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4.
Curr Opin HIV AIDS ; 15(6): 336-340, 2020 11.
Article in English | MEDLINE | ID: covidwho-2315501

ABSTRACT

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) is a highly contagious and potentially lethal pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). No specific antiviral treatment is currently available. The purpose of this review is to highlight the main repurposed drug treatments with in-vitro or in-vivo efficacy against the SARS-CoV-2. RECENT FINDINGS: Recent clinical trials suggested remdesivir, IFN-ß-1b and favipiravir have potential clinical and/or virological benefits on patients with COVID-19. Short course of stress dose of corticosteroids might be used as adjunctive treatment to patients who are late presenters with cytokine storm. Convalescent plasma from recovered COVID-19 patients with high neutralizing antibody might also be beneficial in the treatment of severe disease. SUMMARY: Early effective antiviral therapy in COVID-19 patients will suppress the SARS-CoV-2 viral load. Adjunctive therapy with corticosteroid and convalescent plasma might further ameliorate the cytokine response. Further randomized clinical trials of combination therapy are needed.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adrenal Cortex Hormones/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Humans , Immunization, Passive , Interferon-beta/therapeutic use , Pandemics , Pneumonia, Viral/immunology , SARS-CoV-2 , COVID-19 Drug Treatment , COVID-19 Serotherapy
5.
Euro Surveill ; 25(23)2020 06.
Article in English | MEDLINE | ID: covidwho-2313322

ABSTRACT

We reviewed the diagnostic accuracy of SARS-CoV-2 serological tests. Random-effects models yielded a summary sensitivity of 82% for IgM, and 85% for IgG and total antibodies. For specificity, the pooled estimate were 98% for IgM and 99% for IgG and total antibodies. In populations with ≤ 5% of seroconverted individuals, unless the assays have perfect (i.e. 100%) specificity, the positive predictive value would be ≤ 88%. Serological tests should be used for prevalence surveys only in hard-hit areas.


Subject(s)
Antibodies, Viral/blood , Clinical Laboratory Techniques/methods , Coronaviridae Infections/diagnosis , Coronavirus Infections/diagnosis , Coronavirus/immunology , Pneumonia, Viral/diagnosis , Serologic Tests/standards , Severe Acute Respiratory Syndrome/immunology , Betacoronavirus , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/standards , Coronavirus/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Predictive Value of Tests , SARS-CoV-2 , Sensitivity and Specificity , Serologic Tests/methods , Severe Acute Respiratory Syndrome/blood
7.
Int J Infect Dis ; 99: 92-99, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-2311415

ABSTRACT

OBJECTIVE: To investigate the characteristics and predictive roles of lymphocyte subsets in COVID-19 patients. METHOD: We evaluated lymphocyte subsets and other clinical features of COVID-19 patients, and analyzed their potential impacts on COVID-19 outcomes. RESULTS: 1. Lymphocyte subset counts in the peripheral blood of patients with COVID-19 were significantly reduced, especially in patients with severe disease. 2. In patients with non-severe disease, the time from symptom onset to hospital admission was positively correlated with total T cell counts. 3. Among COVID-19 patients who did not reach the composite endpoint, lymphocyte subset counts were higher than in patients who had reached the composite endpoint. 4. The Kaplan-Meier survival curves showed significant differences in COVID-19 patients, classified by the levels of total, CD8+, and CD4+ T cells at admission. CONCLUSION: Our study showed that total, CD8+, and CD4+ T cell counts in patients with COVID-19 were significantly reduced, especially in patients with severe disease. Lower T lymphocyte subsets were significantly associated with a higher occurrence of composite endpoint events. These subsets may help identify patients with a high risk of composite endpoint events.


