Evaluation of Follow-Up CT Scans in Patients with Severe Initial Pulmonary Involvement by COVID-19.

Objective: To investigate the predictive factors of residual pulmonary opacity on midterm follow-up CT scans in patients hospitalized with COVID-19 pneumonia. Materials and Methods: This prospective study was conducted in a tertiary referral university hospital in Iran, from March 2020 to December 2020. Patients hospitalized due to novel coronavirus pneumonia with bilateral pulmonary involvement in the first CT scan were included and underwent an 8-week follow-up CT scan. Pulmonary involvement (PI) severity was assessed using a 25-scale semiquantitative scoring system. Density of opacities was recorded using the Hounsfield unit (HU). Results: The chest CT scans of 50 participants (mean age = 54.4 ± 14.2 years, 72% male) were reviewed, among whom 8 (16%) had residual findings on follow-up CT scans. The most common residual findings were faint ground-glass opacities (GGOs) (14%); fibrotic-like changes were observed in 2 (4%) patients. Demographic findings, underlying disease, and laboratory findings did not show significant association with remaining pulmonary opacities. The total PI score was significantly higher in participants with remaining parenchymal involvement (14.5 ± 6.5 versus 10.2 ± 3.7; P=0.02). On admission, the HU of patients with remaining opacities was significantly higher (-239.8 ± 107.6 versus -344.0 ± 157.4; P=0.01). Remaining pulmonary findings were more frequently detected in patients who had received antivirals, steroid pulse, or IVIG treatments (P=0.02, 0.02, and 0.001, respectively). Only the PI score remained statistically significant in multivariate logistic regression with 88.1% accuracy (OR = 1.2 [1.01-1.53]; P=0.03). Conclusion: Pulmonary opacities are more likely to persist in midterm follow-up CT scans in patients with severe initial pulmonary involvement.

Spontaneous Loculated Pneumomediastinum in a COVID-19-Infected Patient.

While we are still learning about COVID-19 affecting people, older persons and persons with underlying diseases such as high blood pressure, heart disease, and diabetes mellitus (DM) appear to develop serious illness and more complications often than others. In this report, we presented a patient with spontaneous pneumomediastinum after COVID-19. The patient was a 61-year-old man with a history of DM, hypertension, and heart failure, who has been infected with COVID-19. The patient was diagnosed with COVID-19 based on RT-PCR analysis of nasopharyngeal samples, and chest X-ray showed patchy infiltration upper and lower lobes bilaterally. By day 4, imaging was repeated, performed due to exacerbation of pleuritic chest pain, decreased O2 saturation (80%), and coughing that revealed multiple ground-glass opacities bilaterally, and interlobular septal thickening with emphysema in most of the left upper lobe and a small part of right upper lobe which led to severe spontaneous left pneumomediastinum and parenchymal consolidation was also observed. The combination of a chest tube, antibiotics (vancomycin 1 gr/bid and meropenem 1 g/bid), and antiviral (hydroxychloroquine 200 mg/bid and atazanavir 300 mg/daily) was prescribed, and continued treatment with antiviral and appropriate care for pneumomediastinum was successful. Spontaneous pneumomediastinum in the context of COVID-19 should be considered as a prognostic factor in favor of worsening diseases.

Comparing efficacy and safety of tocilizumab and methylprednisolone in the treatment of patients with severe COVID-19.

OBJECTIVES: This study was designed to compare the efficacy and safety of methylprednisolone and tocilizumab in the treatment of patients with severe COVID-19. METHODS: During a prospective cohort study, hospitalized patients with severe COVID-19 received intravenous methylprednisolone (250-500 mg daily up to three doses), weight-based tocilizumab (maximum 800 mg, one or two doses as daily interval) or dexamethasone (8 mg daily). The primary outcome was time to onset of clinical response. Secondary outcomes were improvement rate of oxygen saturation and CRP, need for ICU admission, duration of hospitalization and 28-day mortality. During study, adverse events of the treatments were recorded. RESULTS: Although the difference was not statistically significant (p = 0.090), clinical response occurred faster in the tocilizumab group than other groups (10 vs. 16 days). Clinical response was detected in 74.19%, 81.25%, and 60% of patients in the methylprednisolone, tocilizumab, and dexamethasone groups respectively (p = 0.238). Based on the Cox regression analysis and considering dexamethasone as the reference group, HR (95% CI) of clinical response was 1.08 (0.65-1.79) and 1.46 (0.89-2.39) in the methylprednisolone and tocilizumab groups respectively. Improvement rate of oxygen saturation and CRP was not significantly different between the groups (p = 0.791 and p = 0.372 respectively). Also need for ICU admission and 28-day mortality was comparable between the groups (p = 0.176 and p = 0.143 respectively). Compared with methylprednisolone, tocilizumab caused more sleep disturbances (p = 0.019). Other adverse events were comparable among patients in the groups. CONCLUSION: When or where access to tocilizumab is a problem, methylprednisolone may be considered as an alternative for the treatment of patients with severe COVID-19.

