Protecting Breastfeeding during the COVID-19 Pandemic.

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has impacted all patient populations including pregnant mothers. There is an incomplete understanding of SARS-CoV-2 pathogenesis and transmission potential at this time and the resultant anxiety has led to variable breastfeeding recommendations for suspected or confirmed mothers with novel coronavirus disease 2019 (COVID-19). Due to the potential concern for transmission of infection from maternal respiratory secretions to the newborn, temporary separation of the maternal-baby dyad, allowing for expressed breast milk to be fed to the infant, was initially recommended but later revised to include breastfeeding by the American Academy of Pediatrics in contrast to international societies, which recommend direct breastfeeding. This separation can have negative health and emotional implications for both mother and baby. Only two publications have reported SARS-CoV-2 in human breast milk but the role of breast milk as a vehicle of transmission of COVID-19 to the newborns still remains unclear and may indeed be providing protective antibodies against SARS-CoV-2 infection even in infected neonates. Other modes of transmission of infection to neonates from infected mothers or any care providers cannot be overemphasized. Symptomatic mothers on hydroxychloroquine can safely breastfeed and no adverse effects were reported in a baby treated with remdesivir in another drug trial. The excretion of sarilumab in human breast milk is unknown at this time. Hence, given the overall safety of breast milk and both short-term and long- term nutritional, immunological, and developmental advantages of breast milk to newborn, breast milk should not be withheld from baby. The setting of maternal care, severity of maternal infection and availability of resources can impact the decision of breastfeeding, the role of shared decision making on breastfeeding between mother and physician needs to be emphasized. We strongly recommend direct breastfeeding with appropriate hygiene precautions unless the maternal or neonatal health condition warrants separation of this dyad. KEY POINTS: · Breastmilk does not appear to play a significant role in transmission of SARS-CoV-2.. · Mother-baby separation has negative health and emotional consequences.. · Mothers with suspected or confirmed COVID-19 can directly breastfeed with appropriate precautions..

Protecting Breastfeeding during the COVID-19 Pandemic.

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has impacted all patient populations including pregnant mothers. There is an incomplete understanding of SARS-CoV-2 pathogenesis and transmission potential at this time and the resultant anxiety has led to variable breastfeeding recommendations for suspected or confirmed mothers with novel coronavirus disease 2019 (COVID-19). Due to the potential concern for transmission of infection from maternal respiratory secretions to the newborn, temporary separation of the maternal-baby dyad, allowing for expressed breast milk to be fed to the infant, was initially recommended but later revised to include breastfeeding by the American Academy of Pediatrics in contrast to international societies, which recommend direct breastfeeding. This separation can have negative health and emotional implications for both mother and baby. Only two publications have reported SARS-CoV-2 in human breast milk but the role of breast milk as a vehicle of transmission of COVID-19 to the newborns still remains unclear and may indeed be providing protective antibodies against SARS-CoV-2 infection even in infected neonates. Other modes of transmission of infection to neonates from infected mothers or any care providers cannot be overemphasized. Symptomatic mothers on hydroxychloroquine can safely breastfeed and no adverse effects were reported in a baby treated with remdesivir in another drug trial. The excretion of sarilumab in human breast milk is unknown at this time. Hence, given the overall safety of breast milk and both short-term and long- term nutritional, immunological, and developmental advantages of breast milk to newborn, breast milk should not be withheld from baby. The setting of maternal care, severity of maternal infection and availability of resources can impact the decision of breastfeeding, the role of shared decision making on breastfeeding between mother and physician needs to be emphasized. We strongly recommend direct breastfeeding with appropriate hygiene precautions unless the maternal or neonatal health condition warrants separation of this dyad. KEY POINTS: · Breastmilk does not appear to play a significant role in transmission of SARS-CoV-2.. · Mother-baby separation has negative health and emotional consequences.. · Mothers with suspected or confirmed COVID-19 can directly breastfeed with appropriate precautions..

