The cytokine storm and COVID‐19

Coronavirus disease 2019 (COVID‐19), which began in Wuhan, China, in December 2019, has caused a large global pandemic and poses a serious threat to public health. More than 4 million cases of COVID‐19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), have been confirmed as of 11 May 2020. SARS‐CoV‐2 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID‐19 severity and is also a crucial cause of death from COVID‐19. In the absence of antivirals and vaccines for COVID‐19, there is an urgent need to understand the cytokine storm in COVID‐19. Here, we have reviewed the current understanding of the features of SARS‐CoV‐2 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID‐19. In addition, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID‐19.     

Multisystem inflammatory syndrome in children related to COVID‐19: A New York City experience

In December 2019, the 2019, a novel coronavirus disease (COVID‐19) caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) first emerged in Wuhan, China. This has now spread worldwide and was declared a pandemic by March 2020. Initially, the pediatric population was described as a low risk for severe COVID‐19. However, reports have emerged recently of cases of COVID‐19 in children with a systemic inflammatory disease, with features that overlap with Kawasaki disease (KD). We describe the first 15 cases with the multi‐systeminflammatory syndrome in children (MIS‐C), temporally related to COVID‐19, who presented for care to a tertiary pediatric referral center in New York City. We discuss the disproportionate burden of disease among Hispanic/Latino and Black/African American ancestry, the distinct cytokine signature across the disease spectrum (IL‐1/IL‐6), and the potential role and pathogenesis of SARS‐CoV‐2 in this new clinical entity.     

Three months of COVID‐19: A systematic review and meta‐analysis

The pandemic of 2019 novel coronavirus (SARS‐CoV‐2019), reminiscent of the 2002‐SARS‐CoV outbreak, has completely isolated countries, disrupted health systems and partially paralyzed international trade and travel. In order to be better equipped to anticipate transmission of this virus to new regions, it is imperative to track the progress of the virus over time. This review analyses information on progression of the pandemic in the past 3 months and systematically discusses the characteristics of SARS‐CoV‐2019 virus including its epidemiologic, pathophysiologic, and clinical manifestations. Furthermore, the review also encompasses some recently proposed conceptual models that estimate the spread of this disease based on the basic reproductive number for better prevention and control procedures. Finally, we shed light on how the virus has endangered the global economy, impacting it both from the supply and demand side.     

Clonal haematopoiesis and COVID‐19: A possible deadly liaison

We provide evidence for a linear correlation between the frequency of clonal haematopoiesis and COVID‐19 mortality rate. We discuss the mechanistic explanations for this association mediated by a pathological inflammatory response. Our hypothesis can be tested in COVID‐19‐infected patients and eventually lead to new approaches to risk stratification and therapy.     

Clinical characteristics and risk factors of mild‐to‐moderate COVID‐19 patients with false‐negative SARS‐CoV‐2 nucleic acid

This study investigates the clinical and imaging characteristics of coronavirus disease 2019 (COVID‐19) patients with false‐negative nucleic acids. Mild‐to‐moderate COVID‐19 patients, including 19 cases of nucleic acid false‐negative patients and 31 cases of nucleic acid positive patients, were enrolled. Their epidemiological, clinical, and laboratory examination data and imaging characteristics were analyzed. Risk factors for false negatives were discussed. Compared with the nucleic acid positive group, the false‐negative group had less epidemiological exposure (52.6% vs 83.9%; P = .025), less chest discomfort (5.3% vs 32.3%; P = .035), and faster recovery (10 [8, 13] vs 15 [11, 18.5] days; P = .005). The number of involved lung lobes was (2 [1, 2.5] vs 3 [2, 4] days; P = .004), and the lung damage severity score was (3 [2.5, 4.5] vs 5 [4, 9] days; P = .007), which was lighter in the nucleic acid false‐negative group. Thus, the absence of epidemiological exposure may be a potential risk factor for false‐negative nucleic acids. The false‐negative cases of COVID‐19 are worth noting because they have a risk of viral transmission without positive test results, lighter clinical manifestations, and less history of epidemiological exposure.     