Subject(s)
Betacoronavirus , Coronavirus Infections/immunology , Lymphocyte Subsets/physiology , Pneumonia, Viral/immunology , Adult , COVID-19 , Female , Humans , Lymphocyte Count , Male , Middle Aged , Pandemics , SARS-CoV-2
9.
Med Hypotheses ; 142: 109814, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-2277430

ABSTRACT

Copper (Cu) is an essential micronutrient for both pathogens and the hosts during viral infection. Cu is involved in the functions of critical immune cells such as T helper cells, B cells, neutrophils natural killer (NK) cells, and macrophages. These blood cells are involved in the killing of infectious microbes, in cell-mediated immunity and the production of specific antibodies against the pathogens. Cu-deficient humans show an exceptional susceptibility to infections due to the decreased number and function of these blood cells. Besides, Cu can kill several infectious viruses such as bronchitis virus, poliovirus, human immunodeficiency virus type 1(HIV-1), other enveloped or nonenveloped, single- or double-stranded DNA and RNA viruses. Moreover, Cu has the potent capacity of contact killing of several viruses, including SARS-CoV-2. Since the current outbreak of the COVID-19 continues to develop, and there is no vaccine or drugs are currently available, the critical option is now to make the immune system competent to fight against the SARS-CoV-2. Based on available data, we hypothesize that enrichment of plasma copper levels will boost both the innate and adaptive immunity in people. Moreover, owing to its potent antiviral activities, Cu may also act as a preventive and therapeutic regime against COVID-19.


Subject(s)
Copper/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adaptive Immunity , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/immunology , Humans , Immune System , Immunity, Innate , Pandemics , Pneumonia, Viral/immunology , Reactive Oxygen Species/metabolism , SARS-CoV-2 , Treatment Outcome , COVID-19 Drug Treatment
12.
Clin Rheumatol ; 39(7): 2025-2029, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-2254707

ABSTRACT

The coronavirus disease 2019 (COVID-19), the result of an infection with the new virus, SARS-CoV-2, is rapidly spreading worldwide. It is largely unknown whether the occurrence of COVID-19 in patients with rheumatic immune diseases has some specific manifestations, or makes them more prone to rapidly progress into severe COVID-19. In this case report, we describe the clinical features of 5 rheumatic immune disease patients with the concomitant presence of COVID-19. Amongst these patients, 4 had rheumatoid arthritis (RA) and 1 had systemic sclerosis (SSc). Two patients had a history of close contact with a COVID-19 patient. The age of the patients ranged between 51 and 79 years. Fever (80%), cough (80%), dyspnea (40%), and fatigue (20%) were the most common presenting symptoms. Laboratory investigations revealed leukopenia and lymphopenia in 2 patients. In all the patients, chest computerized tomography (CT) revealed patchy ground glass opacities in the lungs. During the hospital stay, the condition of two patients remained the same (i.e., mild COVID-19), two patients progressed to the severe COVID-19, and one patient worsened to the critically ill COVID-19. These patients were treated with antiviral agents for COVID-19, antibiotics for secondary bacterial infections, and immunomodulatory agents for rheumatic immune diseases. All the patients responded well, were cured of COVID-19, and subsequently discharged.


Subject(s)
Antiviral Agents/therapeutic use , Arthritis, Rheumatoid , Coronavirus Infections , Immunomodulation , Pandemics , Pneumonia, Viral , Scleroderma, Systemic , Aged , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/therapy , Betacoronavirus/isolation & purification , Blood Cell Count/methods , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Critical Illness/therapy , Disease Progression , Female , Humans , Lung/diagnostic imaging , Male , Middle Aged , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , SARS-CoV-2 , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/epidemiology , Scleroderma, Systemic/therapy , Symptom Assessment/methods , Tomography, X-Ray Computed/methods , Treatment Outcome
13.
J Virol ; 97(3): e0166422, 2023 03 30.
Article in English | MEDLINE | ID: covidwho-2238656

ABSTRACT

Seasonal coronaviruses have been circulating widely in the human population for many years. With increasing age, humans are more likely to have been exposed to these viruses and to have developed immunity against them. It has been hypothesized that this immunity to seasonal coronaviruses may provide partial protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has also been shown that coronavirus disease 2019 (COVID-19) vaccination induces a back-boosting effects against the spike proteins of seasonal betacoronaviruses. In this study, we tested if immunity to the seasonal coronavirus spikes from OC43, HKU1, 229E, or NL63 would confer protection against SARS-CoV-2 challenge in a mouse model, and whether pre-existing immunity against these spikes would weaken the protection afforded by mRNA COVID-19 vaccination. We found that mice vaccinated with the seasonal coronavirus spike proteins had no increased protection compared to the negative controls. While a negligible back-boosting effect against betacoronavirus spike proteins was observed after SARS-CoV-2 infection, there was no negative original antigenic sin-like effect on the immune response and protection induced by SARS-CoV-2 mRNA vaccination in animals with pre-existing immunity to seasonal coronavirus spike proteins. IMPORTANCE The impact that immunity against seasonal coronaviruses has on both susceptibility to SARS-CoV-2 infection as well as on COVID-19 vaccination is unclear. This study provides insights into both questions in a mouse model of SARS-CoV-2.


