IMPORTANCE Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis.OBJECTIVE To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). DESIGN, SETTING, AND PARTICIPANTSMulticenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020.INTERVENTIONS Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. MAIN OUTCOMES AND MEASURESThe primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×10 3 /μL). All outcomes were blindly adjudicated. RESULTS Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, −6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, −ϱ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01).CONCLUSIONS AND RELEVANCE Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days...

Background: Microvascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown. Methods: The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 × 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count < 20,000/fL) for the anticoagulation hypothesis. In a prespecified secondary analysis for non-inferiority, the study will test for the non-inferiority of intermediate intensity versus standard dose anticoagulation for major bleeding, considering a non-inferiority margin of 1.8 based on odds ratio. Key safety endpoints for the statin hypothesis include rise in liver enzymes > 3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts. Conclusions: INSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19.

Background: Thrombotic complications are considered among the main extrapulmonary manifestations of COVID-19. The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. Methods: This manuscript reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. Results: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]; 62 (50, 71) years; 237 (42.2%) women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate-dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, P=0.11). No significant differences were observed between the two groups for other efficacy outcomes, or in the landmark analysis from days 31-90. Overall, there were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24, P=0.33). Conclusion: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

Background: Severe coronavirus disease 2019 (COVID-19) may lead to the cytokine storm syndrome which may cause acute respiratory failure syndrome and death. Our aim was to investigate the therapeutic effects of infliximab, intravenous gammaglobulin (IVIg) or combination therapy in patients with severe COVID-19 disease admitted to the intensive care unit (ICU). Methods: In this observational research, we studied 104 intubated adult patients with severe COVID-19 infection (based on clinical symptoms, and radiographic or CT scan parameters) who were admitted to the ICU of a multispecialty hospital during March 2020 in Tehran, Iran. All cases received standard treatment regimens as local protocol (Oseltamivir + hydroxychloroquine + lopinavir/ritonavir or sofosbuvir or atazanavir ± ribavirin). The cases were grouped as controls (n = 43), infliximab (n = 27), IVIg (n = 23) and combination (n = 11). Results: There was no significant difference between controls and treatment groups in terms of underlying diseases or the number of underlying diseases. The mean age (SD) of cases was 72.42 (16.06) in the control group, 64.52 (12.965) in IVIg, 63.40 (17.57) in infliximab and 64.00 (11.679) in combination therapy; (P = 0.047, 0.031 and 0.11, respectively). Also, 37% in the infliximab group, 26.1% in IVIg, 45.5% in combination therapy, and 62.8% in the control group expired (all P < 0.05). Hazard ratios were 0.31 in IVIg (95% CI: 0.12-0.76, P = 0.01), 0.30 in infliximab (95% CI: 0.13-0.67, P = 0.004), 0.39 in combination therapy (95% CI: 0.12-1.09, P = 0.071). Conclusion: According to the findings of this study, it seems that infliximab and IVIg, alone or together, in patients with severe COVID-19 disease can be considered an effective treatment.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and treatment are significant health organizations' concerns worldwide. Although there is no proven drug license against the virus, a variety of components have under investigation. In this regard, the present study was intended to evaluate the consequences of Sovodak (Sofosbuvir/Daclatasvir) treatment in COVID-19 patients compared with Kaletra (Lopinavir/ritonavir). Methods: This study was conducted as a randomized trial using 120 COVID19 confirmed cases between August 19th and September 19th, 2020, in which subjects were classified into two treatment groups, 58 (Sovodak group) and 54 (Kaletra group). Related statistical operations calculated significant outcomes such as survival rate and hazard ratio via SPSS v.16. Sovodak was composed of Sofosbuvir 400mg and Daclatasvir 60mg, and Kaletra included Lopinavir 400 mg and ritonavir 100 mg. Results: We observed that there was no significant difference concerning the comorbidities, death, ICU admission, remission. Besides, Kaletra had a higher rate of discharge versus Sovodak (HR=1.551 (95% CI=1.008-2.386), P-value=0.046), and a better outcome was observed in patients receiving Conclusion: Sovodak compared to Kaletra by Hazard plot. Sovodak (Sofosbuvir/Daclatasvir) therapy in COVID19 cases was accompanied by a significantly higher survival rate and better outcome than Kaletra (Lopinavir/ritonavir).

