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1.
Int Arch Allergy Immunol ; : 1-11, 2022 Oct 14.
Article in English | MEDLINE | ID: covidwho-2079118

ABSTRACT

INTRODUCTION: Cytokine storm and critical COVID-19 pneumonia are caused in at least 10% of patients by inborn errors of or auto-Abs to type I IFNs. The pathogenesis of life-threatening COVID-19 pneumonia in other patients remains unknown. METHODS: This study was conducted at Masih Daneshvari Hospital, Tehran, Iran. In the period of study, 75 confirmed cases of COVID-19 with presentations ranging from mild upper respiratory tract infection to lower respiratory tract infection, including moderate, severe, and critical disease, were recruited. Expression of STING mRNA was measured in peripheral blood mononuclear cells (PBMCs) and compared between patients with different severity and outcome. RESULTS: There was a significant negative correlation between age and STING expression level (p value = 0.010). Patients with "severe to critical" illness had a 20-fold lower STING expression level compared to the "mild to moderate" group (p value = 0.001). Also, the results showed lower expressions of STING in the patients admitted to the ICU (p value = 0.015). Patients who finally died had lower expression of STING at the time of sampling (p value = 0.041). CONCLUSION: STING mRNA expression in PBMCs was significantly lower in older COVID-19 cases, the patients with more severe illness, who needed intensive care, and who eventually died.

2.
Iran J Pharm Res ; 21(1): e123947, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1847596

ABSTRACT

More than a year after the onset of the coronavirus disease pandemic in 2019, the disease remains a major global health issue. During this time, health organizations worldwide have tried to provide integrated treatment guidelines to control coronavirus disease 2019 (COVID-19) at different levels. However, due to the novel nature of the disease and the emergence of new variants, medical teams' updating medical information and drug prescribing guidelines should be given special attention. This version is an updated instruction of the National Research Institute of Tuberculosis and Lung Disease (NRITLD) in collaboration with a group of specialists from Masih Daneshvari Hospital in Tehran, Iran, which is provided to update the information of caring clinicians for the treatment and care of COVID-19 hospitalized patients.

3.
Iranian Journal of Allergy, Asthma and Immunology ; 20(4):394-401, 2021.
Article in English | ProQuest Central | ID: covidwho-1761411

ABSTRACT

Considering the increasing prevalence and burden of coronavirus disease 2019 (COVID-19) disease and false-negative results in routine reverse transcription-polymerase chain reaction (RT-PCR) tests, additional diagnostic methods are needed to diagnose active cases of this disease. This prospective study was conducted on patients, in whom clinical and radiological symptoms/signs were in favor of COVID-19 while their first PCR test was negative. Later on, a second RT-PCR was performed and serological evaluation was carried out and results were compared with each other. Out of 707 patients who had been referred to the hospital and were clinically and radiologically suspicious of disease, 137 patients with negative RT-PCR tests entered the study. RT-PCR assay became positive for the second time in 45 (32.8%). Anti-COVID-19 IgM and IgG antibodies were positive in 83 (60.6%) and 86 (62.8%) patients, respectively. Finally, it was determined that serological test was diagnostic in 73% of patients and the diagnostic yield of serology was significantly higher after the first week of illness (54.8% in the first week and 88% after that). Taking advantage of both serological tests and RT-PCR helps in diagnosing 83.9% of cases. Based on the present study, the serology may be useful as a complementary test and in parallel to RT-PCR assay for diagnosis of COVID-19 among admitted symptomatic cases.

