Risk and Protective Factors for COVID-19 Morbidity, Severity, and Mortality.

The outbreak of the coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an evolving global health crisis. Currently, a number of risk factors have been identified to have a potential impact on increasing the morbidity of COVID-19 in adults, including old age, male sex, pre-existing comorbidities, and racial/ethnic disparities. In addition to these factors, changes in laboratory indices and pro-inflammatory cytokines, as well as possible complications, could indicate the progression of COVID-19 into a severe and critical stage. Children predominantly suffer from mild illnesses due to COVID-19. Similar to adults, the main risk factors in pediatric patients include age and pre-existing comorbidities. In contrast, supplementation with a healthy diet and sufficient nutrition, COVID-19 vaccination, and atopic conditions may act as protective factors against the infection of SARS-CoV-2. COVID-19 vaccination not only protects vulnerable individuals from SARS-CoV-2 infection, more importantly, it may also reduce the development of severe disease and death due to COVID-19. Currently used therapies for COVID-19 are off-label and empiric, and their impacts on the severity and mortality of COVID-19 are still unclear. The interaction between asthma and COVID-19 may be bidirectional and needs to be clarified in more studies. In this review, we highlight the clinical evidence supporting the rationale for the risk and protective factors for the morbidity, severity, and mortality of COVID-19.

Recent developments in the immunopathology of COVID-19.

There has been an important change in the clinical characteristics and immune profile of Coronavirus disease 2019 (COVID-19) patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID-19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID-19. The efficacy of the COVID-19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4, and BA.5 and the global administration of COVID-19 vaccines have changed the clinical scenario of COVID-19. Multisystem inflammatory syndrome in children (MIS-C) may cause severe and heterogeneous disease but with a lower mortality rate. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long-term symptoms of COVID-19. There is conflicting evidence about whether atopic diseases, such as allergic asthma and rhinitis, are associated with a lower susceptibility and better outcomes of COVID-19. At the beginning of pandemic, the European Academy of Allergy and Clinical Immunology (EAACI) developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID-19 vaccines and emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID-19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID-19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID-19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS-CoV-2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high-risk groups, the development of MIS-C and long COVID-19.

The effect of allergy and asthma as a comorbidity on the susceptibility and outcomes of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic causes an overwhelming number of hospitalization and deaths with a significant socioeconomic impact. The vast majority of studies indicate that asthma and allergic diseases do not represent a risk factor for COVID-19 susceptibility nor cause a more severe course of disease. This raises the opportunity to investigate the underlying mechanisms of the interaction between an allergic background and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The majority of patients with asthma, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, food allergies and drug allergies exhibit an over-expression of type 2 immune and inflammatory pathways with the contribution of epithelial cells, innate lymphoid cells, dendritic cells, T cells, eosinophils, mast cells, basophils, and the type 2 cytokines interleukin (IL)-4, IL-5, IL-9, IL-13, and IL-31. The potential impact of type 2 inflammation-related allergic diseases on susceptibility to COVID-19 and severity of its course have been reported. In this review, the prevalence of asthma and other common allergic diseases in COVID-19 patients is addressed. Moreover, the impact of allergic and non-allergic asthma with different severity and control status, currently available asthma treatments such as inhaled and oral corticosteroids, short- and long-acting ß2 agonists, leukotriene receptor antagonists and biologicals on the outcome of COVID-19 patients is reviewed. In addition, possible protective mechanisms of asthma and type 2 inflammation on COVID-19 infection, such as the expression of SARS-CoV-2 entry receptors, antiviral activity of eosinophils and cross-reactive T-cell epitopes, are discussed. Potential interactions of other allergic diseases with COVID-19 are postulated, including recommendations for their management.

Recent advances and developments in COVID-19 in the context of allergic diseases.

BACKGROUND: Since the first reports of coronavirus disease 2019 (COVID-19) in Wuhan, China, in December 2019, there have been 198 million confirmed cases worldwide as of August 2021. The scientific community has joined efforts to gain knowledge of the newly emerged virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the immunopathological mechanisms leading to COVID-19, and its significance for patients with allergies and asthma. METHODS: Based on the current literature, recent advances and developments in COVID-19 in the context of allergic diseases were reviewed. RESULTS AND CONCLUSIONS: In this review, we discuss the prevalence of COVID-19 in subjects with asthma, attacks of hereditary angioedema, and other allergic diseases during COVID-19. Underlying mechanisms suggest a protective role of allergy in COVID-19, involving eosinophilia, SARS-CoV-2 receptors expression, interferon responses, and other immunological events, but further studies are needed to fully understand those associations. There has been significant progress in disease evaluation and management of COVID-19, and allergy care should continue during the COVID-19 pandemic. The European Academy of Allergy & Clinical Immunology (EAACI) launched a series of statements and position papers providing recommendations on the organization of the allergy clinic, handling of allergen immunotherapy, asthma, drug hypersensitivity, allergic rhinitis, and other allergic diseases. Treatment of allergies using biologics during the COVID-19 pandemic has also been discussed. Allergic reactions to the COVID-19 vaccines, including severe anaphylaxis, have been reported. Vaccination is a prophylactic strategy that can lead to a significant reduction in the mortality and morbidity associated with SARS-CoV-2 infection, and in this review, we discuss the proposed culprit components causing rare adverse reactions and recommendations to mitigate the risk of anaphylactic events during the administration of the vaccines.