Safety and efficacy study of allogeneic human menstrual blood stromal cells secretome to treat severe COVID-19 patients: clinical trial phase I & II.

BACKGROUND: Cell-free Mesenchymal stromal cells (MSCs) have been considered due to their capacity to modulate the immune system and suppress cytokine storms caused by SARS-CoV-2. This prospective randomized double-blind placebo-controlled clinical trial aimed to assess the safety and efficacy of secretome derived from allogeneic menstrual blood stromal cells (MenSCs) as a treatment in patients with severe COVID-19. METHODS: Patients with severe COVID-19 were randomized (1:1) to either MenSC-derived secretome treatment or the control group. Subjects received five intravenous infusions of 5 mL secretome or the same volume of placebo for five days and were monitored for safety and efficacy for 28 days after treatment. Adverse events, laboratory parameters, duration of hospitalization, clinical symptom improvement, dynamic of O2 saturation, lymphocyte number, and serial chest imaging were analyzed. RESULTS: All safety endpoints were observed without adverse events after 72 h of secretome injection. Within 28 days after enrollment, 7 patients (50%) were intubated in the treated group versus 12 patients (80%) in the control group. Overall, 64% of patients had improved oxygen levels within 5 days of starting treatment (P < 0.0001) and there was a survival rate of 57% in the treatment group compared to 28% in the control group was (P < 0.0001). Laboratory values revealed that significant acute phase reactants declined, with mean C-reactive protein, ferritin, and D-dimer reduction of 77% (P < 0.001), 43% (P < 0.001), and 42% (P < 0.05), respectively. Significant improvement in lymphopenia was associated with an increase in mean CD4+ and CD8+ lymphocyte counts of 20% (P = 0.06) and 15% (P < 0.05), respectively. Following treatment, percentage of pulmonary involvement showed a significant improvement in the secretome group (P < 0.0001). This improvement differed significantly between survivors and those who were dying (P < 0.005). CONCLUSIONS: For the first time, this study demonstrated that in hospitalized patients with severe COVID-19, therapy with MenSCs-derived secretome leads to reversal of hypoxia, immune reconstitution, and downregulation of cytokine storm, with no adverse effects attributable to the treatment. Given these outcomes, it may be possible to use this type of treatment for serious inflammatory lung disease with a mechanism similar to COVID-19 in the future. However, it is necessary to evaluate the safety and efficacy of MenSCs-derived secretome therapy in clinical trials on a larger population of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05019287. Registered 24AGUEST 2021, retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT05019287 . IRCT, IRCT20180619040147N6. Registered 04/01/2021.

Chest CT Scan Features to Predict COVID-19 Patients' Outcome and Survival.

Background: Providing efficient care for infectious coronavirus disease 2019 (COVID-19) patients requires an accurate and accessible tool to medically optimize medical resource allocation to high-risk patients. Purpose: To assess the predictive value of on-admission chest CT characteristics to estimate COVID-19 patients' outcome and survival time. Materials and Methods: Using a case-control design, we included all laboratory-confirmed COVID-19 patients who were deceased, from June to September 2020, in a tertiary-referral-collegiate hospital and had on-admission chest CT as the case group. The patients who did not die and were equivalent in terms of demographics and other clinical features to cases were considered as the control (survivors) group. The equivalency evaluation was performed by a fellowship-trained radiologist and an expert radiologist. Pulmonary involvement (PI) was scored (0-25) using a semiquantitative scoring tool. The PI density index was calculated by dividing the total PI score by the number of involved lung lobes. All imaging parameters were compared between case and control group members. Survival time was recorded for the case group. All demographic, clinical, and imaging variables were included in the survival analyses. Results: After evaluating 384 cases, a total of 186 patients (93 in each group) were admitted to the studied setting, consisting of 126 (67.7%) male patients with a mean age of 60.4 ± 13.6 years. The PI score and PI density index in the case vs. the control group were on average 8.9 ± 4.5 vs. 10.7 ± 4.4 (p value: 0.001) and 2.0 ± 0.7 vs. 2.6 ± 0.8 (p value: 0.01), respectively. Axial distribution (p value: 0.01), cardiomegaly (p value: 0.005), pleural effusion (p value: 0.001), and pericardial effusion (p value: 0.04) were mostly observed in deceased patients. Our survival analyses demonstrated that PI score ≥ 10 (p value: 0.02) and PI density index ≥ 2.2 (p value: 0.03) were significantly associated with a lower survival rate. Conclusion: On-admission chest CT features, particularly PI score and PI density index, are potential great tools to predict the patient's clinical outcome.