4.
Curr Ther Res Clin Exp ; 96: 100658, 2022.
Article in English | MEDLINE | ID: covidwho-1712551

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19), an acute, sometimes severe respiratory illness caused by a novel coronavirus has led to a vast pandemic with an astonishing spread rate. Its treatment is unknown, its mortality is significant, and its socioeconomic complications are uncontrollable. Although there is still little known about the pathogenesis of the disease, severe cases of COVID-19 are usually associated with cytokine release syndrome and high serum levels of inflammatory cytokines, which are believed to be a major cause of mortality in these patients. Different pathways cause inflammation and the release of cytokines. One of these pathways is the Bruton tyrosine kinase (BTK) pathway, which is essential for the production of several anti-inflammatory cytokines. Theoretically, the inhibition of BTK signaling can reduce cytokine levels and subsequent anti-inflammatory effects. OBJECTIVE: This review aims to investigate the role of the BTK pathway in the pathogenesis of COVID-19 and the possible effects of its inhibition in the treatment of this disease. METHODS: This narrative review provides information regarding the use of BTK inhibitors in patients with COVID-19 and discusses whether clinicians should consider these medications while managing their patients based on the literature. Data were gathered using the PubMed, Scopus, and Web of Science databases. RESULTS: Some data support the use of BTK inhibitors for treating COVID-19. CONCLUSIONS: It is recommended that patients continue their medications in this class if they develop COVID-19 and were receiving these agents before the disease developed. The use of BTK inhibitors might enable patients to experience less severe immune responses to the COVID-19. Well-designed studies are needed to evaluate the effectiveness of BTKis in the management of COVID-19. (Curr Ther Res Clin Exp. 2022; 82:XXX-XXX) © 2022 Elsevier HS Journals.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323235

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) is a pandemic disease. Experiments with influenza and severe acute respiratory syndrome (SARS) have shown supplemental vitamin D can reduce the risk of infection and death. Aim: This study was performed to evaluate the relationship between vitamin D levels and the severity and outcome of admitted patients with COVID-19. Material: and Methods This cross-sectional study was performed on COVID-19 cases diagnosed by examining RT-PCR assay for SARS-CoV-2 or a set of symptoms and typical findings in lung CT scan. Based on clinical and radiologic characteristics, the patients were categorized as mild, moderate, severe, and critical. Calcium, phosphorus, albumin, creatinine, and serum 25 hydroxy vitamin D were measured and their correlation with the severity and outcome were analyzed. Results: From May 1 to June 31, 2020, 508 patients ((442 patients in general wards and 66 patients in intensive care unit (ICU)) were included in this study. The participants were 56±17 years old (mean ±SD) (range from 14 to 95 years) and 52% were male. According to the past medical history, 190 (37.4%) of them had comorbidity. Concerning severity, 13.2%, 42.3%, 35.4%, and 9.1% had the mild, moderate, severe, and critical disease, respectively. The in-hospital mortality rate was 10.8%. In the multivariate regression analysis, age had a positive correlation and use of vitamin D supplement, serum level of 25 OH vitamin D, calcium, and albumin had a negative correlation with disease severity and admission to ICU. Poor outcome was inversely related to serum levels of vitamin D, calcium, albumin, and renal function. Vitamin D deficiency increased the rate of ICU admission by 2.7 times (95%CI=1.288-5.91, P=0.009). Conclusion: In patients who are hospitalized due to COVID-19, low 25-hydroxyvitamin D, hypocalcemia, and hypoalbuminemia are associated with severe disease, ICU admission, and an increase in mortality.

