COVID-19: Considerations about immune suppression and biologicals at the time of SARS-CoV-2 pandemic

The extent of the profound immunological and nonimmunological responses linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently being investigated worldwide due to the large burden associated with death due to SARS-CoV-2 and the short-term consequences of coronavirus disease 2019 (COVID-19). It has been hypothesized that patients on immunosuppressive treatments, including biologics, may have an augmented risk of being infected by SARS-CoV-2; however, there are currently no definitive data about biological drugs and COVID-19 in immune-mediated inflammatory diseases. Current epidemiological models developed to understand how long the COVID-19 epidemic may last are not conclusive and range from sustained epidemics to complete elimination. Nevertheless, even in the best-case scenario of apparent elimination, there is concordance about a possible contagion resurgence as late as 2024. Therefore, knowledge of the impact of SARS-CoV-2 on immune-mediated diseases and among patients treated with biologicals, together with the results of novel and promising COVID-19 treatment strategies targeting the virus and the host immune response (or both), will help us to best manage our patients during this pandemic over the next few years.     

Current treatment approaches for COVID-19 and the clinical value of transfusion-related technologies

COVID-19 is caused by SARS-CoV-2 which is a new enveloped virus that belongs to the Beta coronavirus genus. As a major health crisis, SARS-CoV-2 has infected over a million people around the world. There is currently no specific treatment available for patients with COVID-19 infection. Numerous potential therapies, including supportive intervention, immunomodulatory agents, antiviral therapy, and convalescent plasma transfusion, have been used in clinical practice. Herein, we summarize the current potential therapeutic approaches for diseases related to COVID-19 infection and discusses the clinical value of blood transfusion-related technologies used in COVID-19 treatment.     

COVID-19: An overview and a clinical update

The outbreak of coronavirus disease-2019 (COVID-19, previously known as 2019 nCoV) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Wuhan City, China, has spread rapidly around the world. Most patients from the first cluster had an epidemiological connection to the Wuhan's Huanan Seafood Wholesale Market. Available evidence has shown that SARS-CoV-2 can be easily transmitted from person to person through close contact and respiratory droplets, posing a substantial challenge to public health. At present, the research on SARS-CoV-2 is still in the primary stages. However, dexa-methasone and remdesivir are appeared to be promising medical therapies. Still, there is no definite specific treatment, and the mainstay of treatment is still focused on supportive therapies. Currently, over 150 vaccines are under investigation. It is necessary to understand the nature of the virus and its clinical characteristics in order to find effectively manage the disease. The knowledge about this virus is rapidly evolving, and clinicians must update themselves regularly. The present review comprehensively summarizes the epidemiology, pathogenesis, clinical characteristics, and management of COVID-19 based on the current evidence.     

Basic immunology may lead to translational therapeutic rationale: SARS-CoV-2 and rheumatic diseases

COVID-19 pandemia is a major concern for patients and healthcare systems. The fear of infection by patients with concomitant rheumatic diseases (either adult or children) and connective tissue diseases is arising worldwide, because of their immunological background and immunological therapies. Analysing the basic biology of single diseases, the data suggest that there is an "immunological umbrella" that seems to protect against the infection, through IFN type 1 and NK cell function. To date, reports from China, United States and Europe did not reveal an higher risk of infection, either for rheumatoid arthritis, juvenile idiopathic arthritis nor for lupus erythematosus. Antimalarials, anti-IL6-Anti-IL6 receptor, anti-IL1, anti-GM-CSF receptor and JAK1/2/3 inhibitors, are under investigation in COVID-dedicated clinical trials to control the inflammation raised by SARS-CoV-2 infection. Initial reports on the occurrence of autoimmune phenomena in the convalescence phase of SARS-CoV-2 infection suggests that the immunological consequences of the infection need to be strictly understood. Reporting of the study conforms to broad EQUATOR guidelines (Simera et al January 2010 issue of EJCI).     

