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Review Article | DOI: https://doi.org/10.31579/2690-8816/028
Department of Clinical and Interventional Cardiology, Lilavati Hospital and Research Center, Mumbai, India.
*Corresponding Author: Charan Reddy Kudumula, Department of Clinical and Interventional Cardiology, Lilavati Hospital and Research Center, Mumbai, India
Citation: Charan R. Kudumula, (2020). Impact of COSARS-Cov-2 on Cardio-Pulmonary-Immune Signatures: A Review of Recent Developments with a Look toward the Future. J Clinical Research Notes, 1(4); DOI:10.31579/2690-8816/028
Copyright: © 2020 Charan Reddy Kudumula. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 30 September 2020 | Accepted: 12 October 2020 | Published: 14 October 2020
Keywords: novel coronavirus; SARS-CoV-2; n CoV-2019; immunity; severe acute respiratory syndrome; middle east respiratory syndrome
In December 2019, the first case of patient with severe acute respiratory syndrome (SARS) caused by the novel coronavirus, SARS-CoV-2, was reported in Wuhan, Hubei Province, Central China. SARS-CoV-2 causes CoronaVirus Disease-2019 (COVID-19 or nCoV-19) disease, which rapidly spread all over the world. In response to this serious situation, on 30 January 2020, the World Health Organization (WHO) declared a global public health emergency of international concern, putting all health organizations on high alert. In mid-March 2020, WHO declared nCoV-19 a pandemic. By the end of September 2020, there were ~33.67 million confirmed cases and ~10.08 lakh deaths worldwide and the trend rising on each passing day. SARS-CoV-2 mainly infects the pulmonary system, but cause damage to other organs such as heart, kidney and intestine. Understanding the cardio-pulmonary issues underpinning of nCOV-19 pathogenesis is key to managing outcomes and mortality. SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease inhibitor TMPRSS2 for S protein priming. Alveolar cells and cardiomyocytes express ACE2 and TMPRSS2. In this Review, we summarize the current understanding of nCOV-19 pandemic from basic mechanisms to clinical perspectives, focusing on the interaction between SARS-CoV-2 and the cardio-pulmonary-immune signatures. The study provides crucial insights into the first step of SARS-CoV-2 infection, and potential targets for antiviral intervention.
History of SARS-CoV-2
Coronaviruses (CoVs) have been identified as human pathogens since early 1960. CoVs belong to the subfamily Orthocoronavirinae in the family Coronaviridae, order Nidovirales. There are four genera within the subfamily Orthocoronavirinae, namely α-coronavirus (α-CoV), β-coronavirus (β-CoV), γ-coronavirus (γ-CoV) and δ-coronavirus (δ-CoV) [1]. Both α-and β-CoV genera are known to infect mammals, whilst δ-and γ-CoVs infect birds [2].
In the 21st century, two highly infectious β-CoVs, such as severe acute respiratory syndrome-coronavirus (SARS-CoV) was first reported in Guangdong province, China in 2002; and Middle East respiratory syndrome-coronavirus (MERS-CoV) first emerged in Saudi Arabia in 2012, subsequently spread to 32 countries [3-6]. SARS-CoV was mainly found in natural reservoir host, horseshoe bats (Rhinolophus affinis) and cause disease outbreak [7, 8]. Human transmission for SARS-CoV was facilitated by intermediate host like palm civet cats (Paguma larvata) and raccoon dogs (Nyctereutes procyonoides), which are frequently sold as food sources in Huanan seafood market, China [9, 10]. For MERS-CoV dromedary camels (Camelus dromedarius) are the reservoir host for human infections.