Phillyrin (KD-1) exerts anti-viral and anti-inflammatory activities against novel coronavirus (SARS-CoV-2) and human coronavirus 229E (HCoV-229E) by suppressing the nuclear factor kappa B (NF-κB) signaling pathway.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has extensively and rapidly spread in the world, causing an outbreak of acute infectious pneumonia. However, no specific antiviral drugs or vaccines can be used. Phillyrin (KD-1), a representative ingredient of Forsythia suspensa, possesses anti-inflammatory, anti-oxidant, and antiviral activities. However, little is known about the antiviral abilities and mechanism of KD-1 against SARS-CoV-2 and human coronavirus 229E (HCoV-229E). PURPOSE: The study was designed to investigate the antiviral and anti-inflammatory activities of KD-1 against the novel SARS-CoV-2 and HCoV-229E and its potential effect in regulating host immune response in vitro. METHODS: The antiviral activities of KD-1 against SARS-CoV-2 and HCoV-229E were assessed in Vero E6 cells using cytopathic effect and plaque-reduction assay. Proinflammatory cytokine expression levels upon infection with SARS-CoV-2 and HCoV-229E infection in Huh-7 cells were measured by real-time quantitative PCR assays. Western blot assay was used to determine the protein expression of nuclear factor kappa B (NF-κB) p65, p-NF-κB p65, IκBα, and p-IκBα in Huh-7 cells, which are the key targets of the NF-κB pathway. RESULTS: KD-1 could significantly inhibit SARS-CoV-2 and HCoV-229E replication in vitro. KD-1 could also markedly reduce the production of proinflammatory cytokines (TNF-α, IL-6, IL-1ß, MCP-1, and IP-10) at the mRNA levels. Moreover, KD-1 could significantly reduce the protein expression of p-NF-κB p65, NF-κB p65, and p-IκBα, while increasing the expression of IκBα in Huh-7 cells. CONCLUSIONS: KD-1 could significantly inhibit virus proliferation in vitro, the up-regulated expression of proinflammatory cytokines induced by SARS-CoV-2 and HCoV-229E by regulating the activity of the NF-кB signaling pathway. Our findings indicated that KD-1 protected against virus attack and can thus be used as a novel strategy for controlling the coronavirus disease 2019.

Guillain-Barré Syndrome in a COVID-19 Patient: A Case Report and Review of Management Strategies.

Guillain-Barré syndrome (GBS) in an immune mediated disease that affects peripheral nerves with possible life-threatening complications. GBS has multiple subtypes including acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN) and acute motor sensory axonal neuropathy (AMSAN), which can make GBS difficult to diagnose. GBS commonly presents after viral infections such as influenza virus, campylobacter jejuni, and zika virus. GBS commonly presents with a prolonged clinical course leading to increased morbidity among affected patients. It is not surprising that COVID-19 has been connected with multiple cases of GBS, which may alter the recovery course for several patients post-COVID. In this report, we present a case of 69-year-old-female who presented with progressive motor weakness and loss of sensation in her extremities after testing positive for antibodies to COVID-19 one-month prior to presentation. Her presentation and treatment of GBS in the setting of COVID-19 is an example of one of the many COVID-19 complications and sheds light on the prolonged recovery course that we may experience as clinicians in the wake of this pandemic.

How to keep the cath-lab of a COVID-free hub center during the pandemic in a hub and spoke cardiology network: a single center's experience.

