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1.
Mayo Clin Proc ; 97(3): 579-599, 2022 03.
Article in English | MEDLINE | ID: covidwho-1720595

ABSTRACT

Coronavirus disease 2019 (COVID-19) is the third deadly coronavirus infection of the 21st century that has proven to be significantly more lethal than its predecessors, with the number of infected patients and deaths still increasing daily. From December 2019 to July 2021, this virus has infected nearly 200 million people and led to more than 4 million deaths. Our understanding of COVID-19 is constantly progressing, giving better insight into the heterogeneous nature of its acute and long-term effects. Recent literature on the long-term health consequences of COVID-19 discusses the need for a comprehensive understanding of the multisystemic pathophysiology, clinical predictors, and epidemiology to develop and inform an evidence-based, multidisciplinary management approach. A PubMed search was completed using variations on the term post-acute COVID-19. Only peer-reviewed studies in English published by July 17, 2021 were considered for inclusion. All studies discussed in this text are from adult populations unless specified (as with multisystem inflammatory syndrome in children). The preliminary evidence on the pulmonary, cardiovascular, neurological, hematological, multisystem inflammatory, renal, endocrine, gastrointestinal, and integumentary sequelae show that COVID-19 continues after acute infection. Interdisciplinary monitoring with holistic management that considers nutrition, physical therapy, psychological management, meditation, and mindfulness in addition to medication will allow for the early detection of post-acute COVID-19 sequelae symptoms and prevent long-term systemic damage. This review serves as a guideline for effective management based on current evidence, but clinicians should modify recommendations to reflect each patient's unique needs and the most up-to-date evidence. The presence of long-term effects presents another reason for vaccination against COVID-19.


Subject(s)
COVID-19/complications , Cardiovascular Diseases/etiology , Humans , Lung Diseases/etiology , Nervous System Diseases/etiology
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324822

ABSTRACT

Background: Optimal fluid management in patients with COVID-19 has not been reported. This retrospective, multicenter study investigated the impact of intravenous infusion volume in the early stage of COVID-19 on clinical outcomes. Methods 127 patients from two tertiary hospitals were separated into the “conservative” and “liberal” groups based on average daily intravenous infusion volume within the first seven days after admission. Basic information, demographic and epidemiological characteristics, laboratory findings, treatments, and outcome measures were retrieved from medical records. The disease progression and prognosis were analyzed and compared. Results The average daily intravenous infusion volume within 7 days was 500 (150–700) ml/day in the conservative-strategy group (n = 87), and 1100 (1000–1288) ml/day in the liberal-strategy group (n = 40) ( p  < 0.001). There were no statistical differences in median age, male-to-female ratio, epidemiology, laboratory findings on admission, comorbidities, and average daily urine output within the seven days ( p  > 0.05). The final K + in the liberal group was slightly higher than that at admission, and the final hematocrit level in the conservative group had a significant difference than that at admission ( p  < 0.05). The mean (± SD) duration of hospitalization was 22.41 ± 11.99 days in the conservative group and 25.28 ± 12.08 days in the liberal group ( p  = 0.120). However, compared to the liberal group, conservative group had statistically lower rates of disease progression (9.3% vs 37.5%, p  < 0.001), mechanical ventilation (2.3% vs 27.5%, p  < 0.001) and in-hospital mortality (2.3% vs 15.0%, p  = 0.012). Conclusions Although there appeared to be no significant difference in the duration of hospitalization between using conservative and liberal fluid management strategies, the former was associated with lower rates of disease progression, mechanical ventilation and in-hospital mortality without increased nonpulmonary-organ dysfunction. These results support the importance of implementing conservative intravenous fluid infusion in the early stage of COVID-19.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322248

ABSTRACT

Epidemiological studies suggest that men exhibit a higher mortality rate to COVID-19 than women, yet the underlying biology is largely unknown. Here, we seek to delineate sex differences in the gene expression of viral entry proteins ACE2 and TMPRSS2, and host transcriptional responses to SARS-CoV-2 through large-scale analysis of genomic and clinical data. We first compiled 220,000 human gene expression profiles from three databases and completed the meta-information through machine learning and manual annotation. Large scale analysis of these profiles indicated that male samples show higher expression levels of ACE2 and TMPRSS2 than female samples, especially in the older group (>60 years) and in the kidney. Subsequent analysis of 6,031 COVID-19 patients at Mount Sinai Health System revealed that men have significantly higher creatinine levels, an indicator of impaired kidney function. Further analysis of 782 COVID-19 patient gene expression profiles taken from upper airway and blood suggested men and women present distinct expression changes. Computational deconvolution analysis of these profiles revealed male COVID-19 patients have enriched kidney-specific mesangial cells in blood compared to healthy patients. Together, this study suggests biological differences in the kidney between sexes may contribute to sex disparity in COVID-19.

