Histopathological, Microbiological and Molecular Aspects of Severe COVID-19

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (20 February 2023) | Viewed by 30212

Special Issue Editors

Department of Pathology, University of Barcelona, 08036 Barcelona, Spain
Interests: infectious disease pathology; global health; AIDS; opportunistic infections; COVID-19; HPV and vulvar cancer; cause of death investigation; minimally invasive autopsy
Department of Pathology, University of Barcelona, 08036 Barcelona, Spain
Interests: infectious disease pathology; global health; AIDS; opportunistic infections; COVID-19; HPV and cervical cancer; cause of death investigation; minimally invasive autopsy

Special Issue Information

Dear Colleagues,

The new coronavirus disease COVID-19 continues to take thousands of lives each day worldwide. Since the start of the pandemic, clinical and epidemiological COVID-19 research has resulted in a high number of scientific reports. Contrarily, the progression of basic laboratory research aiming at characterizing COVID-19 at the histological, microbiological, or purely molecular level has been much slower. Despite the key role of post-mortem examination in exploring the pathogenesis of emerging diseases, the number of autopsy-based studies is particularly small [1]. Existing autopsy-based studies are based on small series of cases and mostly reveal highly heterogenous and non-specific injuries associated with SARS-CoV-2 infection [2,3]. Minimally invasive autopsies, also known as post-mortem biopsies or minimally invasive tissue sampling, could provide relevant results on the characterization of COVID-19 in those settings where full autopsy is not feasible [4].

In the first months of pandemy it has become clear that the virus uses the SARS-CoV receptor ACE2 for entry [5]. However, a large part of the molecular mechanisms involved in the high mortality, multiorgan failure, and occurrence of vascular complications [6] are not fully understood. We invite you to contribute in the form of original research articles and reviews focusing on the different histological, microbiological, and molecular aspects of severe COVID-19. Post-mortem autopsy- or biopsy-based studies with clinico-pathological correlation are particularly welcome. We look forward to receiving your contributions.

References:

  1. Salerno M, Sessa F, Piscopo A, et al No Autopsies on COVID-19 Deaths: A Missed Opportunity and the Lockdown of Science. J Clin Med 2020;9:1472.
  2. Remmelink M, De Mendonça R, D’Haene N, et al Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients. Crit Care 2020;24:495.
  3. Menter T, Haslbauer JD, Nienhold R, et al Post‐mortem examination of COVID19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings of lungs and other organs suggesting vascular dysfunction. Histopathology 2020;77:198–209.
  4. Rakislova N, Ismail MR, Martinez A, et al Minimally Invasive Autopsy: a more feasible and safer alternative to conventional autopsy in the COVID-19 pandemic era? Med Clin Sci 2020;2:1–5.
  5. Hoffmann M, Kleine-Weber H, Schroeder S, et al SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020;181:271-280.e8.
  6. Lax SF, Skok K, Zechner P, et al Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome : Results From a Prospective, Single-Center, Clinicopathologic Case Series. Ann Intern Med 2020;173:350–361.

Dr. Natalia Rakislova
Prof. Dr. Jaume Ordi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • COVID-19
  • SARS-CoV-2
  • Autopsy
  • histology
  • pathology
  • microbiology
  • post-mortem
  • biopsy
  • RT-PCR

Published Papers (7 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Other

12 pages, 2618 KiB  
Article
Study of the Plasma and Buffy Coat in Patients with SARS-CoV-2 Infection—A Preliminary Report
by Karla B. Peña, Francesc Riu, Josep Gumà, Carmen Guilarte, Berta Pique, Anna Hernandez, Alba Àvila, Sandra Parra, Antoni Castro, Conxita Rovira, Pitter Cueto, Immaculada Vallverdu and David Parada
Pathogens 2021, 10(7), 805; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10070805 - 25 Jun 2021
Cited by 2 | Viewed by 2052
Abstract
The pandemic caused by the SARS-CoV-2 infection affects many aspects of public health knowledge, science, and practice around the world. Several studies have shown that SARS-CoV-2 RNA in plasma seems to be associated with a worse prognosis of COVID-19. In the present study, [...] Read more.
The pandemic caused by the SARS-CoV-2 infection affects many aspects of public health knowledge, science, and practice around the world. Several studies have shown that SARS-CoV-2 RNA in plasma seems to be associated with a worse prognosis of COVID-19. In the present study, we investigated plasma and buffy RNA in patients with COVID-19 to determine its prognostic value. A prospective study was carried out in patients hospitalized for COVID-19, in which RNA was analyzed in plasma and the buffy coat. Morphological and immunohistochemical studies were used to detect the presence of SARS-CoV-2 in the buffy coat. In COVID-19 patients, the obtained RNA concentration in plasma was 448.3 ± 31.30 ng/mL. Of all the patients with positive plasma tests for SARS-CoV-2, 46.15% died from COVID-19. In four cases, tests revealed that SARS-CoV-2 was present in the buffy coat. Abnormal morphology of monocytes, lymphocytes and neutrophils was found. An immunohistochemical study showed positivity in mononuclear cells and platelets. Our results suggest that SARS-CoV-2 is present in the plasma. This facilitates viral dissemination and migration to specific organs, where SARS-CoV-2 infects target cells by binding to their receptors. In our study, the presence of plasma SARS-CoV-2 RNA was correlated with worse prognoses. Full article
Show Figures