Etiology of nCoV-19 pandemic
In December 2019, a number of patients with pneumonia of unknown etiology emerged in Wuhan City, Hubei Province, Central China. Based on phylogeny, taxonomy, genome sequencing, and established practices of viruses, on February 11th, 2020, the Coronavirus Study Group (CSG) of international committee designated this novel virus as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) previously known as 2019 novel coronavirus. [11]. On February 12, 2020, World Health Organization (WHO) named the SARS-CoV-2 infection as a novel coronavirus disease-2019 (novel COVID-19) or nCoV-19. Considering the global threat, on January 30, 2020 the WHO has declared nCoV-19 pandemic a public health emergency of international concern (PHEIC).
It has been nine months since health officials reported spread of mysterious invisible SARS-CoV-2 infection in China. Infection quickly spread over 213 countries and territories around the world and 2 international conveyances. The nCOV-19 pandemic is changing our lives in unprecedented ways. At the time of publication of this article (end of September, 2020), based on the WHO epidemiological situation report [12], globally nCoV-19 pandemic has led to ~33.67 million cases and ~10.08 lakh deaths. Since there are no clinically approved safe and effective vaccines or specific therapeutic anti-viral options available for nCOV-19 treatment, most authorities implemented few unprecedented measures to combat the viral transmission. These include the suspension of public transportation, locked down, mask wearing and social distancing.
Genome structure of SARS-CoV-2
The SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA genome named for its solar corona like appearance [13]. Their helical symmetry nucleocapsid is 26-32 kb in size, making it the largest investigated genome among RNA viruses [14]. Like other CoVs, SARS-CoV-2 particles are spherical and have 9-12 nm long special glycoproteins called a “spike” (peplomer) protruding from their surface. The outside of the viral particle is comprised of four main proteins: spike (S), envelope (E), membrane (M), and hemagglutinin esterase (HE) (Fig 1). Inside the viral particle, the viral RNA is encased in a shell made of the nucleocapsid (N) protein. Notably, there are also 16 nonstructural proteins and 5-8 accessory proteins.
SARS-CoV-2, the virus that causes nCOV -19 diseases, shares many biological features with SARS-CoV. A full-length genome sequence SARS-CoV-2 share 80% nucleotides (nt) sequence identity to SARS-CoVs and ~50% to MERS-CoVs. The SARS-CoV-2 sequence is 96% identical at the whole-genome level to a horseshoe bat coronavirus isolate RaTG13 and 88% identical to two bat-derived SARS-CoVs (bat-SL-CoVZC45 and bat-SL-CoVZXC21) [15].
Recent studies have shown that like α-CoVs, the spikes of SARS-CoV-2 latch onto cell surface, then undergo a structural modification that mediates fusion between the envelope and host cell membranes[16,17] via a metallopeptidase like angiotensin-converting enzyme-2 (ACE2) thereby produce more copies of viral particles [18]. SARS-CoV-2 primarily infects ciliated bronchial epithelial cells, type II pneumocytes and cardiomyocytes [15]. Therefore, the presence of such receptors and S protein primer proteases in these cells is a key determinant of SARS-CoV-2 infection.
Human SARS-CoV-2 has a unique furin-like cleavage site, ”RRAR motif” in the spike protein, which is not found in CoVs isolated from pangolins, indicating this virus may not have originated directly from pangolins [19]. The ACE2 abundantly express furin as well as endosomal protease, cathepsin-B (CTS-B). The main host protease that mediates S protein priming and initiates viral entry is the Type II transmembrane serine protease, TMPRSS2 [20]. Besides TMPRSS2, endosomal protease cathepsin-L (CTS-L) also enhances SARS-CoV-2 entry into host alveolar cells and cardiomyocytes [20]. This observation was supported by the fact that, cathepsin B/L involved in vascular remodeling and cardiovascular diseases [21].
