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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.
Tanaffos ; 19(4): 291-299, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1801409

ABSTRACT

BACKGROUND: Inflammatory mediators are an important component in the pathophysiology of the coronavirus disease 2019 (COVID-19). This study aimed to assess the effects of reducing inflammatory mediators using hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the mortality of patients with COVID-19. MATERIALS AND METHODS: Twelve patients with confirmed diagnosis of COVID-19 were included. All patients had acute respiratory distress syndrome (ARDS). Patients were divided into three groups, namely, HP, CRRT and HP+CRRT. The primary outcome was mortality and the secondary outcomes were oxygenation and reduction in inflammatory mediators at the end of the study. RESULTS: Patients were not different at baseline in demographics, inflammatory cytokine levels, and the level of acute phase reactants. Half of the patients (3 out of 6) in the HP+CRRT group survived along with the survival of one patient (1 out of 2) in the HP group. All four patients in the CRRT group died. Serum creatinine (SCr), Interleukin-1 (IL1), Interleukin-6 (IL6), Interleukin-8 (IL8), partial pressure of oxygen (PaO2), O2 saturation (O2 sat), and hemodynamic parameters improved over time in HP+CRRT and CRRT groups, but no significant difference was observed in the HP group (All Ps > 0.05). CONCLUSION: Combined HP and CRRT demonstrated the best result in terms of mortality, reduction of inflammatory mediators and oxygenation. Further investigations are needed to explore the role of HP+CRRT in COVID-19 patients.

4.
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.

5.
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.

6.
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.

7.
ESC Heart Fail ; 9(2): 1483-1486, 2022 04.
Article in English | MEDLINE | ID: covidwho-1664406

ABSTRACT

SARS-CoV-2 vaccines provide a safe solution with a major impact on reducing the spread of the virus and mild side effects. Research has shown rare cases of myocarditis after mRNA vaccines. This study presents a 29-year-old male with chest pain after 48 h of receiving rAd26 and rAd5 vector-based COVID-19 vaccine (Sputnik V vaccine). The electrocardiogram revealed ST-segment elevation. Also, the laboratory screening was remarkable for elevated cardiac Troponin-I level, and leukocytosis; and echocardiography depicted severe left ventricular systolic dysfunction. Overall, endomyocardial biopsy proved lymphocytic myocarditis such that the patient was successfully treated with immunosuppressive and guideline-directed medical treatment.


Subject(s)
COVID-19 , Myocarditis , Adult , COVID-19 Vaccines/adverse effects , Heart , Humans , Male , Myocarditis/diagnosis , Myocarditis/etiology , SARS-CoV-2
8.
Iran J Pharm Res ; 20(4): 1-8, 2021.
Article in English | MEDLINE | ID: covidwho-1579471

ABSTRACT

Coronavirus disease -19 (COVID-19) pandemic, caused by SARS-CoV-2, has gradually spread worldwide, becoming a major public health event. This situation requires designing a novel antiviral agent against the SARS-CoV-2; however, this is time-consuming and the use of repurposed medicines may be promising. One such medicine is favipiravir, primarily introduced as an anti-influenza agent in east world. The aim of this study was to evaluate the efficacy and safety of favipiravir in comparison with lopinavir-ritonavir in SARS-CoV-2 infection. In this randomized clinical trial, 62 patients were recruited. These patients had bilateral pulmonary infiltration with peripheral oxygen saturation lower than 93%. The median time from symptoms onset to intervention initiation was seven days. Favipiravir was not available in the Iranian pharmaceutical market, and it was decided to formulate it at the research laboratory of School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The patients received favipiravir tablet at a dose of 1600 mg orally twice a day for day one and then 600 mg orally twice a day for days 2 to 6. In the second group, the patients received lopinavir-ritonavir combination tablet at a dose of 200/50 mg twice a day for seven days. Fever, cough, and dyspnea were improved significantly in favipiravir group in comparison with lopinavir-ritonavir group on days four and five. Mortality rate and ICU stay in both groups were similar, and there was no significant difference in this regard (P = 0.463 and P = 0.286, respectively). Chest X-ray improvement also was not significantly different between the two groups. Adverse drug reactions occurred in both groups, and impaired liver enzymes were the most frequent adverse effect. In conclusion, early administration of oral favipiravir may reduce the duration of clinical signs and symptoms in patients with COVID-19 and hospitalization period. The mortality rate also should be investigated in future clinical trials.