Figure 1

13 pages, 7532 KiB  
Article
Molecular Pathology Analysis of SARS-CoV-2 in Syncytiotrophoblast and Hofbauer Cells in Placenta from a Pregnant Woman and Fetus with COVID-19
by Denise Morotti, Massimiliano Cadamuro, Elena Rigoli, Aurelio Sonzogni, Andrea Gianatti, Cristina Parolin, Luisa Patanè and David A. Schwartz
Pathogens 2021, 10(4), 479; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10040479 - 15 Apr 2021
Cited by 19 | Viewed by 4050
Abstract
A small number of neonates delivered to women with SARS-CoV-2 infection have been found to become infected through intrauterine transplacental transmission. These cases are associated with a group of unusual placental pathology abnormalities that include chronic histiocytic intervillositis, syncytiotrophoblast necrosis, and positivity of [...] Read more.
A small number of neonates delivered to women with SARS-CoV-2 infection have been found to become infected through intrauterine transplacental transmission. These cases are associated with a group of unusual placental pathology abnormalities that include chronic histiocytic intervillositis, syncytiotrophoblast necrosis, and positivity of the syncytiotrophoblast for SARS-CoV-2 antigen or RNA. Hofbauer cells constitute a heterogeneous group of immunologically active macrophages that have been involved in transplacental infections that include such viral agents as Zika virus and human immunodeficiency virus. The role of Hofbauer cells in placental infection with SARS-CoV-2 and maternal-fetal transmission is unknown. This study uses molecular pathology techniques to evaluate the placenta from a neonate infected with SARS-CoV-2 via the transplacental route to determine whether Hofbauer cells have evidence of infection. We found that the placenta had chronic histiocytic intervillositis and syncytiotrophoblast necrosis, with the syncytiotrophoblast demonstrating intense positive staining for SARS-CoV-2. Immunohistochemistry using the macrophage marker CD163, SARS-CoV-2 nucleocapsid protein, and double staining for SARS-CoV-2 with RNAscope and anti-CD163 antibody, revealed that no demonstrable virus could be identified within Hofbauer cells, despite these cells closely approaching the basement membrane zone of the infected trophoblast. Unlike some other viruses, there was no evidence from this transmitting placenta for infection of Hofbauer cells with SARS-CoV-2. Full article
Show Figures

