The controversial effect of smoking and nicotine in SARS-CoV-2 infection.

The effects of nicotine and cigarette smoke in many diseases, notably COVID-19 infection, are being debated more frequently. The current basic data for COVID-19 is increasing and indicating the higher risk of COVID-19 infections in smokers due to the overexpression of corresponding host receptors to viral entry. However, current multi-national epidemiological reports indicate a lower incidence of COVID-19 disease in smokers. Current data indicates that smokers are more susceptible to some diseases and more protective of some other. Interestingly, nicotine is also reported to play a dual role, being both inflammatory and anti-inflammatory. In the present study, we tried to investigate the effect of pure nicotine on various cells involved in COVID-19 infection. We followed an organ-based systematic approach to decipher the effect of nicotine in damaged organs corresponding to COVID-19 pathogenesis (12 related diseases). Considering that the effects of nicotine and cigarette smoke are different from each other, it is necessary to be careful in generalizing the effects of nicotine and cigarette to each other in the conducted researches. The generalization and the undifferentiation of nicotine from smoke is a significant bias. Moreover, different doses of nicotine stimulate different effects (dose-dependent response). In addition to further assessing the role of nicotine in COVID-19 infection and any other cases, a clever assessment of underlying diseases should also be considered to achieve a guideline for health providers and a personalized approach to treatment.

Exploring the experience of developing COVID-19 vaccines in Iran.

Widespread public vaccination is one of the effective mechanisms to ensure the health and prevent deaths in societies. The coronavirus disease 2019 (COVID-19) vaccine is a stark instance in this regard. Vaccine development is a complex process requiring firm-level capabilities, various infrastructures, long-term planning, and stable and efficient policies. Due to the global demand for vaccines during the pandemic, the national capability to produce vaccines is critical. To this end, the current paper investigates influential factors, at the firm- and policy-level, in the COVID-19 vaccine development process in Iran. By adopting a qualitative research method and conducting 17 semi-structured interviews and analyzing policy documents, news, and reports, we extracted internal and external factors affecting the success and failure of a vaccine development project. We also discuss the characteristics of the vaccine ecosystem and the gradual maturity of policies. This paper draws lessons for vaccine development in developing countries at both firm and policy levels.

Evaluation the efficacy and safety of N-acetylcysteine inhalation spray in controlling the symptoms of patients with COVID-19: An open-label randomized controlled clinical trial.

The aim of this study was to evaluate the effect and safety of N-acetylcysteine (NAC) inhalation spray in the treatment of patients with coronavirus disease 2019 (COVID-19). This randomized controlled clinical trial study was conducted on patients with COVID-19. Eligible patients (n = 250) were randomly allocated into the intervention group (routine treatment + NAC inhaler spray one puff per 12 h, for 7 days) or the control group who received routine treatment alone. Clinical features, hemodynamic, hematological, biochemical parameters and patient outcomes were assessed and compared before and after treatment. The mortality rate was significantly higher in the control group than in the intervention group (39.2% vs. 3.2%, p < 0.001). Significant differences were found between the two groups (intervention and control, respectively) for white blood cell count (6.2 vs. 7.8, p < 0.001), hemoglobin (12.3 vs. 13.3, p = 0.002), C-reactive protein (CRP: 6 vs. 11.5, p < 0.0001) and aspartate aminotransferase (AST: 32 vs. 25.5, p < 0.0001). No differences were seen for hospital length of stay (11.98 ± 3.61 vs. 11.81 ± 3.52, p = 0.814) or the requirement for intensive care unit (ICU) admission (7.2% vs. 11.2%, p = 0.274). NAC was beneficial in reducing the mortality rate in patients with COVID-19 and inflammatory parameters, and a reduction in the development of severe respiratory failure; however, it did not affect the length of hospital stay or the need for ICU admission. Data on the effectiveness of NAC for Severe Acute Respiratory Syndrome Coronavirus-2 is limited and further research is required.