9.
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
10.
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
11.
Front Immunol ; 12: 592727, 2021.
Article in English | MEDLINE | ID: covidwho-1225860

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected over 112M patients and resulted in almost 2.5M deaths worldwide. The major clinical feature of severe COVID-19 patients requiring ventilation is acute respiratory distress syndrome (ARDS) possibly associated with a cytokine storm. Objectives: To elucidate serum levels of TNF-α and soluble TNF-Receptor 1 (sTNFR1) in patients with severe and mild COVID-19 disease as determinants of disease severity. Methods: We determined serum TNF-α and sTNFR1 concentrations in 46 patients with laboratory-confirmed COVID-19 (17 patients with severe disease within the intensive care unit [ICU] and 29 non-severe, non-ICU patients) and 15 healthy controls upon admission using ELISA. Subjects were recruited between March-May 2020 at the Masih Daneshvari Hospital Tehran, Iran. Results: Serum levels of sTNFRI were significantly higher in ICU patients (P<0.0001) and non-ICU patients (P=0.0342) compared with healthy subjects. Serum sTNFR1 were significantly higher in ICU patients than in non-ICU patients (P<0.0001). Serum TNF-α levels were greater in ICU and non-ICU patients than in the healthy subjects group (p<0.0001). The sTNFRI concentration in ICU (r=0.79, p=0.0002) and non-ICU (r=0.42, p=0.02) patients positively correlated with age although serum sTNFRI levels in ICU patients were significantly higher than in older healthy subjects. The sTNFRI concentration in ICU patients negatively correlated with ESR. Conclusions: The study demonstrates higher sTNFRI in ICU patients with severe COVID-19 disease and this be a biomarker of disease severity and mortality. Future studies should examine whether lower levels of systemic sTNFR1 at admission may indicate a better disease outcome.


Subject(s)
COVID-19/blood , COVID-19/mortality , Receptors, Tumor Necrosis Factor, Type I/blood , Tumor Necrosis Factor-alpha/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/pathology , Critical Care , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/mortality , Female , Humans , Intensive Care Units , Interleukin-6/blood , Iran , Male , Middle Aged , Pilot Projects , SARS-CoV-2 , Severity of Illness Index
12.
Eur J Pharmacol ; 897: 173947, 2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1188517

ABSTRACT

The aim of this study was to evaluate the clinical effects of dexamethasone administration in patients with mild to moderate acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). The study included 50 patients who were randomly assigned to the dexamethasone group or control group. Dexamethasone was administered at a dose of 20 mg/day from day 1-5 and then at 10 mg/day from day 6-10. The need for invasive mechanical ventilation, death rate, duration of clinical improvement, length of hospital stay, and radiological changes in the computed tomography scan were assessed. The results revealed that 92% and 96% of patients in the dexamethasone and control groups, respectively, required noninvasive ventilation (P = 0.500). Among them, 52% and 44% of patients in the dexamethasone and control groups, respectively, required invasive mechanical ventilation (P = 0.389). At the end of the study, 64% of patients in the dexamethasone group and 60% of patients in the control group died (P = 0.500); the remaining patients were discharged from the hospital during the 28-day follow-up period. The median length of hospital stay was 11 days in the dexamethasone group and 6 days in the control group (P = 0.036) and the median length of hospital stay was 7 days in the dexamethasone group and 3 days in the control group (P < 0.001). No significant differences were observed in the other outcomes. This study showed that corticosteroid administration had no clinical benefit in patients with COVID-19-induced mild to moderate ARDS.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Dexamethasone/therapeutic use , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/etiology , Adult , Aged , Anti-Inflammatory Agents/administration & dosage , COVID-19/mortality , Dexamethasone/administration & dosage , Female , Humans , Length of Stay , Male , Middle Aged , Negative Results , Respiration, Artificial , Respiratory Distress Syndrome/mortality , Tomography, X-Ray Computed , Treatment Failure
13.
J Investig Med ; 2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-1136102

