Reply to letter to the editor Abd‐Elsalam, Sherief; Medhat, Mohammed A.; Ramadan, Haidi Karam‐Allah ...
Journal of medical virology,
February 2023, 2023-02-00, 20230201, Letnik:
95, Številka:
2
Journal Article
Background & Aims Hepatitis C virus (HCV) infection has hepatic and extrahepatic manifestations with various costs and impairments to health-related quality of life (HRQL). We performed a ...meta-analysis to determine the prevalence of extrahepatic manifestations in patients with HCV infection, how these impair HRQL, and their costs. Methods We performed systematic reviews of the literature using MEDLINE, CINAHL, and the Cochrane Systematic Review Database, from 1996 through December 2014, to identify studies of the following extrahepatic manifestations of HCV infection: mixed cryoglobulinemia, chronic kidney or end-stage renal disease, type 2 diabetes, B-cell lymphoma, lichen planus, Sjögren’s syndrome, porphyria cutanea tarda, rheumatoid-like arthritis, or depression. We performed a separate meta-analysis for each condition to determine prevalence rates of extrahepatic manifestations of HCV infection and their effects on HRQL. We determined the annual costs (inpatient, outpatient, and pharmacy) associated with extrahepatic manifestations of HCV infection. Results In an analysis of data from 102 studies, we found the most common extrahepatic manifestations to be diabetes (in 15% of patients) and depression (in 25% of patients). HRQL data showed that HCV infection had negative effects on overall physical and mental health. Total direct medical costs of extrahepatic manifestations of HCV infection, in 2014 US dollars, were estimated to be $1506 million (range, $922 million–$2208 million in sensitivity analysis). Conclusions In a systematic review and meta-analysis we determined the prevalence, risks, and costs associated with extrahepatic manifestations of HCV infection. These estimates should be added to the liver-related burden of disease to obtain a more accurate assessment of the total burden of chronic HCV infection. Prospective, real-world studies are needed to increase our understanding of the total clinical and economic effects of HCV infection and treatment on patients and society.
•Amongst the gastrointestinal manifestations experienced by COVID-19 patients, those commonly noted are diarrhea, anorexia, nausea, vomiting, and abdominal pain – which can be present even in the ...absence of respiratory symptoms.•Hepatic injury is evident in some patients, the degree of which at times can mirror severity of disease; pancreatic injury has been noted as well.•SARS-CoV-2 RNA has been found in fecal samples even after viral RNA in respiratory samples clears, raising concern for gastrointestinal viral replication and potential for fecal-oral transmission.•While no definitive treatment for COVID-19 exists, mainstay remains supportive including oxygen and mechanical ventilation; at this time, gastrointestinal manifestations are largely managed symptomatically as well.•The potential for fecal-oral spread of infectious virions may warrant additional precautions and patient education about proper hand hygiene, social distancing, and understanding the risk for close contacts and re-infection.
There is an increasing number of confirmed cases and deaths caused by the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributing to the Coronavirus disease 2019 (COVID-19) pandemic. At this point, the need for further disease characterization is critical. COVID-19 is well established as a respiratory tract pathogen; however, recent studies have shown an increasing number of patients reporting gastrointestinal manifestations such as diarrhea, nausea, vomiting, and abdominal pain. The time from onset of gastrointestinal symptoms to hospital presentation is often delayed compared to that of respiratory symptoms. It has been noted that SARS-CoV-2 RNA can be detected in fecal matter for an extended period of time, even after respiratory samples have tested negative and patients are asymptomatic. In this article, SARS-CoV-2 and its disease COVID-19 will be reviewed with consideration of the latest literature about gastrointestinal symptomatology, the mechanisms by which the virus may inflict damage, and the possibility of viral replication contributing to a fecal-oral route of transmission.
The outbreak of the SARS-CoV-2 in mainland China with subsequent human to human transmission worldwide had taken up the shape of a devastating pandemic. The ability of the virus to infect multiple ...species other than humans has currently been reported in experimental conditions. Non-human primates, felines, ferrets, rodents and host of other animals could previously be infected in experimental conditions with SARS-CoV and recently with SARS-CoV-2, both virus using Angiotensin-converting-enzyme 2 receptor for cellular entry. The variations in sequence homology of ACE2 receptor across species is identified as one of the factors determining virulence and pathogenicity in animals. The infection in experimental animals with SARS-CoV or SARS-CoV-2 on most occasions are asymptomatic, however, the virus could multiply within the respiratory tract and extra-pulmonary organs in most of the species. Here, we discuss about the pathogenicity, transmission, variations in angiotensin-converting-enzyme 2 receptor-binding across species and host pathogen interactions of SARS and SARS-CoV-2 in laboratory animals used in research.