Mask assistance to colorimetric sniffers for detection of Covid-19 disease using exhaled breath metabolites.

According to World Health Organization reports, large numbers of people around the globe have been infected or died for Covid-19 due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Researchers are still trying to find a rapid and accurate diagnostic method for revealing infected people by low viral load with the overriding goal of effective diagnostic management. Monitoring the body metabolic changes is known as an effective and inexpensive approach for the evaluation of the infected people. Here, an optical sniffer is introduced to detect exhaled breath metabolites of patients with Covid-19 (60 samples), healthy humans (55 samples), and cured people (15 samples), providing a unique color pattern for differentiation between the studied samples. The sniffer device is installed on a thin face mask, and directly exposed to the exhaled breath stream. The interactions occurring between the volatile compounds and sensing components such as porphyrazines, modified organic dyes, porphyrins, inorganic complexes, and gold nanoparticles allowing for the change of the color, thus being tracked as the sensor responses. The assay accuracy for the differentiation between patient, healthy and cured samples is calculated to be in the range of 80%-84%. The changes in the color of the sensor have a linear correlation with the disease severity and viral load evaluated by rRT-PCR method. Interestingly, comorbidities such as kidney, lung, and diabetes diseases as well as being a smoker may be diagnosed by the proposed method. As a powerful detection device, the breath sniffer can replace the conventional rapid test kits for medical applications.

Visual diagnosis of COVID-19 disease based on serum metabolites using a paper-based electronic tongue.

This study aims to use a paper-based sensor array for point-of-care detection of COVID-19 diseases. Various chemical compounds such as nanoparticles, organic dyes and metal ion complexes were employed as sensing elements in the array fabrication, capturing the metabolites of human serum samples. The viral infection caused the type and concentration of serum compositions to change, resulting in different color responses for the infected and control samples. For this purpose, 118 serum samples of COVID-19 patients and non-COVID controls both men and women with the age range of 14-88 years were collected. The serum samples were initially subjected to the sensor, followed by monitoring the variation in the color of sensing elements for 5 min using a scanner. By taking into consideration the statistical information, this method was capable of discriminating COVID-19 patients and control samples with 83.0% accuracy. The variation of age did not influence the colorimetric patterns. The desirable correlation was observed between the sensor responses and viral load values calculated by the PCR test, proposing a rapid and facile way to estimate the disease severity. Compared to other rapid detection methods, the developed assay is cost-effective and user-friendly, allowing for screening COVID-19 diseases reliably.

Non-invasive detection of COVID-19 using a microfluidic-based colorimetric sensor array sensitive to urinary metabolites.

A colorimetric sensor array designed on a paper substrate with a microfluidic structure has been developed. This array is capable of detecting COVID-19 disease by tracking metabolites of urine samples. In order to determine minor metabolic changes, various colorimetric receptors consisting of gold and silver nanoparticles, metalloporphyrins, metal ion complexes, and pH-sensitive indicators are used in the array structure. By injecting a small volume of the urine sample, the color pattern of the sensor changes after 7 min, which can be observed visually. The color changes of the receptors (recorded by a scanner) are subsequently calculated by image analysis software and displayed as a color difference map. This study has been performed on 130 volunteers, including 60 patients infected by COVID-19, 55 healthy controls, and 15 cured individuals. The resulting array provides a fingerprint response for each category due to the differences in the metabolic profile of the urine sample. The principal component analysis-discriminant analysis confirms that the assay sensitivity to the correctly detected patient, healthy, and cured participants is equal to 73.3%, 74.5%, and 66.6%, respectively. Apart from COVID-19, other diseases such as chronic kidney disease, liver disorder, and diabetes may be detectable by the proposed sensor. However, this performance of the sensor must be tested in the studies with a larger sample size. These results show the possible feasibility of the sensor as a suitable alternative to costly and time-consuming standard methods for rapid detection and control of viral and bacterial infectious diseases and metabolic disorders.

