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Research Article | DOI: https://doi.org/10.31579/2690-1897/189
1Specialist of Internal Medicine, MD, Turkey.
2Manager of Writing and Statistics, Turkey.
3Assistant Professor of Radiology, MD, Turkey.
4Middle-East Academy for Medicine of Aging, MD, Lebanon.
5Medi-WORLD International, Australia.
*Corresponding Author: 10.31579/2690-1897/189
Citation: Mehmet R. Helvaci, Saziye Cayir, Hulya Halici, Alper Sevinc, Celaletdin Camci. et al, (2024), Acute chest syndrome and coronavirus disease may be genetically determined exaggerated immune response syndromes in capillaries all over the body, J, Surgical Case Reports and Images, 7(4); DOI:10.31579/2690-1897/189
Copyright: © 2024, Nonso Mbah. 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: 18 April 2024 | Accepted: 06 May 2024 | Published: 14 May 2024
Keywords: acute chest syndrome; coronavirus disease; sickle cell diseases; exaggerated immune response syndromes; capillary endothelial inflammation; capillary endothelial edema; disseminated tissue hypoxia
Background: Sickle cell diseases (SCD) are severe inflammatory processes mainly on capillaries as the main distributors of hardened red blood cells (RBC) into the tissues. Moderate and severe coronavirus disease (COVID-19) may also be a genetically determined exaggerated inflammatory process on capillary endothelium all over the body terminating with high mortality rates in some families.
Methods: All patients with the SCD were studied.
Results: The study included 222 males and 212 females with similar mean ages (30.8 versus 30.3 years, p>0.05). Smoking (p<0.001), alcohol (p<0.001), disseminated teeth losses (p<0.001), ileus (p<0.001), cirrhosis (p<0.001), leg ulcers (p<0.001), digital clubbing (p<0.001), coronary heart disease (CHD) (p<0.05), chronic renal disease (CRD) (p<0.05), chronic obstructive pulmonary disease (COPD) (p<0.001), and stroke (p<0.05) were all higher but not acute chest syndrome (ACS) in males (p>0.05).
Conclusion: Although smoking, alcohol, disseminated teeth losses, ileus, cirrhosis, leg ulcers, digital clubbing, CHD, CRD, COPD, and stroke-like atherosclerotic risk factors or end-points were all higher in males, prevalences of ACS were similar in both genders. Although ACS and moderate and severe COVID-19 mainly affect the respiratory tract, they may be genetically determined exaggerated immune response syndromes on capillary endothelium all over the body, and immunomodulatory drugs including dexamethasone should take the major role in the treatment of moderate and severe COVID-19 and just after the RBC support in the ACS.
Chronic endothelial damage may be the major cause of aging by causing end-organ insufficiencies in human body [1]. Much higher blood pressures (BP) of the afferent vasculature may be the main accelerating factor by causing recurrent injuries on vascular endothelium. Probably, all afferent vasculature including capillaries are mainly involved in the process. Thus the term of venosclerosis is not as famous as atherosclerosis in the literature. Because of the chronic endothelial damage, inflammation, edema, and fibrosis, vascular walls thicken, their lumens narrow, and they lose their elastic natures, those eventually reduce blood supply to the terminal organs, and increase systolic and decrease diastolic BP further. Some of the well-known accelerating factors of the inflammatory process are physical inactivity, sedentary lifestyle, excess weight, animal-rich diet, smoking, alcohol, chronic inflammations, prolonged infections, and cancers for the development of terminal consequences such as obesity, hypertension (HT), diabetes mellitus (DM), cirrhosis, peripheric artery disease (PAD), chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), chronic renal disease (CRD), mesenteric ischemia, osteoporosis, stroke, dementia, other end-organ insufficiencies, aging, and death [2, 3]. Although early withdrawal of the accelerating factors can delay terminal consequences, after development of HT, DM, cirrhosis, COPD, CRD, CHD, PAD, mesenteric ischemia, osteoporosis, stroke, dementia, other end-organ insufficiencies, and aging, endothelial changes can not be reversed completely due to their fibrotic natures. The accelerating factors and terminal consequences are researched under the titles of metabolic syndrome, aging syndrome, or accelerated endothelial damage syndrome in the literature, extensively [4-6]. On the other hand, sickle cell diseases (SCD) are chronic inflammatory process on vascular endothelium, initiated at birth and terminated with accelerated atherosclerosis induced end-organ failures in early years of life [7, 8]. Hemoglobin S causes loss of elastic and biconcave disc shaped structures of red blood cells (RBC). Probably loss of elasticity instead of shape is the main problem since sickling is rare in peripheric blood samples of the patients with associated thalassemia minors, and human survival is not affected in hereditary spherocytosis or elliptocytosis. Loss of elasticity is present during whole lifespan, but exaggerated with inflammations, infections, and emotional stress in the body. The hardened RBC induced chronic endothelial damage, inflammation, edema, and fibrosis terminate with disseminated tissue hypoxia all over the body [9]. As a difference from other causes of chronic endothelial damage, the SCD may keep vascular endothelium particularly at the capillaries which are the main distributors of the hardened RBC into the tissues [10, 11]. The hardened cells induced chronic endothelial damage builds up an advanced atherosclerosis in early years of life. Vascular narrowing and occlusions induced tissue ischemia and infarctions are the final consequences of the SCD, so the mean life expectancy is decreased by 25 to 30 years in them [8]. Similarly, moderate and severe coronavirus disease (COVID-19) may actually be a genetically determined exaggerated and disseminated inflammatory process on capillary endothelium all over the body terminating with high mortality rates in some families.
