Comments to: A systematic review of pathological findings in COVID-19: a pathophysiological timeline and possible mechanisms of disease progression

Parra‐Medina, Rafael; Herrera, Sabrina; Mejìa, Jaime Piracoca

doi:10.1038/s41379-020-0631-z

Cited by 6 publications

(6 citation statements)

References 25 publications

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“…A total of 201 full-text articles were assessed for eligibility (COVID-19 autopsies). Twenty-eight full-text articles with COVID-19 autopsies were reviewed [ 7 ]. Fifteen articles were added in the second search.…”

Section: Resultsmentioning

confidence: 99%

Systematic Review of Microthrombi in COVID-19 Autopsies

Parra‐Medina

Herrera

Mejìa³

2021

Acta Haematol

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Background: Histopathological analysis can provide additional clues in COVID-19 understanding. During the last year, autopsy reports have revealed that diffuse alveolar damage (DAD) is the most significant observed finding. The aim of this study is to review cases in the literature about COVID-19 autopsies that reported microthrombi in different organs. Methods: We performed a systematic literature review in PubMed, Virtual Health Library (VHL), and Google Scholar. Results: In total, 151 autopsies were included, and 91 cases presented microthrombi in the lung (73%), heart (11.2%), kidney (24%), and liver (16.3%). The age range was between 27 and 96 years. Males were 64.8%. The patients with microthrombi had more comorbidities such as arterial hypertension (62%), obesity or overweight (64%), diabetes mellitus type 2 (51%), and heart disease (53%). The most common histopathological changes found in patients with lung microthrombosis were DAD in exudative phase (78%), pulmonary embolism (59%), and lung infarct (81%). Presence of microthrombi was associated with arterial hypertension (p < 0.0001) and DAD in exudative and proliferative phases (p = 0.02). Discussion: The analysis of these results shows that microthrombi in COVID-19 autopsies may be found in different organs and are more frequent in patients with comorbidities, pulmonary embolism, and lung infarct.

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Section: Resultsmentioning

confidence: 99%

Systematic Review of Microthrombi in COVID-19 Autopsies

Parra‐Medina

Herrera

Mejìa³

2021

Acta Haematol

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“…A hallmark of disease severity in COVID-19 is the uncontrolled inflammatory response, with the detection of IL-6, IL-17, TNFα, and GM-CSF at the serum/blood level ( Chen G. et al, 2020 ; Mehta et al, 2020 ; Parra-Medina et al, 2020 ), the so-called “cytokine storm.” Here we showed a significant increase of those cytokines in the oral cavity of COVID-19 patients, indicating the development of inflammation right at the entry site of the virus. It is noteworthy that the level of oral inflammation paralleled the symptom severity, pointing to the importance of oral conditions for the subsequent systemization of virus infection and inflammation cascade.…”

Section: Discussionmentioning

confidence: 99%

Oral Microbiome Dysbiosis Is Associated With Symptoms Severity and Local Immune/Inflammatory Response in COVID-19 Patients: A Cross-Sectional Study

et al. 2021

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The human oral microbiome (HOM) is the second largest microbial community after the gut and can impact the onset and progression of several localized and systemic diseases, including those of viral origin, especially for viruses entering the body via the oropharynx. However, this important aspect has not been clarified for the new pandemic human coronavirus SARS-CoV-2, causing COVID-19 disease, despite it being one of the many respiratory viruses having the oropharynx as the primary site of replication. In particular, no data are available about the non-bacterial components of the HOM (fungi, viruses), which instead has been shown to be crucial for other diseases. Consistent with this, this study aimed to define the HOM in COVID-19 patients, to evidence any association between its profile and the clinical disease. Seventy-five oral rinse samples were analyzed by Whole Genome Sequencing (WGS) to simultaneously identify oral bacteria, fungi, and viruses. To correlate the HOM profile with local virus replication, the SARS-CoV-2 amount in the oral cavity was quantified by digital droplet PCR. Moreover, local inflammation and secretory immune response were also assessed, respectively by measuring the local release of pro-inflammatory cytokines (L-6, IL-17, TNFα, and GM-CSF) and the production of secretory immunoglobulins A (sIgA). The results showed the presence of oral dysbiosis in COVID-19 patients compared to matched controls, with significantly decreased alpha-diversity value and lower species richness in COVID-19 subjects. Notably, oral dysbiosis correlated with symptom severity (p = 0.006), and increased local inflammation (p < 0.01). In parallel, a decreased mucosal sIgA response was observed in more severely symptomatic patients (p = 0.02), suggesting that local immune response is important in the early control of virus infection and that its correct development is influenced by the HOM profile. In conclusion, the data presented here suggest that the HOM profile may be important in defining the individual susceptibility to SARS-CoV-2 infection, facilitating inflammation and virus replication, or rather, inducing a protective IgA response. Although it is not possible to determine whether the alteration in the microbial community is the cause or effect of the SARS-CoV-2 replication, these parameters may be considered as markers for personalized therapy and vaccine development.