4.
Clin Rev Allergy Immunol ; 59(1): 89-100, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1139384

ABSTRACT

The COVID-19 pandemic is a significant global event in the history of infectious diseases. The SARS-CoV-2 appears to have originated from bats but is now easily transmissible among humans, primarily through droplet or direct contact. Clinical features of COVID-19 include high fever, cough, and fatigue which may progress to ARDS. Respiratory failure can occur rapidly after this. The primary laboratory findings include lymphopenia and eosinopenia. Elevated D-dimer, procalcitonin, and CRP levels may correlate with disease severity. Imaging findings include ground-glass opacities and patchy consolidation on CT scan. Mortality is higher in patients with hypertension, cardiac disease, diabetes mellitus, cancer, and COPD. Elderly patients are more susceptible to severe disease and death, while children seem to have lower rates of infection and lower mortality. Diagnostic criteria and the identification of persons under investigation have evolved as more data has emerged. However, the approach to diagnosis is still very variable from region to region, country to country, and even among different hospitals in the same city. The importance of a clinical pathway to implement the most effective and relevant diagnostic strategy is of critical importance to establish the control of this virus that is responsible for more and more deaths each day.


Subject(s)
Antibodies, Viral/immunology , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Lung/diagnostic imaging , Pneumonia, Viral/diagnosis , RNA, Viral/analysis , Algorithms , Betacoronavirus/immunology , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Critical Pathways , Early Diagnosis , Evidence-Based Practice , False Negative Reactions , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Medical History Taking , Pandemics , Patient Isolation , Quarantine , Real-Time Polymerase Chain Reaction/methods , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2 , Serologic Tests/methods , Severity of Illness Index , Tomography, X-Ray Computed
5.
Int Rev Immunol ; 41(2): 217-230, 2022.
Article in English | MEDLINE | ID: covidwho-1093424

ABSTRACT

The coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) erupted in Hubei Province of China in December 2019 and has become a pandemic. Severe COVID-19 patients who suffer from acute respiratory distress syndrome (ARDS) and multi-organ dysfunction have high mortality. Several studies have shown that this is closely related to the cytokine release syndrome (CRS), often loosely referred to as cytokine storm. IL-6 is one of the key factors and its level is positively correlated with the severity of the disease. The molecular mechanisms for CRS in COVID-19 are related to the effects of the S-protein and N-protein of the virus and its ability to trigger NF-κB activation by disabling the inhibitory component IκB. This leads to activation of immune cells and the secretion of proinflammatory cytokines such as IL-6 and TNF-α. Other mechanisms related to IL-6 include its interaction with GM-CSF and interferon responses. The pivotal role of IL-6 makes it a target for therapeutic agents and studies on tocilizumab are already ongoing. Other possible targets of treating CRS in COVID-19 include IL-1ß and TNF-α. Recently, reports of a CRS like illness called multisystem inflammatory syndrome in children (MIS-C) in children have surfaced, with a variable presentation which in some cases resembles Kawasaki disease. It is likely that the immunological derangement and cytokine release occurring in COVID-19 cases is variable, or on a spectrum, that can potentially be governed by genetic factors. Currently, there are no approved biological modulators for the treatment of COVID-19, but the urgency of the pandemic has led to numerous clinical trials worldwide. Ultimately, there is great promise that an anti-inflammatory modulator targeting a cytokine storm effect may prove to be very beneficial in reducing morbidity and mortality in COVID-19 patients.


Subject(s)
COVID-19 , Cytokine Release Syndrome , COVID-19/complications , Humans , Morbidity , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
6.
Am J Respir Crit Care Med ; 201(11): 1372-1379, 2020 06 01.
Article in English | MEDLINE | ID: covidwho-975792

ABSTRACT

Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined.Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan.Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management.Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively.Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.


