Severe Coronavirus Disease 2019 Pneumonia Research Articles

Tocilizumab versus the Covid19 tempest: All’s well that ends well or much ado about nothing?

Tocilizumab versus the Covid19 tempest: All’s well that ends well or much ado about nothing?

Incidence and determinants of high-sensitivity troponin and natriuretic peptides elevation at admission in hospitalized COVID-19 pneumonia patients.

BackgroundMyocardial involvement in the course of coronavirus disease 2019 (COVID-19) pneumonia has been reported, though not fully characterized yet. The aim of the present study is to undertake a joint evaluation of hs-Troponin and natriuretic peptides (NP) in patients hospitalized for COVID-19 pneumonia.MethodsIn this multicenter observational study, we analyzed data from n = 111 patients. Cardiac biomarkers subgroups were identified according to values beyond reference range.ResultsIncreased hs-Troponin and NP were found in 38 and 56% of the cases, respectively. As compared to those with normal cardiac biomarkers, these patients were older, had higher prevalence of cardiovascular diseases (CVD) and had more severe COVID-19 pneumonia by higher CRP and d-dimer and lower PaO2/FIO2. Two-dimensional echocardiography performed in a subset of patients (n = 24) showed significantly reduced left ventricular ejection fraction in patients with elevated NP (p = 0.02), whereas right ventricular systolic function (tricuspid annular plane systolic excursion) was significantly reduced both in patients with high hs-Troponin and NP (p = 0.022 and p = 0.03, respectively). Both hs-Troponin and NP were higher in patients with in-hospital mortality (p = 0.001 and p = 0.002, respectively). On multivariable analysis, independent associations were found of hs-Troponin with age, PaO2/FIO2 and d-dimer (B = 0.419, p = 0.001; B = − 0.212, p = 0.013; and B = 0.179, p = 0.037, respectively) and of NP with age and previous CVD (B = 0.480, p < 0.001; and B = 0.253, p = 0.001, respectively).ConclusionsMyocardial involvement at admission is common in COVID-19 pneumonia. Independent associations of hs-Troponin with markers of disease severity and of NP with underlying CVD might point toward existing different mechanisms leading to their elevation in this setting.Electronic supplementary materialThe online version of this article (10.1007/s11739-020-02498-7) contains supplementary material, which is available to authorized users.

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.

Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.

Autoantibodies against type I IFNs in patients with life-threatening COVID-19.

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.

Lipoprotein concentrations over time in the intensive care unit COVID-19 patients: Results from the ApoCOVID study.

Severe acute respiratory syndrome coronavirus2 has caused a global pandemic of coronavirus disease 2019 (COVID-19). High-density lipoproteins (HDLs), particles chiefly known for their reverse cholesterol transport function, also display pleiotropic properties, including anti-inflammatory or antioxidant functions. HDLs and low-density lipoproteins (LDLs) can neutralize lipopolysaccharides and increase bacterial clearance. HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) decrease during bacterial sepsis, and an association has been reported between low lipoprotein levels and poor patient outcomes. The goal of this study was to characterize the lipoprotein profiles of severe ICU patients hospitalized for COVID-19 pneumonia and to assess their changes during bacterial ventilator-associated pneumonia (VAP) superinfection. A prospective study was conducted in a university hospital ICU. All consecutive patients admitted for COVID-19 pneumonia were included. Lipoprotein levels were assessed at admission and daily thereafter. The assessed outcomes were survival at 28 days and the incidence of VAP. A total of 48 patients were included. Upon admission, lipoprotein concentrations were low, typically under the reference values ([HDL-C] = 0.7[0.5-0.9] mmol/L; [LDL-C] = 1.8[1.3-2.3] mmol/L). A statistically significant increase in HDL-C and LDL-C over time during the ICU stay was found. There was no relationship between HDL-C and LDL-C concentrations and mortality on day 28 (log-rank p = 0.554 and p = 0.083, respectively). A comparison of alive and dead patients on day 28 did not reveal any differences in HDL-C and LDL-C concentrations over time. Bacterial VAP was frequent (64%). An association was observed between HDL-C and LDL-C concentrations on the day of the first VAP diagnosis and mortality ([HDL-C] = 0.6[0.5-0.9] mmol/L in survivors vs. [HDL-C] = 0.5[0.3-0.6] mmol/L in nonsurvivors, p = 0.036; [LDL-C] = 2.2[1.9-3.0] mmol/L in survivors vs. [LDL-C] = 1.3[0.9-2.0] mmol/L in nonsurvivors, p = 0.006). HDL-C and LDL-C concentrations upon ICU admission are low in severe COVID-19 pneumonia patients but are not associated with poor outcomes. However, low lipoprotein concentrations in the case of bacterial superinfection during ICU hospitalization are associated with mortality, which reinforces the potential role of these particles during bacterial sepsis.