Figure 1

15 pages, 36342 KiB  
Article
Minimally Invasive Autopsy Practice in COVID-19 Cases: Biosafety and Findings
by Natalia Rakislova, Lorena Marimon, Mamudo R. Ismail, Carla Carrilho, Fabiola Fernandes, Melania Ferrando, Paola Castillo, Maria Teresa Rodrigo-Calvo, José Guerrero, Estrella Ortiz, Abel Muñoz-Beatove, Miguel J. Martinez, Juan Carlos Hurtado, Mireia Navarro, Quique Bassat, Maria Maixenchs, Vima Delgado, Edwin Wallong, Anna Aceituno, Jean Kim, Christina Paganelli, Norman J. Goco, Iban Aldecoa, Antonio Martinez-Pozo, Daniel Martinez, José Ramírez-Ruz, Gieri Cathomas, Myriam Haab, Clara Menéndez and Jaume Ordiadd Show full author list remove Hide full author list
Pathogens 2021, 10(4), 412; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10040412 - 01 Apr 2021
Cited by 23 | Viewed by 13450
Abstract
Postmortem studies are crucial for providing insight into emergent diseases. However, a complete autopsy is frequently not feasible in highly transmissible diseases due to biohazard challenges. Minimally invasive autopsy (MIA) is a needle-based approach aimed at collecting samples of key organs without opening [...] Read more.
Postmortem studies are crucial for providing insight into emergent diseases. However, a complete autopsy is frequently not feasible in highly transmissible diseases due to biohazard challenges. Minimally invasive autopsy (MIA) is a needle-based approach aimed at collecting samples of key organs without opening the body, which may be a valid alternative in these cases. We aimed to: (a) provide biosafety guidelines for conducting MIAs in COVID-19 cases, (b) compare the performance of MIA versus complete autopsy, and (c) evaluate the safety of the procedure. Between October and December 2020, MIAs were conducted in six deceased patients with PCR-confirmed COVID-19, in a basic autopsy room, with reinforced personal protective equipment. Samples from the lungs and key organs were successfully obtained in all cases. A complete autopsy was performed on the same body immediately after the MIA. The diagnoses of the MIA matched those of the complete autopsy. In four patients, COVID-19 was the main cause of death, being responsible for the different stages of diffuse alveolar damage. No COVID-19 infection was detected in the personnel performing the MIAs or complete autopsies. In conclusion, MIA might be a feasible, adequate and safe alternative for cause of death investigation in COVID-19 cases. Full article
Show Figures

Figure 1

Other

Jump to: Research

7 pages, 1271 KiB  
Brief Report
SARS-CoV-2 Infection Prompts IL-1β-Mediated Inflammation and Reduces IFN-λ Expression in Human Lung Tissue
by Bianca Vezzani, Margherita Neri, Stefano D’Errico, Alberto Papi, Marco Contoli and Carlotta Giorgi
Pathogens 2022, 11(11), 1390; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11111390 - 21 Nov 2022
Cited by 2 | Viewed by 1326
Abstract
Two years after its spreading, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still responsible for more than 2000 deaths per day worldwide, despite vaccines and monoclonal antibody countermeasures. Therefore, there is a need to understand the immune–inflammatory pathways that prompt the [...] Read more.
Two years after its spreading, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still responsible for more than 2000 deaths per day worldwide, despite vaccines and monoclonal antibody countermeasures. Therefore, there is a need to understand the immune–inflammatory pathways that prompt the manifestation of the disease to identify a novel potential target for pharmacological intervention. In this context, the characterization of the main players in the SARS-CoV-2-induced cytokine storm is mandatory. To date, the most characterized have been IL-6 and the class I and II interferons, while less is known about the proinflammatory cytokine IL-1β and class III interferons. Here, we report a preliminary study aimed at the characterization of the lung inflammatory context in COVID-19 patients, with a special focus on IFN-λ and IL-1β. By investigating IFN and inflammatory cytokine patterns by IHC in 10 deceased patients due to COVID-19 infection, compared to 10 control subjects, we reveal that while IFN-β production was increased in COVID-19 patients, IFN-λ was almost abolished. At the same time, the levels of IL-1β were dramatically improved, while IL-6 lung levels seem to be unaffected by the infection. Our findings highlight a central role of IL-1β in prompting lung inflammation after SARS-CoV-2 infection. Together, we show that IFN-λ is negatively affected by viral infection, supporting the idea that IFN-λ administration together with the pharmaceutical blockage of IL-1β represents a promising approach to revert the COVID-19-induced cytokine storm. Full article
Show Figures

Figure 1

19 pages, 1557 KiB  
Systematic Review
Histopathological Features of SARS-CoV-2 in Extrapulmonary Organ Infection: A Systematic Review of Literature
by Diana Torge, Sara Bernardi, Mauro Arcangeli and Serena Bianchi
Pathogens 2022, 11(8), 867; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11080867 - 31 Jul 2022
Cited by 23 | Viewed by 2304
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health concern responsible for the ongoing pandemic. Histopathological pieces of evidence on COVID-19 are not fully investigated. This review aims to provide, through microscopy investigations, a histopathological overview of COVID-19 structural and ultrastructural [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health concern responsible for the ongoing pandemic. Histopathological pieces of evidence on COVID-19 are not fully investigated. This review aims to provide, through microscopy investigations, a histopathological overview of COVID-19 structural and ultrastructural alterations in different organs and tissues, excluding the respiratory system. The authors systematically reviewed the literature over the period February 2020–July 2022. Selected databases were PubMed, Scopus, and Google Scholar. The search strategy included the following terms: “COVID-19” or SARS-CoV-2 and “histopathology” or “pathology”; and “microscopy” and “liver”, “myocardium”,” spleen”, “testis”, and “placenta”. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Thirty-one articles included in this systematic review demonstrated, at a histopathological level, that COVID-19 exerts detrimental effects on tissues, often promoting degenerative processes. Even if COVID-19 shows a histopathological tropism for the respiratory system, other tissues, from cardiovascular to reproductive, are affected by COVID-19. Therefore, this paper provides an up-to-date view of histopathological observations of the structural and ultrastructural alterations associated with COVID-19 and may contribute to a better knowledge of the physiopathological bases of this disease. Full article
Show Figures