Subject(s)
Coronavirus Infections/mortality , Pneumonia, Viral/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , China/epidemiology , Comorbidity , Coronary Disease/epidemiology , Diabetes Mellitus/epidemiology , Female , Humans , Hypertension/epidemiology , Male , Middle Aged , Multiple Organ Failure/virology , Pandemics , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed , Young Adult
7.
Res Sq ; 2020 Nov 04.
Article in English | MEDLINE | ID: covidwho-918844

ABSTRACT

Epidemiological studies suggest that men exhibit a higher mortality rate to COVID-19 than women, yet the underlying biology is largely unknown. Here, we seek to delineate sex differences in the expression of entry genes ACE2 and TMPRSS2 , host responses to SARS-CoV-2, and in vitro responses to sex steroid hormone treatment. Using over 220,000 human gene expression profiles covering a wide range of age, tissues, and diseases, we found that male samples show higher expression levels of ACE2 and TMPRSS2 , especially in the older group (>60 years) and in the kidney. Analysis of 6,031 COVID-19 patients at Mount Sinai Health System revealed that men have significantly higher creatinine levels, an indicator of impaired kidney function. Further analysis of 782 COVID-19 patient gene expression profiles taken from upper airway and blood suggested men and women present profound expression differences in responses to SARS-CoV-2. Computational deconvolution analysis of these profiles revealed male COVID-19 patients have enriched kidney-specific mesangial cells in blood compared to healthy patients. Finally, we observed selective estrogen receptor modulators, but not other hormone drugs (agonists/antagonists of estrogen, androgen, and progesterone), could reduce SARS-CoV-2 infection in vitro.

11.
Eur J Rheumatol ; 7(Suppl 2): S94-S96, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-160195
12.
J Autoimmun ; 112: 102473, 2020 08.
Article in English | MEDLINE | ID: covidwho-116328

ABSTRACT

COVID-19 has become one of the worst infectious disease outbreaks of recent times, with over 2.1 million cases and 120,000 deaths so far. Our study investigated the demographic, clinical, laboratory and imaging features of 63 patients with COVID-19 in Beijing. Patients were classified into four groups, mild, moderate, severe and critically ill. The mean age of our patients was 47 years of age (range 3-85) and there was a slight male predominance (58.7%). Thirty percent of our patients had severe or critically ill disease, but only 20% of severe and 33% of critically ill patients had been to Wuhan. Fever was the most common presentation (84.1%), but cough was present in only slightly over half of the patients. We found that lymphocyte and eosinophils count were significantly decreased in patients with severe disease (p = 0.001 and p = 0.000, respectively). Eosinopenia was a feature of higher levels of severity. Peripheral CD4+, CD8+ T lymphocytes, and B lymphocytes were significantly decreased in severe and critically ill patients, but there was only a non-statistically significant downward trend in NK cell numbers with severity. Of note is that liver function tests including AST, ALT, GGT and LDH were elevated, and albumin was decreased. The inflammatory markers CRP, ESR and ferritin were elevated in patients with severe disease or worse. IL-6 levels were also higher, indicating that the presence of a hyperimmune inflammatory state portends higher morbidity and mortality. In a binary logistic regression model, C-reactive protein level (OR 1.073, [CI, 1.013-1.136]; p = 0.017), CD8 T lymphocyte counts (OR 0.989, [CI, 0.979-1.000]; p = 0.043), and D-dimer (OR 5.313, [CI, 0.325-86.816]; p = 0.241) were independent predictors of disease severity.


Subject(s)
Betacoronavirus/metabolism , Coronavirus Infections , Pandemics , Pneumonia, Viral , Severity of Illness Index , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19 , Child , Child, Preschool , China/epidemiology , Coronavirus Infections/blood , Coronavirus Infections/epidemiology , Female , Humans , Leukocyte Count , Male , Middle Aged , Pneumonia, Viral/blood , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Sex Factors
13.
Can J Cardiol ; 36(6): 915-930, 2020 06.
Article in English | MEDLINE | ID: covidwho-72377

ABSTRACT

With more than 1,800,000 cases and 110,000 deaths globally, COVID-19 is one of worst infectious disease outbreaks in history. This paper provides a critical review of the available evidence regarding the lessons learned from the Chinese experience with COVID-19 prevention and management. The steps that have led to a near disappearance of new cases in China included rapid sequencing of the virus to establish testing kits, which allowed tracking of infected persons in and out of Wuhan. In addition, aggressive quarantine measures included the complete isolation of Wuhan and then later Hubei Province and the rest of the country, as well as closure of all schools and nonessential businesses. Other measures included the rapid construction of two new hospitals and the establishment of "Fangcang" shelter hospitals. In the absence of a vaccine, the management of COVID-19 included antivirals, high-flow oxygen, mechanical ventilation, corticosteroids, hydroxychloroquine, tocilizumab, interferons, intravenous immunoglobulin, and convalescent plasma infusions. These measures appeared to provide only moderate success. Although some measures have been supported by weak descriptive data, their effectiveness is still unclear pending well controlled clinical trials. In the end, it was the enforcement of drastic quarantine measures that stopped SARS-CoV-2 from spreading. The earlier the implementation, the less likely resources will be depleted. The most critical factors in stopping a pandemic are early recognition of infected individuals, carriers, and contacts and early implementation of quarantine measures with an organised, proactive, and unified strategy at a national level. Delays result in significantly higher death tolls.