For this study, we searched Pubmed, Medline, Embase databases, preprint reports on bioRxiv or medRxiv up to 30 September 2020 utilizing combinations of word variants for coronavirus or nCOV-19, immune signatures, cardiovascular and respiratory system, severe acute respiratory syndrome or SARS-COV-2. In the last century, the world population has witnessed several assaults from RNA viruses, causing millions of deaths. The 21st century is no longer an exception, with the trend continued with significant fear of SARS-COV first appeared in 2002 and rapidly spread to 32 countries and regions. Subsequently the world experienced the outbreak of novel influenza virus in 2009 and MERS-CoV in 2012. In December 2019, a newly emerged pneumonia-associated respiratory syndrome caused by SARS-CoV-2, spread quickly causing significant human loss globally. Based on the WHO global epidemiological situation report [12], currently the 10 most affected countries in the world are: USA, India, Brazil, Argentina, Spain, France, Russia, Colombia, UK and Peru. The first case of nCOV-19 in US was reported on 1/22/2020. Since then, the country has reported ~71.91 lakh cases, and 205,998 deaths, where as in India, the first case of nCOV-19 in was reported on 1/30/2020. Since then, the country has reported ~62.25 lakh cases, and 97,497 deaths.
Impact of SARS-CoV-2 on immune signatures
SARS-CoV-2 infection does not go unnoticed by the immune system. IgM is the first type of antibody appeared in the humoral immune response when a person is infected by SARS-CoV-2. Seropositive of IgM indicates a recent infection so it can be used for early diagnosis of acute phase infections with SARS-CoV-2 [22].Within days to weeks, the short-lived, low-affinity IgM antibodies are converted to long-lived, high-affinity IgG and IgA antibodies. IgG antibodies are especially high in blood, whereas IgA antibodies are high at mucosal surfaces and in secretions. A study by Guo et al [23] involving 208 nCOV-19 patients revealed IgM and IgA antibodies first detected within 3-6 days whereas IgG antibodies detected 10-18 days after symptom onset.
ACE2 expressed in the lung besides heart, kidney, immune cells and intestine [24]. ACE2 is a potential target for SARS-CoV-2 infection, and increased ACE2 expression induced by angiotensin converting enzyme inhibitors (ACEI) / angiotensin-receptor blockers (ARB) would aggravate lung injury in SARS-CoV-2 infected patients [25]. Similar to MERS-CoV and SARS-CoV, the first immune signatures potentially infected by SARS-CoV-2 are type II pneumocytes [19]. Helper T cells are important in the adaptive immune response because they help activate B cells, phagocytes, and killer T cells to target or kill infected cells. Few studies showed that patients who had recovered from SARS-CoV-2 infection carried helper T cells that recognized the S protein [26, 27]. Diao et al [28] reported that total numbers of T-cells (CD4+ T-cells and CD8+ T-cells) are decreased in patients with SARS-CoV-2 infection, and the surviving T-cells are functionally deranged, suggested an altered function of immune signatures in these patients. Thus, immune cells are not only the entry sites for SARS-CoV-2 infection, but they also possess the cellular machinery to mount an inflammatory response toward an infection. ACE2 is a potential target for SARS-CoV-2 infection, and increased ACE2 expression induced by angiotensin converting enzyme inhibitors (ACEI) / angiotensin-receptor blockers (ARB) would aggravate lung injury of patients with SARS-CoV-2 infection.
Furthermore, certain immune related genes such as human leukocyte antigen (HLA) involved in recognizing pathogens, vary from person to person. The individual HLA, haplotype, and genotype variability likely influence how well the immune system recognizes SARS-CoV-2 infection. Poor recognition of immune system could cause a person to be more vulnerable to the virus [29]. Following the development of a vaccine against SARS-Cov-2, individuals with high-risk HLA types may be prioritized for vaccination. It is interesting to study how the variation in HLA affects patients susceptible to SARS-Cov-2 infection. Probably, individual genetic variation may explain differences in the strength of immune responses. This could help identify individuals at higher risk from the SARS-Cov-2 infection.
