infections. During the 2nd wave of the COVID-19 pandemic, there has been an unprecedented epidemic of secondary invasive fungal infections. This study analyses the prevalence, details, and outcomes of secondary infections in critical COVID-19 patients admitted to a tertiary intensive care unit (ICU) in India. Materials and methods: Retrospective study of secondary infections in ICU patients between April and June 2021. Demographic data, details of immunomodulator therapy, secondary bacterial and fungal infections, antimicrobial susceptibility data, and clinical outcomes of these patients were analyzed. Results: 71/238 (29.83%) ICU patients developed secondary bacterial and fungal infections. The mortality in patients with secondary infections was significantly higher [80.28% (p < 0.05)], compared to overall ICU mortality of 51.68%. In patients with secondary infections, 67.6% were referred from other hospitals after receiving initial treatment and 64.79% had received various immunomodulator therapies. Patients on prolonged mechanical ventilation (>7 days) and indwelling central venous (>7 days) and urinary catheters (>7.5 days) had higher secondary infection rates and higher mortality. There was positive significant growth in 80 respiratory samples, 34 blood samples, and 17 urine samples. Gram-negative bacteria were isolated in 85.91% and 32.39% had fungal isolates. Klebsiella pneumoniae followed by Acinetobacter baumannii were the predominant bacteria and Candida spp followed by Mucormycosis were the predominant fungal pathogens. Multi-drug resistant (MDR) infections were common among the isolates (70.59%). 49.3% of secondary infection patients had polymicrobial infections including fungal infections with higher mortality of 83%. Conclusion: There is a significantly high incidence of secondary MDR bacterial and fungal infection including Mucormycosis in critically ill COVID-19 patients, with an adverse impact on mortality. Risk factors included the use of steroids, immunomodulators, severe COVID-19 infection, empiric broad-spectrum antibiotics, invasive ventilation, and central venous and urinary catheterization, and prolonged ICU stay.

7.
BMJ Case Rep ; 15(8), 2022.
Article in English | PubMed | ID: covidwho-2001800

ABSTRACT

Multisystem inflammatory syndrome in adults (MIS-A) is a systemic inflammatory condition that presents roughly 4-6 weeks after initial COVID-19 infection. Patients typically present with persistent fevers, widespread rash, abdominal pain, vomiting and diarrhoea, and new-onset neurological symptoms. Cardiac dysfunction is a prominent feature of COVID-19 sequelae due to the abundance of ACE2 receptors on cardiac tissue. Delayed diagnosis due to the novelty of MIS-A can lead to cardiac complications like heart failure and shock, which could result in chronic cardiac disease. Avoidance of complications and chronic illness is possible with prompt corticosteroid therapy. Despite patient recovery to baseline level of function, surveillance of cardiac function to screen for chronic cardiac disease in the follow-up period is recommended. We present a case of MIS-A in a young man, compare his presentation with other similar cases and discuss implications of delayed diagnosis.

8.
Journal of Hepatology ; 77:S328-S329, 2022.
Article in English | EMBASE | ID: covidwho-1996634

ABSTRACT

Background and aims: Liver injury is common in patients with coronavirus disease-2019 (COVID-19) infection. Recently, few studies have reported the development of autoimmune hepatitis (AIH) following COVID-19 vaccination. However, there is a lack of studies reporting the outcomes of AIH following ChAdOx1 (vector-based) and BBV152 (inactivated virus) from India. Herewe aimed to describe the clinical profile of patients who developed AIH following COVID-19 vaccination. The causal association is attributed based on the temporal relationship in patients with no prior liver diseases. Method: Patients presenting with deranged liver functions following COVID-19 vaccination to hepatology clinic were included. Virus infections were ruled out in all patients either by serology or viral quantification methods. We aimed to assess the demographics, clinical profile, and outcome of patients with vaccine-induced AIH (V-AIH) in the absence of known liver disease. Results: A total of 31 patients presented with altered liver chemistries following vaccination. Seventeen patients were diagnosed with VAIH (age-39.8 ± 11.4 years;males-70.4%). None of the patient had history of alcohol overconsumption. Seventy six percent of patients had received ChAdOx1 and 23.53% had received BBV152 vaccine (Table). Seventy six percent of patients following first dose of vaccine and 23.5% following second dose of vaccinewere diagnosed as V-AIH. Mean duration for development of symptoms after first dosewas 25.7 days. Common symptom at presentation was jaundice in 82.3% of patients. Antinuclear antibodywas positive in 71% of patients and 17% patients were negative for all serological markers of autoimmune hepatitis but had elevated IgG levels. Fifty-nine percent of patients required immunosuppression of which 41% percet of patients received oral steroids, 17% patients received intravenous steroids for 3 days followed by oral steroid, 12% patients received azathioprine. One patient succumbed to pneumonia with multiorgan failure by day 30. At 3 months, it was observed that only 17% patients needed prolonged immunosuppression and had deranged liver functions until last follow-up. Mean duration of recovery amongst rest of 76.4% patients was 5.15 ± 3.1 weeks.