Transmission of severe acute respiratory syndrome coronavirus 2 via fecal-oral: Current knowledge

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 93 million cases and 2 million deaths in the world. SARS-CoV-2 respiratory tract infection and its main clinical manifestations such as cough and shortness of breath are well known to the scientific community. However, a growing number of studies have reported SARS-CoV-2-related gastrointestinal involvement based on clinical manifestations, such as diarrhea, nausea, vomiting, and abdominal pain as well as on the pathophysiological mechanisms associated with coronavirus disease 2019. Furthermore, current evidence suggests SARS-CoV-2 transmission via the fecal-oral route and aerosol dissemination. Moreover, studies have shown a high risk of contamination through hospital surfaces and personal fomites. Indeed, viable SARS-CoV-2 specimens can be obtained from aerosols, which raises the possibility of transmission through aerosolized viral particles from feces. Therefore, the infection by SARS-CoV-2 via fecal-oral route or aerosolized particles should be considered. In addition, a possible viral spread to sources of drinking water, sewage, and rivers as well as the possible risk of viral transmission in shared toilets become a major public health concern, especially in the least developed countries. Since authors have emphasized the presence of viral RNA and even viable SARS-CoV-2 in human feces, studies on the possible fecal-oral coronavirus disease 2019 transmission become essential to understand better the dynamics of its transmission and, then, to reinforce preventive measures against this infection, leading to a more satisfactory control of the incidence of the infection.     

COVID-19 respiratory support in the emergency department setting

IntroductionSevere acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19), may result in severe complications, multiorgan dysfunction, acute respiratory failure, and death. SARS-CoV-2 is highly contagious and places healthcare workers at significant risk, especially during aerosol-generating procedures, including airway management.ObjectiveThis narrative review outlines the underlying respiratory pathophysiology of patients with COVID-19 and discusses approaches to airway management in the emergency department (ED) based on current literature.DiscussionPatients presenting with SARS-CoV-2 infection are at high risk for acute respiratory failure requiring airway management. Among hospitalized patients, 10–20% require intensive care unit admission, and 3–10% require intubation and mechanical ventilation. While providing respiratory support for these patients, proper infection control measures, including adherence to personal protective equipment policies, are necessary to prevent nosocomial transmission to healthcare workers. A structured approach to respiratory failure in these patients includes the use of exogenous oxygen via nasal cannula or non-rebreather, as well as titrated high-flow nasal cannula and non-invasive ventilation. This review offers several guiding principles and resources designed to be adapted in conjunction with local workplace policies for patients requiring respiratory support.ConclusionsWhile the fundamental principles of acute respiratory failure management are similar between COVID-19 and non-COVID-19 patients, there are some notable differences, including a focus on provider safety. This review provides an approach to airway management and respiratory support in the patient with COVID-19.     

COVID-19 and gastroenteric manifestations

Coronavirus disease 2019 (COVID-19), caused by the infection of a novel coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)], has become a pandemic. The infection has resulted in about one hundred million COVID-19 cases and millions of deaths. Although SARS-CoV-2 mainly spreads through the air and impairs the function of the respiratory system, it also attacks the gastrointestinal epithelial cells through the same receptor, angiotensin converting enzyme 2 receptor, which results in gastroenteric symptoms and potential fecal-oral transmission. Besides the infection of SARS-CoV-2, the treatments of COVID-19 also contribute to the gastroenteric manifestations due to the adverse drug reactions of anti-COVID-19 drugs. In this review, we update the clinical features, basic studies, and clinical practices of COVID-19-associated gastroenteric manifestations.     

COVID-19 and liver diseases,what we know so far

Coronavirus disease 2019 (COVID-19) pneumonia outbreak started in December 2019. On March 12, 2020, the World Health Organization (WHO) declared that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a pandemic, and as of May 2021, SARS-CoV-2 has infected over 167.3 million patients, including 3.4 million deaths, reported to WHO. In this review, we will focus on the relationship between SARS-CoV-2 infection and the liver. We will discuss how chronic liver diseases affect the COVID-19 disease course and outcomes. We will also discuss the SARS-CoV-2 effects on the liver, mechanisms of acute liver injury, and potential management plans.     