Cytokine Storm
Upon entry into alveolar epithelial cells, SARS-CoV-2 replicates rapidly and triggers a strong immune response, resulting in cytokine storm [16]. Immune cells then kill-off the infected alveolar cells in a bid to save them. But during a runaway SARS-CoV-2 infection, when the immune system dumps pro-inflammatory cytokines in excess (hypercytokinaemia) into the lungs, this culling becomes a free-for-all, instead of shooting at a target with a gun, cytokines act as missile launcher. That’s where the problem arises. When working properly, inflammatory process is tightly regulated and confined only to infected areas. But sometimes the immune system goes haywire and those cells kill anything in their way, including healthy cells.
Similar to the inflammatory cytokine profile in SARS-CoV and MERS-CoV, patients with SARS-CoV-2 also have increased plasma levels of TNF-α [30, 31]. Such an uncontrolled production of inflammatory cytokine is accompanied by infiltration of inflammatory monocytes/macrophages (IMM) into the lung that weakens blood vessels and causes fluid to seep through to the air sacs. From there things can take a sharp turn for the worse. The storm spills into circulatory system and creates systemic issues across multiple organs leading to the accumulation of excessive numbers of immune cells at the lung epithelium. In some of the most severe SARS-CoV-2 infected patients, the cytokine storm, combined with a diminished capacity to pump oxygen to the rest of the body, can result in pulmonary edema, acute cardiac, renal or hepatic injury and death [32]. These studies were supported by a recent study from Ziegler et al group [24], wherein the authors reported that ACE2 receptors are induced by interferon-γ, thereby amplifying the infectious cycle in the lungs.
Cardiac manifestation of SARS-CoV-2
Evidence about the effects of SARS-CoV-2 infection on the cardiovascular system is rapidly growing. The interaction between the viral spike (S) protein and ACE-2, which triggers entry of the virus into host cells, is likely to be involved in the cardiovascular manifestations of nCOV-19, and ~20% of all infection-associated deaths are from cardiac complications. Following SARS-CoV-2 infection, activated cardiomyocyte resident immune signatures sense invading viral pathogens/antigens. At the site of infection, activated virus-specific cytotoxic T lymphocytes-TCLs (e.g. CD8+ T-cell) produce chemokines and antiviral cytokines (e.g. IFN-γ and TNF-α). These cytokines inhibit viral replication and enhance antigen presentation and kill infected cells, while chemokines recruit more innate immune cells to control pathogen burden (Fig.2). Huang et al [30] high-lighted that in patients with SARS-Cov-2 infection, the imbalance of Th-1 and -2 responses resulted in a cytokine storm. The release of inflammatory cytokines after infection may cause various cardiac manifestation, which include reduction in coronary blood flow, decreases in oxygen supply, destabilization of coronary plaque, and micro thrombogenesis, cardiogenic shock, ST-elevation myocardial injury, viral myocarditis, lymphopaenia [30], arrhythmia-induced cardiomyopathy and venous thrombosis [33-35].
Initiation of immune response against SARS-CoV-2 begins with direct infection of lung alveolar epithelium. Following infection, lung resident immune cells acquire the invading pathogen or antigens from infected alveolar epithelial cells which enter into circulation and adversely influence heart function. The activated virus-specific effector T cells produce antiviral cytokines and chemokines. Cytokines regulate viral replication and enhance antigen presentation and kill infected alveolar cells. The chemokines produced by activated T cells recruit more immune cells to control pathogen load.
Patients with underlying cardiovascular comorbidities are more likely to suffer severe cardiac symptoms, which is associated with high mortality from SARS-CoV-2 infection. Ruan et al [36] claimed that total number of patients who died due to myocardial ischemia or heart failure (HF) with or without respiratory failure consists of 40% of all deaths. Another study indicated that the mortality rate in SARS-CoV-2 infected patients complicated with acute HF is considerably higher as compared to other risk factors, such as elderly, diabetes, chronic pulmonary diseases (CPD) and history of CVD [37]. In a study by Guo et al [23] revealed over 33% of nCOV-19 patients in the ICU have experience cardiomyopathy.