9.
BRITISH JOURNAL OF DERMATOLOGY ; 187:51-51, 2022.
Article in English | Web of Science | ID: covidwho-1935253
10.
BRITISH JOURNAL OF DERMATOLOGY ; 187:152-152, 2022.
Article in English | Web of Science | ID: covidwho-1935252
11.
European Stroke Journal ; 7(1 SUPPL):472, 2022.
Article in English | EMBASE | ID: covidwho-1928118

ABSTRACT

Background: In 2020, North Central (NC) London and East Kent introduced prehospital video triage, where stroke and ambulance clinicians used videoconferencing to assess suspected stroke patients on scene. The aim was to reduce conveyance of non-stroke patients to stroke services and reduce transmission of Covid-19. Methods: Rapid, mixed-method evaluation of prehospital video triage in NC London and East Kent (July 2020-September 2021), drawing on: • Interviews with ambulance and stroke clinicians (n=27);observations (n=12);documents (n=23);• Survey of ambulance clinicians (n=233) in NC London and East Kent. • Descriptive statistical analysis of local ambulance conveyance data (n=1,400;April-September 2020). • Difference-in-differences regression analysis of team-level national audit data, to understand changes in delivery of clinical interventions in NC London and East Kent relative to the rest of England (n=137,650;2018-2020). Results: Interview and survey data suggested clinicians perceived prehospital video triage as usable, safe, and preferable to 'business-as-usual'. Several interrelated factors influenced implementation, including impetus of Covid-19, facilitative local governance, receptive professional values, engaging clinical leadership, active training approaches, and stable audiovisual signal;stroke clinician capacity was a potential risk to sustainability. Neither area saw increased time from symptom onset to arrival at services, while delivery of clinical interventions either remained unchanged or improved significantly, relative to the rest of England. Conclusions: Prehospital video triage in NC London and East Kent was perceived as usable, acceptable, and safe;it was associated with some significant improvements in secondary care processes. Key influences included national and local context, characteristics of triage services, and implementation approaches.

12.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925233

ABSTRACT

Objective: To examine the natural history of neurological symptoms in mild COVID-19. Background: Various neurological manifestations have been reported with COVID-19, mostly in retrospective studies of hospitalized patients. There are few data on patients with mild COVID19. Design/Methods: Consenting participants in the ALBERTA HOPE COVID-19 trial( NCT04329611, hydroxychloroquine vs placebo for 5-days), managed as outpatients, were prospectively assessed 3-months and 1-year after their positive test. They completed detailed neurological symptom questionnaires, Telephone Montreal Cognitive Assessment(T-MoCA), Kessler Psychological Distress Scale(K10), and the EQ-5D-3L(quality-of-life). Informants completed the Mild Behavioural Impairment Checklist(MBI-C) and Informant Questionnaire on Cognitive Decline(IQCODE). We tracked healthcare utilization and neurological investigations using medical records. Results: Among 198 patients (median age:45, IQR:37-54, 43.9% female);28(14.1%) had preexisting neurological/psychiatric disorders. Among 179 patients with symptom assessments, 139(77.7%) reported ≥1 neurological symptom, the most common being anosmia/dysgeusia(56.3%), myalgia(42.6%), and headache(41.8%). Symptoms generally began within 1-week of illness(median:6-days, IQR:4-8). Most resolved after 3-months;40 patients(22.3%) reported persistent symptoms at 1-year, with 27(15.1%) reporting no improvement. Persistent symptoms included confusion(50%), headache(52.5%), insomnia(40%), and depression(35%). Body mass index, prior neurologic/psychiatric history, asthma, and lack of full-time employment were associated with presence and persistence of neurological symptoms;only female sex was independently associated on multivariable logistic regression(aOR:5.04, 95%CI:1.58-16.1). Patients with persistent symptoms had more hospitalizations and family physician visits, worse MBI-C scores, and were less often independent for instrumental daily activities at 1-year(77.8% vs 98.2%, p=0.005). Patients with any or persistent neurological symptoms had greater psychological distress defined as K10≥20(aOR:21.0, 95%CI:1.96-225) and worse quality-of-life ratings(mean EQ-5D VAS:67.0 vs 82.8, p=0.0002). 50.0% of patients had T-MoCA<18 at 3-months versus 42.9% at 1-year;patients reporting memory complaints were more likely to have informant-reported cognitive-behavioural decline (aOR[1-year IQCODE>3.3]:12.7, 95%CI:1.08-150). Conclusions: Neurological symptoms were commonly reported in survivors of mild COVID-19 and persisted in one in five patients 1-year later. These symptoms were associated with worse patient-reported outcomes.