BACKGROUND: Northern Italy has been one of the most affected area in the world by the novel severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). The healthcare system has been overwhelmed by the huge number of patients in need of mechanical ventilation or intensive care, resulting in a delay of treatment of patients with acute coronary syndrome (ACS), due to a crash in STEMI networks and closure of a certain number of hub centers, and to a delay in patients' seeking for medical evaluation for chest pain or angina-equivalent symptoms. METHODS: In the Trentino region, a mountainous area with about 500,000 inhabitants, very close to Lombardy that was the epicenter of the pandemic in Italy, to avoid these dramatic consequences, we developed a new protocol tailored to our specificity to keep our institution, and above all the cath-lab, clean from the SARS-CoV-2 infection, to ensure full operativity for cardiologic emergencies. RESULTS: Applying this protocol during the two months of the peak of the infection in Italy no one of the staff members of the cath-lab, the ICCU or the cardiology ward tested positive to nasal swab for SARS-CoV-2 and the same result was obtained for all the patients admitted to our units. CONCLUSIONS: Our real-world experience shows that during the COVID-19 pandemic, quick activation of an appropriate protocol defining specific pathways for patients with a medical urgency is effective in minimizing healthcare personnel exposure and to preserve full operativity of the hub centers. This issue will be of a crucial importance, now that we are facing the second wave of the pandemic.

Novel coronavirus infection and Kawasaki disease.

There is a global problem of increment of the number of children with clinical features that mimic Kawasaki Disease (KD) during the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. The disease was first reported by Tomisaku Kawasaki, a Japanese pediatrician, in a four-year-old child with a rash and fever at the Red Cross Hospital in Tokyo in January 1961. Now Kawasaki disease is recognized worldwide. The complexity of symptoms was defined as an «acute febrile mucocutaneous lymphnode syndrome". At the moment, it is still unclear whether the coronavirus itself can lead to development of mucocutaneous lymph node syndrome. However, it is believed that COVID-19 virus infection worsens the course of Kawasaki disease, and in some cases, children affected by SARS-V-2 may develop a disease that has a clinical picture similar to Kawasaki disease.

ADRS due to COVID-19 in midterm pregnancy: successful management with plasma transfusion and corticosteroids.

BACKGROUND: Management of acute respiratory distress syndrome (ARDS) in pregnant women infected with new severe acute respiratory syndrome Corona virus 2 (SARS-CoV2) is a challenging clinical task. CASE: A 30- year-old woman (gravid 3, parity 2) presented at her 21 and 2/7 weeks gestation (pre pregnancy BMI: 36.1 kg/m2), with ARDS caused by SARS-CoV2 infection. She received lopinavir/ritonavir and azithromycin as well as early methyl prednisolone therapy. Given the persistent hypoxemia despite oxygen therapy via non rebreather face mask (FiO2:80%), convalescent plasma transfusion was administered that led to a mild clinical improvement as well as decrease in inflammatory markers. Growth of her fetus assessed by obstetric sonography was normal during hospital stay. CONCLUSION: Judicious corticosteroid therapy along with convalescent plasma transfusion to suppress viremia and cytokine storm can lead to favorable outcome in the pregnant women with ARDS caused by SARS-CoV2 infection without superimposed bacterial infection.

Personal Protective Equipment during the COVID-19 pandemic and operative time in cesarean section: retrospective cohort study.

INTRODUCTION: The covid-19 pandemic has meant a change in working protocols, as well as in Personal Protective Equipment (PPE). Obstetricians have had to adapt quickly to these changes without knowing how they affected their clinical practice. The aim of the present study was to evaluate how COVID-19 pandemic and PPE can affect operative time, operating room time, transfer into the operating room to delivery time and skin incision to delivery time in cesarean section. METHODS: This is a single-center retrospective cohort study. Women with confirmed or suspected SARS-CoV-2 infection having a cesarean section after March 7th, 2020 during the COVID-19 pandemic were included in the study. For each woman with confirmed or suspected SARS-CoV-2 infection, a woman who had a cesarean section for the same indication during the COVID-19 pandemic and with similar clinical history but not affected by SARS-CoV-2 was included. RESULTS: 42 cesarean sections were studied. The operating room time was longer in the COVID-19 confirmed or suspected women: 90 (73.0 to 110.0) versus 61 (48.0 to 70.5) minutes; p < .001. The transfer into the operating room to delivery time was longer, but not statistically significant, in urgent cesarean sections in COVID-19 confirmed or suspected women: 25.5 (17.5 to 31.75) versus 18.0 (10.0 to 26.25) minutes; p = .113. CONCLUSIONS: There were no significant differences in the operative time, transfer into the operating room to delivery time and skin incision to delivery time when wearing PPE in cesarean section. The COVID-19 pandemic and the use of PPE resulted in a significant increase in operating room time.