Clinical descriptions about influenza-like illnesses (ILI) in COVID-19 seem non-specific. We aimed to compare the clinical features of COVID-19 and influenza. We retrospectively investigated the ...clinical features and outcomes of confirmed cases of COVID-19 and influenza in Nord Franche-Comté Hospital between February 26th and March 14th 2020. We used SARS-CoV-2 RT-PCR and influenza virus A/B RT-PCR in respiratory samples to confirm the diagnosis. We included 124 patients. The mean age was 59 (±19 19–98) years with 69% female. 70 patients with COVID-19 and 54 patients with influenza A/B. Regarding age, sex and comorbidities, no differences were found between the two groups except a lower Charlson index in COVID-19 group (2 ±2.5 vs 3 ±2.4,p = 0.003). Anosmia (53% vs 17%,p < 0.001), dysgeusia (49% vs 20%,p = 0.001), diarrhea (40% vs 20%,p = 0.021), frontal headache (26% vs 9%,p = 0.021) and bilateral cracklings sounds (24% vs 9%,p = 0.034) were statistically more frequent in COVID-19. Sputum production (52% vs 29%,p = 0.010), dyspnea (59% vs 34%,p = 0.007), sore throat (44% vs 20%,p = 0.006), conjunctival hyperhemia (30% vs 4%,p < 0.001), tearing (24% vs 6%,p = 0.004), vomiting (22% vs 3%,p = 0.001) and rhonchi sounds (17% vs 1%,p = 0.002) were more frequent with influenza infection. We described several clinical differences which can help the clinicians during the co-circulation of influenza and SARS-CoV-2.
We aimed to systematically review the clinical characteristics of coronavirus disease 2019 (COVID‐19). Seven databases were searched to collect studies about the clinical characteristics of COVID‐19 ...from January 1, 2020 to February 28, 2020. Then, meta‐analysis was performed by using Stata12.0 software. A total of 38 studies involving 3062 COVID‐19 patients were included. Meta‐analysis showed that a higher proportion of infected patients was male (56.9%). The incidence rate of respiratory failure or acute respiratory distress syndrome was 19.5% and the fatality rate was 5.5%. Fever (80.4%), fatigue (46%), cough (63.1%), and expectoration (41.8%) were the most common clinical manifestations. Other common symptoms included muscle soreness (33%), anorexia (38.8%), chest tightness (35.7%), shortness of breath (35%), dyspnea (33.9%). Minor symptoms included nausea and vomiting (10.2%), diarrhea (12.9%), headache (15.4%), pharyngalgia (13.1%), shivering (10.9%), and abdominal pain (4.4%). The proportion of patients that was asymptomatic was 11.9%. Normal leukocyte counts (69.7%), lymphopenia (56.5%), elevated C‐reactive protein levels (73.6%), elevated ESR (65.6%), and oxygenation index decreased (63.6%) were observed in most patients. About 37.2% of patients were found with elevated D‐dimer, 25.9% of patients with leukopenia, along with abnormal levels of liver function (29%), and renal function (25.5%). Other findings included leukocytosis (12.6%) and elevated procalcitonin (17.5%). Only 25.8% of patients had lesions involving a single lung and 75.7% of patients had lesions involving bilateral lungs. The most commonly experienced symptoms of COVID‐19 patients were fever, fatigue, cough, and expectoration. A relatively small percentage of patients were asymptomatic. Most patients showed normal leucocytes counts, lymphopenia, elevated levels of C‐reactive protein and ESR. Bilateral lung involvement was common.
Highlights
COVID‐19 is a new respiratory disease which needs quick identification of infected patients.
The most common symptoms of COVID‐19 patients were fever, fatigue, cough, and expectoration.
A relatively small percentage of patients were asymptomatic.
Most patients showed normal leucocytes counts, lymphopenia, elevated levels of C‐reactive protein and ESR.
Post-mortem studies can provide important information for understanding new diseases and small autopsy case series have already reported different findings in COVID-19 patients.