Role of SARS-CoV-2 associated molecules in cardio-pulmonary signatures
The range of human cells and tissues targeted by SARS-CoV-2, its potential receptors and associated regulating factors are still largely unknown. Cardiac ACE2 expression was strongest in pericytes and cardiomyocytes. The expression of the proteases encoded by TMPRSS2 and CTSL, which facilitate membrane fusion and viral uptake during SARS-CoV-2 infection, was very high in cardiomyocytes. The S protein of SARS-CoV-2 undergoes cleavage by a cell surface serine protease, TMPRSS2 [19]. Whether ACE2 and TMPRSS2 are required on the same cell to activate SARS-CoV-2 S protein to invade ACE2 expressing alveolar or cardiomyocytes is yet to be elucidated. However, as active S protein has a finite lifetime [38], its priming at alveolar or cardiomyocytes will make it effective for viral entry. Thus, we believe that for SARS-CoV-2, the ACE2 and TMPRSS2 co-expressing cells may have the highest infectivity. SARS-CoV-2
Beyond the canonical ACE2 and TMPRSS2 based entry, another receptor-CD147 (also known as basigin; encoded by BSG) has been shown to act as a receptor for SARS-CoV-2 in T cell lines and in cell lines of epithelial origin [39]. Presently, the mechanism by which BSG/CD147 mediates non-canonical mode of viral entry in alveolar cells or cardiomyocytes is unknown. In other cells, BSG/CD147 promotes entry of viruses by endocytosis [40]. It is possible that the same mechanism may be operative in the case of SARS-CoV-2.
Once the virus binds to its receptors on host alveolar cells or cardiomyocytes and gains entry, it utilizes a plethora of host genes for its replication. Post replication, most enveloped viruses complete their life-cycle by forming vesicles that bud from the plasma membrane via the cellular endosomal sorting complexes required for transport (ESCRT) machinery. It will be essential to determine how SARS-CoV-2 infection alters the temporal dynamics of host responses cardiomyocyte or alveolar resolution. Such studies would aid in developing rational strategies for management of SARS-CoV-2 infection.
Vaccines
Currently worldwide, there are several ongoing efforts for vaccine development against SARS-CoV-2 infection. WHO says 172 countries engaging with global vaccine plan against SARS-CoV-2? As per the WHO's latest draft landscape, over 110 vaccines are in different stages of development, and a dozen candidate vaccines for SARS-CoV-2 treatment are in the preclinical/clinical evaluation stage. Phase-I nCOV-19 vaccine, Moderna’s messenger RNA (mRNA) candidate (mRNA-127) induced rapid and strong immune responses against SARS-CoV-2 in patients older than 55 yrs. It induces CD4+ T-cells of the Th-1 phenotype 14 days after the second dose was given. Moderna is also studying mRNA-1273 in a NIAID-led Phase II trial (NCT04283461) designed to assess the safety, reactogenicity, and immunogenicity. The other closely watched vaccine, Oxford-AstraZeneca (SII-ChAdOx1 nCoV-19) prevents SARS-CoV-2 pneumonia. Russian President Vladimir Putin on 11 August 2020 announced that vaccine, Sputnik-V developed by Moscow-based Gamaleya Research Institute of Epidemiology and Microbiology had been registered as world first vaccine against nCOV-19 pandemic. Sinovac Biotech Ltd coronavirus vaccine candidate, CoronaVac was approved in July 2020 for emergency use as part of a programme in China to vaccinate high-risk groups. In real situation like this, developing a safe and effective vaccine against SARS-CoV-2 infection is still months away to become available over the counter for public use.
The COVID-19 pandemic, which has exhausted the momentum in China, is still in the exponential phase in the rest of the world. There is still much is unknown about nCoV-19 pandemic including what actually happens to the body when infected by this virus, and how long it can last for any period of time outside of the host. Till date, the association between SARS-CoV-2 infection and its progression has not been confirmed by animal experiments. To meet the urgent need for effective treatment and preventative strategies, global co-ordinate action by researchers is essential to deal health challenges the nCoV-19 pandemic poses to people. It is also important to share information on health technology developments vital to treat nCoV-19 patients. Lastly, strict regulations against the wildlife domestication and consumption should be implemented.
