The first, holistic immunological model of COVID‐19: Implications for prevention, diagnosis, and public health measures

Matricardi, Paolo Maria; Negro, Roberto W. Dal; Nisini, Roberto

doi:10.1111/pai.13271

Cited by 178 publications

(235 citation statements)

References 118 publications

(224 reference statements)

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“…Elucidating the underlying in ammatory mechanism of COVID-19 may aid clinicians' comprehension of the disease and clarify the deterioration in clinical course on Day 10 of illness as well as trends of laboratory ndings. [7,26] In our study, the median day of illness on ICU admission and intubation was [29] In this study, D-dimer peaked on Day 20 of illness. Recognition of these changes guided the institutional clinical practice for active surveillance for the detection of thromboembolism and early administration of prophylaxis.…”

Section: Discussionmentioning

confidence: 48%

Clinical Characteristics and Outcomes of Critically Ill COVID-19 Patients in Tokyo: A Single-Center Observational Study

Banno

Hifumi

Okamoto

et al. 2020

Preprint

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Background: Japan has been successful in maintaining low mortality rates during the coronavirus disease 2019 (COVID-19) pandemic. We sought to investigate the characteristics, inflammatory laboratory finding trends, and outcomes among critically ill Japanese patients who were admitted to the intensive care unit (ICU) with COVID-19. Methods: A retrospective observational study was performed in a single institution in the center of Tokyo. Laboratory-confirmed COVID-19 patients admitted to the ICU from March 19 to April 30, 2020 were included. Trends for significant inflammatory laboratory findings were analyzed. In-hospital death, days of mechanical ventilation or oxygen supplementation, days of ICU or hospital stay were followed until May 26, 2020. Results: Twenty-four patients were included. Median age was 57.5 years, and 79% were male. The neutrophil-to-lymphocyte ratio was elevated to a median of 10.1 on admission and peaked on Day 10 of illness. Seventeen patients were intubated on Day 11 of illness and received mechanical ventilation. One patient underwent extracorporeal membrane oxygenation. The majority (88%) received systemic steroids, including 16 patients who received high dose methylprednisolone (500-1000 mg). Favipiravir was used in 38% of patients. Two patients, including 1 who refused intensive care, died. Eighteen patients were discharged. Median length of ICU and hospital stay for all patients was 6 and 22 days, respectively. Median length of ventilator dependency was 7 days. Four patients underwent a tracheostomy and received prolonged ventilation for more than 21 days. One patient receiving mechanical ventilation died. All survivors discontinued ventilator use. Mortality was remarkably low and prolonged ventilation was inevitable yet discontinued.Conclusions: Mortality was remarkably low in our single institutional study. Prolonged ventilation was inevitable yet discontinued. Trends of systemic inflammatory laboratory markers reflected the clinical course of COVID-19.

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Section: Discussionmentioning

confidence: 48%

Clinical Characteristics and Outcomes of Critically Ill COVID-19 Patients in Tokyo: A Single-Center Observational Study

Banno

Hifumi

Okamoto

et al. 2020

Preprint

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“…IL-6 is also thrombogenic, which may well account for this signi cant cause of death from the virus 21 . Intense exercise also produces large quantities of IL-6 22 , which may account for the more severe clinical manifestations of infection amongst athletes 23 .…”

Section: Discussionmentioning

confidence: 99%

Premorbid IL-6 levels may predict mortality from COVID-19

Silberstein

2020

Preprint

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Purpose: There is evidence that interleukin-6 (IL-6) levels are elevated in cases of complicated COVID-19, but it is also possible that this cytokine has a far more important role in the pathogenesis of viral infection. Methods: Data on COVID-19 mortality from Italy and the UK were compared with previously published results of mean IL-6 levels from these countries as well as from the USA. Results: There was a highly significant correlation (r = 0.9883; p = 0.00025) between age-stratified mortality rates and IL-6 levels from similar healthy individuals. Levels of IL-6 were proportionately higher in males, the elderly, individuals of black ethnicity and obese individuals, with similar findings in relation to COVID-19 mortality in these groups. Conclusions: IL-6 levels prior to infection may predict mortality, given that this cytokine directly facilitates viral cell entry and replication. This provides a rationale for prophylactic and therapeutic measures directed at lowering IL-6, including Vitamin D prescription.

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“…It's supposed to be related to direct viral infection or dysregulated immune response (10,25,26). SARS-CoV-2 enters cells by binding angiotensin-converting enzyme-2 (ACE2) (27,28). Theoretically, the decrease of ACE2, caused by SARS-CoV-2 infection, would break the balance between ACE and ACE2.…”

Section: Discussionmentioning

confidence: 99%

“…Emerging data have reported that patients with preexisting comorbidities were more likely to suffer acute organ injury (7-9), which has been recently implicated as an independent risk for increased in-hospital death in COVID-19 patients (10-12). As reported by T. Guo,27.8% of the hospitalized COVID-19 patients exhibited myocardial injury (8) while up to 75% of the COVID-19 patients experienced different degree of kidney function decline (13). However, the exact role of this universal alternation has not been gured out.…”

Section: Introductionmentioning

confidence: 96%

Mediating Effect of Deteriorated Kidney Function in Comorbidity-related Excess Deaths in COVID-19: A Retrospective Cohort Study

Luo

Liu

Xie

et al. 2020

Preprint

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Background In-hospital death risks vary in COVID-19 patients with comorbidities. Kidney function decline is prevalent in this course. Methods To explore the exact role of deteriorated kidney function, we applied a retrospective cohort study including 1266 participants in Wuhan Tongren Hospital between January 27 and March 3, 2020. Demographic characteristics, preexisting comorbidities history, organ function data and outcomes were extracted. Deteriorated kidney function was identified as the decline percentage, assessed by an increase in peak serum creatinine from the baseline. Mediating effect was calculated by mediation analysis. Key Results 1266 hospitalized COVID-19 patients (60±15 years, 47.8% are male) were included, with an overall in-hospital death rate of 4.42% (56/1266). For critical cases, 77.02% had at least one preexisting comorbidity. Patients with comorbidities suffered higher in-hospital death and more severe decline of kidney function. Compared to patients with minor function decline (<10%), significant risk increase was found in those with more severe one (OR 3.57; 95%CI 1.70 to 7.52; P=.001 for moderate with 10-50% decline, and 37.45; 95%CI 18.71 to 74.55; P＜.001 for severe with>50%). More interestingly, the mediation analysis found deteriorated kidney function played as an important mediator between different comorbidities and COVID-19 patients’ in-hospital death, with the mediation effect of 11%, 12%, 16% and 32% respectively for hypertension, COPD, CVD and CKD.Conclusions Deteriorated kidney function is strongly associated with increase of in-hospital death in COVID-19 and partially mediates the facilitating effect of preexisting comorbidities on in-hospital death. Thus, dynamic monitoring kidney function, preventing the deterioration of kidney function might be helpful to improve survival in COVID-19 patients, especially those with preexisting comorbidities.

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The first, holistic immunological model of COVID‐19: Implications for prevention, diagnosis, and public health measures

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 178 publications

References 118 publications

Clinical Characteristics and Outcomes of Critically Ill COVID-19 Patients in Tokyo: A Single-Center Observational Study

Clinical Characteristics and Outcomes of Critically Ill COVID-19 Patients in Tokyo: A Single-Center Observational Study

Premorbid IL-6 levels may predict mortality from COVID-19

Mediating Effect of Deteriorated Kidney Function in Comorbidity-related Excess Deaths in COVID-19: A Retrospective Cohort Study

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