BACKGROUND: Fiberoptic bronchoscopy (FOB) guided bronchoalveolar lavage (BAL) remains as the chief diagnostic tool in respiratory disorders. 1.2-16% of patients frequently experience fever after bronchoscopy. To exclude the need for multiple antibiotic prescribing in patients with post-bronchoscopy fever, the presence of the self-limiting inflammatory responses should be excluded. AIM: The current study was conducted to test the serum of patients undergoing bronchoscopy for some proinflammatory cytokines including Tumor Necrosis Factor-alpha (TNF-ɑ), Interleukin-1beta (IL-1β), Interleukin-8 (IL-8) and Interleukin-6 (IL-6) and the value of Procalcitonin (PCT). MATERIAL AND METHODS: Current case-control study was conducted at the National Research Institute of Tuberculosis and Lung Disease in Iran. Nineteen patients (48.72%) that attended with a reasonable sign for a diagnostic bronchoscopy from January 2016 to December 2017 were included in the case group. The control group consisted of 20 patients who underwent a simple bronchoscopy and without FOB-BAL. The laboratory findings for PCT concentrations and cytokine levels in the three serum samples (before FOB-BAL (t0), after 6 hr. (t1), and at 24 hr. past (t2) FOB-BAL) were compared between two groups. RESULTS: The frequency of post-bronchoscopy fever was 5.12, and the prevalence of post-bronchoscopy infectious fever was 2.56%. PCT level was considerably higher in the patient with a confirmed bacterial infection when compared to other participants (p-value < 0. 05). Interestingly, IL-8 level in the bacterial infection proven fever patient was higher than in other patients (p < 0.001). IL-8 levels displayed a specificity of 72.7% and a sensitivity of 100%, at the threshold point of 5.820 pg/ml. PCT levels had a specificity of 84% and a sensitivity of 81%, at the threshold point of 0.5 ng/ml. CONCLUSION: The present findings show that in patients with fever after bronchoscopy, PCT levels and IL-8 levels are valuable indicators for antibiotic therapy, proving adequate proof for bacterial infection. The current findings also illustrate that to monitor the serum levels of PCT and proinflammatory cytokines in the patients undergoing FOB-BAL, the best time is the 24-hour postoperative bronchoscopy.

BACKGROUND: Abdominal compartment syndrome patients suffer severe obstacles such as kidney failure and shock. To evade further complications, identifying the abdominal compartment syndrome (ACS) and Intra-abdominal hypertension (IAH), in critically ill individuals and hospitalised in the intensive care unit (ICU) is obligated. AIM: The current study intended to study the abdominal compartment syndrome and the concomitant risk factors among hospitalised patients in ICU, by using the Intra-abdominal pressure test. MATERIAL AND METHODS: One hundred and twenty-five hospitalised patients at ICU entered the current survey. Abdominal pressure was measured by standard intravesical technique. The SPSS 21 analysed the preoperative and intraoperative factors such as demographic records and comorbidities. RESULTS: Seventy-three (58.4%) participants were males, and 52 (41.6%) were women in the mean age of 55.1 ± 18.3 years. Eighty-nine patients (71.2%) showed normal intra-abdominal pressure since 31 patients (24.8%), and 5 patients (4%) developed IAH and ACS. The intra-abdominal pressure (IAP) applied to Glasgow Coma Scale (GCS), Acute Physiology, shock, Systemic Inflammatory Response Syndrome (SIRS), central venous oxygen saturation and Chronic Health Evaluation (APACHE II) score (P < 0.05). Patients with high IAP have shown a higher mortality frequency, compared to others (P < 0.05). CONCLUSION: Current findings showed a correlation between IAP hospitalised patients in ICU and shock, SIRS, APACHE II, central venous oxygen saturation and GCS. Intra-abdominal pressure test, as a valuable prognosis test for the abdominal compartment syndrome (ACS) and Intra-abdominal hypertension (IAH), may offer better results when added to the routine medical checkup of ICU patients.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.