6.
Sci Rep ; 11(1): 17594, 2021 09 02.
Article in English | MEDLINE | ID: covidwho-1392891

ABSTRACT

Supplemental vitamin D can reduce the risk and mortality of viral pneumonia. The relationship between 25 hydroxyvitamin D [25(OH)D] levels and the severity and mortality of Coronavirus disease 2019 (COVID-19) was evaluated. In this cross-sectional study, the admitted patients with COVID-19 were categorized as mild, moderate, severe, and critical based on clinical and radiologic characteristics. Calcium, phosphorus, albumin, creatinine, and serum 25(OH)D were measured and their correlation with the severity of disease and mortality were analyzed. During 2 months, 508 patients (442 patients in general wards and 66 patients in the intensive care unit (ICU)) were included. The participants were 56 ± 17 years old (52% male, 37% with comorbidity). Concerning severity, 13%, 42%, 36%, and 9% had mild, moderate, severe, and critical diseases, respectively. The mortality rate was 10.8%. Admission to ICU, severity of disease and mortality decreased significantly across quartiles of 25(OH)D. According to multivariate logistic regression analysis, disease mortality had a positive correlation with age and had a negative correlation with the serum level of 25(OH)D, calcium, and albumin. In hospitalized patients with COVID-19, low 25(OH)D was associated with severe disease and increased ICU admission and mortality rate.


Subject(s)
COVID-19/blood , COVID-19/mortality , SARS-CoV-2/metabolism , Severity of Illness Index , Vitamin D/analogs & derivatives , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Vitamin D/blood
7.
BMC Infect Dis ; 21(1): 646, 2021 Jul 05.
Article in English | MEDLINE | ID: covidwho-1344082

ABSTRACT

BACKGROUND: Although there are a growing number of studies on evaluating lymphocyte subset counts as prognostic factors for COVID-19 disease severity, the lymphocyte subsets' analyses of both IgM and IgG responders and non-responders during the periods after onset of symptoms, have not been conducted yet. So, this study aimed to evaluate immune cell profiling of COVID-19 patients with and without antibody responses. METHODS: In this cross-sectional study, the levels of peripheral lymphocyte subsets were measured using flow cytometry in 53 patients with positive SARS-CoV-2 RT-PCR, for whom antibody testing of COVID-19 was performed. RESULTS: The white blood cell, neutrophil, and lymphocyte counts consistently decreased in the IgM and IgG non-responder group, while the differences in the median value between the two study groups were found to be statistically significant only in terms of neutrophil counts (P = 0.024 for IgM response and p-value = 0.046 for IgG response, respectively). Moreover, the level of neutrophil-to-lymphocyte ratio was observed to be significantly lower in the IgM or IgG non-responder group compared to the IgM or IgG responder group (3.6 ± 3.1 vs. 6.3 ± 4.2; p-value = 0.021). The patients with IgM antibody response had a significantly lower CD20+ lymphocytes (11% versus 15% in the groups without IgM antibody response, p-value = 0.031), The percentages of NK cells and CD4+ T cells significantly increased in the patients with IgG antibody response compared to those without IgG antibody response (13% versus 10%, p-value = 0.028, and 41.5% versus 34%; p-value = 0.03, respectively). Moreover, the patients who produced IgM or IgG antibody had significantly higher percentages of total T lymphocytes (64% versus 54%; p-value = 0.017), CD4+ T cells (41% versus 34%; p-value = 0.038), and NK cells (13% versus 9%, p-value = 0.023) compared to the group with no serological response. No significant difference was observed in the percentage of other lymphocyte subsets, including CD8+ T cells, Treg cells, and CD19+ B cells. CONCLUSION: Our results suggest that the total T cells, CD4+ T cells, and NK cells percentages are linked to serological response. Moreover, our findings suggested that neutrophil absolute counts and neutrophil-to-lymphocyte ratio may be valuable predictors of IgM or IgG antibody response.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Lymphocyte Subsets/immunology , SARS-CoV-2/immunology , Adult , Aged , Antibody Formation , Cross-Sectional Studies , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged
8.
Arch Iran Med ; 24(5): 419-426, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1308612