The study was performed in Medical Faculty of the Mustafa Kemal University between March 2007 and June 2016. All patients with the SCD were studied. The SCD were diagnosed with the hemoglobin electrophoresis performed via high performance liquid chromatography (HPLC). Medical histories including smoking, alcohol, painful crises per year, transfused units of RBC in their lives, leg ulcers, stroke, surgical operations, deep venous thrombosis (DVT), epilepsy, and priapism were learnt. Patients with a history of one pack-year were accepted as smokers, and one drink-year were accepted as drinkers. A complete physical examination was performed by the Same Internist, and patients with disseminated teeth losses (<20>1.0, and with the presence of Schamroth’s sign [17, 18]. An exercise electrocardiogram is performed in cases with an abnormal electrocardiogram and/or angina pectoris. Coronary angiography is taken for the exercise electrocardiogram positive cases. So CHD was diagnosed either angiographically or with the Doppler echocardiographic findings as the movement disorders in the cardiac walls. Rheumatic heart disease is diagnosed with the echocardiographic findings, too. Stroke is diagnosed by the CT of brain. Sickle cell retinopathy is diagnosed with ophthalmologic examination in patients with visual complaints. Eventually, mean age, associated thalassemia minors, smoking, alcohol, painful crises per year, transfused units of RBC in their lives, disseminated teeth losses, COPD, ileus, cirrhosis, leg ulcers, digital clubbing, CHD, CRD, stroke, PHT, autosplenectomy, DVT and/or varices and/or telangiectasias, rheumatic heart disease, avascular necrosis of bones, sickle cell retinopathy, epilepsy, ACS, mortality, and mean age of mortality were detected in both genders, and compared in between. Mann-Whitney U test, Independent-Samples t test, and comparison of proportions were used as the methods of statistical analyses.
The study included 434 patients with the SCD (222 males and 212 females). Mean ages of the patients were similar in males and females (30.8 versus 30.3 years, p>0.05, respectively). Prevalences of associated thalassemia minors were similar in both genders, too (72.5% versus 67.9%, p>0.05, respectively). Smoking (23.8% versus 6.1%) and alcohol (4.9% versus 0.4%) were higher in males, significantly (p<0>Table 1).
| Variables | Male patients with SCD* | p-value | Female patients with SCD |
| Prevalence | 51.1% (222) | Ns† | 48.8% (212) |
| Mean age (year) | 30.8 ± 10.0 (5-58) | Ns | 30.3 ± 9.9 (8-59) |
| Associated thalassemia minors | 72.5% (161) | Ns | 67.9% (144) |
| Smoking | 23.8% (53) | <0> | 6.1% (13) |
| Alcoholism | 4.9% (11) | <0> | 0.4% (1) |
*Sickle cell diseases †Nonsignificant (p>0.05)
Table 1: Characteristic features of the study cases
Similarly, transfused units of RBC in their lives (48.1 versus 28.5, p=0.000), disseminated teeth losses (5.4% versus 1.4%, p<0>p<0>p<0>p<0>p<0>p<0>p<0>p<0>p<0>p>0.05), PHT (12.6% versus 11.7, p>0.05), and DVT and/or varices and/or telangiectasias were similar in both genders (9.0% versus 6.6%, p>0.05), significantly (Table 2).