COVID-19 in patients with cancer: Risks and precautions

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the coronavirus family, which causes coronavirus disease 2019 (COVID-19). The phenotype of the disease varies from asymptomatic, to a mild phenotype, through to the severe form of acute respiratory distress syndrome (ARDS), which often leads to death, especially in those with underlying diseases. It has been reported that those who suffer from cancer (especially lung cancer and hematological malignancies) are at higher risk of serious complications and death from COVID-19. Some cancer treatments such as CAR T cell therapy can produce a cytokine storm, which is also a hallmark of severe COVID-19. Therefore, patients receiving CAR T cells are at higher risk if they become infected with COVID-19, and could be treated with anti-cytokine approaches.     

Special features of SARS-CoV-2 in daily practice

The severe acute respiratory syndrome-coronavirus-2 (commonly known as SARS-CoV-2) is a novel coronavirus (designated as 2019-nCoV), which was isolated for the first time after the Chinese health authorities reported a cluster of pneumonia cases in Wuhan, China in December 2019. Optimal management of the Coronavirus Disease-2019 disease is evolving quickly and treatment guidelines, based on scientific evidence and experts’ opinions with clinical experience, are constantly being updated. On January 30, 2020, the World Health Organization declared the SARS-CoV-2 outbreak as a "Public Health Emergency of International Concern". The total lack of immune protection brought about a severe spread of the contagion all over the world. For this reason, diagnostic tools, patient management and therapeutic approaches have been tested along the way, in the desperate race to break free from the widespread infection and its fatal respiratory complications. Current medical knowledge and research on severe and critical patients’ management and experimental treatments are still evolving, but several protocols on minimizing risk of infection among the general population, patients and healthcare workers have been approved and diffused by International Health Authorities.     

Nonalcoholic fatty liver disease and COVID-19: An epidemic that begets pandemic

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, affecting all the individuals across the planet. COVID-19 has gained significant attention due to its high prevalence among individuals with diabetes, nonalcoholic fatty liver disease (NAFLD), and metabolic syndrome. NAFLD is the hepatic manifestation of metabolic syndrome and can be associated with a high risk of developing type 2 diabetes. The association of COVID-19 and NAFLD has also gained more attention because NAFLD is highly associated with the epidemic of obesity. NAFLD is a potential risk factor for SARS-CoV-2 infection and severe COVID-19, independent of metabolic syndrome. Importantly, it is not yet clear whether the epidemics of obesity and NAFLD have perpetuated the current pandemic of COVID-19. Further research is urgently needed to assess the following: (1) Whether NAFLD is a high risk factor for SARS-CoV-2 infection; (2) Whether NAFLD is associated with the severe form of COVID-19; and (3) Whether the presence of NAFLD can explain the racial variation in the morbidity and mortality associated with COVID-19. This review summarizes the interactions between COVID-19 and NAFLD, mechanism of liver injury by COVID-19, and effect of lockdown due to COVID- 19 on patients with NAFLD.     

Diabetes mellitus and COVID-19: Understanding the association in light of current evidence

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have posed a problematic healthcare situation worldwide since December 2019. Diabetes mellitus is associated with an increased risk and severity of coronavirus disease 2019 (COVID-19). While interacting with various other risk factors, high blood sugar was found to reduce immunity and increase the replication of SARS-CoV-2. Oxidative stress and the release of pro-inflammatory cytokines are greater in diabetic individuals than in healthy people, worsening the outcome of SARS-CoV-2 infection in diabetics. Increased expression of furin and angiotensin converting enzyme 2 (ACE-2) receptor in the hyperglycemic environment may promote the entry of SARS-CoV-2 in the host cell. COVID-19 infection primarily modulates immune and inflammatory responses, and may cause a cytokine storm, resulting in possible lethal outcomes in diabetics. An experimental report suggests that ACE expressed in the pancreas and the SARS-CoV-2 virus invariably destroy β-cells which contain ACE-2 receptors and results in acute diabetes. Moreover, COVID-19 also causes hyperglycemia in an individual with diabetes which may be related to insulin resistance and destruction of β-cells during SARS-CoV-2 infection. Early observations also suggest a correlation between oral hypoglycemic agents and the risk of COVID-19. This review focused on the possible cause and mechanism involved in SARS-CoV-2 infection in diabetics and the role of antidiabetic drugs in COVID-19.     