High percentage of smudge cells in a patient with COVID19: Rediscovering their utility.

We present a patient with SARS-CoV-2 infection, with an unexpected presence of lymphocytosis. Examination of blood film revealed mature small lymphocytes associated with high percentage of smudge cells (63%). A peripheral flow cyometry evidenced a CD5 negative CLL. A high percentage of smudge cells is associated with CLL diagnosis and has an important prognostic value: better survival and prolonged time to first treatment. It is a useful index in developing countries with low access to molecular testing.

The impact of obesity on severe disease and mortality in people with SARS-CoV-2: A systematic review and meta-analysis.

Background: Obesity accompanied by excess ectopic fat storage has been postulated as a risk factor for severe disease in people with SARS-CoV-2 through the stimulation of inflammation, functional immunologic deficit and a pro-thrombotic disseminated intravascular coagulation with associated high rates of venous thromboembolism. Methods: Observational studies in COVID-19 patients reporting data on raised body mass index at admission and associated clinical outcomes were identified from MEDLINE, Embase, Web of Science and the Cochrane Library up to 16 May 2020. Mean differences and relative risks (RR) with 95% confidence intervals (CIs) were aggregated using random effects models. Results: Eight retrospective cohort studies and one cohort prospective cohort study with data on of 4,920 patients with COVID-19 were eligible. Comparing BMI ≥ 25 vs <25 kg/m2, the RRs (95% CIs) of severe illness and mortality were 2.35 (1.43-3.86) and 3.52 (1.32-9.42), respectively. In a pooled analysis of three studies, the RR (95% CI) of severe illness comparing BMI > 35 vs <25 kg/m2 was 7.04 (2.72-18.20). High levels of statistical heterogeneity were partly explained by age; BMI ≥ 25 kg/m2 was associated with an increased risk of severe illness in older age groups (≥60 years), whereas the association was weaker in younger age groups (<60 years). Conclusions: Excess adiposity is a risk factor for severe disease and mortality in people with SARS-CoV-2 infection. This was particularly pronounced in people 60 and older. The increased risk of worse outcomes from SARS-CoV-2 infection in people with excess adiposity should be taken into account when considering individual and population risks and when deciding on which groups to target for public health messaging on prevention and detection measures. Systematic review registration: PROSPERO 2020: CRD42020179783.

Continuous positive airway pressure and pronation outside the Intensive Care Unit in COVID-19 acute respiratory distress syndrome.

BACKGROUND: The efficacy and safety of continuous positive airway pressure and respiratory physiotherapy outside the Intensive Care Unit during a pandemic. METHODS: In this cohort study performed in February-May 2020 in a large teaching hospital in Milan, COVID-19 patients with adult respiratory distress syndrome receiving continuous positive airway pressure (positive end-expiratory pressure =10 cm H2O, FiO2=0.6, daily treatment duration: 4×3h-cycles) and respiratory physiotherapy including pronation outside the Intensive Care Unit were followed-up. RESULTS: Of 90 acute respiratory distress syndrome (ARDS) patients treated with continuous positive airway pressure (45/90, 50% pronated at least once) outside the Intensive Care Unit and with a median (interquartile) follow-up of 37 (11-46) days, 45 (50%) were discharged at home, 28 (31%) were still hospitalized, and 17 (19%) died. Continuous positive airway pressure failure was recorded for 35 (39%) patients. Patient mobilization was associated with reduced failure rates (P=0.033). No safety issues were observed. CONCLUSIONS: Continuous positive airway pressure with patient mobilization (including pronation) was effective and safe in patients with ARDS due to COVID-19 managed outside the Intensive Care Unit setting during the pandemic.

