Radiological Findings as Predictors of COVID-19 Lung Sequelae: A Systematic Review and Meta-Analysis

Background This systematic review and meta-analysis aimed to investigate the radiological predictors of post- coronavirus disease 19 (COVID-19) pulmonary fibrosis and incomplete absorption of pulmonary lesions. Method We systematically searched PubMed, EMBASE, and Web of Science for studies reporting the predictive value of radiological findings in patients with post-COVID-19 lung residuals published through November 11, 2022. The pooled odds ratios with a 95% confidence interval (CI) were assessed. The random-effects model was used due to the heterogeneity of the true effect sizes. Results We included 11 studies. There were 1777 COVID-19-positive patients, and 1014 (57 %) were male. All studies used chest computed tomography (CT) as a radiologic tool. Moreover, chest X-ray (CXR) and lung ultrasound were used in two studies, along with a CT scan. CT severity score, Radiographic Assessment of Lung Edema score (RALE), interstitial score, lung ultrasound score (LUS), patchy opacities, abnormal CXR, pleural traction, and subpleural abnormalities were found to be predictors of post-COVID-19 sequels. CT severity score (CTSS) and consolidations were the most common predictors among included studies. Pooled analysis revealed that pulmonary residuals in patients with initial consolidation are about four times more likely than in patients without this finding (OR: 3.830;95% CI: 1.811-8.102, I2: 4.640). Conclusion Radiological findings can predict the long-term pulmonary sequelae of COVID-19 patients. CTSS is an important predictor of lung fibrosis and COVID-19 mortality. Lung fibrosis can be diagnosed and tracked using the LUS. Changes in RALE score during hospitalization can be used as an independent predictor of mortality.

Is it necessary to define new diagnostic reference levels during pandemics like the Covid19-?

Introduction: This study intended to assess the dose length product (DLP), effective cumulative radiation dose (E.D.), and additional cancer risk (ACR) due to a chest CT scan to detect or follow up the Covid-19 disease in four university-affiliated hospitals that used different imaging protocols. Indeed, this study aimed to examine the differences in decision-making between different imaging centers in choosing chest CT imaging protocols during the pandemic, and to assess whether a new diagnostic reference level (DRL) is needed in pandemic situations. Methods: This retrospective study assessed the E.D. of all chest imagings for Covid-19 for six months in four different hospitals in our country. Imaging parameters and DLP (mGy.cm) were recorded. The E.D.s and ACRs from chest CT scans were calculated using an online calculator. Results: Thousand-six hundred patients were included in the study. The mean cumulative dose due to chest CT was 3.97 mSv which might cause 2.59 × 10-2 ACR. The mean cumulative E.D. in different hospitals was in the range of 1.96-9.51 mSv. Conclusions: The variety of mean E.D.s shows that different hospitals used different imaging protocols. Since there is no defined DRL in the pandemic, some centers use routine protocols, and others try to reduce the dose but insufficiently.In pandemics such as Covid-19, when CT scan is used for screening or follow-up, DLPs can be significantly lower than in normal situations. Therefore, international regularized organizations such as the international atomic energy agency (IAEA) or the international commission on radiological protection (IRCP) should provide new DRL ranges.

Bronchial wall necrosis secondary to mucormycosis following SARS-Cov2 infection: A case report.

Coronavirus 2019 infection (COVID-19) has a broad spectrum of clinical complications, some unrecognized. Herein, a case of a diabetic patient with multiple episodes of hemoptysis 2 months following her recovery from SARS-CoV-2 infection is reported. The initial computed tomography (CT scan) revealed the left lower lobe collapsed secondary to bronchial narrowing and obliteration. Bronchoscopy was performed, indicating necrotic endobronchial tissue, which was confirmed histopathologically as invasive mucormycosis. Bronchial necrosis due to mucormycosis is an unusual presentation of COVID-19-associated pulmonary mucormycosis. The accurate diagnosis could be challenging as it can resemble other pathologies such as malignancies. Therefore, it is crucial to identify this fatal complication in patients with prolonged COVID-19 and lung collapse.

