Cytokine release syndrome in COVID-19 patients, a new scenario for an old concern. The fragile balance between infections and autoimmunity

On 7 January 2020, researchers isolated and sequenced in China from patients with severe pneumonitis a novel coronavirus, then called SARS-CoV-2, which rapidly spread worldwide, becoming a global health emergency. Typical manifestations consist of flu-like symptoms such as fever, cough, fatigue, and dyspnea. However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). CRS represents an emergency scenario of a frequent challenge, which is the complex and interwoven link between infections and autoimmunity. Indeed, treatment of CRS involves the use of both antivirals to control the underlying infection and immunosuppressive agents to dampen the aberrant pro-inflammatory response of the host. Several trials, evaluating the safety and effectiveness of immunosuppressants commonly used in rheumatic diseases, are ongoing in patients with COVID-19 and CRS, some of which are achieving promising results. However, such a use should follow a multidisciplinary approach, be accompanied by close monitoring, be tailored to patient’s clinical and serological features, and be initiated at the right time to reach the best results. Autoimmune patients receiving immunosuppressants could be prone to SARS-CoV-2 infections; however, suspension of the ongoing therapy is contraindicated to avoid disease flares and a consequent increase in the infection risk

Diagnosis and Management of COVID-19 Disease

SARS-CoV-2 is a novel coronavirus that was identified in late 2019 as the causative agent of COVID-19 (aka coronavirus disease 2019). On March 11, 2020, the World Health Organization (WHO) declared the world-wide outbreak of COVID-19 a pandemic. This document summarizes the most recent knowledge regarding the biology, epidemiology, diagnosis, and management of COVID-19

CORTICOSTEROIDS AND SECONDARY INFECTIONS: AN INSIGHT INTO CORONAVIRUS DISEASE-2019

Coronavirus disease 2019 (COVID-19), which is caused by novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged at Wuhan in China in December 2019 and has rapidly spread throughout the world. The droplets expelled during face-to-face exposure, mainly through talking, coughing, or sneezing, are the most common mode of transmission. So far, children have not been affected frequently without deaths. However, the course of this virus in the future is unknown. The diagnosis is mainly made through reverse transcription-polymerase chain reaction (RT-PCR) and serology testing. Treatment with dexamethasone at an early phase of developed acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 alters the pulmonary and systemic inflammatory response and decreases mortality. Corticosteroid therapy is associated with a sizable reduction in the duration of mechanical ventilation and hospital mortality. One of the major risk factor associated with corticosteroid therapy is associated with acquiring secondary infections. Pulmonary epithelial damage and inflammatory disease are the predisposing risk factors for pulmonary aspergillosis due to the release of danger molecular patterns during severe COVID-19. Galactomannan and culture testing of bronchoalveolar lavage fluid are the most sensitive diagnostic measures for aspergillosis in intensive care unit (ICU). Finally, the treatment of coronavirus associated pulmonary aspergillosis is complex. The only way one can prevent the spread of infection by following precautions such as frequent hand washing, wearing a mask in public places, social distancing, and by avoiding unnecessary gatherings

Respiratory viruses: their importance and lessons learned from COVID-19

Respiratory virus infection can cause severe illnesses capable of inducing acute respiratory failure that can progress rapidly to acute respiratory distress syndrome (ARDS). ARDS is related to poor outcomes, especially in individuals with a higher risk of infection, such as the elderly and those with comorbidities, i.e. obesity, asthma, diabetes mellitus and chronic respiratory or cardiovascular disease. Despite this, effective antiviral treatments available for severe viral lung infections are scarce. The coronavirus disease 2019 (COVID-19) pandemic demonstrated that there is also a need to understand the role of airborne transmission of respiratory viruses. Robust evidence supporting this exists, but better comprehension could help implement adequate measures to mitigate respiratory viral infections. In severe viral lung infections, early diagnosis, risk stratification and prognosis are essential in managing patients. Biomarkers can provide reliable, timely and accessible information possibly helpful for clinicians in managing severe lung viral infections. Although respiratory viruses highly impact global health, more research is needed to improve care and prognosis of severe lung viral infections. In this review, we discuss the epidemiology, diagnosis, clinical characteristics, management and prognosis of patients with severe infections due to respiratory viruses

Repurposing existing drugs for the treatment of COVID-19

The rapid global spread and significant mortality associated with the coronavirus disease (COVID-19) caused by SARS-CoV-2 viral infection has spurred an urgent race to find effective treatments. Repurposing existing drugs is a particularly attractive approach as pharmacokinetic and safety data already exist, thus development can leapfrog straight to clinical trials of efficacy, generating results far more quickly than de novo drug development. This review summarizes the state of play for the principle drugs identified as candidates to be repurposed for treating COVID-19 grouped by broad mechanism of action: antiviral, immune enhancing, and anti-inflammatory or immunomodulatory. Patient selection, particularly with regard to disease stage, is likely to be key. To date only dexamethasone and remedesivir have been shown to be effective, but several other promising candidates are in trials

Update March 2022:management of hospitalised adults with coronavirus disease-19 (COVID-19): a european respiratory society living guideline

The ERS COVID-19 guidelines make recommendations for corticosteroids, anti-IL-6 monoclonal antibodies, baricitinib, anticoagulation and non-invasive respiratory support for hospitalised patients with COVID-19 https://bit.ly/3QgHH7

Therapeutic strategies against COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that mainly affects the upper and lower respiratory tract and is responsible for extremely different degrees of disease, ranging from flu-like symptoms to atypical pneumonia that may evolve to acute respiratory distress syndrome and, ultimately, death. No specific therapy for SARS-CoV-2 has yet been identified, but since the beginning of the outbreak, several pre-existing therapeutics have been reconsidered for the treatment of infected patients. The aim of this article is to discuss current therapeutics against SARS-CoV-2. A literature review was performed using PubMed, collecting data from English-language articles published until June 20th, 2020. Literature analysis showed that with the acquisition of more in-depth knowledge on the characteristics of SARS-CoV-2 and the pathogenesis of the different clinical manifestations, a more rationale use of available drugs has become possible. However, the road to defining which drugs are effective and which schedules of administration must be used to maximize efficacy and minimize adverse events is still very long. To date, it is only clear that no drug can alone cope with all the problems posed by SARS-CoV-2 infection and effective antivirals and inflammatory drugs must be given together to reduce COVID-19 clinical manifestations. Moreover, choice of therapy must always be tailored on clinical manifestations and, when they occur, drugs able to fight coagulopathy and venous thromboembolism that may contribute to respiratory deterioration must be prescribed. (www.actabiomedica.com)