Performance evaluation of antibody-based point-of-care devices intended for the identification of immune responses to SARS-CoV-2

The novel coronavirus outbreak caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) was first identified in December of 2019 in Wuhan, China. The local outbreak quickly rose to pandemic level that has spread to more than 188 countries with more than 19 million cases and 732,467 deaths worldwide. The current recommendation for testing is RT-PCR based tests of nasopharyngeal or alternatively nasal- and/or oropharyngeal swabs that detects infection with SARS-CoV-2 to diagnose acute infection. However, there is an urgent need for a quick and accurate antibody-based point-of-care test method to quickly identify evidence of SARS-CoV-2 infection among people who might be missed through active case finding and surveillance efforts. Serology tests measure the presence of antibodies in serum after infection. Here we compared the performance characteristics of 6 commercially available antibody-based point-of-care devices and their potential for identification of individuals infected at some time by SARS-CoV-2.     

Risk of SARS-CoV-2 Transmission Among Coworkers in a Surgical Environment

Health care workers are at high risk for contracting coronavirus disease 2019. However, little is known about the risk of transmission between coworkers. The objective of this study was to determine the risk of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between coworkers in a surgical environment. This was an observational study of 394 health care workers in a surgical environment who were exposed to 2 known SARS-CoV-2–positive coworkers. Standard infection precautions were in place at the time of the exposure. All 394 exposed workers initially underwent nasopharyngeal swab testing for SARS-CoV-2 using the polymerase chain reaction technique. Of the original group, 387 were tested again with the same technique 1 week later. Of 394 SARS-CoV-2–exposed health care workers initially tested, 1 was positive. No new positive cases were found on repeated testing of 387 participants 1 week later. The risk of transmission of SARS-CoV-2 in a health care unit with universal masking and appropriate hand hygiene is low. This finding should provide some reassurance to surgical practices as they reopen.     

Persistent viral shedding of severe acute respiratory syndrome coronavirus 2 after treatment with bendamustine and rituximab: A case report

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is detectable in nasopharyngeal specimens for up to 12–20 days regardless of the presence of chronic diseases in patients. We report a case of prolonged SARS-CoV-2 infection that lasted for more than eight weeks. The patient had persistent lymphopenia after receiving six cycles of bendamustine and rituximab (BR) therapy for follicular lymphoma; the last chemotherapy session was completed nine months before admission. The first nasopharyngeal specimen (NPS) for the SARS-CoV-2 polymerase chain reaction assay tested positive for the N501Y variant five weeks before admission. The patient's general and respiratory conditions gradually worsened; therefore, he was admitted to our hospital, and the same SARS-CoV-2 variant was subsequently identified on admission. Treatment for coronavirus disease was initiated, and the patient's condition improved; however, the NPS tested positive on day 15. The patient was discharged on day 28 and was instructed to isolate at home for a month. Hence, possible prolonged SARS-CoV-2 shedding should be considered in patients who receive BR therapy.     