Assessment of Risk Factors for Severe Coronavirus Disease 2019 among Iranian Patients

Background: The outbreak of Coronavirus Disease 2019 (COVID-19) has led to a major concern for those who are more vulnerable to infections. Objectives: This study aimed to evaluate the most important risk factors for severe COVID-19 pneumonia. Methods: This retrospective study included information on clinical and epidemiological features of 105 patients with severe COVID-19 pneumonia hospitalized in Tajrish Hospital, Tehran, Iran. Initially, the medical records of the patients were investigated, and an interview was conducted based on a pre-prepared checklist to seek information about symptoms, past medical history, medication history, and behavior before hospitalization. Results: Out of 105 participants, 76 (72.5%) cases were male, and 54 (51.4%) patients were older than 54 years old. The majority of the patients (n=18; 17.1%) had both hypertension and diabetes (n=12; 11.4%). Metformin (n=36; 34.3%) was the most used medication amongst the studied patient. In addition, 24 (22.9%) patients were recreational hookah smokers, and the majority (75%) of them were under the age of 46 years old. Eventually, 19 patients were excluded from the study, of whom 11 individuals had diabetes, and 10 cases were using metformin. Conclusion: Apparently, hookah smoking played a critical role in the spread of COVID-19 in Iran and has made younger people more susceptible. In addition to older age, the immunosuppressive effects of Metformin seem to make diabetic patients with an impaired immune system more vulnerable to severe COVID-19 pneumonia. More studies on the immune system of vulnerable individuals by identifying their differences can help to protect them.

Severe COVID-19 during pregnancy and the subsequent premature delivery

Severe COVID-19 during pregnancy and the subsequent premature delivery

Dabigatran, the oral anticoagulant of choice at discharge in patients with non-valvular atrial fibrillation and COVID-19 infection: the ANIBAL protocol.

Atrial fibrillation is a frequent complication among patients with severe coronavirus disease-2019 (COVID-19) infection. Both direct and indirect mechanisms through COVID-19 have been described to explain this relationship. COVID-19 infection increases the risk of developing both arterial and venous thrombotic complications through systemic coagulation activation, leading to increased mortality. Chronic oral anticoagulation is essential to reduce the thromboembolic risk among AF patients. Switching to low-molecular-weight heparin has been recommended during hospitalization for COVID-19 infection. Of note, at discharge, the prescription of direct oral anticoagulants may offer some advantages over vitamin K antagonists. However, oral anticoagulants should only be prescribed after the consideration of drug–drug interactions with antiviral therapies as well as of the risk of hepatotoxicity, which is common among individuals with severe COVID-19 pneumonia. Not all anticoagulants have the same risk of hepatotoxicity; dabigatran has shown a good efficacy and safety profile and could have a lower risk of hepatotoxicity. Furthermore, its metabolism by cytochrome P450 is absent and it has a specific reversal agent. Therefore, dabigatran may be considered as a first-line choice for oral anticoagulation at discharge after COVID-19 infection. In this review, the available information on the antithrombotic management of AF patients at discharge after COVID-19 infection is updated. In addition, a practical algorithm, considering renal and liver function, which facilitates the anticoagulation choice at discharge is presented.

Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia.

BackgroundIn hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality.MethodsWe conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels.ResultsFindings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24–0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (P = .07) and 14 vs 26 (P = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12–0.73) and more days off invasive MV (24.0 ± 9.0 vs 17.5 ± 12.8; P = .001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (P = .84).ConclusionIn patients with severe COVID-19 pneumonia, early administration of prolonged, low dose MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration. ClinicalTrials.gov NCT04323592.