14.
Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research ; 25(7):S496-S496, 2022.
Article in English | EuropePMC | ID: covidwho-1905007
15.
American Journal of Respiratory and Critical Care Medicine ; 205:2, 2022.
Article in English | English Web of Science | ID: covidwho-1880474
16.
Archives of Disease in Childhood ; 107(5):4, 2022.
Article in English | EMBASE | ID: covidwho-1868713

ABSTRACT

Aim On 12 March 2020, the COVID-19 outbreak was declared as a pandemic by the World Health Organisation.1 During this time, paediatric services saw dramatic reductions in children accessing emergency care and routine operations were cancelled, which enabled the paediatric intensive care unit (PICU) team to support the adult critical care expansion by repurposing paediatric beds to open an adult intensive care unit (AICU). Here we describe the pharmacy experience, challenges and learning outcomes faced in converting a PICU to an AICU. Method A trust-wide multidisciplinary critical care tactical group including pharmacy representation was established to coordinate strategy planning, troubleshoot operational and clinical difficulties, and manage communications on a wider scale. Within pharmacy, clinical and operational lead pharmacists led the pharmacy response and supported the front-line pharmacy teams to coordinate and make quick informed decisions to daily challenges. The challenges were made even greater by the need to co-deliver a mixed paediatric/adult unit meaning we had to ensure the safety of both the adults and children receiving medicines. Results Paediatric pharmacy staff were upskilled by the adult critical care pharmacy team, extrapolating existing PICU knowledge and experience and expanding on key differences, as well as offering weekly shadowing opportunities. The use of a mnemonic pharmaceutical tool to review patients enabled paediatric pharmacists to ask the right questions and ensure medicines were managed appropriately. In addition, a quick reference guide to common adult drug doses, bite size educational sessions and use of an app called Clinibee® were developed to disseminate important adult learning points and new guidance. The PICU electronic prescribing system Metavision® was adapted and configured for adult dosing and administration. To reduce prescribing errors and improve safety, doctors on the unit were assigned to either managing adults or paediatric patients. Further informatic changes were required in real time in response to drug supply chain and equipment shortages and changes in clinical policies. A risk assessment of adult medicine stock holding, including high-risk medicines and location of them on the unit helped reduce the risk of mis-selection. Extra nursing support was provided by pharmacy by manufacturing ready to administer injectables and existing medicines management policies adapted. Regular check-ins and staff huddles kept staff updated and provided support where needed. Conclusion Providing an AICU on PICU was one of the biggest challenges ever faced but provided excellent cooperation and collaboration between pharmacy teams. PICU pharmacists have a strong foundation of ICU knowledge to enable them to be redeployed to AICU. Strong clinical and operational leadership is required to navigate uncertain times when staff are working outside their normal practice. Good communication is vital, both upwards, downwards and to the front line to ensure safe ways of working. Resilience planning including staffing, drug and equipment shortages ensured that resources were prioritised. Teamwork with a dedicated focus on wellbeing enabled staff to be supported where needed and ensured our patients received the most clinically effective care.