Subject(s)
COVID-19 Vaccines , Coronavirus Infections , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Animals , Humans , Mice , COVID-19/immunology , COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , Seasons , Spike Glycoprotein, Coronavirus/immunology , Vaccination , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cross Protection/immunology
14.
Rev Med Virol ; 30(4): e2116, 2020 07.
Article in English | MEDLINE | ID: covidwho-2231826

ABSTRACT

In late December 2019, a group of patients was observed with pneumonia-like symptoms that were linked with a wet market in Wuhan, China. The patients were found to have a novel coronavirus genetically related to a bat coronavirus that was termed SARS-CoV-2. The virus gradually spread worldwide and was declared a pandemic by WHO. Scientists have started trials on potential preventive and treatment options. Currently, there is no specific approved treatment for SARS-CoV-2, and various clinical trials are underway to explore better treatments. Some previously approved antiviral and other drugs have shown some in vitro activity. Here we summarize the fight against this novel coronavirus with particular focus on the different treatment options and clinical trials exploring treatment as well as work done toward development of vaccines.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/immunology , Coronavirus Infections/drug therapy , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/drug therapy , Pneumonia, Viral/prevention & control , Viral Vaccines , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 , COVID-19 Vaccines , Clinical Trials as Topic , Coronavirus Infections/immunology , Humans , SARS-CoV-2 , Viral Vaccines/immunology , COVID-19 Drug Treatment
16.
Sci Rep ; 13(1): 2310, 2023 02 09.
Article in English | MEDLINE | ID: covidwho-2235297

ABSTRACT

Four endemic human coronaviruses (HCoV), HCoV-229E, HCoV-NL63, HCoV-HKU1, and HCoV-OC43, are closely related to SARS-CoV-2. These coronaviruses are known to infect humans living in temperate areas, including children under 5 years old; however, the seroprevalence of four HCoVs among children in tropical areas, including the Philippines, remains unclear. This study aimed to assess the prevalence of antibodies against four HCoVs and to determine the reactivity and neutralization of these antibodies against SARS-CoV-2 among children in the Philippines. A total of 315 serum samples collected from 2015 to 2018, before the emergence of SARS-CoV-2, in Biliran island, Philippines, were tested for the presence of antibodies against four HCoVs and SARS-CoV-2 using recombinant spike ectodomain proteins by IgG-enzyme-linked immunosorbent assay (ELISA). Reactivity to and neutralization of SARS-CoV-2 were also investigated. The seroprevalence of the four HCoVs was 63.8% for HCoV-229E, 71.4% for HCoV-NL63, 76.5% for HCoV-HKU1, and 83.5% for HCoV-OC43 by ELISA. Age group analysis indicated that seropositivity to all HCoVs reached 80% by 2-3 years of age. While 69/315 (21.9%) of the samples showed reactive to SARS-CoV-2, almost no neutralization against SARS-CoV-2 was detected using neutralization assay. Reactivity of antibodies against SARS-CoV-2 spike protein obtained by ELISA may not correlate with neutralization capability.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Coronavirus Infections , Coronavirus , Child , Child, Preschool , Humans , Antibodies, Viral , Coronavirus 229E, Human , Coronavirus NL63, Human , Coronavirus OC43, Human , COVID-19/epidemiology , COVID-19/immunology , Philippines/epidemiology , Recombinant Proteins , SARS-CoV-2 , Seroepidemiologic Studies , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Coronavirus/genetics , Coronavirus/immunology , Betacoronavirus , Antibodies, Neutralizing/immunology
17.
J Virol ; 97(2): e0175122, 2023 02 28.
Article in English | MEDLINE | ID: covidwho-2237611

