Interferon therapy in patients with SARS, MERS, and COVID-19: A systematic review and meta-analysis of clinical studies.

Concern regarding coronavirus (CoV) outbreaks has stayed relevant to global health in the last decades. Emerging COVID-19 infection, caused by the novel SARS-CoV2, is now a pandemic, bringing a substantial burden to human health. Interferon (IFN), combined with other antivirals and various treatments, has been used to treat and prevent MERS-CoV, SARS-CoV, and SARS-CoV2 infections. We aimed to assess the clinical efficacy of IFN-based treatments and combinational therapy with antivirals, corticosteroids, traditional medicine, and other treatments. Major healthcare databases and grey literature were investigated. A three-stage screening was utilized, and included studies were checked against the protocol eligibility criteria. Risk of bias assessment and data extraction were performed, followed by narrative data synthesis. Fifty-five distinct studies of SARS-CoV2, MERS-CoV, and SARS-CoV were spotted. Our narrative synthesis showed a possible benefit in the use of IFN. A good quality cohort showed lower CRP levels in Arbidol (ARB) + IFN group vs. IFN only group. Another study reported a significantly shorter chest X-ray (CXR) resolution in IFN-Alfacon-1 + corticosteroid group compared with the corticosteroid only group in SARS-CoV patients. In a COVID-19 trial, total adverse drug events (ADEs) were much lower in the Favipiravir (FPV) + IFN-α group compared with the LPV/RTV arm (P = 0.001). Also, nausea in patients receiving FPV + IFN-α regimen was significantly lower (P = 0.03). Quantitative analysis of mortality did not show a conclusive effect for IFN/RBV treatment in six moderately heterogeneous MERS-CoV studies (log OR = -0.05, 95% CI: (-0.71,0.62), I2 = 44.71%). A meta-analysis of three COVID-19 studies did not show a conclusive nor meaningful relation between receiving IFN and COVID-19 severity (log OR = -0.44, 95% CI: (-1.13,0.25), I2 = 31.42%). A lack of high-quality cohorts and controlled trials was observed. Evidence suggests the potential efficacy of several combination IFN therapies such as lower ADEs, quicker resolution of CXR, or a decrease in inflammatory cytokines; Still, these options must possibly be further explored before being recommended in public guidelines. For all major CoVs, our results may indicate a lack of a definitive effect of IFN treatment on mortality. We recommend such therapeutics be administered with extreme caution until further investigation uncovers high-quality evidence in favor of IFN or combination therapy with IFN.

Similarities and Differences of Early Pulmonary CT Features of Pneumonia Caused by SARS-CoV-2, SARS-CoV and MERS-CoV: Comparison Based on a Systemic Review.

Objective To compare the similarities and differences of early CT manifestations of three types of viral pneumonia induced by SARS-CoV-2 (COVID-19), SARS-CoV (SARS) and MERS-CoV (MERS) using a systemic review. Methods Electronic database were searched to identify all original articles and case reports presenting chest CT features for adult patients with COVID-19, SARS and MERS pneumonia respectively. Quality of literature and completeness of presented data were evaluated by consensus reached by three radiologists. Vote-counting method was employed to include cases of each group. Data of patients' manifestations in early chest CT including lesion patterns, distribution of lesions and specific imaging signs for the three groups were extracted and recorded. Data were compared and analyzed using SPSS 22.0. Results A total of 24 studies were included, composing of 10 studies of COVID-19, 5 studies of MERS and 9 studies of SARS. The included CT exams were 147, 40, and 122 respectively. For the early CT features of the 3 pneumonias, the basic lesion pattern with respect to "mixed ground glass opacity (GGO) and consolidation, GGO mainly, or consolidation mainly" was similar among the 3 groups (χ2=7.966, P>0.05). There were no significant differences on the lesion distribution (χ2=13.053, P>0.05) and predominate involvement of the subpleural area of bilateral lower lobes (χ 2=4.809, P>0.05) among the 3 groups. The lesions appeared more focal in COVID-19 pneumonia at early phase (χ 2=23.509, P<0.05). The proportions of crazy-paving pattern (χ 2=23.037, P<0.001), organizing pneumonia pattern (P<0.05) and pleural effusions (P<0.001) in COVID-19 pneumonia were significantly lower than the other two. Although rarely shown in the early CT findings of all three viral pneumonias, the fibrotic changes were more frequent in SARS than COVID-19 and MERS (χ 2=6.275, P<0.05). For other imaging signs, only the MERS pneumonia demonstrated tree-in-buds, cavitation, and its incidence rate of interlobular or intralobular septal thickening presented significantly increased as compared to the other two pneumonia (χ 2=22.412, P<0.05). No pneumothorax, pneumomediastinum and lymphadenopathy was present for each group. Conclusions Imaging findings on early stage of these three coronavirus pneumonias showed similar basic lesion patterns, including GGO and consolidation, bilateral distribution, and predominant involvement of the subpleural area and the lower lobes. Early signs of COVID-19 pneumonia showed less severity of inflammation. Early fibrotic changes appeared in SARS only. MERS had more severe inflammatory changes including cavitation and pleural effusion. The differences may indicate the specific pathophysiological processes for each coronavirus pneumonia.