The association between frailty and severe disease among COVID-19 patients aged over 60\xa0years in China: a prospective cohort study

BackgroundThe coronavirus disease 2019 (COVID-19) has been a pandemic worldwide. Old age and underlying illnesses are associated with poor prognosis among COVID-19 patients. However, whether frailty, a common geriatric syndrome of reduced reserve to stressors, is associated with poor prognosis among older COVID-19 patients is unknown. The aim of our study is to investigate the association between frailty and severe disease among COVID-19 patients aged ≥ 60 years.MethodsA prospective cohort study of 114 hospitalized older patients (≥ 60 years) with confirmed COVID-19 pneumonia was conducted between 7 February 2020 and 6 April 2020. Epidemiological, demographic, clinical, laboratory, and outcome data on admission were extracted from electronic medical records. All patients were assessed for frailty on admission using the FRAIL scale, in which five components are included: fatigue, resistance, ambulation, illnesses, and loss of weight. The outcome was the development of the severe disease within 60 days. We used the Cox proportional hazards models to identify the unadjusted and adjusted associations between frailty and severe illness. The significant variables in univariable analysis were included in the adjusted model.ResultsOf 114 patients, (median age, 67 years; interquartile range = 64–75 years; 57 [50%] men), 39 (34.2%), 39 (34.2%), and 36 (31.6%) were non-frail, pre-frail, and frail, respectively. During the 60 days of follow-up, 43 severe diseases occurred including eight deaths. Four of 39 (10.3%) non-frail patients, 15 of 39 (38.5%) pre-frail patients, and 24 of 36 (66.7%) frail patients progressed to severe disease. After adjustment of age, sex, body mass index, haemoglobin, white blood count, lymphocyte count, albumin, CD8+ count, D-dimer, and C-reactive protein, frailty (HR = 7.47, 95% CI 1.73–32.34, P = 0.007) and pre-frailty (HR = 5.01, 95% CI 1.16–21.61, P = 0.03) were associated with a higher hazard of severe disease than the non-frail.ConclusionsFrailty, assessed by the FRAIL scale, was associated with a higher risk of developing severe disease among older COVID-19 patients. Our findings suggested that the use of a clinician friendly assessment of frailty could help in early warning of older patients at high-risk with severe COVID-19 pneumonia.

GM-CSF Neutralization With Lenzilumab in Severe COVID-19 Pneumonia: A Case-Cohort Study

ObjectiveTo assess the efficacy and safety of lenzilumab in patients with severe coronavirus disease 2019 (COVID-19) pneumonia. MethodsHospitalized patients with COVID-19 pneumonia and risk factors for poor outcomes were treated with lenzilumab 600 mg intravenously for three doses through an emergency single-use investigational new drug application. Patient characteristics, clinical and laboratory outcomes, and adverse events were recorded. We also identified a cohort of patients matched to the lenzilumab patients for age, sex, and disease severity. Study dates were March 13, 2020, to June 18, 2020. All patients were followed through hospital discharge or death. ResultsTwelve patients were treated with lenzilumab; 27 patients comprised the matched control cohort (untreated). Clinical improvement, defined as improvement of at least 2 points on the 8-point ordinal clinical endpoints scale, was observed in 11 of 12 (91.7%) patients treated with lenzilumab and 22 of 27 (81.5%) untreated patients. The time to clinical improvement was significantly shorter for the lenzilumab-treated group compared with the untreated cohort with a median of 5 days versus 11 days (P=.006). Similarly, the proportion of patients with acute respiratory distress syndrome (oxygen saturation/fraction of inspired oxygen<315 mm Hg) was significantly reduced over time when treated with lenzilumab compared with untreated (P<.001). Significant improvement in inflammatory markers (C-reactive protein and interleukin 6) and markers of disease severity (absolute lymphocyte count) were observed in patients who received lenzilumab, but not in untreated patients. Cytokine analysis showed a reduction in inflammatory myeloid cells 2 days after lenzilumab treatment. There were no treatment-emergent adverse events attributable to lenzilumab. ConclusionIn high-risk COVID-19 patients with severe pneumonia, granulocyte-macrophage colony-stimulating factor neutralization with lenzilumab was safe and associated with faster improvement in clinical outcomes, including oxygenation, and greater reductions in inflammatory markers compared with a matched control cohort of patients hospitalized with severe COVID-19 pneumonia. A randomized, placebo-controlled clinical trial to validate these findings is ongoing (NCT04351152).