ABSTRACT

BACKGROUND: Bromhexine is a potent inhibitor of transmembrane serine protease 2 and appears to have an antiviral effect in controlling influenza and parainfluenza infection; however, its efficacy in COVID-19 is controversial. METHODS: A group of hospitalized patients with confirmed COVID-19 pneumonia were randomized using 1:1 allocation to either standard treatment lopinavir/ritonavir and interferon beta-1a or bromhexine 8 mg four times a day in addition to standard therapy. The primary outcome was clinical improvement within 28 days, and the secondary outcome measures were time to hospital discharge, all-cause mortality, duration of mechanical ventilation, the temporal trend in 2019-nCoV reverse transcription-polymerase chain reaction positivity and the frequency of adverse drug events within 28 days from the start of medication. RESULTS: A total of 111 patients were enrolled in this randomized clinical trial and data from 100 patients (48 patients in the treatment arm and 52 patients in the control arm) were analyzed. There was no significant difference in the primary outcome of this study, which was clinical improvement. There was no significant difference in the average time to hospital discharge between the two arms. There were also no differences observed in the mean intensive care unit stay, frequency of intermittent mandatory ventilation, duration of supplemental oxygenation or risk of death by day 28 noted between the two arms. CONCLUSION: Bromhexine is not an effective treatment for hospitalized patients with COVID-19. The potential prevention benefits of bromhexine in asymptomatic postexposure or with mild infection managed in the community remain to be determined.

14.
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
15.
Int Immunopharmacol ; 90: 107205, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1065216

ABSTRACT

BACKGROUND: The newly discovered coronavirus has turned into coronavirus disease 2019 (COVID-19) pandemic and it rages at an unprecedented rate. Considering the findings of previous studies on the use of Intravenous Immunoglobulin (IVIg) for treating severe H1N1 infection and the satisfying results for reducing viral load and mortality, this study aimed to investigate the potential usefulness of IVIg for the management of severe cases. METHODS: In this randomized controlled trial, 84 patients were included: 52 in the IVIg group and 32 in the control group. The intervention group received IVIg at a dose of 400 mg/kg, IV, daily for three days. Both groups received hydroxychloroquine, lopinavir/ritonavir and supportive care. The demographic data, mortality rate, the need for mechanical ventilation, length of stay in hospital and in Intensive Care Unit (ICU), and imaging findings were recorded and compared in terms of the mentioned factors. RESULTS: The mean time from admission to IVIg initiation was 3.84 ± 3.35 days. There was no significant difference between the two groups in terms of mortality rate (P-value = 0.8) and the need for mechanical ventilation (P-value = 0.39). The length of hospital stay was significantly lower for the control group than that of the intervention group (P-value = 0.003). There was a significant positive relationship between the time from hospital admission to IVIg initiation and the length of stay in the hospital and ICU among the survivors (P-value < 0.001 and =0.01, respectively). CONCLUSIONS: Our findings did not support the use of IVIg in combination with hydroxychloroquine and lopinavir/ritonavir in treatment of severe COVID-19 cases.


Subject(s)
COVID-19/drug therapy , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , SARS-CoV-2 , Adult , Aged , Antiviral Agents/therapeutic use , Drug Therapy, Combination , Female , Humans , Hydroxychloroquine/therapeutic use , Length of Stay , Lopinavir/therapeutic use , Male , Middle Aged , Ritonavir/therapeutic use , Treatment Outcome
16.
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
17.
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
18.
Int Immunopharmacol ; 92: 107329, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1014566

ABSTRACT

Interferon Beta-1a (IFN-ß1-a), an immunomodulatory mediator with antiviral effects, has shown in vivo and in vitro activities especially on coronavirus including SARS-CoV-2. COVID-19 defined as the disease caused by infection with SARS-CoV-2. The virus has been illustrated inhibits the production of IFN-ß1-a from inflammatory cells. We conducted a retrospective study of all adult confirmed COVID-19 hospitalized patients who received combination of three doses of 12 million international units of IFN-ß1-a and Lopinavir 400 mg and Ritonavir 100 mg every 12 h (case group) for 14 days besides standard care and age- and sex- matched COVID-19 patients with receiving lopinavir/ritonavir (control group) at Masih Daneshvari Hospital as a designated hospital for COVID-19 between Feb 19 and Apr 30, 2020. Multivariate analysis was done to determine the impact of IFN-ß1-a on outcome and all-cause mortality. 152 cases in IFN-ß1-a group and 304 cases as control group were included. IFN-ß1-a group stayed at hospital longer and required noninvasive ventilation more than control group (13 vs. 6 days, p = 0.001) and (34% vs. 24%, p = 0.04), respectively. During treatment, 57 (12.5%) patients died. The death rate in case and control groups was 11% and 13% respectively. In multivariate analysis, not receiving IFN-ß1-a (HR 5.12, 95% CI: 2.77-9.45), comorbidity (HR 2.28, 95% CI: 1.13-4.60) and noninvasive ventilation (HR 2.77, 95% CI: 1.56-4.93) remained significantly associated with all-cause mortality. In this study, risk of death decreased by using IFN-ß1-a in COVID-19 patients. More clinical study will be necessary to measure efficacy of IFN-ß1-a in COVID-19 treatment.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , HIV Protease Inhibitors/therapeutic use , Interferon-beta/therapeutic use , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Drug Combinations , Female , Humans , Interferon-beta/administration & dosage , Lopinavir/administration & dosage , Male , Middle Aged , Retrospective Studies , Ritonavir/administration & dosage , Young Adult
19.
Tanaffos ; 19(2): 122-128, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-964064