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18.
Journal of the American College of Cardiology ; 79(9):176-176, 2022.
Article in English | Web of Science | ID: covidwho-1848486
19.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-333509

ABSTRACT

BACKGROUND: Data for frontline healthcare workers (HCWs) and risk of SARS-CoV-2 infection are limited and whether personal protective equipment (PPE) mitigates this risk is unknown. We evaluated risk for COVID-19 among frontline HCWs compared to the general community and the influence of PPE. METHODS: We performed a prospective cohort study of the general community, including frontline HCWs, who reported information through the COVID Symptom Study smartphone application beginning on March 24 (United Kingdom, U.K.) and March 29 (United States, U.S.) through April 23, 2020. We used Cox proportional hazards modeling to estimate multivariate-adjusted hazard ratios (aHRs) of a positive COVID-19 test. FINDINGS: Among 2,035,395 community individuals and 99,795 frontline HCWs, we documented 5,545 incident reports of a positive COVID-19 test over 34,435,272 person-days. Compared with the general community, frontline HCWs had an aHR of 11.6 (95% CI: 10.9 to 12.3) for reporting a positive test. The corresponding aHR was 3.40 (95% CI: 3.37 to 3.43) using an inverse probability weighted Cox model adjusting for the likelihood of receiving a test. A symptom-based classifier of predicted COVID-19 yielded similar risk estimates. Compared with HCWs reporting adequate PPE, the aHRs for reporting a positive test were 1.46 (95% CI: 1.21 to 1.76) for those reporting PPE reuse and 1.31 (95% CI: 1.10 to 1.56) for reporting inadequate PPE. Compared with HCWs reporting adequate PPE who did not care for COVID-19 patients, HCWs caring for patients with documented COVID-19 had aHRs for a positive test of 4.83 (95% CI: 3.99 to 5.85) if they had adequate PPE, 5.06 (95% CI: 3.90 to 6.57) for reused PPE, and 5.91 (95% CI: 4.53 to 7.71) for inadequate PPE. INTERPRETATION: Frontline HCWs had a significantly increased risk of COVID-19 infection, highest among HCWs who reused PPE or had inadequate access to PPE. However, adequate supplies of PPE did not completely mitigate high-risk exposures. FUNDING: Zoe Global Ltd., Wellcome Trust, EPSRC, NIHR, UK Research and Innovation, Alzheimer's Society, NIH, NIOSH, Massachusetts Consortium on Pathogen Readiness.

20.
Open Forum Infectious Diseases ; 8(SUPPL 1):S320-S321, 2021.
Article in English | EMBASE | ID: covidwho-1746558

ABSTRACT

Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections peak during an inflammatory 'middle' phase and lead to severe illness predominately among those with certain comorbid noncommunicable diseases (NCDs). We used network machine learning to identify inflammation biomarker patterns associated with COVID-19 among those with NCDs. Methods. SARS-CoV-2 RT-PCR positive subjects who had specimens available within 15-28 days post-symptom onset were selected from the DoD/USU EPICC COVID-19 cohort study. Plasma levels of 15 inflammation protein biomarkers were measured using a broad dynamic range immunoassay on samples collected from individuals with COVID-19 at 8 military hospitals across the United States. A network machine learning algorithm, topological data analysis (TDA), was performed using results from the 'hyperinflammatory' middle phase. Backward selection stepwise logistic regression was used to identify analytes associated with each cluster. NCDs with a significant association (0.05 significance level) across clusters using Fisher's exact test were further evaluated comparing the NCD frequency in each cluster against all other clusters using a Kruskal-Wallis test. A sensitivity analysis excluding mild disease was also performed. Results. The analysis population (n=129, 33.3% female, median 41.3 years of age) included 77 ambulatory, 31 inpatient, 16 ICU-level, and 5 fatal cases. TDA identified 5 unique clusters (Figure 1). Stepwise regression with a Bonferroni-corrected cutoff adjusted for severity identified representative analytes for each cluster (Table 1). The frequency of diabetes (p=0.01), obesity (p< 0.001), and chronic pulmonary disease (p< 0.001) differed among clusters. When restricting to hospitalized patients, obesity (8 of 11), chronic pulmonary disease (6 of 11), and diabetes (6 of 11) were more prevalent in cluster C than all other clusters. Conclusion. Machine learning clustering methods are promising analytical tools for identifying inflammation marker patterns associated with baseline risk factors and severe illness due to COVID-19. These approaches may offer new insights for COVID19 prognosis, therapy, and prevention.

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