COVID‐19 and pregnancy: An opportunity to correct an historic gender bias

Current literature and clinical guidelines do not include pregnant women as an a priori risk group for COVID‐19. However, a gender vision of health begs the question: Why are pregnant women not considered a risk group for COVID‐19? The answer is clear: historically, most community scientific studies have not considered female gender, or pregnancy as a state, to be a focus of special interest or effort. Unfortunately, this bias seems to be maintained in the COVID‐19 epidemic: most current guidelines for diagnosing SARS‐CoV‐2 infection during pregnancy apply the same standard criteria as for the general population.     

The “scar” of a pandemic: Cumulative incidence of COVID‐19 during the first trimester of pregnancy

Congenitally‐ or perinatally‐acquired viral infections can be harmful to the fetus but data are limited about prevalence and outcomes of coronavirus disease 2019 (COVID‐19) disease during the first trimester of pregnancy. We report epidemiologic data from a study investigating a cohort of women who became pregnant just before or during the COVID‐19 pandemic. We recruited 138 consecutive pregnant women attending for first trimester screening (11‐13 weeks of gestation) at Sant'Anna Hospital, Turin, Piedmont, Italy, during the plateau and the falling phase of the COVID‐19 epidemic curve. Patients were tested for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) immunoglobulin M/immunoglobulin G antibody levels and SARS‐CoV‐2 detection in sera and nasopharyngeal swab samples. COVID‐19 cumulative incidence during the first trimester was of 10.1% with high prevalence of asymptomatic patients (42.8%). Similar to the course of the disease in non pregnant adults, 80% to 90% of infections were not severe.The prevalence of reported symptoms was four‐fold higher in SARS‐CoV‐2 positive patients (57%) than in those negative (13%) (P < .001), suggesting that direct self‐testing should open doors to confirmatory testing for COVID‐19. Our findings support the need for COVID‐19 screening in early pregnancy in epidemic areas to plan materno‐fetal health surveillance programs.     

Diagnostic efficacy of anti‐SARS‐CoV‐2 IgG/IgM test for COVID‐19: A meta‐analysis

The serological testing of anti‐SARS‐CoV‐2 immunoglobulin G (IgG) and/or IgM is widely used in the diagnosis of COVID‐19. However, its diagnostic efficacy remains unclear. In this study, we searched for diagnostic studies from the Web of Science, PubMed, Embase, CNKI, and Wanfang databases to calculate the pooled diagnostic accuracy measures using bivariate random‐effects model meta‐analysis. As a result, 22 from a total of 1613 articles, including 2282 patients with SARS‐CoV‐2 and 1485 healthy persons or patients without SARS‐CoV‐2, were selected for a meta‐analysis. Pooled sensitivity, specificity, and area under curve of the summary receiver operator curve (SROC) were: (a) 0.85 (95% confidence interval [CI]: 0.79‐0.90), 0.99 (95% CI: 0.98‐1.00), and 0.99 (95% CI: 0.97‐0.99) for anti‐SARS‐CoV‐2 IgG and (b) 0.74 (95% CI: 0.65‐0.81), 0.99 (95% CI: 0.97‐1.00), and 0.95 (95% CI: 0.93‐0.97) for IgM. A subgroup analysis among detection methods indicated the sensitivity of IgG and IgM using enzyme‐linked immunosorbent assay were slightly lower than those using gold immunochromatography assay (GICA) and chemiluminescence immunoassay (P > .05). These results showed that the detection of anti‐SARS‐CoV‐2 IgG and IgM had high diagnostic efficiency to assist the diagnosis of SARS‐CoV‐2 infection. And, GICA might be used as the preferred method for its accuracy and simplicity.     

SARS‐CoV‐2 replicating in nonprimate mammalian cells probably have critical advantages for COVID‐19 vaccines due to anti‐Gal antibodies: A minireview and proposals

Glycoproteins of enveloped viruses replicating in nonprimate mammalian cells carry α‐1,3‐galactose (α‐Gal) glycans, and can bind to anti‐Gal antibodies which are abundant in humans. The antibodies have protected humans and their ancestors for millions of years, because they inhibit replication of many kinds of microbes carrying αGal glycans and aid complements and macrophages to destroy them. Therefore, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) replicating in nonprimate mammalian cells (eg, PK‐15 cells) carry αGal glycans and could be employed as a live vaccine for corona virus 2019 (COVID‐19). The live vaccine safety could be further enhanced through intramuscular inoculation to bypass the fragile lungs, like the live unattenuated adenovirus vaccine safely used in US recruits for decades. Moreover, the immune complexes of SARS‐CoV‐2 and anti‐Gal antibodies could enhance the efficacy of COVID‐19 vaccines, live or inactivated, carrying α‐Gal glycans. Experiments are imperatively desired to examine these novel vaccine strategies which probably have the critical advantages for defeating the pandemic of COVID‐19 and preventing other viral infectious diseases.     

