Background Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the dise...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2015432

Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19.

A report of two cases

The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.

/pdf/sars-cov-2-viral-load-is-associated-with-increased-disease-31g9gh44ki.pdf

SARS-CoV-2 viral load is associated with increased disease severity and mortality.

Recommendations Infection Control • For health care workers who are performing aerosol-generating procedures on patients with COVID-19, the COVID-19 Treatment Guidelines Panel (the Panel) recommends using an N95 respirator (or equivalent or higher-level respirator) rather than surgical masks, in addition to other personal protective equipment (PPE) (i.e., gloves, gown, and eye protection such as a face shield or safety goggles) (AIII). • The Panel recommends minimizing the use of aerosol-generating procedures on intensive care unit patients with COVID-19 and carrying out any necessary aerosol-generating procedures in a negative-pressure room, also known as an airborne infection isolation room, when available (AIII). • For health care workers who are providing usual care for nonventilated patients with COVID-19, the Panel recommends using an N95 respirator (or equivalent or higher-level respirator) or a surgical mask in addition to other PPE (i.e., gloves, gown, and eye protection such as a face shield or safety goggles) (AII). • For health care workers who are performing non-aerosol-generating procedures on patients with COVID-19 who are on closed-circuit mechanical ventilation, the Panel recommends using an N95 respirator (or equivalent or higher-level respirator) in addition to other PPE (i.e., gloves, gown, and eye protection such as a face shield or safety goggles) because ventilator circuits may become disrupted unexpectedly (BIII). • The Panel recommends that endotracheal intubation in patients with COVID-19 be performed by health care providers with extensive airway management experience, if possible (AIII). • The Panel recommends that intubation be performed using video laryngoscopy, if possible (CIII).

https://jamanetwork.com/journals/jama/articlepdf/2762996/jama_murthy_2020_it_200008.pdf

Care for Critically Ill Patients With COVID-19.

According to the World Health Organization (WHO), viral diseases continue to emerge and represent a serious issue to public health. In the last twenty years, several viral epidemics such as the severe acute respiratory syndrome coronavirus (SARS-CoV) from 2002 to 2003, and H1N1 influenza in 2009, have been recorded. Most recently, the Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012.In a timeline that reaches the present day, an epidemic of cases with unexplained low respiratory infections detected in Wuhan, the largest metropolitan area in China's Hubei province, was first reported to the WHO Country Office in China, on December 31, 2019. Published literature can trace the beginning of symptomatic individuals back to the beginning of December 2019. As they were unable to identify the causative agent, these first cases (n=29) were classified as "pneumonia of unknown etiology." The Chinese Center for Disease Control and Prevention (CDC) and local CDCs organized an intensive outbreak investigation program. The etiology of this illness was attributed to a novel virus belonging to the coronavirus (CoV) family.On February 11, 2020, the WHO Director-General, Dr. Tedros Adhanom Ghebreyesus, announced that the disease caused by this new CoV was a "COVID-19," which is the acronym of "coronavirus disease 2019". In the past twenty years, two additional CoVs epidemics have occurred. SARS-CoV provoked a large-scale epidemic beginning in China and involving two dozen countries with approximately 8000 cases and 800 deaths (fatality rate of 9,6%), and the MERS-CoV that began in Saudi Arabia and has approximately 2,500 cases and 800 deaths (fatality rate of 35%) and still causes as sporadic cases.This new virus is very contagious and has quickly spread globally. In a meeting on January 30, 2020, per the International Health Regulations (IHR, 2005), the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC) as it had spread to 18 countries with four countries reporting human-to-human transmission. An additional landmark occurred on February 26, 2020, as the first case of the disease, not imported from China, was recorded in the United States (US).Initially, the new virus was called 2019-nCoV. Subsequently, the task of experts of the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is very similar to the one that caused the SARS outbreak (SARS-CoVs).The CoVs have become the major pathogens of emerging respiratory disease outbreaks. They are a large family of single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species. For reasons yet to be explained, these viruses can cross species barriers and can cause, in humans, illness ranging from the common cold to more severe diseases such as MERS and SARS. Interestingly, these latter viruses have probably originated from bats and then moving into other mammalian hosts — the Himalayan palm civet for SARS-CoV, and the dromedary camel for MERS-CoV — before jumping to humans. The dynamics of SARS-Cov-2 are currently unknown, but there is speculation that it also has an animal origin.The potential for these viruses to grow to become a pandemic worldwide represents a serious public health risk. Concerning COVID-19, the WHO raised the threat to the CoV epidemic to the "very high" level, on February 28, 2020. On March 11, as the number of COVID-19 cases outside China has increased 13 times and the number of countries involved has tripled with more than 118,000 cases in 114 countries and over 4,000 deaths, WHO declared the COVID-19 a pandemic.World governments are at work to establish countermeasures to stem the devastating effects and it has been estimated that strict shutdowns may have saved 3 million lives across 11 European countries. Health organizations coordinate information flows and issues directives and guidelines to best mitigate the impact of the threat. At the same time, scientists around the world work tirelessly, and information about the transmission mechanisms, the clinical spectrum of disease, new diagnostics, and prevention and therapeutic strategies are rapidly developing. Many uncertainties remain with regard to both the virus-host interaction and the evolution of the pandemic, with specific reference to the times when it will reach its peak.At the moment, the therapeutic strategies to deal with the infection are only supportive, and prevention aimed at reducing transmission in the community is our best weapon. Aggressive isolation measures in China have led to a progressive reduction of cases. From China, the disease spread to Europe. In Italy, in geographic regions of the north, initially, and subsequently throughout the peninsula, political and health authorities have made incredible efforts to contain a shock wave that has severely tested the health system. Afterward, the COVID-19 quickly crossed the ocean and as of June 20, 2020, about 2,282,000 cases (with 121,000 deaths) have been recorded in the US, whereas Brazil with more than 1,000,000 cases and about 50,000 deaths is the most affected state in South America and the second in the world after the US. Although over time the lethality rate (total number of deaths for a given disease in relation to the total number of patients) of COVID-19 has been significantly lower than that of the SARS and MERS epidemics, the transmission of the SARS-CoV-2 virus is much larger than that of the previous viruses, with a much higher total number of deaths. It has been estimated that about one in five individuals worldwide could be at increased risk of severe COVID-19 disease if they become infected, due to underlying health conditions.In the midst of the crisis, the authors have chosen to use the "Statpearls" platform because, within the PubMed scenario, it represents a unique tool that may allow them to make updates in real-time. The aim, therefore, is to collect information and scientific evidence and to provide an overview of the topic that will be continuously updated.