ABSTRACT

BACKGROUND: The pathogenesis of the COVID19 pandemic, that has killed one million nine hundred people and infected more the 90 million until end of 2020, has been studied by many researchers. Here, we try to explain its biological behavior based on our recent autopsy information and review of literature. METHODS: In this study, patients with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) result were considered eligible for enrollment. Histopathological examinations were done on 13 people who were hospitalized in Afzalipour hospital, Kerman, Iran. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry and electron microscopy. RESULTS: The most frequent co-morbidity in the patients was cardiovascular disease. The common initial symptoms of COVID-19 infection were dyspnea and cough. In all cases, the number of white blood cells was higher than the normal range. Common histopathological findings were variable degrees of vasculitis as degenerative to necrotic changes of endothelium and trafficking of inflammatory cells in the vessel wall with fibrinoid necrosis. Tissue damage included interstitial acute inflammatory cells reaction with degenerative to necrotic changes of the parenchymal cells. CD34 and Factor VIII immunohistochemistry staining showed endothelial cell degeneration to necrosis at the vessel wall and infiltration by inflammatory cells. Electron microscopic features confirmed the degenerative damages in the endothelial cells. CONCLUSION: Our histopathological studies suggest that the main focus of the viral damage is the endothelial cells (endotheliopathica) in involved organs. Also, our findings suggest that degeneration of leukocytes occurs at the site of inflammation and release of cytokines (leukocytoclastica) resulting in a cytokine storm.


Subject(s)
COVID-19/complications , COVID-19/pathology , Endothelial Cells/pathology , Leukocytes/pathology , Adult , Aged , COVID-19/metabolism , Cohort Studies , Cytokines/metabolism , Female , Humans , Iran , Male , Middle Aged , Pericarditis/pathology , Pericarditis/virology , Skin Diseases/pathology , Skin Diseases/virology
9.
Int Immunopharmacol ; 99: 107961, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1300823

ABSTRACT

BACKGROUND: COVID-19, which is a disease caused by the SARS-CoV-2 virus, has spread around the world since late 2019. Studies have found associations between the rising levels of TNF-α and severe COVID-19 cases. Hence, TNF-α blocking can possibly be a favorable intervention in modifying COVID-19. To this end, in order to manage pneumonia caused by COVID-19, adalimumab may potentially be considered as a potential therapeutic agent. The present study aimed to investigate the potential therapeutic role of adalimumab in treating COVID-19 cases in combination therapy with remdesivir and dexamethasone. METHODS: Among the 68 patients who were included in the current randomized controlled trial, 34 were assigned to the adalimumab group and the remaining 34 were assigned to the control group. Adalimumab at a dose of 40 mg, subcutaneous for once, was used for the intervention group. Both the intervention and control groups received remdesivir, dexamethasone, and supportive care. The data gathered to make comparisons of the groups included demographic information, the rate of mortality, mechanical ventilation requirement, length of stay in hospital and Intensive Care Unit (ICU), and imaging findings. RESULTS: There was no significant difference between the two groups in the terms of mortality rate (P-value = 1) and mechanical ventilation requirement (P-value = 1). The length of hospital and ICU stay as well as radiologic changes were not affected either (P-value = 1, 0.27, and 0.53, respectively). CONCLUSIONS: Our findings did not support the use of adalimumab in combination with remdesivir and dexamethasone in the treatment of severe COVID-19 cases.


Subject(s)
Adalimumab/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adult , Aged , Alanine/analogs & derivatives , Alanine/therapeutic use , Dexamethasone/therapeutic use , Drug Therapy, Combination , Female , Humans , Middle Aged , Pregnancy , Respiration, Artificial
10.
Hum Antibodies ; 29(2): 109-113, 2021.
Article in English | MEDLINE | ID: covidwho-1133885