Nosocomial COVID-19 Infection and Severe COVID-19 Pneumonia in Patients Hospitalized for Alcoholic Liver Disease: A Case Report.

BACKGROUND COVID-19 is an infectious disease caused by SARS-CoV-2. It has spread rapidly through the world, endangering human life. The main target of COVID-19 is the lungs; however, it can involve other organs, including the liver. Patients with severe COVID-19 have an increased incidence of abnormal liver function, and patients with liver disorders are considered to be at a higher risk of severe COVID-19 infection. The mechanism of liver injury reported in 14% to 53% of COVID-19 patients is poorly recognized and several possibilities need to be considered (cytokine storm, direct viral action, hypoxia). The incidence of underlying liver comorbidities in patients with a COVID-19 infection ranges from 1% to 11%. CASE REPORT This is a report of 2 nosocomial COVID-19 infections and severe COVID-19 pneumonia in 2 patients who were hospitalized during treatment for alcoholic liver disease (ALD). Case 1 and case 2 were a 31-year-old woman and a 40-year-old woman, respectively, with decompensated ALD and symptoms of the COVID-19 infection. Both patients were transferred from another hospital to our hospital after confirmation of COVID-19 during their hospitalization. The course of the infection progressed rapidly in both patients with the development of multiple-organ failure and death over a short period. CONCLUSIONS There are no clear recommendations on the management of ALD in the COVID-19 pandemic. Alcoholic hepatitis may be a risk factor for severe COVID-19 and a poor outcome. A high percentage of nosocomial COVID-19 infections are observed; therefore, special precautions should be taken to minimize the risk of COVID-19 exposure.

Atypical Chest Computed Tomography Finding of Predominant Interstitial Thickening in a Patient with Coronavirus Disease 2019 (COVID-19) Pneumonia.

BACKGROUND Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, SARS-CoV-2, and is associated with severe respiratory disease. There are extensive publications on the chest computed tomography (CT) findings of COVID-19 pneumonia, with ground-glass opacities (GGO) and mixed GGO and consolidation being the most common findings. Those with interstitial thickening manifesting as reticular opacities typically show superimposed ground-glass opacities, giving a crazy-paving pattern. CASE REPORT We report the case of a 77-year-old man with a background of asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) who presented with progressive cough and shortness of breath for 2 days. He was in close contact with a confirmed COVID-19 case. Reverse-transcription polymerase chain reaction analysis of a nasopharyngeal swab was positive for SARS-CoV-2. The initial chest radiograph was negative for lung consolidation and ground-glass opacities. During admission, he had worsening shortness of breath with desaturation, prompting a chest CT examination, which was performed on day 14 of illness. The chest CT revealed an atypical finding of predominant focal subpleural interstitial thickening in the right lower lobe. He was provided supportive treatment along with steroid and antibiotics. He recovered well and subsequently tested negative for 2 consecutive swabs. He was discharged after 34 days. CONCLUSIONS Interstitial thickening or reticular pattern on CT has been described in COVID-19 pneumonia, but largely in association with ground-glass opacity or consolidation. This case demonstrates an atypical predominance of interstitial thickening on chest CT in COVID-19 pneumonia on day 14 of illness, which is the expected time of greatest severity of the disease.