Figure 1

10 pages, 1800 KiB  
Brief Report
A Plausible Link of TMPRSS2/ACE2/AR Signaling to Male Mortality during the COVID-19 Pandemic in the United States
by Lilly M. Wong and Guochun Jiang
Pathogens 2021, 10(11), 1378; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10111378 - 26 Oct 2021
Cited by 3 | Viewed by 2360
Abstract
The COVID-19 pandemic continues around the world, where the United States is among the worst in terms of both morbidity and fatality of the viral infection. We aim to investigate the plausible link of tissue SARS-CoV-2 viral entry gene expression, such as TMPRSS2 [...] Read more.
The COVID-19 pandemic continues around the world, where the United States is among the worst in terms of both morbidity and fatality of the viral infection. We aim to investigate the plausible link of tissue SARS-CoV-2 viral entry gene expression, such as TMPRSS2 and ACE2, with infection and death by gender during the COVID-19 pandemic in the United States. We find a significantly higher incidence of COVID-19 death in men than in women, even though SARS-CoV-2 infection in women is higher than in men. We discover that the expression of TMPRSS2 and ACE2 in intestine, but not in lung, tends to be positively associated with the incidence of SARS-CoV-2 infection in men. In contrast, the high incidence of death in men is negatively correlated with TMPRSS2/ACE2 expression in intestine. Strikingly, the correlation of TMPRSS2/ACE2 expression with SARS-CoV-2 infection and death is the opposite in females, compared with that in males. Interestingly, male hormone signaling seems to be involved in mortality, as the low expression of testosterone receptor AR in the prostate contributes to death in men according to age. These observations point to a plausible contribution of male hormone metabolism in the regulation of TMPRSS2/ACE2 signaling to fatality by SARS-CoV-2 infection in men. Full article
Show Figures

Figure 1

13 pages, 412 KiB  
Systematic Review
Description and Analysis of Cytokine Storm in Registered COVID-19 Clinical Trials: A Systematic Review
by Khalid Eljaaly, Husam Malibary, Shaimaa Alsulami, Muradi Albanji, Mazen Badawi and Jaffar A. Al-Tawfiq
Pathogens 2021, 10(6), 692; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10060692 - 02 Jun 2021
Cited by 9 | Viewed by 3201
Abstract
The purpose of this systematic review was to describe the characteristics of clinical trials that focused on COVID-19 patients with cytokine release syndrome (CRS) and the variability in CRS definitions. Two authors independently searched three clinical trial registries and included interventional clinical trials [...] Read more.
The purpose of this systematic review was to describe the characteristics of clinical trials that focused on COVID-19 patients with cytokine release syndrome (CRS) and the variability in CRS definitions. Two authors independently searched three clinical trial registries and included interventional clinical trials on COVID-19 hospitalized patients that required at least one elevated inflammatory biomarker. Relevant data, including the type and cutoff of the measured biomarker, oxygen/respiratory criteria, fever, radiologic criteria, and medications, were summarized. A total of 47 clinical trials were included. The included studies considered the following criteria: oxygen/respiratory criteria in 42 trials (89%), radiologic criteria in 29 trials (62%), and fever in 6 trials (18%). Serum ferritin was measured in 35 trials (74%), CRP in 34 trials (72%), D-dimer in 26 trials (55%), LDH in 24 trials (51%), lymphocyte count in 14 trials (30%), and IL-6 in 8 trials (17%). The cutoff values were variable for the included biomarkers. The most commonly used medications were tocilizumab, in 15 trials (32%), and anakinra in 10 trials (24.4%). This systematic review found high variability in CRS definitions and associated biomarker cutoff values in COVID-19 clinical trials. We call for a standardized definition of CRS, especially in COVID-19 patients. Full article
Show Figures

Figure 1

Back to TopTop