Risk factors for severe and critically ill COVID-19 patients: A review.

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1ß, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.

Clinical, radiological, and laboratory characteristics and risk factors for severity and mortality of 289 hospitalized COVID-19 patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has become a global pandemic, with 10%-20% of severe cases and over 508 000 deaths worldwide. OBJECTIVE: This study aims to address the risk factors associated with the severity of COVID-19 patients and the mortality of severe patients. METHODS: 289 hospitalized laboratory-confirmed COVID-19 patients were included in this study. Electronic medical records, including patient demographics, clinical manifestation, comorbidities, laboratory tests results, and radiological materials, were collected and analyzed. According to the severity and outcomes of the patients, they were divided into three groups: nonsurvived (n = 49), survived severe (n = 78), and nonsevere (n = 162) groups. Clinical, laboratory, and radiological data were compared among these groups. Principal component analysis (PCA) was applied to reduce the dimensionality and visualize the patients on a low-dimensional space. Correlations between clinical, radiological, and laboratory parameters were investigated. Univariate and multivariate logistic regression methods were used to determine the risk factors associated with mortality in severe patients. Longitudinal changes of laboratory findings of survived severe cases and nonsurvived cases during hospital stay were also collected. RESULTS: Of the 289 patients, the median age was 57 years (range, 22-88) and 155 (53.4%) patients were male. As of the final follow-up date of this study, 240 (83.0%) patients were discharged from the hospital and 49 (17.0%) patients died. Elder age, underlying comorbidities, and increased laboratory variables, such as leukocyte count, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) on admission, were found in survived severe cases compared to nonsevere cases. According to the multivariate logistic regression analysis, elder age, a higher number of affected lobes, elevated CRP levels on admission, increased prevalence of chest tightness/dyspnea, and smoking history were independent risk factors for death of severe patients. A trajectory in PCA was observed from "nonsevere" toward "nonsurvived" via "severe and survived" patients. Strong correlations between the age of patients, the affected lobe numbers, and laboratory variables were identified. Dynamic changes of laboratory findings of survived severe cases and nonsurvived cases during hospital stay showed that continuing increase of leukocytes and neutrophil count, sustained lymphopenia and eosinopenia, progressing decrease in platelet count, as well as high levels of NLR, CRP, PCT, AST, BUN, and serum creatinine were associated with in-hospital death. CONCLUSIONS: Survived severe and nonsurvived COVID-19 patients had distinct clinical and laboratory characteristics, which were separated by principle component analysis. Elder age, increased number of affected lobes, higher levels of serum CRP, chest tightness/dyspnea, and smoking history were risk factors for mortality of severe COVID-19 patients. Longitudinal changes of laboratory findings may be helpful in predicting disease progression and clinical outcome of severe patients.

Clinical characteristics of 182 pediatric COVID-19 patients with different severities and allergic status.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID-19 children with different severities and allergic status. METHODS: Data extracted from the electronic medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results, and radiological images of 182 hospitalized COVID-19 children, were summarized and analyzed. RESULTS: The median age was 6 years, ranging from 3 days to 15 years, and there were more boys (male-female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort, and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground-glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia (manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase, and serum interleukins (IL)-2, IL-4, IL-6, IL-10, and TNF-α. There were no differences in treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing, and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID-19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID-19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy, and asthma. Demographics and clinical features were not significantly different between allergic and nonallergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D-dimer, and aspartate aminotransferase levels compared with all patients. Immunological profiles including circulating T, B, and NK lymphocyte subsets, total immunoglobulin and complement levels, and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subset numbers, and serum cytokine levels. CONCLUSION: Pediatric COVID-19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and nonallergic COVID-19 children in disease incidence, clinical features, and laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS-CoV-2 infection and hardly influenced the disease course of COVID-19 in children.

Advances and recent developments in asthma in 2020.