We evaluated whether ...some specific post-mortem features are observed in these patients and if these changes are related to the presence of the virus in different organs. Complete macroscopic and microscopic autopsies were performed on different organs in 17 COVID-19 non-survivors. Presence of SARS-CoV-2 was evaluated with immunohistochemistry (IHC) in lung samples and with real-time reverse-transcription polymerase chain reaction (RT-PCR) test in the lung and other organs.
Pulmonary findings revealed early-stage diffuse alveolar damage (DAD) in 15 out of 17 patients and microthrombi in small lung arteries in 11 patients. Late-stage DAD, atypical pneumocytes, and/or acute pneumonia were also observed. Four lung infarcts, two acute myocardial infarctions, and one ischemic enteritis were observed. There was no evidence of myocarditis, hepatitis, or encephalitis. Kidney evaluation revealed the presence of hemosiderin in tubules or pigmented casts in most patients. Spongiosis and vascular congestion were the most frequently encountered brain lesions. No specific SARS-CoV-2 lesions were observed in any organ. IHC revealed positive cells with a heterogeneous distribution in the lungs of 11 of the 17 (65%) patients; RT-PCR yielded a wide distribution of SARS-CoV-2 in different tissues, with 8 patients showing viral presence in all tested organs (i.e., lung, heart, spleen, liver, colon, kidney, and brain).
In conclusion, autopsies revealed a great heterogeneity of COVID-19-associated organ injury and the remarkable absence of any specific viral lesions, even when RT-PCR identified the presence of the virus in many organs.
The SARS-CoV-2 pandemic has resulted in millions of infections, yet the role of host immune responses in early COVID-19 pathogenesis remains unclear. By investigating 17 acute and 24 convalescent ...patients, we found that acute SARS-CoV-2 infection resulted in broad immune cell reduction including T, natural killer, monocyte, and dendritic cells (DCs). DCs were significantly reduced with functional impairment, and ratios of conventional DCs to plasmacytoid DCs were increased among acute severe patients. Besides lymphocytopenia, although neutralizing antibodies were rapidly and abundantly generated in patients, there were delayed receptor binding domain (RBD)- and nucleocapsid protein (NP)-specific T cell responses during the first 3 weeks after symptoms onset. Moreover, acute RBD- and NP-specific T cell responses included relatively more CD4 T cells than CD8 T cells. Our findings provided evidence that impaired DCs, together with timely inverted strong antibody but weak CD8 T cell responses, could contribute to acute COVID-19 pathogenesis and have implications for vaccine development.
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•Acute SARS-CoV-2 infection results in broad immune cell reduction•Both dendritic cells and T cells are functionally impaired•Neutralizing antibodies are rapidly and abundantly generated•RBD- and NP-specific T cells are delayed at the acute stage
COVID-19 is an acute disease caused by SARS-CoV-2 infection. We determine how the immune system responds to SARS-CoV-2 at both acute and convalescent stages. Acute SARS-CoV-2 infection results in broad immune cell reduction and functional impairment. While neutralizing antibodies are rapidly generated, antigen-specific T cells are delayed at the acute stage.
Neurological complications are common in patients with COVID-19. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal pathogen of COVID-19, has been detected in some ...patient brains, its ability to infect brain cells and impact their function is not well understood. Here, we investigated the susceptibility of human induced pluripotent stem cell (hiPSC)-derived monolayer brain cells and region-specific brain organoids to SARS-CoV-2 infection. We found that neurons and astrocytes were sparsely infected, but choroid plexus epithelial cells underwent robust infection. We optimized a protocol to generate choroid plexus organoids from hiPSCs and showed that productive SARS-CoV-2 infection of these organoids is associated with increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. Together, our findings provide evidence for selective SARS-CoV-2 neurotropism and support the use of hiPSC-derived brain organoids as a platform to investigate SARS-CoV-2 infection susceptibility of brain cells, mechanisms of virus-induced brain dysfunction, and treatment strategies.
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•SARS-CoV-2 minimally infects human neurons and astrocytes in 2D and brain organoids•Model developed for hiPSC-derived choroid plexus organoids (CPOs)•SARS-CoV-2 productively infects CPOs and increases cell death•SARS-CoV-2 CPO infection leads to transcriptional upregulation of inflammatory genes
SARS-CoV-2 causes neurological symptoms in a significant portion of patients with COVID-19. Ming and colleagues tested SARS-CoV-2 neurotropism by using monolayer neural cells and brain organoids generated from human pluripotent stem cells and show minimal neuron and astrocyte infection but efficient choroid plexus infection, leading to cell death and functional deficits.
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