ABSTRACT

BACKGROUND: There are few studies to compare antibody response against anti-spike (S) and anti- nucleoprotein (N) SARS-CoV-2. OBJECTIVE: The aim of this study was to evaluate the IgG antibody production against S and N antigens of the virus and their correlation with the time and severity of the disease. METHODS: The IgG antibodies against S and N antigens of SARS-CoV-2 in serum specimens of 72 symptomatic patients who tested real-time reverse transcription polymerase chain reaction positive for SARS-CoV-2 were detected using the ELISA technique. Different antibody response was compared and the correlation with the time from disease onset and the severity was evaluated. RESULTS: Forty-eight of 72 (67%) patients tested positive for anti-SARS-CoV-2 antibodies, while 24 (33%) did not have detectable antibodies. Comparison of antibody levels for N and S antibodies showed that they correlate with each other well (r= 0.81; P< 0.001). However, sensitivity of anti-S SARS-CoV-2 IgG and anti-N SARS-CoV-2 IgG was 30% and 60%, during the first 7 days after symptom onset (r= 0.53; P= 0.111), but increased to 73% and 68% at more than 1-week post symptom onset (r= 0.89, P= 0.111), respectively. Cases with positive IgG response showed a decreased CD8+ T cells percentage compared to the negative IgG groups (26 ± 14 vs. 58 ± 32, p= 0.066 in anti-N IgG group and 28 ± 15 vs. 60 ± 45, p= 0.004 in anti-S IgG group, respectively). CONCLUSION: Nearly one-third of the confirmed COVID-19 patients had negative serology results. Lower percent positivity at early time points after symptom onset (less than 1 week) was seen using anti-S SARS-COV-2 IgG kit compare to the anti-N SARS-CoV-2 IgG; therefore, clinicians should interpret negative serology results of especially anti-S SARS-CoV-2 IgG with caution.


Subject(s)
COVID-19/immunology , Coronavirus Nucleocapsid Proteins/immunology , Immunoglobulin G/analysis , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , CD8-Positive T-Lymphocytes/immunology , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Humans , Lymphocyte Subsets/immunology , Male , Middle Aged , Negative Results , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity , Severity of Illness Index
11.
Int Arch Allergy Immunol ; 182(3): 254-262, 2021.
Article in English | MEDLINE | ID: covidwho-1048726

ABSTRACT

BACKGROUND: Although the pathophysiology of coronavirus disease 2019 (COVID-19) is not clearly defined, among the proposed mechanisms, immune system dysfunction is more likely than others. The aim of this study was to clarify the characteristics and clinical significance of dynamic changes of lymphocyte subsets in the course of COVID-19. METHODS: In this prospective study, the levels of peripheral lymphocyte subsets including CD4+, CD8+, CD4+CD25+FOXP3+, CD38+, CD3+HLA-DR+, CD19+, CD20+, and CD16+CD56+ cells were measured by flow cytometry in 52 confirmed hospitalized patients with COVID-19 at the day of admission and after 7 days of care. Clinical response was defined as improvement in symptoms (fever, dyspnea, and cough as well as blood oxygen saturation), and patients who met these criteria after 1 week of admission were classified as early responders; others who survived and finally discharged from the hospital were classified as late responders and patients who died were categorized as nonresponders. Immunophenotyping of studied cell changes on the first day of admission and 7 days after treatment were compared. Besides, the correlation between cellular subset variation and clinical response and outcome were analyzed. RESULTS: Total counts of white blood cell, T cells, CD4+ T cells, CD8+ T cells, CD38+ lymphocytes, and CD3+HLA-DR+ lymphocytes were significantly increased in both early and late responders. No statistically significant difference was observed in CD4+/CD8+ ratio, B cells, FOXP3+Treg lymphocytes, and FOXP3 median fluorescence intensity among studied groups. According to the multivariate analysis, an increase in CD4+ T cells (p = 0.019), CD8+ T cells (p = 0.001), and administration of interferon (p < 0.001) were independent predictors of clinical response. CONCLUSION: We found an increasing trend in total T cells, T helpers, cytotoxic T cells, activated lymphocytes, and natural killer cells among responders. This trend was not statistically significant among nonresponders. The findings of this study may enhance our knowledge about the pathogenesis of COVID-19.