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The author declares no conflict of interest.
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Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
I would like to offer my testimony in the support. I have received through the peer review process and support the editorial office where they are to support young authors like me, encourage them to publish their work in your esteemed journals, and globalize and share knowledge globally. I really appreciate your journal, peer review, and editorial office.
Dear Agrippa Hilda- Editorial Coordinator of Journal of Neuroscience and Neurological Surgery, "The peer review process was very quick and of high quality, which can also be seen in the articles in the journal. The collaboration with the editorial office was very good."
I would like to express my sincere gratitude for the support and efficiency provided by the editorial office throughout the publication process of my article, “Delayed Vulvar Metastases from Rectal Carcinoma: A Case Report.” I greatly appreciate the assistance and guidance I received from your team, which made the entire process smooth and efficient. The peer review process was thorough and constructive, contributing to the overall quality of the final article. I am very grateful for the high level of professionalism and commitment shown by the editorial staff, and I look forward to maintaining a long-term collaboration with the International Journal of Clinical Case Reports and Reviews.
To Dear Erin Aust, I would like to express my heartfelt appreciation for the opportunity to have my work published in this esteemed journal. The entire publication process was smooth and well-organized, and I am extremely satisfied with the final result. The Editorial Team demonstrated the utmost professionalism, providing prompt and insightful feedback throughout the review process. Their clear communication and constructive suggestions were invaluable in enhancing my manuscript, and their meticulous attention to detail and dedication to quality are truly commendable. Additionally, the support from the Editorial Office was exceptional. From the initial submission to the final publication, I was guided through every step of the process with great care and professionalism. The team's responsiveness and assistance made the entire experience both easy and stress-free. I am also deeply impressed by the quality and reputation of the journal. It is an honor to have my research featured in such a respected publication, and I am confident that it will make a meaningful contribution to the field.
"I am grateful for the opportunity of contributing to [International Journal of Clinical Case Reports and Reviews] and for the rigorous review process that enhances the quality of research published in your esteemed journal. I sincerely appreciate the time and effort of your team who have dedicatedly helped me in improvising changes and modifying my manuscript. The insightful comments and constructive feedback provided have been invaluable in refining and strengthening my work".
I thank the ‘Journal of Clinical Research and Reports’ for accepting this article for publication. This is a rigorously peer reviewed journal which is on all major global scientific data bases. I note the review process was prompt, thorough and professionally critical. It gave us an insight into a number of important scientific/statistical issues. The review prompted us to review the relevant literature again and look at the limitations of the study. The peer reviewers were open, clear in the instructions and the editorial team was very prompt in their communication. This journal certainly publishes quality research articles. I would recommend the journal for any future publications.
Dear Jessica Magne, with gratitude for the joint work. Fast process of receiving and processing the submitted scientific materials in “Clinical Cardiology and Cardiovascular Interventions”. High level of competence of the editors with clear and correct recommendations and ideas for enriching the article.
We found the peer review process quick and positive in its input. The support from the editorial officer has been very agile, always with the intention of improving the article and taking into account our subsequent corrections.
My article, titled 'No Way Out of the Smartphone Epidemic Without Considering the Insights of Brain Research,' has been republished in the International Journal of Clinical Case Reports and Reviews. The review process was seamless and professional, with the editors being both friendly and supportive. I am deeply grateful for their efforts.