ABSTRACT

BACKGROUND: Following the recent epidemic of coronavirus disease 2019 (COVID-19) in Wuhan, China, a novel betacoronavirus was isolated from two patients in Iran on February 19, 2020. In this study, we aimed to determine the clinical manifestations and outcomes of the first confirmed cases of COVID-19 infection (n=127). MATERIALS AND METHODS: This prospective study was conducted on all COVID-19-suspected cases, admitted to Masih Daneshvari Hospital (a designated hospital for COVID-19), Tehran, Iran, since February 19, 2020. All patients were tested for COVID-19, using reverse transcription-polymerase chain reaction (RT-PCR) assay. Data of confirmed cases, including demographic characteristics, clinical features, and outcomes, were collected and compared between three groups of patients, requiring different types of admission (requiring ICU admission, admission to the general ward, and transfer to ICU). RESULTS: Of 412 suspected cases, with the mean age of 54.1 years (SD=13.4), 127 (31%) were positive for COVID-19. Following the patients' first visit to the clinic, 115 cases were admitted to the general ward, while ten patients required ICU admission. Due to clinical deterioration in the condition of 25 patients (out of 115 patients), ICU admission was essential. Based on the results, the baseline characteristics of the groups were similar. Patients requiring ICU admission were more likely to have multiorgan involvement (liver involvement, P<0.001; renal involvement, P<0.001; and cardiac involvement, P=0.02), low O2 saturation (P<0.001), and lymphopenia (P=0.05). During hospital admission, 21 (16.5%) patients died, while the rest (83.5%) were discharged and followed-up until March 26, 2020. Also, the survival rate of patients, who received immunoglobulin, was higher than other patients (60.87% vs. 39.13%). CONCLUSION: The mortality rate of COVID-19 patients was considerable in our study. Based on the present results, this infection can cause multiorgan damage. Therefore, intensive monitoring of these patients needs to be considered.

20.
Pulmonology ; 27(6): 486-492, 2021.
Article in English | MEDLINE | ID: covidwho-957366

ABSTRACT

BACKGROUND: In December 2019, pneumonia associated with a novel coronavirus (COVID-19) was reported in Wuhan, China. Acute respiratory distress syndrome (ARDS) is the most frequently observed complication in COVID-19 patients with high mortality rates. OBJECTIVE OF STUDY: To observe the clinical effect of plasmapheresis on excessive inflammatory reaction and immune features in patients with severe COVID-19 at risk of ARDS. MATERIALS AND METHODS: In this single-center study, we included 15 confirmed cases of COVID-19 at Masih Daneshvari Hospital, in March 2020 in Tehran, Iran. COVID-19 cases were confirmed by RT-PCR and CT imaging according to WHO guidelines. Plasmapheresis was performed to alleviate cytokine-induced ARDS. The improvement in oxygen delivery (PaO2/FiO2), total number of T cells, liver enzymes, acute reaction proteins, TNF-α and IL-6 levels were evaluated. RESULTS: Inflammatory cytokine levels (TNF-α, IL-6), and acute phase reaction proteins including ferritin and CRP were high before plasmapheresis. After plasmapheresis, the levels of PaO2/FiO2, acute phase reactants, inflammatory mediators, liver enzymes and bilirubin were significantly reduced within a week (p < 0.05). In contrast, although the number of T helper cells decreased immediately after plasmapheresis, they rose to above baseline levels after 1 week. Nine out of fifteen patients on non-invasive positive-pressure ventilation (NIPPV) survived whilst the six patients undergoing invasive mechanical ventilation (IMV) died. CONCLUSION: Our data suggests that plasmapheresis improves systemic cytokine and immune responses in patients with severe COVID-19 who do not undergo IMV. Further controlled studies are required to explore the efficacy of plasmapheresis treatment in patients with COVID-19.


Subject(s)
COVID-19 , Plasmapheresis , Respiratory Distress Syndrome , COVID-19/mortality , COVID-19/therapy , Cytokines/blood , Humans , Interleukin-6/blood , Iran , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , T-Lymphocytes, Helper-Inducer , Tumor Necrosis Factor-alpha/blood
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