Encephalopathy in patients with COVID‐19: A review

Encephalopathy and encephalitis are major and devastating severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) virus‐associated central nervous system complications. Hypoxic/metabolic changes produced by intense inflammatory response against the virus triggers cytokine storm and subsequently acute respiratory distress syndrome and multiple organ failure. Hypoxic/metabolic changes result in encephalopathy. The presence of comorbidities predisposes to hypoxic/metabolic changes responsible for encephalopathy. Altered consciousness, ranging from mild confusion, delirium, to deep coma, is hallmark clinical features. Cortical and subcortical T2/FLAIR signal changes are common neuroimaging abnormalities. In a few isolated case reports of SARS‐CoV‐2 encephalitis, the virus has been demonstrated in cerebrospinal fluid. The presence of anosmia and ageusia can help in differentiation from other encephalopathies. We analyzed published reports on coronavirus disease 2019‐associated encephalopathy. Encephalopathy is common in older patients, the majority are more than 50 years of age. The patients having encephalopathy/encephalitis are either severely or critically ill. Many patients were already on mechanical ventilation. Lung abnormalities are noted in almost all of the patients, presenting with encephalopathy. Encephalopathy is always preceded by commoner clinical features, like, fever, cough, dyspnoea, and headache. In majority, patients are already in the intensive care unit, when encephalopathy develops.     

YouTube as a source of patient information for Coronavirus Disease (COVID‐19): A content‐quality and audience engagement analysis

YouTube is the second most popular website in the world and is increasingly being used as a platform for disseminating health information. Our aim was to evaluate the content‐quality and audience engagement of YouTube videos pertaining to the SARS (severe acute respiratory syndrome)‐CoV‐2 virus which causes the Coronavirus Disease 2019 (COVID‐19), during the early phase of the pandemic. We chose the first 30 videos for seven different search phrases: “2019 nCoV,” “SARS CoV‐2,” “COVID‐19 virus,” “coronavirus treatment,” “coronavirus explained,” “what is the coronavirus” and “coronavirus information.” Video contents were evaluated by two independent medical students with more than 5 years of experience using the DISCERN instrument. Qualitative data, quantitative data and upload source for each video was noted for a quality and audience engagement analysis. Out of the total 210 videos, 137 met our inclusion criteria and were evaluated. The mean DISCERN score was 31.33 out of 75 possible points, which indicates that the quality of YouTube videos on COVID‐19 is currently poor. There was excellent reliability between the two raters (intraclass correlation coefficient = 0.96). 55% of the videos discussed prevention, 49% discussed symptoms and 46% discussed the spread of the virus. Most of the videos were uploaded by news channels (50%) and education channels (40%). The quality of YouTube videos on SARS‐CoV‐2 and COVID‐19 is poor, however, we have listed the top‐quality videos in our article as they may be effective tools for patient education during the pandemic.     

The impact of the SARS‐CoV‐2 infection,with special reference to the hematological setting

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a disease known from a few months, caused by a recently arisen virus and, consequently, it is little known. The disease has a benign course in most infected subjects (children and young adults), is often symptomatic in adults over the age of 50 and often serious and life threatening in people with comorbidities and the elderly. The few data published on coronavirus disease‐2019 (COVID‐19) in the blood‐oncology field report a serious clinical presentation, a serious course of the disease, and a high mortality rate, as has also been reported for other cancer contexts. The current strategy for treating patients with SARS‐CoV‐2 includes antivirals that are effective against other viral infections and drugs that can moderate the cytokine storm. There is no specific vaccine and consequently all possible precautions must be taken to prevent SARS‐CoV‐2 infection in the areas of oncology, oncohematology, and bone marrow transplantation. In this reviewer's article, we report the information currently available on SARS‐CoV‐2 infection to help young doctors and hematologists to successfully manage patients with COVID‐19.     