| Variables | Male patients with SCD* | p-value | Female patients with SCD |
| Painful crises per year | 5.0 ± 7.1 (0-36) | Ns† | 4.9 ± 8.6 (0-52) |
| Transfused units of RBC‡ | 48.1 ± 61.8 (0-434) | 0.000 | 28.5 ± 35.8 (0-206) |
| Disseminated teeth losses (<20> | 5.4% (12) | <0> | 1.4% (3) |
| COPD§ | 25.2% (56) | <0> | 7.0% (15) |
| Ileus | 7.2% (16) | <0> | 1.4% (3) |
| Cirrhosis | 8.1% (18) | <0> | 1.8% (4) |
| Leg ulcers | 19.8% (44) | <0> | 7.0% (15) |
| Digital clubbing | 14.8% (33) | <0> | 6.6% (14) |
| CHD¶ | 18.0% (40) | <0> | 13.2% (28) |
| CRD** | 9.9% (22) | <0> | 6.1% (13) |
| Stroke | 12.1% (27) | <0> | 7.5% (16) |
| PHT*** | 12.6% (28) | Ns | 11.7% (25) |
| Autosplenectomy | 50.4% (112) | Ns | 53.3% (113) |
| DVT**** and/or varices and/or telangiectasias | 9.0% (20) | Ns | 6.6% (14) |
| Rheumatic heart disease | 6.7% (15) | Ns | 5.6% (12) |
| Avascular necrosis of bones | 24.3% (54) | Ns | 25.4% (54) |
| Sickle cell retinopathy | 0.9% (2) | Ns | 0.9% (2) |
| Epilepsy | 2.7% (6) | Ns | 2.3% (5) |
| ACS***** | 2.7% (6) | Ns | 3.7% (8) |
| Mortality | 7.6% (17) | Ns | 6.6% (14) |
| Mean age of mortality (year) | 30.2 ± 8.4 (19-50) | Ns | 33.3 ± 9.2 (19-47) |
*Sickle cell diseases †Nonsignificant (p>0.05) ‡Red blood cells §Chronic obstructive pulmonary disease ¶Coronary heart disease **Chronic renal disease ***Pulmonary hypertension ****Deep venous thrombosis *****Acute chest syndrome
Table 2: Associated pathologies of the study cases
Beside that mean ages of all of the terminal consequences were detected (Table 3).
| Variables | Mean age (year) |
| Ileus | 29.8 ± 9.8 (18-53) |
| Hepatomegaly | 30.2 ± 9.5 (5-59) |
| ACS* | 30.3 ± 10.0 (5-59) |
| Sickle cell retinopathy | 31.5 ± 10.8 (21-46) |
| Rheumatic heart disease | 31.9 ± 8.4 (20-49) |
| Autosplenectomy | 32.5 ± 9.5 (15-59) |
| Disseminated teeth losses (<20> | 32.6 ± 12.7 (11-58) |
| Avascular necrosis of bones | 32.8 ± 9.8 (13-58) |
| Epilepsy | 33.2 ± 11.6 (18-54) |
| Priapism | 33.4 ± 7.9 (18-51) |
| Left lobe hypertrophy of the liver | 33.4 ± 10.7 (19-56) |
| Stroke | 33.5 ± 11.9 (9-58) |
| COPD† | 33.6 ± 9.2 (13-58) |
| PHT‡ | 34.0 ± 10.0 (18-56) |
| Leg ulcers | 35.3 ± 8.8 (17-58) |
| Digital clubbing | 35.4 ± 10.7 (18-56) |
| CHD§ | 35.7 ± 10.8 (17-59) |
| DVT¶ and/or varices and/or telangiectasias | 37.0 ± 8.4 (17-50) |
| Cirrhosis | 37.0 ± 11.5 (19-56) |
| CRD** | 39.4 ± 9.7 (19-59) |
*Acute chest syndrome †Chronic obstructive pulmonary disease ‡Pulmonary hypertension §Coronary heart disease ¶Deep venous thrombosis **Chronic renal disease
Table 3: Mean ages of the consequences of the sickle cell diseases
ACS is a significant cause of mortality in the SCD (19). It occurs most often as a single episode, and a past history is associated with a high mortality rate [19]. Similarly, all of 14 cases with the ACS had just a single episode, and two of them were fatal in spite of the rigorous RBC and ventilation supports and antibiotic therapy in the present study. The remaining 12 patients are still alive without a recurrence at the end of the ten-year follow up period. ACS is the most common between the ages of 2 to 4 years, and its incidence decreases with aging [20]. As a difference from atherosclerotic consequences, the incidence of ACS did not show an increase with aging in the present study, too, and the mean ages of the ACS and SCD were similar (30.3 and 30.5 years, p>0.05, respectively). The decreased incidence with aging may be due to the high mortality rate during the first episode and/or an acquired immunity against various antigens, and/or decreased strength of immune system. Probably, ACS shows an inborn severity of the SCD, and the incidence of ACS is higher in severe cases such as cases with the SCA or higher white blood cells (WBC) counts [19, 20]. According to our experiences, the increased metabolic rate during infections accelerates sickling, thrombocytosis, leukocytosis, and capillary endothelial damage, and terminates with end-organ insufficiencies. Although ACS may be thought as a collapse of the lungs during such infections, all capillary systems of the body may probably be involved in the process, and an exaggerated and diffuse immune response syndrome against some infectious pathogens and abnormal RBC may be the cause of diffuse capillary endothelial damage, inflammation, and edema all over the body, and may even terminate with a sudden stroke or myocardial infarction. A preliminary result from the Multi-Institutional Study of Hydroxyurea in the SCD indicating a significant reduction of episodes of ACS with hydroxyurea therapy suggests that a considerable number of episodes are exaggerated with the increased numbers of WBC and platelets (PLT) [21]. Similarly, we strongly recommend hydroxyurea therapy for all patients with the SCD that may also be the cause of the low incidence of ACS among our follow up cases (2.7% in males and 3.7% in females). Although the ACS did not show an infectious etiology in 66% of cases [19, 20], and 12 of 27 cases with ACS had evidence of fat embolism in the other study [22], and some authors indicated that antibiotics do not shorten