Nintedanib: a review of the properties, function, and usefulness to minimize COVID-19-induced lung injury.

INTRODUCTION: In severe COVID-19 patients, acute respiratory distress syndrome (ARDS)-induced lung injury regularly causes a pulmonary fibrotic phase. There is no approved therapy for the COVID-19-induced pulmonary fibrosis. However, administration of an anti-fibrotic agent, in the early acute phase of the severe COVID-19 with ARDS, may improve the infection outcomes. AREAS COVERED: In this review, the main characteristics of nintedanib and its usefulness to treat COVID-19-induced fibrosis were studied. In July 2022, a literature search was performed from PubMed, Google Scholar, and the WHO databases for studies focusing on the properties, function, efficacy, and safety of nintedanib against different lung injuries. EXPERT OPINION: Nintedanib interferes with lung fibrosis and tumor angiogenesis by targeting multiple receptor tyrosine kinases (RTKs). Loss of RTKs activity leads to blocking downstream signaling cascades and inhibiting the proliferation and migration of lung fibroblasts. Targeting RTKs may be useful in the treatment of COVID-19 lung fibrosis. Nintedanib may be a superior agent compared to pirfenidone for the treatment of COVID-19 ARDS-related pulmonary fibrosis. Investigation of the efficacy and safety of nintedanib in the early stages of COVID-19-induced ARDS is critical since it may decrease the oxygen dependency and degree of lung fibrosis after the hospital discharge.

Effect of COVID-19 pandemic on incidence of mycobacterial diseases among suspected tuberculosis pulmonary patients in Tehran, Iran.

Background: Recent pandemic of coronavirus SARS-CoV-2 (COVID-19) caused limitations in the country's strategies to fight against mycobacterial infections. The aim of this study was to compare the suspected tuberculosis (TB) pulmonary patients before and during the COVID-19 pandemic (January 2018-December 2021) who were referred to the National Reference TB Laboratory (NRL TB), Tehran, Iran. The mycobacterial isolated strains were identified and compared with previous data. Methods: A total of 16,899 clinical samples collected from 7041 suspected pulmonary TB patients were received from 2018 to 2021. Primary isolation of Mycobacterium isolates was done on Löwenstein-Jensen medium. Then, the DNA was extracted from acid-fast bacillus culture-positive samples and identification was performed by IS6110, Hsp65, and 16S-23S rRNA genes using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, and nested PCR methods. Results: A total of 11679 specimens (69.1%) from 4866 suspected TB patients were collected in 2018-2019 and 5220 specimens (30.8%; from 2175 patients) in 2020-2021. Out of 11679 specimens, 2046 samples that belong to 852 patients were infected with Mycobacterium tuberculosis, and the remaining were non-TB Mycobacterium (NTM) species (n = 244) isolated from 102 patients. The cultures for 12894 specimens were either negative (76.3%) or contaminated (845/16899; 5%). A comparison of the total number of patients who were referred for diagnosis and treatment (954/666 patients, P > 0.05) showed a 30.1% reduction during the COVID-19 pandemic. Although, with these low number of patients, the significant increases of NTM species (P < 0.05) among suspected TB pulmonary patients were observed. Besides, new species of NTM, for example, Mycobacterium peregrinum and Mycobacterium montefiorense, were detected. For the past 20 years, these two species were not reported from pulmonary patients in Iran. Conclusions: During the pandemic of COVID-19, the TB diagnosis network became irregular, as a consequence, many patients could not reach the treatment center, and this could increase the circulation of mycobacterial diseases (TB and NTM). The study shows the emergence of new opportunistic NTM species also.

Correlation of single-nucleotide polymorphism at interferon-gamma R1 (at Position - 56) in positive purified protein derivative health workers with COVID-19 infection.