Subject(s)
Betacoronavirus , Communicable Disease Control , Coronavirus Infections , Pandemics , Patient Care Management , Pneumonia, Viral , Betacoronavirus/isolation & purification , Betacoronavirus/pathogenicity , COVID-19 , China/epidemiology , Communicable Disease Control/methods , Communicable Disease Control/organization & administration , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Humans , Pandemics/prevention & control , Patient Care Management/methods , Patient Care Management/organization & administration , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/therapy , Pneumonia, Viral/transmission , SARS-CoV-2
14.
J Autoimmun ; 112: 102463, 2020 08.
Article in English | MEDLINE | ID: covidwho-46938

ABSTRACT

It has been reported that SARS-CoV-2 may use ACE2 as a receptor to gain entry into human cells, in a way similar to that of SARS-CoV. Analyzing the distribution and expression level of ACE2 may therefore help reveal underlying mechanisms of viral susceptibility and post-infection modulation. In this study, we utilized previously uploaded information on ACE2 expression in various conditions including SARS-CoA to evaluate the role of ACE2 in SARS-CoV and extrapolate that to COVID-19. We found that the expression of ACE2 in healthy populations and patients with underlying diseases was not significantly different. However, based on the elevated expression of ACE2 in cigarette smokers, we speculate that long-term smoking may be a risk factor for COVID-19. Analysis of ACE2 in SARS-CoV infected cells suggests that ACE2 is not only a receptor but is also involved in post-infection regulation, including immune response, cytokine secretion, and viral genome replication. Moreover, we constructed Protein-protein interaction (PPI) networks and identified hub genes in viral activity and cytokine secretion. Our findings may help clinicians and researchers gain more insight into the pathogenesis of SARS-CoV-2 and design therapeutic strategies for COVID-19.


Subject(s)
Betacoronavirus/metabolism , Coronavirus Infections/enzymology , Gene Expression Regulation, Enzymologic , Lung/enzymology , Peptidyl-Dipeptidase A/biosynthesis , Pneumonia, Viral/enzymology , Smoking/adverse effects , Angiotensin-Converting Enzyme 2 , COVID-19 , Coronavirus Infections/pathology , Humans , Pandemics , Pneumonia, Viral/pathology , Protein Interaction Maps , SARS-CoV-2
15.
J Autoimmun ; 109: 102434, 2020 05.
Article in English | MEDLINE | ID: covidwho-4387

ABSTRACT

The 2019-nCoV is officially called SARS-CoV-2 and the disease is named COVID-19. This viral epidemic in China has led to the deaths of over 1800 people, mostly elderly or those with an underlying chronic disease or immunosuppressed state. This is the third serious Coronavirus outbreak in less than 20 years, following SARS in 2002-2003 and MERS in 2012. While human strains of Coronavirus are associated with about 15% of cases of the common cold, the SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death. It is currently believed that this deadly Coronavirus strain originated from wild animals at the Huanan market in Wuhan, a city in Hubei province. Bats, snakes and pangolins have been cited as potential carriers based on the sequence homology of CoV isolated from these animals and the viral nucleic acids of the virus isolated from SARS-CoV-2 infected patients. Extreme quarantine measures, including sealing off large cities, closing borders and confining people to their homes, were instituted in January 2020 to prevent spread of the virus, but by that time much of the damage had been done, as human-human transmission became evident. While these quarantine measures are necessary and have prevented a historical disaster along the lines of the Spanish flu, earlier recognition and earlier implementation of quarantine measures may have been even more effective. Lessons learned from SARS resulted in faster determination of the nucleic acid sequence and a more robust quarantine strategy. However, it is clear that finding an effective antiviral and developing a vaccine are still significant challenges. The costs of the epidemic are not limited to medical aspects, as the virus has led to significant sociological, psychological and economic effects globally. Unfortunately, emergence of SARS-CoV-2 has led to numerous reports of Asians being subjected to racist behavior and hate crimes across the world.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Severe Acute Respiratory Syndrome/history , Animals , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , COVID-19 , COVID-19 Testing , China/epidemiology , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/economics , Coronavirus Infections/prevention & control , Genome, Viral , History, 21st Century , Humans , Information Dissemination , Pandemics/economics , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/economics , Pneumonia, Viral/prevention & control , Pyroptosis , Quarantine , SARS-CoV-2 , Severe Acute Respiratory Syndrome/prevention & control , Zoonoses/virology
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