the clinical course [23], some viral causes as in the COVID-19 may actually take role here, and the main cause of the exaggerated and diffuse immune response syndrome may be such viruses, and the anti-inflammatory and immunomodulatory drugs including dexamethasone may be important just after the RBC support in the treatment of ACS. On the other hand, RBC support must be given early in the course of ACS since it has also prophylactic benefit. RBC support has the obvious benefits of decreasing sickle cell concentration directly, and suppressing bone marrow for the production of abnormal RBC and excessive WBC and PLT. So they prevent further sickling and the exaggerated immune response induced endothelial damage, not in the lungs alone instead all over the body. According to our experiences, simple and repeated transfusions are superior to RBC exchange [24, 25]. First of all, preparation of one or two units of RBC suspensions in each time rather than preparation of six units or more provides time to doctors to prepare more units by preventing sudden death of such high-risk patients. Secondly, transfusions of one or two units of RBC suspensions in each time decrease the severity of pain, and relax anxiety of the patients and their surroundings, since RBC transfusions probably have the strongest analgesic effects during the severe painful crises. Actually, the decreased severity of pain by transfusions may also indicate the decreased inflammation all over the body. Thirdly, transfusions of lesser units of RBC suspensions in each time by means of the simple transfusions will decrease transfusion-related complications such as infections, iron overload, and blood group mismatch in the future. Fourthly, transfusion of RBC suspensions in the secondary health centers may prevent some deaths developed during the transport to the tertiary centers for the exchange. Finally, cost of the simple and repeated transfusions on insurance system is much lower than the exchange that needs trained staff and additional devices. COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. Most patients experience mild to moderate respiratory disease, and recover without a need for special treatment. However, some patients become seriously ill. Older individuals and those with underlying diseases such as SCD, HT, DM, PAD, COPD, CHD, CRD, cirrhosis, stroke, rheumatological disorders, or cancers are more likely to develop serious illness. But actually everybody can get the disease with COVID-19 and become seriously ill or die at any age even in the absence of the predisposing factors. Genetic susceptibility may be one of the major risk factors to have the severe form of the disease since the COVID-19 mortality rates may be much higher in some families. As in the ACS and rheumatic disorders, a genetically determined exaggerated and disseminated immune response syndrome against the virus in capillaries all over the body may be the major underlying cause of the severity of the COVID-19. As in the ACS, the disease probably keeps whole body circulation but the respiratory capillaries are mainly involved due to the highest viral load in them. This mechanism may explain the pathophysiology of the ACS, and there may be a superimposed viral infection keeping the respiratory system in the ACS, too. On the other hand, the respiratory tract may have the most sensitive capillaries against the immune damage in the body. The highest prevalences of lung cancers in both genders among all of the other cancers may also support the hypothesis. So both of the ACS and severe COVID-19 may prominently be a vasculitis, and both of them actually keep the whole body capillary systems. Disseminated capillary inflammation and edema may accelerate tissue hypoxia, and a sudden stroke or myocardial infarction may actually be the terminal drop in both pathologies. Therefore, anti-inflammatory and immunomodulatory drugs including dexamethasone probably should take the major role in the treatment. On the other hand, since the virus is changing its genetic codes continuously, probably all people will get the disease several times with different severity in their lives. Thus the chance of getting a severe form of the disease is always present for all individuals in the world. PHT is a condition of increased BP within the arteries of the lungs. Shortness of breath, fatigue, chest pain, palpitation, swelling of legs and ankles, and cyanosis are common symptoms of PHT. Actually, it is not a diagnosis itself, instead solely a hemodynamic state characterized by resting mean pulmonary artery pressure of ≥25 mmHg. An increase in pulmonary artery systolic pressure, estimated noninvasively by the echocardiography, helps to identify patients with PHT [26]. The cause is often unknown. The underlying mechanism typically involves inflammation, fibrosis, and subsequent remodelling of the arteries. PHT affects about 1% of the world population, and its prevalence may reach 10
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Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
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.