Spontaneous pneumothorax and pneumomediastinum: an unusual presentation of COVID-19

The coronavirus disease 2019 (COVID-19) pneumonia was a recent worldwide outbreak During chest computed tomography (CT) we may observe pulmonary parenchymal opacity, as sign of COVID-19 Very few have reported pneumothorax and pneumomediastinum as complications of severe COVID-19 pneumonia We describe a 44-year-old male admitted to our department after the onset of sudden chest pain and high fever and evidence on computed tomography of spontaneous pneumothorax and pneumomediastinum, subsequently confirming COVID-19 pneumonia

Tocilizumab and steroid treatment in patients with COVID-19 pneumonia.

Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome. This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24th, also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HROW). Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30-100) and median PaO2/FiO2 200 mmHg (IQR 133-289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n = 29, 22.3%), methylprednisolone (n = 45, 34.6%), or both (n = 56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8-86.7) vs. 64.1% (95%CI, 51.3-74.0), HROW 0.48, 95%CI, 0.23-0.99; p = 0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7-92.6) vs. 71.9% (95%CI, 46-73), HROW 0.41, 95%CI: 0.19-0.89, p = 0.025. Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.

Treatment of COVID-19 With Conestat Alfa, a Regulator of the Complement, Contact Activation and Kallikrein-Kinin System.

A dysregulated immune response with hyperinflammation is observed in patients with severe coronavirus disease 2019 (COVID-19). The aim of the present study was to assess the safety and potential benefits of human recombinant C1 esterase inhibitor (conestat alfa), a complement, contact activation and kallikrein-kinin system regulator, in severe COVID-19. Patients with evidence of progressive disease after 24 h including an oxygen saturation <93% at rest in ambient air were included at the University Hospital Basel, Switzerland in April 2020. Conestat alfa was administered by intravenous injections of 8400 IU followed by 3 additional doses of 4200 IU in 12-h intervals. Five patients (age range, 53–85 years; one woman) with severe COVID-19 pneumonia (11–39% lung involvement on computed tomography scan of the chest) were treated a median of 1 day (range 1–7 days) after admission. Treatment was well-tolerated. Immediate defervescence occurred, and inflammatory markers and oxygen supplementation decreased or stabilized in 4 patients (e.g., median C-reactive protein 203 (range 31–235) mg/L before vs. 32 (12–72) mg/L on day 5). Only one patient required mechanical ventilation. All patients recovered. C1INH concentrations were elevated before conestat alfa treatment. Levels of complement activation products declined after treatment. Viral loads in nasopharyngeal swabs declined in 4 patients. In this uncontrolled case series, targeting multiple inflammatory cascades by conestat alfa was safe and associated with clinical improvements in the majority of severe COVID-19 patients. Controlled clinical trials are needed to assess its safety and efficacy in preventing disease progression.

Concerns About the Timing and Settings of Initiating Extracorporeal Membrane Oxygenation in Patients With Severe Coronavirus Disease 2019 Pneumonia