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) belongs to the genus Alphacoronavirus of the Coronaviridae family and can cause fatal watery diarrhea in piglets, causing significant economic losses. Heterogeneous nuclear protein U (HNRNPU) is a novel RNA sensor involved in sensing viral RNA in the nucleus and mediating antiviral immunity. However, it remains elusive whether and how cytoplasmic PEDV can be sensed by the RNA sensor HNRNPU. In this study we determined that HNRNPU was the binding partner of Nsp13 by immunoprecipitation-liquid chromatography-tandem mass spectrometry (IP/LC-MS/MS) analysis. The interaction between Nsp13 and HNRNPU was demonstrated by using coimmunoprecipitation and confocal immunofluorescence. Next, we identified that HNRNPU expression is significantly increased during PEDV infection, whereas the transcription factor hepatocyte nuclear factor 1α (HNF1A) could negatively regulate HNRNPU expression. HNRNPU was retained in the cytoplasm by interaction with PEDV Nsp13. We found that HNRNPU overexpression effectively facilitated PEDV replication, while knockdown of HNRNPU impaired viral replication, suggesting a promoting function of HNRNPU to PEDV infection. Additionally, HNRNPU was found to promote PEDV replication by affecting TRAF3 degradation at the transcriptional level to inhibit PEDV-induced beta interferon (IFN-ß) production. Mechanistically, HNRNPU downregulates TRAF3 mRNA levels via the METTL3-METTL14/YTHDF2 axis and regulates immune responses through YTHDF2-dependent mRNA decay. Together, our findings reveal that HNRNPU serves as a negative regulator of innate immunity by degrading TRAF3 mRNA in a YTHDF2-dependent manner and consequently facilitating PEDV propagation. Our findings provide new insights into the immune escape of PEDV. IMPORTANCE PEDV, a highly infectious enteric coronavirus, has spread rapidly worldwide and caused severe economic losses. During virus infection, the host regulates innate immunity to inhibit virus infection. However, PEDV has evolved a variety of different strategies to suppress host IFN-mediated antiviral responses. Here, we identified that HNRNPU interacted with viral protein Nsp13. HNRNPU protein expression was upregulated, and the transcription factor HNF1A could negatively regulate HNRNPU expression during PEDV infection. HNRNPU also downregulated TRAF3 mRNA through the METTL3-METTL14/YTHDF2 axis to inhibit the production of IFN-ß and downstream antiviral genes in PEDV-infected cells, thereby promoting viral replication. Our findings reveal a new mechanism with which PEDV suppresses the host antiviral response.


Subject(s)
Coronavirus Infections , Nuclear Proteins , Porcine epidemic diarrhea virus , Swine Diseases , Virus Replication , Animals , Cell Line , Coronavirus Infections/immunology , Coronavirus Infections/virology , Nuclear Proteins/metabolism , Porcine epidemic diarrhea virus/physiology , RNA, Messenger/metabolism , Swine , Swine Diseases/immunology , Swine Diseases/virology , TNF Receptor-Associated Factor 3/metabolism , Transcription Factors/metabolism , Virus Replication/physiology
18.
J Virol ; 96(5): e0088921, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-2223570

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) causes a porcine disease associated with swine epidemic diarrhea. Different antagonistic strategies have been identified, and the mechanism by which PEDV infection impairs the production of interferon (IFN) and delays the activation of the IFN response to escape host innate immunity has been determined, but the pathogenic mechanisms of PEDV infection remain enigmatic. Our preliminary results revealed that endogenous F-box and WD repeat domain-containing 7 (FBXW7) protein, the substrate recognition component of the SCF-type E3 ubiquitin ligase, is downregulated in PEDV-infected Vero E6 cells, according to the results from an isobaric tags for relative and absolute quantification (iTRAQ) analysis. Overexpression of FBXW7 in target cells makes them more resistant to PEDV infection, whereas ablation of FBXW7 expression by small interfering RNA (siRNA) significantly promotes PEDV infection. In addition, FBXW7 was verified as an innate antiviral factor capable of enhancing the expression of RIG-I and TBK1, and it was found to induce interferon-stimulated genes (ISGs), which led to an elevated antiviral state of the host cells. Moreover, we revealed that PEDV nonstructural protein 2 (nsp2) interacts with FBXW7 and targets FBXW7 for degradation through the K48-linked ubiquitin-proteasome pathway. Consistent with the results proven in vitro, FBXW7 reduction was also confirmed in different intestinal tissues from PEDV-infected specific-pathogen-free (SPF) pigs. Taken together, the data indicated that PEDV has evolved with a distinct antagonistic strategy to circumvent the host antiviral response by targeting the ubiquitin-proteasome-mediated degradation of FBXW7. Our findings provide novel insights into PEDV infection and pathogenesis. IMPORTANCE To counteract the host antiviral defenses, most viruses, including coronaviruses, have evolved with diverse strategies to dampen host IFN-mediated antiviral response, by interfering with or evading specific host regulators at multiple steps of this response. In this study, a novel antagonistic strategy was revealed showing that PEDV infection could circumvent the host innate response by targeted degradation of endogenous FBXW7 in target cells, a process that was verified to be a positive modulator for the host innate immune system. Degradation of FBXW7 hampers host innate antiviral activation and facilitates PEDV replication. Our findings reveal a new mechanism exploited by PEDV to suppress the host antiviral response.