Background: The aim of the present study was to investigate the susceptibility of purified protein derivative (PPD) plus health-care workers to SARS-CoV-2 (COVID-19). For this reason, single-nucleotide polymorphism (SNP) of interferon-gamma (IFN-γ) gene at position +2109 and IFN-γ receptor 1 (R1) at position -56 was assessed in PPD plus group before and after COVID-19 infection (2017-2018; 2020-2021). Methods: The selected study cases (n = 100) that were working in tuberculosis (TB) unite (5-10 years) with PPD positivity >15 mm (16-20 mm) were included in this investigation. Sampling was done twice, once before and after the COVID-19 pandemic. Group A contains 50 samples collected from the GenBank TB laboratory that belong to TB staff before the pandemic (2017-2018). The other sample (Group B; 2021) was collected from the same unite during the COVID-19 pandemic. The SNP in the IFN-γ gene (+2109; 670 bp) and IFN-γ R 1 (-56; 366 bp) was performed using a specific primer and the polymerase chain reaction products were digested using restriction enzyme Fau I and Bts I, respectively. Statistical analyses were used to obtain the frequency of alleles among all studied cases. The confidence intervals (CIs) and t-test were calculated using the SPSS and GraphPad Prism software. Results: In overall, the most frequent genotype in Group A was AA (41/50; 82%) and Group B was 76% (38/50) in position + 2109 (odds ratio [OR] = 0.69, 95% CI, 0.26-1.83, and P = 0.46). Although in position -56, the most frequent genotype in Group A was TT (35/50; 70%) which significantly was than Group B TT (15/50; 30%) (OR = 0.184, 95% CI, 0.78-0.43, and P = 0.00). The frequency of allele A was more in both groups at position + 2109 (OR = 0.815, 95% CI, 0.23-2.86, and P = 0.75), whereas the dominate allele at position -56 was T in Group A (OR = 1.37, 95% CI, 0.62-3.02, and P = 0.42). Conclusion: No significant differences were observed in + 2109 in genotype among Group A and B. The main differences were seen in IFN-γ R1 at position (-56) between Group A and B. Hence, the IFN-γ R1 may play important role in COVID-19 infection. However, more study is needed to clear the IFN-γ correlation to COVID-19 infection.

Fixed drug eruption after the Sinopharm COVID-19 vaccine

After coronavirus disease 2019 (COVID-19) became widespread around the world, several vaccines have been developed with variable efficacy and potency and based on different platforms to control the pandemic. One of these vaccines is Sinopharm (BBIBP-CorV), which is an inactivated virus that was released by Sinopharm's Beijing institute in the summer of 2020. The most commonly reported side effects of the Sinopharm vaccine have included pain at the injection site, muscle pain, headache and fatigue. Dermatological reactions are also reported as less common and were mainly local injection site reactions. Fixed drug eruption (FDE) is a rare and unusual adverse effect and accounts for less than 1% of all severe acute respiratory syndrome coronavirus 2 vaccine-related cutaneous manifestations. FDE has not been reported following the COVID-19 inactivated vaccine. Here, we describe a rare case of FDE following the administration of the first shot of the Sinopharm vaccine.

Allergic shiners in a patient with cough-variant asthma: a case report.

BACKGROUND: Chronic cough, with a duration of coughing of more than 8 weeks in adults, affects 5-10% of the general population. One of the most common causes of chronic cough is cough-variant asthma, which accounts for approximately one-third of cases. This phenotype of asthma is characterized by extreme sensitivity of the neuronal pathways mediating cough to environmental irritants, which results in an urge to cough. This case is an example of cough-variant asthma presenting with allergic shiners due to her severe cough. CASE PRESENTATION: A 38-year-old Iranian woman, who was well before the start of the coronavirus disease 2019 pandemic, presented with a nonproductive hacking cough that had begun after excessive use of antiseptic solutions. The only positive finding on physical examination was a reddish-purple rash on and around the eyelids mimicking a heliotrope rash, which had probably evolved due to the severity of the cough. The results of the pulmonary function test were within normal limits. Methacholine challenge test and chest x-ray were both normal. Chest high-resolution computed tomography revealed hyperinflation and tree-in-bud opacities. All other laboratory tests were normal. Because of the reversibility in her pulmonary function test, despite normal baseline parameters, asthma treatment was initiated, resulting in disappearance of the cough and the eye discoloration, being indicative of the correct diagnosis and proper treatment. CONCLUSION: Patients with cough-variant asthma may often have no other classic symptoms of asthma other than cough.

National Research Institute of Tuberculosis and Lung Disease (NRITLD) Protocol for the Treatment of Patients with COVID-19.

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.

Favipiravir Effects on the Control of Clinical Symptoms of Hospitalized COVID-19 Cases: An Experience with Iranian Formulated Dosage Form.

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.

Comparative evaluation of SARS-CoV-2 IgG assays against nucleocapsid and spike antigens.

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.