Statistical analysis of COVID-19 infection severity in lung lobes from chest CT.

Detection of the COVID 19 virus is possible through the reverse transcription-polymerase chain reaction (RT-PCR) kits and computed tomography (CT) images of the lungs. Diagnosis via CT images provides a faster diagnosis than the RT-PCR method does. In addition to low false-negative rate, CT is also used for prognosis in determining the severity of the disease and the proposed treatment method. In this study, we estimated a probability density function (PDF) to examine the infections caused by the virus. We collected 232 chest CT of suspected patients and had them labeled by two radiologists in 6 classes, including a healthy class and 5 classes of different infection severity. To segment the lung lobes, we used a pre-trained U-Net model with an average Dice similarity coefficient (DSC) greater than 0.96. First, we extracted the PDF to grade the infection of each lobe and selected five specific thresholds as feature vectors. We then assigned this feature vector to a support vector machine (SVM) model and made the final prediction of the infection severity. Using the T-Test statistics, we calculated the p-value at different pixel thresholds and reported the significant differences in the pixel values. In most cases, the p-value was less than 0.05. Our developed model was developed on roughly labeled data without any manual segmentation, which estimated lung infection involvements with the area under the curve (AUC) in the range of [0.64, 0.87]. The introduced model can be used to generate a systematic automated report for individual patients infected by COVID-19.

Acute disseminated encephalomyelitis (ADEM) after SARS- CoV-2 vaccination: A case report.

Acute disseminated encephalomyelitis (ADEM) is an acute demyelinating disorder of the central nervous system that is ordinarily monophasic. ADEM can develop following infection or vaccination. Here, we present a 37 y/o male patient with progressive muscle weakness in all limbs along with dysphagia following COVID-19 vaccination. Brain magnetic resonance imaging (MRI) revealed typical imaging findings which presented as multifocal T2-FLAIR signal changes in the corticospinal tract, pons, and temporal lobe with diffusion restriction. Magnetic resonance spectroscopy (MRS) further confirmed the diagnosis by the typical elevation of the Choline and Myoinositol peaks. Neurologic impairments have been reported as the potential side effects of COVID-19 vaccines. Appropriate imaging modalities together with a thorough clinical examination are essential for making a correct diagnosis.

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.

Organizing pneumonia-like pattern in COVID-19.

INTRODUCTION: Organizing pneumonia (OP) is a radio-histologic pattern that forms in response to lung damage in patients with focal or diffuse lung injury. OP is frequently observed subsequent to viral-induced lung damage and is associated with a diverse range of clinical outcomes. MATERIAL AND METHODS: We included 210 patients (mean age: 55.8 ± 16.5 years old; 61% male) with mild Coronavirus disease 2019 (COVID-19) who underwent chest computed tomography (CT) from 25 February to 22 April, 2020. The patients were divided into two groups based on the presence (n = 103) or absence of typical OP-like pattern (n =107) on initial chest CT. The extent of lung involvement and final outcome was compared across the two groups. Serial changes in imaging were also evaluated in 36 patients in the OP-group with a second CT scan. RESULTS: Duration from symptom onset to presentation was significantly higher in the OP group (7.07 ± 3.71 versus 6.13 ± 4.96 days, p = 0.008). A higher COVID-19-related mortality rate was observed among patients with OP-like pattern (17.5% vs 3.7%, p = 0.001).There was no significant difference in the overall involvement of the lungs (p = 0.358), but lower lobes were significantly more affected in the OP group (p < 0.001). Of the 36 patients with follow-up imaging (mean duration of follow-up = 8.3 ± 2.1 days), progression of infiltration was seen in more than 61% of patients while lesions had resolved in only 22.2% of cases. CONCLUSIONS: Our observation indicates that physicians should carefully monitor for the presence of OP-like pattern on initial CT as it is associated with a poor outcome. Furthermore, we recommend interval CT to evaluate the progression of infiltrations in these patients.