To Dear Erin Aust – Editorial Coordinator of Journal of General Medicine and Clinical Practice! I declare that I am absolutely satisfied with your work carried out with great competence in following the manuscript during the various stages from its receipt, during the revision process to the final acceptance for publication. Thank Prof. Elvira Farina
Dear Jessica, and the super professional team of the ‘Clinical Cardiology and Cardiovascular Interventions’ I am sincerely grateful to the coordinated work of the journal team for the no problem with the submission of my manuscript: “Cardiometabolic Disorders in A Pregnant Woman with Severe Preeclampsia on the Background of Morbid Obesity (Case Report).” The review process by 5 experts was fast, and the comments were professional, which made it more specific and academic, and the process of publication and presentation of the article was excellent. I recommend that my colleagues publish articles in this journal, and I am interested in further scientific cooperation. Sincerely and best wishes, Dr. Oleg Golyanovskiy.
Dear Ashley Rosa, Editorial Coordinator of the journal - Psychology and Mental Health Care. " The process of obtaining publication of my article in the Psychology and Mental Health Journal was positive in all areas. The peer review process resulted in a number of valuable comments, the editorial process was collaborative and timely, and the quality of this journal has been quickly noticed, resulting in alternative journals contacting me to publish with them." Warm regards, Susan Anne Smith, PhD. Australian Breastfeeding Association.
Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. I appreciate the journal (JCCI) editorial office support, the entire team leads were always ready to help, not only on technical front but also on thorough process. Also, I should thank dear reviewers’ attention to detail and creative approach to teach me and bring new insights by their comments. Surely, more discussions and introduction of other hemodynamic devices would provide better prevention and management of shock states. Your efforts and dedication in presenting educational materials in this journal are commendable. Best wishes from, Farahnaz Fallahian.
Dear Maria Emerson, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. I am delighted to have published our manuscript, "Acute Colonic Pseudo-Obstruction (ACPO): A rare but serious complication following caesarean section." I want to thank the editorial team, especially Maria Emerson, for their prompt review of the manuscript, quick responses to queries, and overall support. Yours sincerely Dr. Victor Olagundoye.
Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews. Many thanks for publishing this manuscript after I lost confidence the editors were most helpful, more than other journals Best wishes from, Susan Anne Smith, PhD. Australian Breastfeeding Association.
Dear Agrippa Hilda, Editorial Coordinator, Journal of Neuroscience and Neurological Surgery. The entire process including article submission, review, revision, and publication was extremely easy. The journal editor was prompt and helpful, and the reviewers contributed to the quality of the paper. Thank you so much! Eric Nussbaum, MD
Dr Hala Al Shaikh This is to acknowledge that the peer review process for the article ’ A Novel Gnrh1 Gene Mutation in Four Omani Male Siblings, Presentation and Management ’ sent to the International Journal of Clinical Case Reports and Reviews was quick and smooth. The editorial office was prompt with easy communication.
Dear Erin Aust, Editorial Coordinator, Journal of General Medicine and Clinical Practice. We are pleased to share our experience with the “Journal of General Medicine and Clinical Practice”, following the successful publication of our article. The peer review process was thorough and constructive, helping to improve the clarity and quality of the manuscript. We are especially thankful to Ms. Erin Aust, the Editorial Coordinator, for her prompt communication and continuous support throughout the process. Her professionalism ensured a smooth and efficient publication experience. The journal upholds high editorial standards, and we highly recommend it to fellow researchers seeking a credible platform for their work. Best wishes By, Dr. Rakhi Mishra.
Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. The peer review process of the journal of Clinical Cardiology and Cardiovascular Interventions was excellent and fast, as was the support of the editorial office and the quality of the journal. Kind regards Walter F. Riesen Prof. Dr. Dr. h.c. Walter F. Riesen.
Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. Thank you for publishing our article, Exploring Clozapine's Efficacy in Managing Aggression: A Multiple Single-Case Study in Forensic Psychiatry in the international journal of clinical case reports and reviews. We found the peer review process very professional and efficient. The comments were constructive, and the whole process was efficient. On behalf of the co-authors, I would like to thank you for publishing this article. With regards, Dr. Jelle R. Lettinga.
Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, I would like to express my deep admiration for the exceptional professionalism demonstrated by your journal. I am thoroughly impressed by the speed of the editorial process, the substantive and insightful reviews, and the meticulous preparation of the manuscript for publication. Additionally, I greatly appreciate the courteous and immediate responses from your editorial office to all my inquiries. Best Regards, Dariusz Ziora
Dear Chrystine Mejia, Editorial Coordinator, Journal of Neurodegeneration and Neurorehabilitation, Auctores Publishing LLC, We would like to thank the editorial team for the smooth and high-quality communication leading up to the publication of our article in the Journal of Neurodegeneration and Neurorehabilitation. The reviewers have extensive knowledge in the field, and their relevant questions helped to add value to our publication. Kind regards, Dr. Ravi Shrivastava.
Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, Auctores Publishing LLC, USA Office: +1-(302)-520-2644. I would like to express my sincere appreciation for the efficient and professional handling of my case report by the ‘Journal of Clinical Case Reports and Studies’. The peer review process was not only fast but also highly constructive—the reviewers’ comments were clear, relevant, and greatly helped me improve the quality and clarity of my manuscript. I also received excellent support from the editorial office throughout the process. Communication was smooth and timely, and I felt well guided at every stage, from submission to publication. The overall quality and rigor of the journal are truly commendable. I am pleased to have published my work with Journal of Clinical Case Reports and Studies, and I look forward to future opportunities for collaboration. Sincerely, Aline Tollet, UCLouvain.
Dear Ms. Mayra Duenas, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews. “The International Journal of Clinical Case Reports and Reviews represented the “ideal house” to share with the research community a first experience with the use of the Simeox device for speech rehabilitation. High scientific reputation and attractive website communication were first determinants for the selection of this Journal, and the following submission process exceeded expectations: fast but highly professional peer review, great support by the editorial office, elegant graphic layout. Exactly what a dynamic research team - also composed by allied professionals - needs!" From, Chiara Beccaluva, PT - Italy.
Dear Maria Emerson, Editorial Coordinator, we have deeply appreciated the professionalism demonstrated by the International Journal of Clinical Case Reports and Reviews. The reviewers have extensive knowledge of our field and have been very efficient and fast in supporting the process. I am really looking forward to further collaboration. Thanks. Best regards, Dr. Claudio Ligresti
Dear Chrystine Mejia, Editorial Coordinator, Journal of Neurodegeneration and Neurorehabilitation. “The peer review process was efficient and constructive, and the editorial office provided excellent communication and support throughout. The journal ensures scientific rigor and high editorial standards, while also offering a smooth and timely publication process. We sincerely appreciate the work of the editorial team in facilitating the dissemination of innovative approaches such as the Bonori Method.” Best regards, Dr. Matteo Bonori.
I recommend without hesitation submitting relevant papers on medical decision making to the International Journal of Clinical Case Reports and Reviews. I am very grateful to the editorial staff. Maria Emerson was a pleasure to communicate with. The time from submission to publication was an extremely short 3 weeks. The editorial staff submitted the paper to three reviewers. Two of the reviewers commented positively on the value of publishing the paper. The editorial staff quickly recognized the third reviewer’s comments as an unjust attempt to reject the paper. I revised the paper as recommended by the first two reviewers.
Dear Maria Emerson, Editorial Coordinator, Journal of Clinical Research and Reports. Thank you for publishing our case report: "Clinical Case of Effective Fetal Stem Cells Treatment in a Patient with Autism Spectrum Disorder" within the "Journal of Clinical Research and Reports" being submitted by the team of EmCell doctors from Kyiv, Ukraine. We much appreciate a professional and transparent peer-review process from Auctores. All research Doctors are so grateful to your Editorial Office and Auctores Publishing support! I amiably wish our article publication maintained a top quality of your International Scientific Journal. My best wishes for a prosperity of the Journal of Clinical Research and Reports. Hope our scientific relationship and cooperation will remain long lasting. Thank you very much indeed. Kind regards, Dr. Andriy Sinelnyk Cell Therapy Center EmCell