Combatting COVID-19: is ultrasound an important piece in the diagnostic puzzle?

The current COVID-19 pandemic is causing diagnostic and risk stratification difficulties in Emergency Departments (ED) worldwide. Molecular tests are not sufficiently sensitive, and results are usually not available in time for decision making in the ED. Chest x-ray (CXR) is a poor diagnostic test for COVID-19, and computed tomography (CT), while sensitive, is impractical as a diagnostic test for all patients. Lung ultrasound (LUS) has an established role in the evaluation of acute respiratory failure and has been used during the COVID-19 outbreak as a decision support tool. LUS shows characteristic changes in viral pneumonitis, and while these changes are not specific for COVID-19, it may be a useful adjunct during the diagnostic process. It is quick to perform and repeat and may be done at the bedside. The authors believe that LUS can help to mitigate uncertainty in undifferentiated patients with respiratory symptoms. This review aims to provide guidance regarding indications for LUS, describe the typical sonographic abnormalities seen in patients with COVID-19 and provide recommendations around the logistics of performing LUS on patients with COVID-19 and managing the infection control risk of the procedure. The risk of anchoring bias during a pandemic and the need to consider alternative pathologies are emphasised throughout this review. LUS may be a useful point-of-care test for emergency care providers during the current COVID-19 pandemic if used within a strict framework that governs education, quality assurance and proctored scanning protocols.

Clinical and imaging findings of discharged patients with SARS-CoV-2 positive anal swab samples: a descriptive study.

BACKGROUND: To explore the clinical features and CT findings of clinically cured coronavirus disease 2019 (COVID-19) patients with viral RNA positive anal swab results after discharge. METHODS: Forty-two patients with COVID-19 who were admitted to Yongzhou Central Hospital, Hunan, China, between January 20, 2020, and March 2, 2020, were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using anal swab viral RT-PCR. In this report, we present the clinical characteristics and chest CT features of six patients with positive anal swab results and compare the clinical, laboratory, and CT findings between the positive and negative groups. RESULTS: The anal swab positivity rate for SARS-CoV-2 RNA in discharged patients was 14.3% (6/42). All six patients were male. In the positive group, 40% of the patients (2/5) had a positive stool occult blood test (OBT), but none had diarrhea. The median duration of fever and major symptoms (except fever) in the positive patients was shorter than that of the negative patients (1 day vs. 6 days, 4.5 days vs. 10.5 days, respectively). The incidence of asymptomatic cases in the positive group (33.3%) was also higher than that of the negative group (5.6%). There were no significant differences in the CT manifestation or evolution of the pulmonary lesions between the two groups. CONCLUSION: In our case series, patients with viral RNA positive anal swabs did not exhibit gastrointestinal symptoms, and their main symptoms disappeared early. They had similar CT features to the negative patients, which may be easier to be ignored. A positive OBT may indicate gastrointestinal damage caused by SARS-CoV-2 infection.

Lung ultrasonography in patients with COVID-19: comparison with CT.