Caring for acute coronary syndrome and other time-sensitive medical emergencies during the coronavirus disease 2019 pandemic in Northern Italy: report from a hub center.

BACKGROUND: The Lombardy region, in Northern Italy, suffered a major outbreak of Coronavirus disease 2019 (COVID-19) at the end of February 2020. The health system was rapidly overwhelmed by the pandemic. It became evident that patients suffering from time-sensitive medical emergencies like stroke, cerebral hemorrhage, trauma and acute myocardial infarction required timely, effective and safe pathways to be treated. The problem was addressed by a regional decree that created a hub-and-spoke system for time-sensitive medical emergencies. METHODS: We report the re-organizational changes adopted at a hub hospital (despite having already destined to COVID-19 patients most resources), and the number of emergent procedures for medical emergencies on the first 30-day of activity. These data were compared with the hospital activity in the same period of the previous year. RESULTS: Organizational changes were implemented in few hours. Dedicated pathways for non-COVID-19 patients affected by a medical emergency were set up in the emergency department, in the labs and in the operating theater. Ten intensive beds were implemented from a high-dependency unit; two operating rooms were reserved 24 h/day to neurosurgical or trauma emergencies. The number of emergent procedures was not different from that of the previous year, no admission refusal, no treatment delay and no viral transmission to the treated patients were recorded. No viral transmission to health care workers was observed. CONCLUSIONS: Re-organization of a hospital in order to adopt a hub-and-spoke model resulted feasible and allowed to face acute coronary syndrome and other time-sensitive medical emergencies timely and safely.

Blood Purification Techniques, Inflammatory Mediators and Mortality in COVID-19 Patients.

BACKGROUND: Inflammatory mediators are an important component in the pathophysiology of the coronavirus disease 2019 (COVID-19). This study aimed to assess the effects of reducing inflammatory mediators using hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the mortality of patients with COVID-19. MATERIALS AND METHODS: Twelve patients with confirmed diagnosis of COVID-19 were included. All patients had acute respiratory distress syndrome (ARDS). Patients were divided into three groups, namely, HP, CRRT and HP+CRRT. The primary outcome was mortality and the secondary outcomes were oxygenation and reduction in inflammatory mediators at the end of the study. RESULTS: Patients were not different at baseline in demographics, inflammatory cytokine levels, and the level of acute phase reactants. Half of the patients (3 out of 6) in the HP+CRRT group survived along with the survival of one patient (1 out of 2) in the HP group. All four patients in the CRRT group died. Serum creatinine (SCr), Interleukin-1 (IL1), Interleukin-6 (IL6), Interleukin-8 (IL8), partial pressure of oxygen (PaO2), O2 saturation (O2 sat), and hemodynamic parameters improved over time in HP+CRRT and CRRT groups, but no significant difference was observed in the HP group (All Ps > 0.05). CONCLUSION: Combined HP and CRRT demonstrated the best result in terms of mortality, reduction of inflammatory mediators and oxygenation. Further investigations are needed to explore the role of HP+CRRT in COVID-19 patients.

In Silico Modeling of Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: Pathophysiologic Insights and Potential Management Implications.