Pleural Effusion as a Sign of Coronavirus Disease 2019 (COVID-19) Pneumonia: A Case Report.

BACKGROUND: Recently, COVID-19 infection has become a public health concern. On March 12th, 2020, the World Health Organization (WHO) announced it as a global pandemic. Early diagnosis of atypical cases of COVID-19 infection is critical in reducing the transmission and controlling the present pandemic. In the present report, we described a patient with the chief complaints of dyspnea and dry cough referred to the oncology center at Imam Khomeini Hospital, Tehran, with the differential diagnosis of lung cancer who was diagnosed and treated for COVID-19 infection in follow up. CASE PRESENTATION: A 59-year-old patient complained of fever, dry cough, and dyspnea from two weeks ago. The patient had been referred to this center with the differential diagnosis of lung cancer due to the massive pleural effusion in the initial chest CT scan. Dyspnea was the patient's main complaint at the time of admission in this center and the oxygen saturation was 84%. In the new chest CT scan, similar findings were observed. Due to the severe respiratory distress, a chest tube was placed in the chest cavity to remove the pleural effusion fluid on day one. The patient's felt relieved immediately after the procedure; however, the oxygen saturation did not rise above 85% despite the oxygen therapy. The cytology of pleural fluid was negative for malignant cells. On day 2, the lymphopenia and high level of CRP suggested the COVID-19 infection. Therefore, a control chest CT scan was conducted and the test for COVID-19 was performed. The CT report indicated the clear pattern of COVID-19's lung involvement in the absence of pleural effusion. Thus, the treatment for COVID-19 was immediately initiated. On day 4, the test reported positive for COVID-19. CONCLUSION: Currently, it is important to bear in mind the COVID-19 infection in evaluating patients with respiratory symptoms. This report indicated how misleading the presentation of a chest CT scan could be in clinical judgment. Therefore, we recommend ruling out the COVID-19 infection in all the patients with any pattern of lung involvement to avoid missing the potential cases of this vicious infection.

Factors Predicting Outcome in Intensive Care Unit-Admitted COVID-19 Patients: Using Clinical, Laboratory, and Radiologic Characteristics.

PURPOSE: To investigate the factors contributing to mortality in coronavirus disease 2019 (COVID-19) patients admitted in the intensive care unit (ICU) and design a model to predict the mortality rate. METHOD: We retrospectively evaluated the medical records and CT images of the ICU-admitted COVID-19 patients who had an on-admission chest CT scan. We analyzed the patients' demographic, clinical, laboratory, and radiologic findings and compared them between survivors and nonsurvivors. RESULTS: Among the 121 enrolled patients (mean age, 62.2 ± 14.0 years; male, 82 (67.8%)), 41 (33.9%) survived, and the rest succumbed to death. The most frequent radiologic findings were ground-glass opacity (GGO) (71.9%) with peripheral (38.8%) and bilateral (98.3%) involvement, with lower lobes (94.2%) predominancy. The most common additional findings were cardiomegaly (63.6%), parenchymal band (47.9%), and crazy-paving pattern (44.4%). Univariable analysis of radiologic findings showed that cardiomegaly (p : 0.04), pleural effusion (p : 0.02), and pericardial effusion (p : 0.03) were significantly more prevalent in nonsurvivors. However, the extension of pulmonary involvement was not significantly different between the two subgroups (11.4 ± 4.1 in survivors vs. 11.9 ± 5.1 in nonsurvivors, p : 0.59). Among nonradiologic factors, advanced age (p : 0.002), lower O2 saturation (p : 0.01), diastolic blood pressure (p : 0.02), and hypertension (p : 0.03) were more commonly found in nonsurvivors. There was no significant difference between survivors and nonsurvivors in terms of laboratory findings. Three following factors remained significant in the backward logistic regression model: O2 saturation (OR: 0.91 (95% CI: 0.84-0.97), p : 0.006), pericardial effusion (6.56 (0.17-59.3), p : 0.09), and hypertension (4.11 (1.39-12.2), p : 0.01). This model had 78.7% sensitivity, 61.1% specificity, 90.0% positive predictive value, and 75.5% accuracy in predicting in-ICU mortality. CONCLUSION: A combination of underlying diseases, vital signs, and radiologic factors might have prognostic value for mortality rate prediction in ICU-admitted COVID-19 patients.