Correction: ai-corona: Radiologist-assistant deep learning framework for COVID-19 diagnosis in chest CT scans.

[This corrects the article DOI: 10.1371/journal.pone.0250952.].

A Systematic Review of Imaging Studies in Olfactory Dysfunction Secondary to COVID-19.

RATIONALE AND OBJECTIVES: Hyposmia/anosmia is common among patients with coronavirus disease-2019 (COVID-19). Various imaging modalities have been used to assess olfactory dysfunction in COVID-19. In this systematic review, we sought to categorize and summarize the imaging data in COVID-19-induced anosmia. MATERIAL AND METHODS: Eligible articles were included after a comprehensive review using online databases including Google scholar, Scopus, PubMed, Web of science and Elsevier. Duplicate results, conference abstracts, reviews, and studies in languages other than English were excluded. RESULTS: In total, 305 patients undergoing MRI/functional MRI (177), CT of paranasal sinuses (129), and PET/CT or PET/MRI scans (14) were included. Out of a total of 218 findings reported on MRI, 80 were reported on early (≤ 1 month) and 85 on late (>1 month) imaging in relation to the onset of anosmia. Overall, OB morphology and T2-weighted or FLAIR signal intensity were normal in 68/218 (31.2%), while partial or complete opacification of OC was observed in 60/218 (27.5%). T2 hyperintensity in OB was detected in 11/80 (13.75%) and 18/85 (21.17%) on early and late imaging, respectively. Moreover, OB atrophy was reported in 1/80 (1.25%) on early and in 9/85 (10.58%) on late imaging. Last, among a total of 129 CT scans included, paranasal sinuses were evalualted in 88 (68.21%), which were reported as normal in most cases (77/88, [87.5%]). CONCLUSION: In this systematic review, normal morphology and T2/FLAIR signal intensity in OB and OC obstruction were the most common findings in COVID-19-induced anosmia, while paranasal sinuses were normal in most cases. OC obstruction is the likely mechanism for olfactory dysfunction in COVID-19. Abnormalities in OB signal intensity and OB atrophy suggest that central mechanisms may also play a role in late stage in COVID-19-induced anosmia.

Combined Therapy of Ciclosporin Plus Favipiravir in the Management of Patients with Severe COVID-19, not Responding to Dexamethasone: A non-Controlled Prospective Trial.

BACKGROUND: Regarding the COVID-19 pandemic, potential therapeutic agents are being evaluated almost every day. Ciclosporin, a calcineurin inhibitor, is characterized by beneficial antiviral and immunomodulatory effects. The present study aimed to evaluate the efficacy of ciclosporin in managing COVID-19. METHODS: This study was a prospective non-controlled clinical trial carried out on 20 patients. Confirmed COVID-19 patients received two doses of ciclosporin (10 mg/kg and 5 mg/kg injections) 24 h apart. Mortality rate and the lengths of intensive care unit (ICU) and hospital stays were assessed for all 20 patients. RESULTS: The mortality rate and the need for mechanical ventilation were calculated as 50%. The percentage of ICU admission was 70%. The lengths of ICU and hospital stays were 8.13 ± 6.81 and 14.25 ± 8.55 days, respectively. The levels of ferritin and white blood cells were significantly higher after injecting the second dose of ciclosporin. Seven patients (35%) had radiologically improved lungs after ciclosporin therapy. CONCLUSION: It seems that the protocol of two doses of ciclosporin in combination with favipiravir does not have favorable effects among COVID-19 patients that do not respond to dexamethasone. Controlled trials are needed to confirm the results.

IgM-enriched immunoglobulin in COVID-19: Case series of 15 severely ill SARS-CoV-2-infected patients.