Mortality rate of people exposed to Mustard Gas during Iran-Iraq war in Sardasht, Iran: a 32 years retrospective cohort study.

BACKGROUND: Mustard gas (MG) is one of the most widely used chemical weapons in the past century. However, little information exists concerning long-term mortality from MG exposure. In this study, we investigated mortality rate among civilian people exposed to MG during Iran-Iraq war in Sardasht in Iran after 32 years.  METHODS: In this retrospective cohort study, data of people exposed to MG in Sardasht in 1987 were extracted from the Veterans and Martyr Affair Foundation of Iran up to March 20, 2019. Mortality rate, cumulative mortality and standardized mortality ratio with 95% confidence interval were calculated to explain mortality in the cohort, and then compared with general Iranian population. Cox regression analysis was used to indicate factor affecting the risk of death in the cohort.  RESULTS: Out of 1,203 exposed people at the beginning of the period, 148 people died by the end of the study, with an average age of 66.42 at the time of death. Total person-years of the people up to end of the study were 38,198.63 and mortality rate was equal to 387 per 100,000 persons-years. Total number of observed deaths was less than expected death and the all-cause standardized mortality ratio (SMR) was determined as 0.680 (95% CI: 0.574 - 0.798). Cause-specific SMR showed that observed death due to respiratory diseases was higher than expected (SMR: 1.75) (95% CI: 1.145 - 2.569). The results of univariate and multivariate cox regression analysis showed that increasing age and having severe late complications in lung were associated with increased risk of death among people in the cohort. CONCLUSION: In general, this result indicated that acute exposure to MG, even without wearing protective clothing and masks, could not increase all-cause mortality after 32 years if accompanied by special and ongoing care for those exposed.

A colorimetric electronic tongue for point-of-care detection of COVID-19 using salivary metabolites.

The monitoring of profile concentrations of chemical markers in saliva samples can be used to diagnose COVID-19 patients, and differentiate them from healthy individuals. Here, this purpose is achieved by designing a paper-based colorimetric sensor with an origami structure, containing general receptors such as pH-sensitive organic dyes, Lewis donors or acceptors, functionalized nanoparticles, and ion metal complexes. The color changes taking place in the receptors in the presence of chemical markers are visually observed and recorded with a digital instrument. Different types and amounts of the chemical markers provide the sensor with a unique response for patients (60 samples) or healthy (55 samples) individuals. These two categories can be discriminated with 84.3% accuracy. This study evidences that the saliva composition of cured and healthy participants is different from each other with accuracy of 85.7%. Moreover, viral load values obtained from the rRT-PCR method can be estimated by the designed sensor. Besides COVID-19, it may possible to simultaneously identify smokers and people with kidney disease and diabetes using the specified electronic tongue. Due to its high efficiency, the prepared paper device can be employed as a rapid detection kit to detect COVID-19.

The efficacy of corticosteroids therapy in patients with moderate to severe SARS-CoV-2 infection: a multicenter, randomized, open-label trial.