Features, Evaluation, and Treatment of Coronavirus

Aims Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly evolved into a sweeping pandemic. Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID-19-associated organ alterations. Methods and results This article reports the autopsy findings of 21 COVID-19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland. An in-corpore technique was performed to ensure optimal staff safety. The primary cause of death was respiratory failure with exudative diffuse alveolar damage and massive capillary congestion, often accompanied by microthrombi despite anticoagulation. Ten cases showed superimposed bronchopneumonia. Further findings included pulmonary embolism (n = 4), alveolar haemorrhage (n = 3), and vasculitis (n = 1). Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised and five of pulmonary thrombotic microangiopathy. Six patients were diagnosed with senile cardiac amyloidosis upon autopsy. Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, and diabetes mellitus). Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively). All relevant histological slides are linked as open-source scans in supplementary files. Conclusions This study provides an overview of postmortem findings in COVID-19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID-19. This provides a pathophysiological explanation for higher mortality rates among these patients.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/his.14134

Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction.

Brown tumors are rare and generally self-limiting mass lesions of bone occurring in the context of hyperparathyroidism. Although commonly regarded as endocrine-driven tumor-like lesions, we detected pathogenic hotspot KRAS mutations in 10/16 brown tumors (62%) with similar frequencies found in cases affecting the peripheral and axial skeleton. Pathogenic mutations in other driver genes of the RAS-MAPK pathway were not identified. Our findings suggest brown tumors to represent true neoplasms driven by the activation of the RAS-MAPK signaling pathway. The frequent regression of brown tumors after normalization of hyperparathyroidism points to a second hit mediated by endocrine stimulation to be required for tumor development. Our findings underline the pathogenic relation of brown tumors to nonossifying fibroma and giant cell granuloma of the jaws which both appear histologically similar to brown tumors and are also driven by RAS-MAPK signaling pathway activation.

Brown Tumors Belong to the Spectrum of KRAS-driven Neoplasms

Cemento-osseous dysplasia is caused by RAS-MAPK activation.

CME Rheumatology 26: Rheumatological Cases Abstract. Special rheumatological cases are illustrated using various examples. On the one hand we present differential diagnoses and causes of a "Baker's cyst", on the other hand a case of involvement of the cervical spine in rheumatoid arthritis. Usually, the medical history and precise clinical examination will lead us in the right diagnostic direction. Further clarifications such as laboratory analyses or imaging procedures are used in a targeted manner, taking into account the clinic.

[CME Rheumatology 26: Rheumatological Cases].

Zusammenfassung. Anhand verschiedener Beispiele werden besondere rheumatologische Fälle illustriert. Zum einen stellen wir Differenzialdiagnosen und Ursachen einer «Bakerzyste» vor, zum anderen einen Fall mit Befall der Halswirbelsäule bei rheumatoider Arthritis. In der Regel führen uns bereits die Anamnese und die präzise klinische Untersuchung in die richtige diagnostische Richtung. Die weiteren Abklärungen, wie Laboranalysen oder bildgebende Verfahren, werden gezielt unter Berücksichtigung der Klinik eingesetzt.

Daniel Turek

Papers

Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction.

Brown Tumors Belong to the Spectrum of KRAS-driven Neoplasms

Cemento-osseous dysplasia is caused by RAS-MAPK activation.

[CME Rheumatology 26: Rheumatological Cases].

CME-Rheumatologie 25: Rheumatologische Fälle CME Fragen