Subject(s)
COVID-19/immunology , Lymphocyte Subsets/immunology , SARS-CoV-2 , Adult , Aged , Female , Humans , Male , Middle Aged , Prospective Studies
12.
Int Immunopharmacol ; 93: 107407, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1046364

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected 86,4 M patients and resulted in 1,86 M deaths worldwide. Severe COVID-19 patients have elevated blood levels of interleukin-6 (IL-6), IL-1ß, tumor necrosis factor (TNF)α, IL-8 and interferon (IFN)γ. OBJECTIVE: To investigate the effect of antiviral treatment serum cytokines in severe COVID-19 patients. METHODS: Blood was obtained from 29 patients (aged 32-79 yr) with laboratory-confirmed COVID-19 upon admission and 7 days after antiviral (Favipiravir or Lopinavir/Ritonavir) treatment. Patients also received standard supportive treatment in this retrospective observational study. Chest computed tomography (CT) scans were evaluated to investigate lung manifestations of COVID-19. Serum was also obtained and cytokines levels were evaluated. 19 age- and gender-matched healthy controls were studied. RESULTS: Anti-viral therapy significantly reduced CT scan scores and the elevated serum levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH). In contrast, serum levels of IL-6, IL-8 and IFNγ were elevated at baseline in COVID-19 subjects compared to healthy subjects with IL-6 (p = 0.006) and IL-8 (p = 0.011) levels being further elevated after antiviral therapy. IL-1ß (p = 0.01) and TNFα (p = 0.069) levels were also enhanced after treatment but baseline levels were similar to those of healthy controls. These changes occurred irrespective of whether patients were admitted to the intensive care unit. CONCLUSION: Antiviral treatments did not suppress the inflammatory phase of COVID-19 after 7 days treatment although CT, CRP and LDH suggest a decline in lung inflammation. There was limited evidence for a viral-mediated cytokine storm in these COVID-19 subjects.


Subject(s)
Amides/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/blood , COVID-19/drug therapy , Cytokines/blood , Lopinavir/therapeutic use , Pyrazines/therapeutic use , Ritonavir/therapeutic use , Adult , Aged , COVID-19/immunology , Drug Combinations , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purification
14.
Tanaffos ; 19(2): 85-88, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-952690
15.
Pathol Res Pract ; 216(10): 153228, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-779554

ABSTRACT

BACKGROUND: Since the outbreak of the novel coronavirus disease-2019 (COVID-19) in December 2019, limited studies have investigated the histopathologic findings of patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). MATERIAL AND METHODS: This study was conducted on 31 deceased patients who were hospitalized for COVID-19 in a tertiary hospital in Tehran, Iran. A total of 52 postmortem tissue biopsy samples were obtained from the lungs and liver of decedents. Clinical characteristics, laboratory data, and microscopic features were evaluated. Reverse transcription polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 was performed on specimens obtained from nasopharyngeal swabs and tissue biopsies. RESULTS: The median age of deceased patients was 66 years (range, 30-87 years) and 25 decedents (81 %) were male. The average interval from symptom onset to death was 13 days (range, 6-34 days). On histopathologic examination of the lung specimens, diffuse alveolar damage and thrombotic microangiopathy were the most common findings (80 % and 60 %, respectively). Liver specimens mainly showed macrovesicular steatosis, portal lymphoplasmacytic inflammation and passive congestion. No definitive viral inclusions were observed in any of the specimens. In addition, 92 % of lung tissue samples tested positive for SARS-CoV-2 by RT-PCR. CONCLUSIONS: Further studies are needed to investigate whether SARS-CoV-2 causes direct cytopathic changes in various organs of the human body.


Subject(s)
Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Pulmonary Alveoli/pathology , Thrombotic Microangiopathies/pathology , Thrombotic Microangiopathies/virology , Adult , Aged , Aged, 80 and over , Autopsy , Betacoronavirus , Biopsy , COVID-19 , Female , Humans , Liver/pathology , Lung/pathology , Male , Middle Aged , Pandemics , SARS-CoV-2
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