Subject(s)
Coronavirus Infections/veterinary , F-Box-WD Repeat-Containing Protein 7/metabolism , Immune Evasion , Immunity, Innate , Porcine epidemic diarrhea virus/immunology , Swine Diseases/immunology , Animals , Antiviral Agents/immunology , Chlorocebus aethiops , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Interferon Type I/metabolism , Proteasome Endopeptidase Complex/metabolism , Signal Transduction/immunology , Swine , Swine Diseases/prevention & control , Swine Diseases/virology , Ubiquitins/metabolism , Vero Cells
19.
J Virol ; 97(1): e0161422, 2023 01 31.
Article in English | MEDLINE | ID: covidwho-2223572

ABSTRACT

Porcine epidemic diarrhea (PED) indicates the disease of the acute and highly contagious intestinal infection due to porcine epidemic diarrhea virus (PEDV), with the characteristics of watery diarrhea, vomiting, and dehydration. One of the reasons for diarrhea and death of piglets is PEDV, which leads to 100% mortality in neonatal piglets. Therefore, it is necessary to explore the interaction between virus and host to prevent and control PEDV. This study indicated that the host protein, pre-mRNA processing factor 19 (PRPF19), could be controlled by the signal transducer as well as activator of transcription 1 (STAT1). Thus, PEDV replication could be hindered through selective autophagy. Moreover, PRPF19 was found to recruit the E3 ubiquitin ligase MARCH8 to the N protein for ubiquitination. For the purpose of degradation, the ubiquitin N protein is acknowledged by the cargo receptor NDP52 and transported to autolysosomes, thus inhibiting virus proliferation. To conclude, a unique antiviral mechanism of PRPF19-mediated virus restriction was shown. Moreover, a view of the innate immune response and protein degradation against PEDV replication was provided in this study. IMPORTANCE The highly virulent porcine epidemic diarrhea virus (PEDV) emerged in 2010, and causes high mortality rates in newborn pigs. There are no effective and safe vaccines against the highly virulent PEDV. This virus has caused devastating economic losses in the pork industry worldwide. Studying the relationship between virus and host antiviral factors is important to develop the new antiviral strategies. This study identified the pre-mRNA processing factor 19 (PRPF19) as a novel antiviral protein in PEDV replication and revealed its viral restriction mechanisms for the first time. PRPF19 recruited the E3 ubiquitin ligase MARCH8 to the PEDV N protein for ubiquitination, and the ubiquitin N protein was acknowledged by the cargo receptor NDP52 and transported to autolysosomes for degradation. Our findings provide new insights in host antiviral factors PRPF19 that regulate the selective autophagy protein degradation pathway to inhibit PEDV replication.


Subject(s)
Capsid Proteins , Coronavirus Infections , Porcine epidemic diarrhea virus , Swine Diseases , Animals , Capsid Proteins/metabolism , Coronavirus Infections/immunology , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Porcine epidemic diarrhea virus/physiology , Swine , Swine Diseases/immunology , Swine Diseases/virology , Ubiquitin-Protein Ligases/metabolism , Ubiquitins , Virus Replication/genetics , Nuclear Proteins/metabolism , Autophagy
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