BACKGROUND: We performed a multicenter, randomized open-label trial in patients with moderate to severe Covid-19 treated with a range of possible treatment regimens. METHODS: Patients were randomly assigned to one of three regimen groups at a ratio of 1:1:1. The primary outcome of this study was admission to the intensive care unit. Secondary outcomes were intubation, in-hospital mortality, time to clinical recovery, and length of hospital stay (LOS). Between April 13 and August 9, 2020, a total of 336 patients were randomly assigned to receive one of the 3 treatment regimens including group I (hydroxychloroquine stat, prednisolone, azithromycin and naproxen; 120 patients), group II (hydroxychloroquine stat, azithromycin and naproxen; 116 patients), and group III (hydroxychloroquine and lopinavir/ritonavir (116 patients). The mean LOS in patients receiving prednisolone was 5.5 in the modified intention-to-treat (mITT) population and 4.4 days in the per-protocol (PP) population compared with 6.4 days (mITT population) and 5.8 days (PP population) in patients treated with Lopinavir/Ritonavir. RESULTS: The mean LOS was significantly lower in the mITT and PP populations who received prednisolone compared with populations treated with Lopinavir/Ritonavir (p = 0.028; p = 0.0007). We observed no significant differences in the number of deaths, ICU admission, and need for mechanical ventilation between the Modified ITT and per-protocol populations treated with prednisolone and Lopinavir/Ritonavir, although these outcomes were better in the arm treated with prednisolone. The time to clinical recovery was similar in the modified ITT and per-protocol populations treated with prednisolone, lopinavir/ritonavir, and azithromycin (P = 0.335; P = 0.055; p = 0.291; p = 0.098). CONCLUSION: The results of the present study show that therapeutic regimen (regimen I) with low dose prednisolone was superior to other regimens in shortening the length of hospital stay in patients with moderate to severe COVID-19. The steroid sparing effect may be utilized to increase the effectiveness of corticosteroids in the management of diabetic patients by decreasing the dosage.

Safety and efficacy of Favipiravir in moderate to severe SARS-CoV-2 pneumonia.

BACKGROUND: We examined the safety and efficacy of a treatment protocol containing Favipiravir for the treatment of SARS-CoV-2. METHODS: We did a multicenter randomized open-labeled clinical trial on moderate to severe cases infections of SARS-CoV-2. Patients with typical ground glass appearance on chest computerized tomography scan (CT scan) and oxygen saturation (SpO2) of less than 93% were enrolled. They were randomly allocated into Favipiravir (1.6 gr loading, 1.8 gr daily) and Lopinavir/Ritonavir (800/200 mg daily) treatment regimens in addition to standard care. In-hospital mortality, ICU admission, intubation, time to clinical recovery, changes in daily SpO2 after 5 min discontinuation of supplemental oxygen, and length of hospital stay were quantified and compared in the two groups. RESULTS: 380 patients were randomly allocated into Favipiravir (193) and Lopinavir/Ritonavir (187) groups in 13 centers. The number of deaths, intubations, and ICU admissions were not significantly different (26, 27, 31 and 21, 17, 25 respectively). Mean hospital stay was also not different (7.9 days [SD = 6] in the Favipiravir and 8.1 [SD = 6.5] days in Lopinavir/Ritonavir groups) (p = 0.61). Time to clinical recovery in the Favipiravir group was similar to Lopinavir/Ritonavir group (HR = 0.94, 95% CI 0.75 - 1.17) and likewise the changes in the daily SpO2 after discontinuation of supplemental oxygen (p = 0.46) CONCLUSION: Adding Favipiravir to the treatment protocol did not reduce the number of ICU admissions or intubations or In-hospital mortality compared to Lopinavir/Ritonavir regimen. It also did not shorten time to clinical recovery and length of hospital stay.

The risk factors and related hospitalizations for cases with positive and negative COVID-19 tests: A case-control study.

BACKGROUND: The aim of this study was to evaluate the risk factors for hospitalizations of cases with positive and negative COVID-19 tests. METHODS: In this case-control study, the case and control groups consisted of 292 COVID-19 patients and 296 non-COVID-19 patients. Patients who referred to a reference laboratory in Tehran (Iran) in March 2020 were selected and interviewed. The patients were contacted by telephone and data were recorded through a questionnaire. RESULTS: The sample of this study consisted of 588 patients (349 [59%] females, 239 [41%] males) with a mean age of 42 ± 15. The results of this study showed that comorbidities like diabetes (OR = 7.42), hypertension (OR = 4.85), asthma and respiratory diseases (OR = 5.64) in addition to symptoms including fever (OR = 6.67), chills (OR = 11.2), anorexia (OR = 11.3), dyspnea (OR = 4.8), weakness and lethargy (OR = 5.7) were the most predictive variables for hospitalization of non-COVID-19 cases. Furthermore, demographical variables like male gender (OR = 3.71), high age (>50; OR = 3.12), BMI (>25; OR = 2.37), travel (OR = 2.79), comorbidities including diabetes (OR = 5.26), hypertension (OR = 3.7) and underlying immunosuppressant patients receiving corticosteroid therapy (OR = 3.62) in addition to symptoms like anorexia [OR = 2.55] and dyspnea (OR = 6.99) tend to increase the risk of hospital admission in COVID-19 patients, suggesting their predictive values for hospitalization of COVID-19 patients. CONCLUSION: Our results indicated that different factors tend to increase the odds of hospital admission in patients with positive and negative COVID-19 tests, suggesting their predictive values for hospitalization.