OBJECTIVES: Patients with coronavirus disease 2019 acute respiratory distress syndrome appear to present with at least two distinct phenotypes: severe hypoxemia with relatively well-preserved lung compliance and lung gas volumes (type 1) and a more conventional acute respiratory distress syndrome phenotype, displaying the typical characteristics of the "baby lung" (type 2). We aimed to test plausible hypotheses regarding the pathophysiologic mechanisms underlying coronavirus disease 2019 acute respiratory distress syndrome and to evaluate the resulting implications for ventilatory management. DESIGN: We adapted a high-fidelity computational simulator, previously validated in several studies of acute respiratory distress syndrome, to: 1) develop quantitative insights into the key pathophysiologic differences between the coronavirus disease 2019 acute respiratory distress syndrome and the conventional acute respiratory distress syndrome and 2) assess the impact of different positive end-expiratory pressure, Fio2, and tidal volume settings. SETTING: Interdisciplinary Collaboration in Systems Medicine Research Network. SUBJECTS: The simulator was calibrated to represent coronavirus disease 2019 acute respiratory distress syndrome patients with both normal and elevated body mass indices undergoing invasive mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An acute respiratory distress syndrome model implementing disruption of hypoxic pulmonary vasoconstriction and vasodilation leading to hyperperfusion of collapsed lung regions failed to replicate clinical data on type 1 coronavirus disease 2019 acute respiratory distress syndrome patients. Adding mechanisms to reflect disruption of alveolar gas-exchange due to the effects of pneumonitis and heightened vascular resistance due to the emergence of microthrombi produced levels of ventilation perfusion mismatch and hypoxemia consistent with data from type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, while preserving close-to-normal lung compliance and gas volumes. Atypical responses to positive end-expiratory pressure increments between 5 and 15 cm H2O were observed for this type 1 coronavirus disease 2019 acute respiratory distress syndrome model across a range of measures: increasing positive end-expiratory pressure resulted in reduced lung compliance and no improvement in oxygenation, whereas mechanical power, driving pressure, and plateau pressure all increased. Fio2 settings based on acute respiratory distress syndrome network protocols at different positive end-expiratory pressure levels were insufficient to achieve adequate oxygenation. Incrementing tidal volumes from 5 to 10 mL/kg produced similar increases in multiple indicators of ventilator-induced lung injury in the type 1 coronavirus disease 2019 acute respiratory distress syndrome model to those seen in a conventional acute respiratory distress syndrome model. CONCLUSIONS: Our model suggests that use of standard positive end-expiratory pressure/Fio2 tables, higher positive end-expiratory pressure strategies, and higher tidal volumes may all be potentially deleterious in type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, and that a highly personalized approach to treatment is advisable.

Placenta-Derived Cell Therapy to Treat Patients With Respiratory Failure Due to Coronavirus Disease 2019.

OBJECTIVES: To determine whether placental cell therapy PLacental eXpanded (PLX)-PAD (Pluristem Therapeutics, Haifa, Israel) may be beneficial to treating critically ill patients suffering from acute respiratory distress syndrome due to coronavirus disease 2019. DESIGN: Retrospective case report of critically ill coronavirus disease 2019 patients treated with PLacental eXpanded (PLX)-PAD from March 26, 2020, to April 4, 2020, with follow-up through May 2, 2020. SETTING: Four hospitals in Israel (Rambam Health Care Campus, Bnai Zion Medical Center, and Samson Assuta Ashdod University Hospital), and Holy Name Medical Center in New Jersey. PATIENTS: Eight critically ill patients on invasive mechanical ventilation, suffering from acute respiratory distress syndrome due to coronavirus disease 2019. INTERVENTIONS: Intramuscular injection of PLacental eXpanded (PLX)-PAD (300 × 106 cells) given as one to two treatments. MEASUREMENTS AND MAIN RESULTS: Mortality, time to discharge, and changes in blood and respiratory variables were monitored during hospitalization to day 17 posttreatment. Of the eight patients treated (median age 55 yr, seven males and one female), five were discharged, two remained hospitalized, and one died. By day 3 postinjection, mean C-reactive protein fell 45% (240.3-131.3 mg/L; p = 0.0019) and fell to 77% by day 5 (56.0 mg/L; p < 0.0001). Pao2/Fio2 improved in 5:8 patients after 24-hour posttreatment, with similar effects 48-hour posttreatment. A decrease in positive end-expiratory pressure and increase in pH were statistically significant between days 0 and 14 (p = 0.0032 and p = 0.00072, respectively). A decrease in hemoglobin was statistically significant for days 0-5 and 0-14 (p = 0.015 and p = 0.0028, respectively), whereas for creatinine, it was statistically significant between days 0 and 14 (p = 0.032). CONCLUSIONS: Improvement in several variables such as C-reactive protein, positive end-expiratory pressure, and Pao2/Fio2 was observed following PLacental eXpanded (PLX)-PAD treatment, suggesting possible therapeutic effect. However, interpretation of the data is limited due to the small sample size, use of concomitant investigational therapies, and the uncontrolled study design. The efficacy of PLacental eXpanded (PLX)-PAD in coronavirus disease 2019 should be further evaluated in a controlled clinical trial.