The clinical characteristics of pediatric inpatients with SARS‐CoV‐2 infection: A meta‐analysis and systematic review

Millions of people were infected with the coronavirus disease 2019 (COVID‐19) all over the world. Data on clinical symptoms of pediatric inpatients with COVID‐19 infection were unclear. The aim of study was to investigate the clinical features of pediatric inpatients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. PubMed, EMBASE, and the Cochrane Library were searched to seek for studies providing details on pediatric inpatients with SARS‐CoV‐2 infection which were published from 1st January to 21st April 2020. Studies with more than five pediatric inpatients were included in our meta‐analysis.This study was registered in the PROSPERO database (CRD42020183550). As the results shown, fever (46%) and cough (42%) were the main clinical characters of pediatric inpatients with SARS‐CoV‐2 infection and the other clinical characters, such as diarrhea, vomiting, nasal congestion, and fatigue account for 10% in pediatric inpatients. The proportion of asymptomatic cases was 0.42 (95% confidence interval [CI]: 0.27‐0.59) and severe cases was 0.03 (95% CI: 0.01‐0.06). For the laboratory result, leukopenia (21%) and lymphocytosis (22%) were the mainly indicators for pediatric inpatients, followed by high aspartate aminotransferase (19%), lymphopenia (16%), high alanine aminotransferase (15%), high C‐reactive protein (17%), leukocytosis (13%), high D‐dimer (12%) and high creatine kinase‐MB (5%). Regard to chest imaging features, unilateral and bilateral accounts for 22% in pediatric inpatients, respectively. In conclusion, compared with adult inpatients with SARS‐CoV‐2 infection, the pediatric inpatients had mild clinical characters, lab test indicators, and chest imaging features. More clinical studies focus on the pediatric patients with SARS‐CoV‐2 infection in other countries should be conducted.     

Angiotensin‐converting enzyme 2: The old door for new severe acute respiratory syndrome coronavirus 2 infection

Coronavirus (CoV) disease 2019 (COVID‐19) is an ongoing pandemic caused by severe acute respiratory syndrome CoV 2 (SARS‐CoV‐2). The highly contagious SARS‐CoV‐2 belongs to the genus Betacoronavirus, and it is phylogenetically closely related to SARS‐CoV, a human CoV that caused an outbreak back in 2002 to 2003. Both SARS‐CoV‐2 and SARS‐CoV enter human cells via the interactions between viral crown‐like spike protein and human angiotensin‐converting enzyme 2 (ACE2) receptor. Here, we aim to review the involvement of ACE2 in human CoV infections by discussing the roles of ACE2 in CoV evolution, cross‐species transmissibility, and COVID‐19 susceptibility. We also provide our perspectives on COVID‐19 treatment and prevention.     

Meta‐analysis of chest CT features of patients with COVID‐19 pneumonia

The objective of this paper is to perform a meta‐analysis regarding the chest computed tomography (CT) manifestations of coronavirus disease‐2019 (COVID‐19) pneumonia patients. PubMed, Embase, and Cochrane Library databases were searched from 1 December 2019 to 1 May 2020 using the keywords of “COVID‐19 virus,” “the 2019 novel coronavirus,” “novel coronavirus,” and “COVID‐19.” Studies that evaluated the CT manifestations of common and severe COVID‐19 pneumonia were included. Among the 9736 searched results, 15 articles describing 1453 common patients and 697 severe patients met the inclusion criteria. Based on the CT images, the common patients were less frequent to exhibit consolidation (odds ratio [OR] = 0.31), pleural effusion (OR = 0.19), lymphadenopathy (OR = 0.17), crazy‐paving pattern (OR = 0.22), interlobular septal thickening (OR = 0.27), reticulation (OR = 0.20), traction bronchiectasis (OR = 0.40) with over two lobes involved (OR = 0.07) and central distribution (OR = 0.18) while more frequent to bear unilateral pneumonia (OR = 4.65) involving one lobe (OR = 13.84) or two lobes (OR = 6.95) when compared with severe patients. Other CT features including ground‐glass opacities (P = .404), air bronchogram (P = .070), nodule (P = .093), bronchial wall thickening (P = .15), subpleural band (P = .983), vascular enlargement (P = .207), and peripheral distribution (P = .668) did not have a significant association with the severity of the disease. No publication bias among the selected studies was suggested (Harbord's tests, P > .05 for all.) We obtained reliable estimates of the chest CT manifestations of COVID‐19 pneumonia patients, which might provide an important clue for the diagnosis and classification of COVID‐19 pneumonia.