To the Editor: We read with great interest the clinical investigation reported by Yang et al (1) published in a recent issue of Critical Care Medicine. The authors describe the characteristics of patients with acute respiratory distress syndrome (ARDS) induced by the novel coronavirus disease 2019 (COVID-19) requiring extracorporeal membrane oxygenation (ECMO). They reported the mortality rate of COVID-19-induced ARDS requiring ECMO as 57.1%, which is similar to the 58.3% reported for outcomes (death or coma) in another case series (2). They also described the timing of initiation and the initial settings of ECMO in patients with severe ARDS induced by COVID-19. We would like to discuss whether the strategy they reported can be considered as standard for ECMO treatment for severe COVID-19 pneumonia. First, regarding the timing of initiating ECMO, the authors state that earlier initiation after mechanical ventilation may be associated with improved outcomes. Although early initiation is reported to be associated with good prognosis in adult ARDS patients (3), COVID-19 pneumonia is reported to present with features different from typical ARDS (4). Would different phenotypes of respiratory failure require different ECMO treatment strategies? We are still doubtful whether early initiation of ECMO can be considered similarly for typical ARDS and COVID-19 pneumonia. Addressing this will require comparisons between early initiation and late initiation groups. Second, the initial setting of ECMO in the study by Yang et al (1) seems to be unique. The authors report that many patients developed bradycardia while the centrifugal pump was on. This raises the question of whether this phenomenon is unique to COVID-19 pneumonia. Looking at the many COVID-19 case series reported to date, we find no descriptions of bradycardia elsewhere. To avoid bradycardia, the authors suggest increasing ECMO pump rotation slowly from 1,500 revolutions per minute (rpm) to the target rotation at increments of 500 rpm every 10 minutes. We speculate venovenous ECMO does not, in fact, have a significant effect on hemodynamics when initiating ECMO as long as a sufficient intravascular volume is maintained. Another report of patients with COVID-19 pneumonia requiring ECMO also described gradually increasing the rotation speed of the centrifugal pump when starting ECMO (5), but at a seemingly faster rate than Yang et al (1) reported. We question then whether it is actually possible to prevent bradycardia using the authors’ method. Finally, have the laboratory test values presented for survivors and nonsurvivors in Table 2 in (1) mistakenly been switched, given that the authors state that “survivors had a significant lower creatinine than nonsurvivors prior to ECMO”; the numbers in Table 2 in (1) are reversed. We are still in the pandemic phase of COVID-19, and thus, appropriate indications and methods for initiating ECMO support in critically ill patients with COVID-19 pneumonia are important to establish.

A 57-Year-Old African American Man with Severe COVID-19 Pneumonia Who Responded to Supportive Photobiomodulation Therapy (PBMT): First Use of PBMT in COVID-19

Patient: Male, 57-year-oldFinal Diagnosis: COVID-19Symptoms: Shortness of breath • hypoxiaMedication: —Clinical Procedure: Photobiomodulation therapy (PBMT)Specialty: Infectious Diseases • PulmonologyObjective:Unusual or unexpected effect of treatmentBackground:Coronavirus disease 2019 (COVID-19) is associated with lung inflammation and cytokine storm. Photobiomodulation therapy (PBMT) is a safe, non-invasive therapy with significant anti-inflammatory effects. Adjunct PBMT has been employed in treating patients with lung conditions. Human studies and experimental models of respiratory disease suggest PBMT reduces inflammation and promotes lung healing. This is the first time supportive PBMT was used in a severe case of COVID-19 pneumonia.Case Report:A 57-year-old African American man with severe COVID-19 received 4 once-daily PBMT sessions by a laser scanner with pulsed 808 nm and super-pulsed 905 nm modes for 28 min. The patient was evaluated before and after treatment via radiological assessment of lung edema (RALE) by CXR, pulmonary severity indices, blood tests, oxygen requirements, and patient questionnaires. Oxygen saturation (SpO2) increased from 93–94% to 97–100%, while the oxygen requirement decreased from 2–4 L/min to 1 L/min. The RALE score improved from 8 to 5. The Pneumonia Severity Index improved from Class V (142) to Class II (67). Additional pulmonary indices (Brescia-COVID and SMART-COP) both decreased from 4 to 0. CRP normalized from 15.1 to 1.23. The patient reported substantial improvement in the Community-Acquired Pneumonia assessment tool.Conclusions:This report has presented supportive PBMT in a patient with severe COVID-19 pneumonia. Respiratory indices, radiological findings, oxygen requirements, and patient outcomes improved over several days and without need for a ventilator. Future controlled clinical trials are required to evaluate the effects of PBMT on clinical outcomes in patients with COVID-19 pneumonia.