The association between serum levels of micronutrients and the severity of disease in patients with COVID-19.

OBJECTIVES: This study aimed to compare the serum level of micronutrients with normal amounts, and assess their association with the severity of disease and inflammatory cytokines in patients with coronavirus disease 2019 (COVID-19). METHODS: The present cross-sectional study included 60 patients admitted to the intensive care unit with COVID-19. We recorded data on demographic characteristics, anthropometric information, and medical history. Serum levels of inflammatory markers (erythrocyte sedimentation rate, C-reactive protein, interferon-gamma, tumor necrosis factor-alpha, interleukin-6), vitamins (A, B9, B12, C, D, E), and minerals (magnesium, zinc, iron) were measured. A radiologist assessed the severity of lung involvement according to patient computed tomography scans. The severity of illness was evaluated with the Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) score, oxygen saturation, and body temperature. Independent associations among the serum levels of micronutrients with the severity of COVID-19 were measured. RESULTS: Median patient age was 53.50 years (interquartile range, 12.75 years). Except for vitamin A and zinc, serum levels of other micronutrients were lower than the minimum normal. Patients with APACHE score ≥25 had a higher body mass index (P = 0.044), body temperature (P = 0.003), erythrocyte sedimentation rate (P = 0.008), C-reactive protein (P = 0.003), and lower oxygen saturation (P = 0.005), serum levels of vitamin D (P = < 0.001), and zinc (P = < 0.001) compared with patients with APACHE score <25. We found that lower serum levels of vitamin D, magnesium, and zinc were significantly and independently associated with higher APACHE scores (P = 0.001, 0.028, and < 0.001, respectively) and higher lung involvement (P = 0.002, 0.045, and < 0.001, respectively). CONCLUSIONS: Lower serum levels of vitamin D, zinc, and magnesium were involved in severe COVID-19.

Proven Aspergillus flavus pulmonary aspergillosis in a COVID-19 patient: A case report and review of the literature.

Severe COVID-19 patients complicated with aspergillosis are increasingly reported. We present a histopathological proven case of fatal COVID-19-associated pulmonary aspergillosis (CAPA), due to Aspergillus flavus. This report and existing published literature indicate diagnostic challenges and poor outcomes of CAPA in ICU patients.

Safety and effectiveness of high-dose vitamin C in patients with COVID-19: a randomized open-label clinical trial.

BACKGROUND: Vitamin C is an essential water-soluble nutrient that functions as a key antioxidant and has been proven to be effective for boosting immunity. In this study, we aimed to assess the efficacy of adding high-dose intravenous vitamin C (HDIVC) to the regimens for patients with severe COVID-19 disease. METHODS: An open-label, randomized, and controlled trial was conducted on patients with severe COVID-19 infection. The case and control treatment groups each consisted of 30 patients. The control group received lopinavir/ritonavir and hydroxychloroquine and the case group received HDIVC (6 g daily) added to the same regimen. RESULTS: There were no statistically significant differences between two groups with respect to age and gender, laboratory results, and underlying diseases. The mean body temperature was significantly lower in the case group on the 3rd day of hospitalization (p = 0.001). Peripheral capillary oxygen saturations (SpO2) measured at the 3rd day of hospitalization was also higher in the case group receiving HDIVC (p = 0.014). The median length of hospitalization in the case group was significantly longer than the control group (8.5 days vs. 6.5 days) (p = 0.028). There was no significant difference in SpO2 levels at discharge time, the length of intensive care unit (ICU) stay, and mortality between the two groups. CONCLUSIONS: We did not find significantly better outcomes in the group who were treated with HDIVC in addition to the main treatment regimen at discharge. Trial registration irct.ir (IRCT20200411047025N1), April 14, 2020.

Clinical and chest CT features as a predictive tool for COVID-19 clinical progress: introducing a novel semi-quantitative scoring system.