From Radiological Manifestations to Pulmonary Pathogenesis of COVID-19: A Bench to Bedside Review.

In this review, we aim to assess previous radiologic studies in COVID-19 and suggest a pulmonary pathogenesis based on radiologic findings. Although radiologic features are not specific and there is heterogeneity in symptoms and radiologic and clinical manifestation, we suggest that the dominant pattern of computed tomography is consistent with limited pneumonia, followed by interstitial pneumonitis and organizing pneumonia.

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.

Multiple potential targets of opioids in the treatment of acute respiratory distress syndrome from COVID-19.

COVID-19 can present with a variety of clinical features, ranging from asymptomatic or mild respiratory symptoms to fulminant acute respiratory distress syndrome (ARDS) depending on the host's immune responses and the extent of the associated pathologies. This implies that several measures need to be taken to limit severely impairing symptoms caused by viral-induced pathology in vital organs. Opioids are most exploited for their analgesic effects but their usage in the palliation of dyspnoea, immunomodulation and lysosomotropism may represent potential usages of opioids in COVID-19. Here, we describe the mechanisms involved in each of these potential usages, highlighting the benefits of using opioids in the treatment of ARDS from SARS-CoV-2 infection.

The clinical value of two combination regimens in the Management of Patients Suffering from Covid-19 pneumonia: a single centered, retrospective, observational study.

BACKGROUND: There is no identified pharmacological therapy for COVID-19 patients, where potential therapeutic strategies are underway to determine effective therapy under such unprecedented pandemic. Therefore, combination therapies may have the potential of alleviating the patient's outcome. This study aimed at comparing the efficacy of two different combination regimens in improving outcomes of patients infected by novel coronavirus (COVID-19). METHODS: This is a single centered, retrospective, observational study of 60 laboratory-confirmed COVID-19 positive inpatients (≥18 years old) at two wards of the Baqiyatallah Hospital, Tehran, Iran. Patient's data including clinical and laboratory parameters were recorded. According to the drug regimen, the patients were divided into two groups; group I who received regimen I consisting azithromycin, prednisolone, naproxen, and lopinavir/ritonavir and group II who received regimen II including meropenem, levofloxacin, vancomycin, hydroxychloroquine, and oseltamivir. RESULTS: The oxygen saturation (SpO2) and temperature were positively changed in patients receiving regimen I compared to regimen II (P = 0.013 and P = 0.012, respectively). The serum level of C-reactive protein (CRP) changed positively in group I (P < 0.001). Although there was a significant difference in platelets between both groups (75.44 vs 51.62, P < 0.001), their change did not clinically differ between two groups. The findings indicated a significant difference of the average length of stay in hospitals (ALOS) between two groups, where the patients under regimen I showed a shorter ALOS (6.97 vs 9.93, P = 0.001). CONCLUSION: This study revealed the beneficial effect of the short-term use of low-dose prednisolone in combination with azithromycin, naproxen and lopinavir/ritonavir (regimen I), in decreasing ALOS compared to regimen II. Since there is still lack of evidence for safety of this regimen, further investigation in our ongoing follow-up to deal with COVID-19 pneumonia is underway. Graphical abstract.