SARS-CoV­2, a virus with many faces: a series of cases with prolonged persistence of COVID-19 symptoms.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as the causative agent of the ongoing pandemic, has spread into more than 200 countries to date. The disease which is caused by the virus is termed COVID-19. In most cases, it presents at first like common flu with cough and other respiratory symptoms. Nevertheless, other symptoms have been reported, such as a feeling of extreme fatigue, gastrointestinal symptoms, or acute onset of olfactory and gustatory dysfunction. Here we report a series of 10 cases (1 male, 9 females) observed between February and April 2020, with an undulating appearance and disappearance of symptoms. Weeks passed before the diagnosis was established. Symptoms resolved rapidly after treatment with hydroxychloroquine. It seems that the course of COVID-19 can be mild or moderate but with a long persistence of symptoms, and may therefore remain obscure. This may cause a public health issue because of the long infectivity of these patients.

A review on favipiravir: the properties, function, and usefulness to treat COVID-19.

INTRODUCTION: At this time, there is no specific therapeutic or vaccine for treatment of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, available drugs for treatment of other viral infections may be useful to treat COVID-19. AREAS COVERED: The focus of the current review was studying the main characteristics of favipiravir and its usefulness to treat COVID-19. An electronic search was done by using Pubmed and Google scholar. EXPERT OPINION: Based on the mechanism of action and safety of favipiravir, the drug may be a promising candidate for compassionate use against the SARS-CoV-2 infection. Favipiravir has a wide range of activity against many single-stranded RNA viruses, is well tolerated in humans and has a high barrier to resistance. However, high doses of the agent are necessary to obtain an efficient antiviral activity. Favipiravir is teratogen in pregnant women and associated with the hyperuricemia. Therefore, the administration of the drug should be well controlled. Investigating the antiviral prophylactic potency of favipiravir and search for its pro-drugs and/or analogs showing improved activity and/or safety are critical.

Real Clinical Practice and Therapeutic Management Following COVID-19 Crisis in two Hospitals in Iran: A Statistical and Conceptual View.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) outbreak quickly has spread and became a pandemic. However, no approved therapeutics or effective treatment is available for the treatment of these patients. The present study was done to retrospectively assess the treatment strategies (e.g., pharmaceutical care services) for COVID-19 patients in selected hospitals and highlight the importance of such services in the management of a pandemic. MATERIALS AND METHODS: Data from a series of COVID-19 patients (978 patients; 658 males [66.9%] and 324 females [33.1%]) admitted to the selected hospitals in Tehran from 20 February to 19 March 2020 were retrieved retrospectively from the Health Information System (HIS) of the hospitals. The statistical tests were used for analyzing the effect and correlation of the variables (drugs) with the average length of stay (ALOS) in the hospital. RESULTS: Diverse medication classes and old drugs with or without strong evidence of therapeutic effects against the novel coronavirus, some previously tried as a treatment for SARS-CoV and MERS-CoV, were mostly used for the treatment of patients in the hospitals. Many medications (broad-spectrum antibiotics and antivirals) or combination therapies are used without evidence of their therapeutic effects during pandemics. CONCLUSION: Therefore, guidelines should be provided for the off-label use of these drugs by policymakers and stakeholders during a pandemic emergency due to high demands. Also, monitoring of the HIS data can play an important role in improving public health response to emerging diseases.

Clinical Manifestations of Patients with Coronavirus Disease 2019 (COVID-19) in a Referral Center in Iran.

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.

A Review on Remdesivir: A Possible Promising Agent for the Treatment of COVID-19.

The novel coronavirus 2019 (2019-nCoV), formally named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a novel human infectious coronavirus. The disease caused by SARS-CoV-2 is named COVID-19. Development and manufacturing of specific therapeutics and vaccines to treat COVID-19 are time-consuming processes. At this time, using available conventional therapeutics along with other treatment options may be useful to fight COVID-19. In different clinical trials, efficacy of remdesivir (GS-5734) against Ebola virus has been demonstrated. Moreover, remdesivir may be an effective therapy in vitro and in animal models infected by SARS and MERS coronaviruses. Hence, the drug may be theoretically effective against SARS-CoV-2. Remdesivir is a phosphoramidate prodrug of an adenosine C-nucleoside. By entrance into respiratory epithelial cells in human, the prodrug is metabolized to a nucleoside triphosphate as the active form. The nucleoside analog inhibits the viral RNA-dependent RNA polymerase (RdRp) by competing with the usual counterpart adenosine triphosphate (ATP). The nucleoside analog is incorporated into the generating RNA strand and causes a delayed stop in the viral replication process. Knowledge about the potential efficacy of remdesivir against coronaviruses has been restricted to in vitro studies and animal models. However, information related to COVID-19 is rapidly growing. Several clinical trials are ongoing for the management of COVID-19 using remdesivir. In this study, characteristics of remdesivir and its usage for treatment of COVID-19 are reviewed based on an electronic search using PubMed and Google Scholar.