Implications of COVID-19 for inflammatory bowel disease: Opportunities and challenges amidst the pandemic

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic various measures have been taken to mitigate the effects of the global health crisis in this unprecedented time. According to the World Health Organization, more than 5 million people have been infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and with more than 300000 deaths attributed to COVID-19 worldwide. There is emerging evidence that SARS-CoV-2 utilizes angiotensin-converting enzyme 2 receptors to enter human cells which are found in abundance in the alveoli and intestines. In addition, the infection is noted to be more severe in patients with co-morbid conditions, those who are malnourished, immunosuppressed and immunocompromised. Inflammatory bowel disease (IBD) which includes ulcerative colitis and Crohn’s disease is chronic remitting and relapsing disorders with intestinal and extraintestinal manifestation. IBD patients are often malnourished and on immunosuppressive medications and there is a hypothetical concern that IBD patients are at substantial risk of COVID-19 infection. The management of IBD patients is often complex and poses unique challenges for gastroenterologists during the pandemic. The purpose of this review article is to summarize the growing level of evidence and understanding of the management of IBD during the COVID-19 pandemic, in the light of international and national gastroenterology society guidelines. We performed a thorough literature search on IBD, SARS-CoV-2 and COVID-19 on PubMed, EMBASE, OVID Medline and Google Scholar and pertaining literature was critically examined and summarized. Per national and international society guidelines and recommendations, IBD is not a risk factor for SARS-CoV-2 infection. IBD patients should continue with their medications and they should follow universal precautions i.e. masks, hand and respiratory hygiene and avoidance of health care facilities and public toilets as general population. Among IBD patients older age, having active disease, and co-morbid conditions are risk factors for a severe SARS-CoV-2 infection. Furthermore, elective endoscopic and surgical procedures can be delayed or deferred until discussing the risks and benefits with patients.     

关注SARS-CoV-2致病机制的研究

严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）传染性强,可导致患者出现严重急性呼吸道感染（SARI）和多器官系统功能损害。SARS-CoV-2致病机制尚不明确,推测免疫炎症反应紊乱在其发生发展中发挥至关重要的作用。结合相关领域的研究进展,梳理SARS-CoV-2可能的致病机制,厘清未来研究方向,具有重要临床意义。     

Distinctive features of severe SARS-CoV-2 pneumonia

The coronavirus disease 2019 (COVID-19) pandemic is among the most important public health crises of our generation. Despite the promise of prevention offered by effective vaccines, patients with severe COVID-19 will continue to populate hospitals and intensive care units for the foreseeable future. The most common clinical presentation of severe COVID-19 is hypoxemia and respiratory failure, typical of the acute respiratory distress syndrome (ARDS). Whether the clinical features and pathobiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia differ from those of pneumonia secondary to other pathogens is unclear. This uncertainty has created variability in the application of historically proven therapies for ARDS to patients with COVID-19. We review the available literature and find many similarities between patients with ARDS from pneumonia attributable to SARS-CoV-2 versus other respiratory pathogens. A notable exception is the long duration of illness among patients with COVID-19, which could result from its unique pathobiology. Available data support the use of care pathways and therapies proven effective for patients with ARDS, while pointing to unique features that might be therapeutically targeted for patients with severe SARS-CoV-2 pneumonia.     

Gastroenterology and liver disease during COVID-19 and in anticipation of post-COVID-19 era: Current practice and future directions

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global public health. The virus causes the clinical syndrome known as coronavirus disease 2019 (COVID-19), in which multiple organs can get affected. Apart from manifestations of the respiratory system, which predominate, its clinical presentation is frequently accompanied by symptoms of the gastro-intestinal (GI) tract and liver abnormalities. The correlation of symptoms and abnormalities with disease severity is discussed, leading to ambiguous results from international literature. Moreover, the disease infects patients with co-existing liver and GI disorders affecting both their health status and the availability of healthcare services provided to them. The risk of transmission of the disease during aerosol-generating procedures has changed the diagnostic approach and follow-up algorithms for liver and GI diseases. For the safety of both doctors and patients, telemedicine and distant evaluation have become everyday practice, whereas several routines and emergency visits at outpatient and emergency departments have been postponed or delayed. Vaccination against SARS-CoV-2 is underway, providing hope to humanity and the expectation that the post-COVID-19 era is near. This review aims to update knowledge about the manifestations of COVID-19 related to liver and GI diseases and the effect of the pandemic on the diagnostic and therapeutic procedures for these diseases with a special focus on how current practices have changed and what changes will possibly remain in the future.