Disseminated Multifocal Intracerebral Bleeding Events in Three Coronavirus Disease 2019 Patients on Extracorporeal Membrane Oxygenation As Rescue Therapy.

OBJECTIVES: To describe three coronavirus disease 2019 patients suffering from acute respiratory distress syndrome under venovenous extracorporeal membrane oxygenation therapy and tight anticoagulation monitoring presenting a novel pattern of multifocal brain hemorrhage in various degrees in all cerebral and cerebellar lobes. DESIGN: Clinical observation of three patients. Post mortem examinations. SETTING: Two ICUs at the University Hospital Erlangen. PATIENTS: Three patients (medium age 56.6 yr, two male with hypertension and diabetes, one female with no medical history) developed severe acute respiratory distress syndrome on the basis of a severe acute respiratory syndrome coronavirus 2 infection. All required mechanical ventilation and venovenous extracorporeal membrane oxygenation support. INTERVENTIONS: Clinical observation, CT, data extraction from electronic medical records, and post mortem examinations. MAIN RESULTS: We report on an unusual multifocal bleeding pattern in the white matter in three cases with severe acute respiratory distress syndrome due to coronavirus disease 2019 undergoing venovenous extracorporeal membrane oxygenation therapy. Bleeding pattern with consecutive herniation was found in CT scans as well as in neuropathologic post mortem examinations. Frequency for this unusual brain hemorrhage in coronavirus disease 2019 patients with extracorporeal membrane oxygenation therapy at our hospital is currently 50%, whereas bleeding events in extracorporeal membrane oxygenation patients generally occur at 10-15%. CONCLUSIONS: Multifocality and high frequency of the unusual white matter hemorrhage pattern suggest a coherence to coronavirus disease 2019. Neuropathological analyses showed circumscribed thrombotic cerebrovascular occlusions, which eventually led to microvascular and later on macrovascular disseminated bleeding events. However, signs of cerebrovascular inflammation could not be detected. Polymerase chain reaction analyses of brain tissue or cerebrospinal fluid remained negative. Increased susceptibility for fatal bleeding events should be taken into consideration in terms of systemic anticoagulation strategies in coronavirus disease 2019.

Prioritizing Cleft/Craniofacial Surgical Care after the COVID-19 Pandemic.

BACKGROUND: It is anticipated that in due course the burden of emergency care due to COVID-19 infected patients will reduce sufficiently to permit elective surgical procedures to recommence. Prioritizing cleft/craniofacial surgery in the already overloaded medical system will then become an issue. The European Cleft Palate Craniofacial Association, together with the European Cleft and Craniofacial Initiative for Equality in Care, performed a brief survey to capture a current snapshot during a rapidly evolving pandemic. METHODS: A questionnaire was sent to the 2242 participants who attended 1 of 3 recent international cleft/craniofacial meetings. RESULTS: The respondents indicated that children with Robin sequence who were not responding to nonsurgical options should be treated as emergency cases. Over 70% of the respondents indicated that palate repair should be performed before the age of 15 months, an additional 22% stating the same be performed by 18 months. Placement of middle ear tubes, primary cleft lip surgery, alveolar bone grafting, and velopharyngeal insufficiency surgery also need prioritization. Children with craniofacial conditions such as craniosynostosis and increased intracranial pressure need immediate care, whilst children with craniosynostosis and associated obstructive sleep apnea syndrome or proptosis need surgical care within 3 months of the typical timing. Craniosynostosis without signs of increased intracranial pressure needs correction before the age of 18 months. CONCLUSIONS: This survey indicates several areas of cleft and craniofacial conditions that need prioritization, but also certain areas where intervention is less urgent. We acknowledge that there will be differences in the post COVID-19 response according to circumstances and policies in individual countries.