OBJECTIVE: Proposing a scoring tool to predict COVID-19 patients' outcomes based on initially assessed clinical and CT features. METHODS: All patients, who were referred to a tertiary-university hospital respiratory triage (March 27-April 26, 2020), were highly clinically suggestive for COVID-19 and had undergone a chest CT scan were included. Those with positive rRT-PCR or highly clinically suspicious patients with typical chest CT scan pulmonary manifestations were considered confirmed COVID-19 for additional analyses. Patients, based on outcome, were categorized into outpatient, ordinary-ward admitted, intensive care unit (ICU) admitted, and deceased; their demographic, clinical, and chest CT scan parameters were compared. The pulmonary chest CT scan features were scaled with a novel semi-quantitative scoring system to assess pulmonary involvement (PI). RESULTS: Chest CT scans of 739 patients (mean age = 49.2 ± 17.2 years old, 56.7% male) were reviewed; 491 (66.4%), 176 (23.8%), and 72 (9.7%) cases were managed outpatient, in an ordinary ward, and ICU, respectively. A total of 439 (59.6%) patients were confirmed COVID-19 cases; their most prevalent chest CT scan features were ground-glass opacity (GGO) (93.3%), pleural-based peripheral distribution (60.3%), and multi-lobar (79.7%), bilateral (76.6%), and lower lobes (RLL and/or LLL) (89.1%) involvement. Patients with lower SpO2, advanced age, RR, total PI score or PI density score, and diffuse distribution or involvement of multi-lobar, bilateral, or lower lobes were more likely to be ICU admitted/expired. After adjusting for confounders, predictive models found cutoffs of age ≥ 53, SpO2 ≤ 91, and PI score ≥ 8 (15) for ICU admission (death). A combination of all three factors showed 89.1% and 95% specificity and 81.9% and 91.4% accuracy for ICU admission and death outcomes, respectively. Solely evaluated high PI score had high sensitivity, specificity, and NPV in predicting the outcome as well. CONCLUSION: We strongly recommend patients with age ≥ 53, SpO2 ≤ 91, and PI score ≥ 8 or even only high PI score to be considered as high-risk patients for further managements and care plans. KEY POINTS: • Chest CT scan is a valuable tool in prioritizing the patients in hospital triage. • A more accurate and novel 35-scale semi-quantitative scoring system was designed to predict the COVID-19 patients' outcome. • Patients with age ≥ 53, SpO2 ≤ 91, and PI score ≥ 8 or even only high PI score should be considered high-risk patients.

Imaging data in COVID-19 patients: focused on echocardiographic findings.

To assess imaging data in COVID-19 patients and its association with clinical course and survival and 86 consecutive patients (52 males, 34 females, mean age = 58.8 year) with documented COVID-19 infection were included. Seventy-eight patients (91%) were in severe stage of the disease. All patients underwent transthoracic echocardiography. Mean LVEF was 48.1% and mean estimated systolic pulmonary artery pressure (sPAP) was 27.9 mmHg. LV diastolic dysfunction was mildly abnormal in 49 patients (57.6%) and moderately abnormal in 7 cases (8.2%). Pericardial effusion was present in 5/86 (minimal in size in 3 cases and mild- moderate in 2). In 32/86 cases (37.2%), the severity of infection progressed from "severe" to "critical". Eleven patients (12.8%) died. sPAP and computed tomography score were associated with disease progression (P value = 0.002, 0.002 respectively). Tricuspid annular plane systolic excursion (TAPSE) was significantly higher in patients with no disease progression compared with those who deteriorated (P value = 0.005). Pericardial effusion (minimal, mild or moderate) was detected more often in progressive disease (P = 0.03). sPAP was significantly lower among survivors (P value = 0.007). Echocardiographic findings (including systolic PAP, TAPSE and pericardial effusion), total CT score may have prognostic and therapeutic implication in COVID-19 patients.

Management of colon and rectal cancers during COVID-19 pandemic: A clinical guideline (TUMS-CRC-CoV19 Guideline).

Background: In a resource-demanding COVID-19 pandemic, guidelines can free up health care resources needed for providing better care to those with COVID-19 and other patients. This study was performed to design a guideline to manage patients with colorectal cancers during the COVID-19pandemic. Methods: To design this guideline, major topics and headings of colon and rectal cancers (CRC) were selected and included. Based on the extent of COVID-19 infection in the community and availability of hospital resources, the guideline has been designed for 2 major COVID-19 phases. Several multidisciplinary discussion sessions were held to review the comments of experts, finalize the data, and write the guideline. Results: This guideline has been prepared in 2 main COVID-19 phases of the community/hospital. Phase A refers to the condition where a large number of COVID-19 patients are admitted to the hospital, but limited surgical ICU beds and facilities are still accessible. In phase B, many people are affected by COVID-19, and all hospital resources are allocated for COVID 19 patients. In phase A, 4 major groups are discussed, including malignant and suspicious colorectal polyps, colon cancers, rectal cancers, and recurrent cancers. The approach to emergent cases, including obstruction, bleeding, and perforation, will be presented in phase B. Conclusion: This guideline is a comprehensive instruction on the approach to colorectal cancers during the COVID-19 pandemic that covers the major topics of colon and rectal cancers in detail.