AIM: To determine whether findings from lung ultrasound and chest high-resolution computed tomography (HRCT) correlate when evaluating COVID-19 pulmonary involvement. MATERIALS AND METHODS: The present prospective single-centre study included consecutive symptomatic patients with reverse transcription polymerase chain reaction (RT-PCR)-proven COVID-19 who were not in the intensive care unit. All patients were assessed using HRCT and ultrasound of the lungs by distinct operators blinded to each other's findings. The number of areas (0-12) with B-lines and/or consolidations was evaluated using ultrasound and compared to the percentage and classification (absent or limited, <10%; moderate, 10-25%; extensive, 25-50%; severe, 50-75%; critical, >75%) of lung involvement on chest HRCT. RESULTS: Data were analysed for 21 patients with COVID-19 (median [range] age 65 [37-90] years, 76% male) and excellent correlation was found between the ultrasound score for B-lines and the classification (p<0.01) and percentage of lung involvement on chest HRCT (r=0.935, p<0.001). In addition, the ultrasound score correlated positively with supplemental oxygen therapy (r=0.45, p=0.041) and negatively with minimal oxygen saturation at ambient air (r=-0.652, p<0.01). CONCLUSION: The present study suggests that among COVID-19 patients, lung ultrasound and HRCT findings agree in quantifying lung involvement and oxygen parameters. In the context of the COVID-19 pandemic, lung ultrasound could be a relevant alternative to chest HRCT.

Chest CT findings in asymptomatic cases with COVID-19: a systematic review and meta-analysis.

AIM: To determine the overall rate of chest imaging findings in asymptomatic cases, describe the most common patterns found, and determine the rate of later symptom development in these initially asymptomatic cases. MATERIALS AND METHODS: The PubMed and EMBASE databases were searched until 1 May 2020, for studies examining the proportion of positive chest imaging findings in asymptomatic cases diagnosed with COVID-19 and a random-effects meta-analysis of proportions was performed. Heterogeneity was assessed using the I2 statistic. RESULTS: Among 858 non-duplicate studies, seven studies with a total of 231 asymptomatic cases met the inclusion criteria. In the primary analysis, the pooled estimate of the overall rate of positive chest computed tomography (CT) findings among asymptomatic cases was 63% (95% confidence interval [CI]: 44-78%). Among 155/231 cases that were followed up for later symptom development, 90/155 remained asymptomatic and 65/155 developed symptoms during the study period (that ranged between seven and 30 days of follow-up). The pooled estimate of the rate of positive chest CT findings was 62% (95% CI: 38-81%) in cases that remained asymptomatic, while it was 90% (95% CI: 49-99%) in cases that developed symptoms. Among CT findings, the pooled estimate of the overall rate of ground-glass opacities (GGO) at CT alone was 71% (95% CI: 50-86%). Among other CT findings reported, 22/231 patients had GGO with consolidation, 7/231 patients had stripe shadows with or without GGO, and 8/231 patients had GGO with interlobular septal thickening. Among initially asymptomatic cases with positive CT findings, the pooled estimate of the overall rate of later symptom development was 26% (95% CI: 14-43%). CONCLUSION: In COVID-19, asymptomatic cases can have positive chest CT findings, and COVID-19 should be considered among cases with CT abnormalities even when there are no other symptoms. There is a need for close clinical monitoring of asymptomatic cases with radiographic findings as a significant percentage will develop symptoms.

Point-of-Care Ultrasound in the Evaluation of COVID-19.

BACKGROUND: The novel coronavirus SARS-CoV-2 has caused a pandemic, overwhelming health care systems around the world. Hospitals around the world, including the United States, have been struggling to adapt to the influx of patients with COVID-19, the illness caused by SARS-CoV2, given limited resources and high demand for medical care. OBJECTIVES: This article seeks to provide emergency physicians with a guide to sonographic findings in COVID-19 and an algorithm by which point-of-care lung ultrasound may assist emergency physicians caring for these patients during the SARS-CoV-2 pandemic. DISCUSSION: The studies currently being published have established a typical set of ultrasound findings in COVID-19. Point-of-care lung ultrasound is rapid and accessible in most emergency departments in the United States, and even in many resource-poor settings. CONCLUSION: Point-of-care ultrasound provides numerous benefits to emergency providers caring for patients with COVID-19, including decreasing resource utilization, assisting in diagnosis, guiding management of the critically ill patient, and aiding in rapid triage of patients under investigations for COVID-19.