The healthcare system in Iran, like most around the world, is managing thousands of patients hospitalised with COVID-19. In Iran, in-hospital mortality is in the region of 25%, rising to 50-60% in patients admitted to intensive care. Hyperinflammation, characterised by cytokine storm, appears to be a hallmark of severe COVID-19 and to date only the anti-inflammatory drug dexamethasone has been shown to reduce mortality in those hospitalised with the disease. There is a sound scientific rationale behind the use of IgM-enriched immunoglobulin in the management of patients with severe COVID-19. It has been used successfully in the management of hyperinflammation in patients with sepsis and has led to improved radiographic scores in patients with severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. Recently the successful treatment of a patient with COVID-19 with IgM-enriched immunoglobulin was reported. Here we report the outcome of a further 15 patients hospitalised with COVID-19 treated with IgM-enriched immunoglobulin. Improvements in computed tomography (CT) score were observed in nine patients, indicating that further clinical studies into the use of IgM-enriched immunoglobulin in the treatment of severe COVID-19 are warranted.

Evaluation of adalimumab effects in managing severe cases of COVID-19: A randomized controlled trial.

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.

ai-corona: Radiologist-assistant deep learning framework for COVID-19 diagnosis in chest CT scans.

The development of medical assisting tools based on artificial intelligence advances is essential in the global fight against COVID-19 outbreak and the future of medical systems. In this study, we introduce ai-corona, a radiologist-assistant deep learning framework for COVID-19 infection diagnosis using chest CT scans. Our framework incorporates an EfficientNetB3-based feature extractor. We employed three datasets; the CC-CCII set, the MasihDaneshvari Hospital (MDH) cohort, and the MosMedData cohort. Overall, these datasets constitute 7184 scans from 5693 subjects and include the COVID-19, non-COVID abnormal (NCA), common pneumonia (CP), non-pneumonia, and Normal classes. We evaluate ai-corona on test sets from the CC-CCII set, MDH cohort, and the entirety of the MosMedData cohort, for which it gained AUC scores of 0.997, 0.989, and 0.954, respectively. Our results indicates ai-corona outperforms all the alternative models. Lastly, our framework's diagnosis capabilities were evaluated as assistant to several experts. Accordingly, We observed an increase in both speed and accuracy of expert diagnosis when incorporating ai-corona's assistance.

No clinical benefit of high dose corticosteroid administration in patients with COVID-19: A preliminary report of a randomized clinical trial.

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.

Radiological and Laboratory Findings of Patients with COVID-19 Infection at the Time of Admission.

BACKGROUND & OBJECTIVE: Diagnosis of coronavirus disease 2019 (COVID-19) can be challenging, especially when the real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) is not available or it is negative. In this study, we evaluated imaging and laboratory findings in a group of patients with a multidisciplinary diagnosis of COVID-19 pneumonia. METHODS: A total of 163 patients with a clinical diagnosis of COVID-19 pneumonia admitted to a specialised respiratory centre in Tehran, Iran were enrolled in this study. The distribution and characteristics of presenting radiological and laboratory findings were evaluated and the relationship to the outcome was investigated. RESULTS: RT-PCR was positive in 92 patients. The diagnosis of COVID-19 in RT-PCR negative patients was made on clinical and radiological features (n=71) and 24 (14.7%) patients died of disease. The common computed tomography (CT) scan findings included ground-glass (94%) and consolidating opacification (12%), mainly in the lower lobes (90%). Peripheral and central lung changes were observed in 90% and 52% of patients, respectively. Lymphopenia, positive CRP, and raised LDH were present in 32%, 65%, and 96% of cases, respectively. A raised LDH of >500U/L was the best predictor of death in these patients (R2=0.6623; OR=24.4). Other markers of outcome included male gender, age (>50 years), lymphopenia, and severe CXR changes. CONCLUSION: Diagnosis of COVID-19 can be challenging, and a multidisciplinary approach is often needed. Whilst RT-PCR is still the standard diagnostic test, a negative test should be interpreted with caution. Blood tests and imaging can be useful in the diagnosis, monitoring, and risk assessment in patients with COVID-19.

Evaluating the effects of Intravenous Immunoglobulin (IVIg) on the management of severe COVID-19 cases: A randomized controlled trial.

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.