Inpatient Care during the COVID-19 Pandemic: A Survey of Italian Physicians

Background: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease that is of great global public health concern. Objective: We explored the clinical management of inpatients with COVID-19 in Italy. Methods: A self-administered survey was sent by email to Italian physicians caring for adult patients with COVID-19. A panel of experts was selected according to their clinical curricula and their responses were analyzed. Results: A total of 1,215 physicians completed the survey questionnaire (17.4% response rate). Of these, 188 (15.5%) were COVID-19 experts. Chest computed tomography was the most used method to detect and monitor COVID-19 pneumonia. Most of the experts managed acute respiratory failure with CPAP (56.4%), high flow nasal cannula (18.6%), and non-invasive mechanical ventilation (8%), while an intensivist referral for early intubation was requested in 17% of the cases. Hydroxychloroquine was prescribed as an antiviral in 90% of cases, both as monotherapy (11.7%), and combined with protease inhibitors (43.6%) or azithromycin (36.2%). The experts unanimously prescribed low-molecular-weight heparin to patients with severe COVID-19 pneumonia, and half of them (51.6%) used a dose higher than standard. The respiratory burden in patients who survived the acute phase was estimated as relevant in 28.2% of the cases, modest in 39.4%, and negligible in 9%. Conclusions: In our survey some major topics, such as the role of non-invasive respiratory support and drug treatments, show disagreement between experts, likely reflecting the absence of high-quality evidence studies. Considering the significant respiratory sequelae reported following COVID-19, proper respiratory and physical therapy programs should be promptly made available.

Chest Radiography in Coronavirus Disease 2019 (COVID-19): Correlation with Clinical Course

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 and was declared a global pandemic by the World Health Organization on 11 March 2020. A definitive diagnosis of COVID-19 is made after a positive result is obtained on reverse transcription-polymerase chain reaction assay. In Singapore, rigorous contact tracing was practised to contain the spread of the virus. Nasal swabs and chest radiographs (CXR) were also taken from individuals who were suspected to be infected by COVID-19 upon their arrival at a centralised screening centre. From our experience, about 40% of patients who tested positive for COVID-19 had initial CXR that appeared "normal". In this case series, we described the temporal evolution of COVID-19 in patients with an initial "normal" CXR. Since CXR has limited sensitivity and specificity in COVID-19, it is not suitable as a first-line diagnostic tool. However, when CXR changes become unequivocally abnormal, close monitoring is recommended to manage potentially severe COVID-19 pneumonia.

Tocilizumab for the treatment of adult patients with severe COVID‐19 pneumonia: A single‐center cohort study

Coronavirus disease 2019 (COVID‐19) can lead to a massive cytokine release. The use of the anti‐interleukin‐6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID‐19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6‐point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6‐point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon‐β (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06‐0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06‐0.99; P = .048) were negatively associated with clinical improvement by day 7. All‐cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO2 ratio increased by days 3 and 5, whereas C‐reactive protein levels dropped by day 2. There were no TCZ‐attributable adverse events. In this observational single‐center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID‐19 pneumonia.

Chest CT practice and protocols for COVID-19 from radiation dose management perspective.

The global pandemic of coronavirus disease 2019 (COVID-19) has upended the world with over 6.6 million infections and over 391,000 deaths worldwide. Reverse-transcription polymerase chain reaction (RT-PCR) assay is the preferred method of diagnosis of COVID-19 infection. Yet, chest CT is often used in patients with known or suspected COVID-19 due to regional preferences, lack of availability of PCR assays, and false-negative PCR assays, as well as for monitoring of disease progression, complications, and treatment response. The International Atomic Energy Agency (IAEA) organized a webinar to discuss CT practice and protocol optimization from a radiation protection perspective on April 9, 2020, and surveyed participants from five continents. We review important aspects of CT in COVID-19 infection from the justification of its use to specific scan protocols for optimizing radiation dose and diagnostic information. Key Points • Chest CT provides useful information in patients with moderate to severe COVID-19 pneumonia. • When indicated, chest CT in most patients with COVID-19 pneumonia must be performed with non-contrast, low-dose protocol. • Although chest CT has high sensitivity for diagnosis of COVID-19 pneumonia, CT findings are non-specific and overlap with other viral infections including influenza and H1N1.