Lung ultrasound in a respiratory pandemic.

Australian hospitals have prepared for a major surge in patients due to the infectious respiratory pandemic COVID-19. In other nations, patient presentations have overwhelmed resources. Ultrasound has been shown to be an effective tool to exclude significant life-threats in resource poor settings. In this article, we will describe three lung ultrasound algorithms for the emergency diagnosis of patients presenting with respiratory symptoms during a COVID-19 pandemic: (i) LUSC19: lung ultrasound to assess the severity of COVID-19; (ii) LUSAC: lung ultrasound to exclude alternative causes of respiratory distress; and (iii) LUSI: lung ultrasound following intubation. We anticipate that emergency physicians will use these algorithms during the upcoming respiratory pandemic to rapidly determine the severity of COVID-19 infection, to seek and treat significant alternative diagnoses and ensure endotracheal intubation.

Should point-of-care ultrasound become part of healthcare worker testing for COVID?

The NHS in England has rapidly expanded staff testing for COVID-19 in order to allow healthcare workers who would otherwise be isolating with symptoms suspicious of COVID-19 to be cleared to work. However, the high false negative rate associated with current RT-PCR tests could put other staff, family members and patients at risk. We believe combining swab testing with real-time lung ultrasound (LUS) would improve the ability to rule-in COVID-19 infection in those requiring screening.

The Potential for Remotely Mentored Patient-Performed Home Self-Monitoring for New Onset Alveolar-Interstitial Lung Disease.

Purpose: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is an acute respiratory illness. Although most infected persons are asymptomatic or have only mild symptoms, some patients progress to devastating disease; such progression is difficult to predict or identify in a timely manner. COVID-19 patients who do not require hospitalization can self-isolate at home. Calls from one disease epicenter identify the need for homebased isolation with telemedicine surveillance to monitor for impending deterioration. Methodology: Although the dominant approach for these asymptomatic/paucisymptomatic patients is to monitor oxygen saturation, we suggest additionally considering the potential merits and utility of home-based imaging. Chest computed tomography is clearly impractical, but ultrasound has shown comparable sensitivity for lung involvement, with major advantages of short and simple procedures, low cost, and excellent repeatability. Thoracic ultrasound may thus allow remotely identifying the development of pneumonitis at an early stage of illness and potentially averting the risk of insidious deterioration to severe pneumonia and critical illness while in home isolation. Conclusions: Lung sonography can be easily performed by motivated nonmedical caregivers when directed and supervised in real time by experts. Remote mentors could thus efficiently monitor, counsel, and triage multiple home-based patients from their "control center." Authors believe that this approach deserves further attention and study to reduce delays and failures in timely hospitalization of home-isolated patients.

Imaging findings in coronavirus infections: SARS-CoV, MERS-CoV, and SARS-CoV-2.

During the first two decades of the 21st century, there have been three coronavirus infection outbreaks raising global health concerns by severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the SARS-CoV-2. Although the reported imaging findings of coronavirus infection are variable and non-specific, the most common initial chest radiograph (CXR) and CT findings are ground-glass opacities and consolidation with peripheral predominance and eventually spread to involve both lungs as the disease progresses. These findings can be explained by the immune pathogenesis of coronavirus infection causing diffuse alveolar damage. Although it is insensitive in mild or early coronavirus infection, the CXR remains as the first-line and the most commonly used imaging modality. That is because it is rapid and easily accessible and helpful for monitoring patient progress during treatment. CT is more sensitive to detect early parenchymal lung abnormalities and disease progression, and can provide an alternative diagnosis. In this pictorial review, various coronavirus infection cases are presented to provide imaging spectrums of coronavirus infection and present differences in imaging among them or from other viral infections, and to discuss the role of imaging in viral infection outbreaks.

COVID-19 in the radiology department: What radiographers need to know.