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“…A hallmark of severe COVID-19 disease is an uncontrolled inflammatory response; specifically, a fulminant and fatal hypercytokinemia that causes an uncontrolled flood of immune cells into the lung 20-22 . In these patients, it’s their own uncontrolled inflammatory response, rather than the virus, that causes severe lung injury and multi-organ failures leading to death.…”

Section: Discussionmentioning

confidence: 99%

“…Enterococcus faecalis can be cultured from feces representing a cost-effective, rapid, and relatively easy test to implement in clinical settings. As such we urge the medical community that in addition to observable clinical variables, indicator species of the microbiome, specifically Enterococcus faecalis, can serve as robust predictor of COVID-19 severity and to quickly identify patients who are likely to require more supportive care or therapeutic interventions to improve chances of survival.A hallmark of severe COVID-19 disease is an uncontrolled inflammatory response; specifically, a fulminant and fatal hypercytokinemia that causes an uncontrolled flood of immune cells into the lung[20][21][22] .…”

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confidence: 99%

The Intestinal and Oral Microbiomes Are Robust Predictors of Covid-19 Severity the Main Predictor of Covid-19-Related Fatality

Ward

Bhattarai

Rojas-Correa

et al. 2021

Preprint

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The reason for the striking differences in clinical outcomes of SARS-CoV-2 infected patients is still poorly understood. While most recover, a subset of people become critically ill and succumb to the disease. Thus, identification of biomarkers that can predict the clinical outcomes of COVID-19 disease is key to help prioritize patients needing urgent treatment. Given that an unbalanced gut microbiome is a reflection of poor health, we aim to identify indicator species that could predict COVID-19 disease clinical outcomes. Here, for the first time and with the largest COVID-19 patient cohort reported for microbiome studies, we demonstrated that the intestinal and oral microbiome make-up predicts respectively with 92% and 84% accuracy (Area Under the Curve or AUC) severe COVID-19 respiratory symptoms that lead to death. The accuracy of the microbiome prediction of COVID-19 severity was found to be far superior to that from training similar models using information from comorbidities often adopted to triage patients in the clinic (77% AUC). Additionally, by combining symptoms, comorbidities, and the intestinal microbiota the model reached the highest AUC at 96%. Remarkably the model training on the stool microbiome found enrichment of Enterococcus faecalis, a known pathobiont, as the top predictor of COVID-19 disease severity. Enterococcus faecalis is already easily cultivable in clinical laboratories, as such we urge the medical community to include this bacterium as a robust predictor of COVID-19 severity when assessing risk stratification of patients in the clinic.

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Comments to: A systematic review of pathological findings in COVID-19: a pathophysiological timeline and possible mechanisms of disease progression

Cited by 6 publications

References 25 publications

Systematic Review of Microthrombi in COVID-19 Autopsies

Systematic Review of Microthrombi in COVID-19 Autopsies

Oral Microbiome Dysbiosis Is Associated With Symptoms Severity and Local Immune/Inflammatory Response in COVID-19 Patients: A Cross-Sectional Study

The Intestinal and Oral Microbiomes Are Robust Predictors of Covid-19 Severity the Main Predictor of Covid-19-Related Fatality

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