Thrombotic events following tocilizumab therapy in critically ill COVID-19 patients: a Façade for prognostic markers.

BACKGROUND: Hospitals in the Middle East Gulf region have experienced an influx of COVID-19 patients to their medical wards and intensive care units. The hypercoagulability of these patients has been widely reported on a global scale. However, many of the experimental treatments used to manage the various complications of COVID-19 have not been widely studied in this context. The effect of the current treatment protocols on patients' diagnostic and prognostic biomarkers may thus impact the validity of the algorithms adopted. CASE PRESENTATION: In this case series, we report four cases of venous thromboembolism and 1 case of arterial thrombotic event, in patients treated with standard or intensified prophylactic doses of unfractionated heparin or low molecular weight heparin at our institution. Tocilizumab has been utilized as an add-on therapy to the standard of care to treat patients with SARS-CoV-2 associated acute respiratory distress syndrome, in order to dampen the hyperinflammatory response. It is imperative to be aware that this drug may be masking the inflammatory markers (e.g. IL6, CRP, fibrinogen, and ferritin), without reducing the risk of thrombotic events in this population, creating instead a façade of an improved prognostic outcome. However, the D-dimer levels remained prognostically reliable in these cases, as they were not affected by the drug and continued to be at the highest level until event occurrence. CONCLUSIONS: In the setting of tocilizumab therapy, traditional prognostic markers of worsening infection and inflammation, and thus potential risk of acute thrombosis, should be weighed carefully as they may not be reliable for prognosis and may create a façade of an improved prognostic outcome insteasd. Additionally, the fact that thrombotic events continued to be observed despite decrease in inflammatory markers and the proactive anticoagulative approach adopted, raises more questions about the coagulative mechanisms at play in COVID-19, and the appropriate management strategy.

Assessment of Coronavirus in the Conjunctival Tears and Secretions in Patients with SARS-CoV-2 Infection in Sohag Province, Egypt.

PURPOSE: To assess SARS-CoV-2 virus in conjunctival tears and secretions of positive confirmed COVID-19 patients. METHODS: A case series study that included 28 positive COVID-19 patients confirmed with nasopharyngeal swab in the period 18-28 May 2020 at Sohag Tropical Medicine Hospital. Tears and conjunctival secretions of these confirmed positive cases were collected with disposable sampling swabs at interval of 3 days after admission due to respiratory symptoms. They were examined for the presence of SARS-CoV-2 by reverse transcription-polymerase chain reaction (RT-PCR) assay. RESULTS: Thirteen (46.43%) patients were stable, 4 (14.28%) patients suffered from dyspnea, 3 (10.72%) patients suffered from high fever, 5 (17.85%) patients suffered from cough, and 3 (10.72%) patients were on mechanical ventilation. Ten (35.71%) patients suffered from conjunctivitis. Tear and conjunctival swabs were positive in 8 (28.57%) patients, while other patients' swabs were negative (71.43%). Out of 10 patients with conjunctival manifestations, 3 patients had SARS-CoV-2 in their conjunctiva using (RT-PCR) test. Out of the 18 patients with no conjunctival manifestations, 5 patients had positive SARS-CoV-2 in their conjunctiva using (RT-PCR) test. CONCLUSION: The SARS-CoV-2 virus could be found in tears and conjunctival secretions in SARS-CoV-2 patients with or without conjunctivitis.