OBJECTIVES: The aim is to review current literature related to the diagnosis, management, and follow-up of suspected and confirmed Covid-19 cases. KEY FINDINGS: Medical Imaging plays an important auxiliary role in the diagnosis of Covid-19 patients, mainly those most seriously affected. Practice differs widely among different countries, mainly due to the variability of access to resources (viral testing and imaging equipment, specialised staff, protective equipment). It has been now well-documented that chest radiographs should be the first-line imaging tool and chest CT should only be reserved for critically ill patients, or when chest radiograph and clinical presentation may be inconclusive. CONCLUSION: As radiographers work on the frontline, they should be aware of the potential risks associated with Covid-19 and engage in optimal strategies to reduce these. Their role in vetting, conducting and often reporting the imaging examinations is vital, as well as their contribution in patient safety and care. Medical Imaging should be limited to critically ill patients, and where it may have an impact on the patient management plan. IMPLICATIONS FOR PRACTICE: At the time of publication, this review offers the most up-to-date recommendations for clinical practitioners in radiology departments, including radiographers. Radiography practice has to significantly adjust to these new requirements to support optimal and safe imaging practices for the diagnosis of Covid-19. The adoption of low dose CT, rigorous infection control protocols and optimal use of personal protective equipment may reduce the potential risks of radiation exposure and infection, respectively, within Radiology departments.

Clinical characteristics of COVID-19 in 104 people with SARS-CoV-2 infection on the Diamond Princess cruise ship: a retrospective analysis.

BACKGROUND: The ongoing COVID-19 pandemic is a global threat. Identification of markers for symptom onset and disease progression is a pressing issue. We described the clinical features of people infected on board the Diamond Princess cruise ship who were diagnosed with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or mild or severe COVID-19, on admission to the Self-Defense Forces Central Hospital (Tokyo, Japan) and at the end of observation. METHODS: This retrospective, single-centre study included participants with laboratory-detected SARS-CoV-2 infection who were admitted to the Self-Defense Forces Central Hospital from Feb 11 to Feb 25, 2020. Clinical records, laboratory data, and radiological findings were analysed. Clinical outcomes were followed up until discharge or Feb 26, 2020, whichever came first. We defined asymptomatic infection as SARS-CoV-2 infection with no history of clinical signs and symptoms, severe COVID-19 as clinical symptoms of pneumonia (dyspnoea, tachypnoea, peripheral capillary oxygen saturation <93%, and need for oxygen therapy), and mild COVID-19 as all other symptoms. Clinical features on admission were compared among patients with different disease severity, including asymptomatic infection, at the end of observation. We used univariable analysis to identify factors associated with symptomatic illness among asymptomatic people infected with SARS-CoV-2 and disease progression in patients with COVID-19. FINDINGS: Among the 104 participants included in the final analysis, the median age was 68 years (IQR 47-75) and 54 (52%) were male. On admission, 43 (41%) participants were classified as asymptomatic, 41 (39%) as having mild COVID-10, and 20 (19%) as having severe COVID-19. At the end of observation, 33 (32%) participants were confirmed as being asymptomatic, 43 (41%) as having mild COVID-19, and 28 (27%) as having severe COVID-19. Serum lactate hydrogenase concentrations were significantly higher in the ten participants who were asymptomatic on admission but developed symptomatic COVID-19 compared with the 33 participants who remained asymptomatic throughout the observation period (five [50%] vs four [12%] participants; odds ratio 7·25, 95% CI 1·43-36·70; p=0·020). Compared with patients with mild disease at the end of observation, patients with severe COVID-19 were older (median age 73 years [IQR 55-77] vs 60 years [40-71]; p=0·028) and had more frequent consolidation on chest CT (13 [46%] of 28 vs nine [21%] of 43; p=0·035) and lymphopenia (16 [57%] vs ten [23%]; p=0·0055) on admission. INTERPRETATION: Older age, consolidation on chest CT images, and lymphopenia might be risk factors for disease progression of COVID-19 and contribute to improved clinical management. FUNDING: None.