In this review, we discuss recent publications on asthma and review the studies that have reported on the different aspects of the prevalence, risk factors and prevention, mechanisms, diagnosis, and treatment of asthma. Many risk and protective factors and molecular mechanisms are involved in the development of asthma. Emerging concepts and challenges in implementing the exposome paradigm and its application in allergic diseases and asthma are reviewed, including genetic and epigenetic factors, microbial dysbiosis, and environmental exposure, particularly to indoor and outdoor substances. The most relevant experimental studies further advancing the understanding of molecular and immune mechanisms with potential new targets for the development of therapeutics are discussed. A reliable diagnosis of asthma, disease endotyping, and monitoring its severity are of great importance in the management of asthma. Correct evaluation and management of asthma comorbidity/multimorbidity, including interaction with asthma phenotypes and its value for the precision medicine approach and validation of predictive biomarkers, are further detailed. Novel approaches and strategies in asthma treatment linked to mechanisms and endotypes of asthma, particularly biologicals, are critically appraised. Finally, due to the recent pandemics and its impact on patient management, we discuss the challenges, relationships, and molecular mechanisms between asthma, allergies, SARS-CoV-2, and COVID-19.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

A compendium answering 150 questions on COVID-19 and SARS-CoV-2.

In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID-19). This disease, caused by the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), has developed into a pandemic. To date, it has resulted in ~9 million confirmed cases and caused almost 500 000 related deaths worldwide. Unequivocally, the COVID-19 pandemic is the gravest health and socioeconomic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence-based medical advice on SARS-CoV-2 and COVID-19. Although the majority of the patients show a very mild, self-limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID-19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a "cytokine storm" leading to acute respiratory distress syndrome, endothelitis, thromboembolic complications, and multiorgan failure. The epidemiologic features of COVID-19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID-19-related topics should be based on more coordinated high-quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS-CoV-2, COVID-19, and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development, and epidemiology. A total of 150 questions were answered by experts in the field providing a comprehensive and practical overview of COVID-19 and allergic disease.

Eleven faces of coronavirus disease 2019.

BACKGROUND AND AIMS: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has recently spread worldwide and been declared a pandemic. We aim to describe here the various clinical presentations of this disease by examining eleven cases. METHODS: Electronic medical records of 11 patients with COVID-19 were collected, and demographics, clinical manifestations, outcomes, key laboratory results, and radiological images are discussed. RESULTS: The clinical course of the eleven cases demonstrated the complexity of the COVID-19 profile with different clinical presentations. Clinical manifestations range from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Laboratory detection of the viral nucleic acid can yield false-negative results, and serological testing of virus-specific IgG and IgM antibodies should be used as an alternative for diagnosis. Patients with common allergic diseases did not develop distinct symptoms and severe courses. Cases with a pre-existing condition of chronic obstructive pulmonary disease or complicated with a secondary bacterial pneumonia were more severe. CONCLUSION: All different clinical characteristics of COVID-19 should be taken into consideration to identify patients that need to be in strict quarantine for the efficient containment of the pandemic.

Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been widely spread. We aim to investigate the clinical characteristic and allergy status of patients infected with SARS-CoV-2. METHODS: Electronic medical records including demographics, clinical manifestation, comorbidities, laboratory data, and radiological materials of 140 hospitalized COVID-19 patients, with confirmed result of SARS-CoV-2 viral infection, were extracted and analyzed. RESULTS: An approximately 1:1 ratio of male (50.7%) and female COVID-19 patients was found, with an overall median age of 57.0 years. All patients were community-acquired cases. Fever (91.7%), cough (75.0%), fatigue (75.0%), and gastrointestinal symptoms (39.6%) were the most common clinical manifestations, whereas hypertension (30.0%) and diabetes mellitus (12.1%) were the most common comorbidities. Drug hypersensitivity (11.4%) and urticaria (1.4%) were self-reported by several patients. Asthma or other allergic diseases were not reported by any of the patients. Chronic obstructive pulmonary disease (COPD, 1.4%) patients and current smokers (1.4%) were rare. Bilateral ground-glass or patchy opacity (89.6%) was the most common sign of radiological finding. Lymphopenia (75.4%) and eosinopenia (52.9%) were observed in most patients. Blood eosinophil counts correlate positively with lymphocyte counts in severe (r = .486, P < .001) and nonsevere (r = .469, P < .001) patients after hospital admission. Significantly higher levels of D-dimer, C-reactive protein, and procalcitonin were associated with severe patients compared to nonsevere patients (all P < .001). CONCLUSION: Detailed clinical investigation of 140 hospitalized COVID-19 cases suggests eosinopenia together with lymphopenia may be a potential indicator for diagnosis. Allergic diseases, asthma, and COPD are not risk factors for SARS-CoV-2 infection. Older age, high number of comorbidities, and more prominent laboratory abnormalities were associated with severe patients.