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2.
Cell Host Microbe ; 30(2): 154-162.e5, 2022 02 09.
Article in English | MEDLINE | ID: covidwho-1708092

ABSTRACT

Characterizing SARS-CoV-2 evolution in specific geographies may help predict properties of the variants that come from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from ancestral virus in a person with advanced HIV disease in South Africa; this person was infected prior to emergence of the Beta and Delta variants. We longitudinally tracked the evolved virus and tested it against self-plasma and convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral, but it evolved a multitude of mutations found in Omicron and other variants. It showed substantial but incomplete Pfizer BNT162b2 escape, weak neutralization by self-plasma, and despite pre-dating Delta, it also showed extensive escape of Delta infection-elicited neutralization. This example is consistent with the notion that SARS-CoV-2 evolving in individual immune-compromised hosts, including those with advanced HIV disease, may gain immune escape of vaccines and enhanced escape of Delta immunity, and this has implications for vaccine breakthrough and reinfections.


Subject(s)
Antibodies, Neutralizing/blood , HIV Infections/pathology , Immune Evasion/immunology , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , Adult , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Cell Line , Chlorocebus aethiops , Female , HIV-1/immunology , Humans , Immunocompromised Host/immunology , Neutralization Tests , SARS-CoV-2/isolation & purification , South Africa , Vaccination , Vero Cells
3.
PLoS One ; 16(12): e0260251, 2021.
Article in English | MEDLINE | ID: covidwho-1546950

ABSTRACT

There continue to be conflicting data regarding the outcomes of people with HIV (PWH) who have COVID-19 infection with most studies describing the early epidemic. We present a single site experience spanning a later timeframe from the first report on January 21, 2020 to January 20, 2021 and describe clinical outcomes and predictors of hospitalization among a cohort of PWH in an urban center in Connecticut, USA. Among 103 PWH with controlled HIV disease, hospitalization occurred in 33% and overall mortality was 1%. HIV associated factors (CD4 count, HIV viral suppression) were not associated with hospitalization. Chronic lung disease (OR: 3.35, 95% CI:1.28-8.72), and cardiovascular disease (OR: 3.4, 95% CI:1.27-9.12) were independently associated with hospitalization. An increasing number of non-communicable comorbidities increased the likelihood of hospitalization (OR: 1.61, 95% CI:1.22-2.13).


Subject(s)
COVID-19/diagnosis , HIV Infections/pathology , Hospitalization/statistics & numerical data , Adult , Age Factors , Aged , CD4 Lymphocyte Count , COVID-19/complications , COVID-19/virology , Cardiovascular Diseases/complications , Comorbidity , Connecticut , Female , HIV Infections/complications , HIV Infections/mortality , Humans , Male , Middle Aged , Noncommunicable Diseases/epidemiology , Odds Ratio , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification
5.
PLoS One ; 16(8): e0256601, 2021.
Article in English | MEDLINE | ID: covidwho-1372016

ABSTRACT

Networks science techniques are frequently used to provide meaningful insights into the populations underlying medical and social data. This paper examines SATHCAP, a dataset related to HIV and drug use in three US cities. In particular, we use network measures such as betweenness centrality, closeness centrality, and eigenvector centrality to find central, important nodes in a network derived from SATHCAP data. We evaluate the attributes of these important nodes and create an exceptionality score based on the number of nodes that share a particular attribute. This score, along with the underlying network itself, is used to reveal insight into the attributes of groups that can be effectively targeted to slow the spread of disease. Our research confirms a known connection between homelessness and HIV, as well as drug abuse and HIV, and shows support for the theory that individuals without easy access to transportation are more likely to be central to the spread of HIV in urban, high risk populations.


Subject(s)
Social Network Analysis , Cities , Databases, Factual , HIV Infections/pathology , HIV Infections/transmission , Homeless Persons , Humans , Substance-Related Disorders/pathology
8.
AIDS Res Ther ; 18(1): 28, 2021 05 05.
Article in English | MEDLINE | ID: covidwho-1216906

ABSTRACT

Coronavirus disease 2019 (COVID-19) was first detected in December 2019. In March 2020, the World Health Organization declared COVID-19 a pandemic. People with underlying medical conditions may be at greater risk of infection and experience complications from COVID-19. COVID-19 has the potential to affect People living with HIV (PLWH) in various ways, including be increased risk of COVID-19 acquisition and interruptions of HIV treatment and care. The purpose of this review article is to evaluate the impact of COVID-19 among PLWH. The contents focus on 4 topics: (1) the pathophysiology and host immune response of people infected with both SARS-CoV-2 and HIV, (2) present the clinical manifestations and treatment outcomes of persons with co-infection, (3) assess the impact of antiretroviral HIV drugs among PLWH infected with COVID-19 and (4) evaluate the impact of the COVID-19 pandemic on HIV services.


Subject(s)
Anti-Retroviral Agents/therapeutic use , COVID-19/pathology , Coinfection/pathology , HIV Infections/pathology , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Adult , COVID-19/complications , COVID-19/drug therapy , COVID-19/immunology , Coinfection/immunology , Cytokines/blood , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/immunology , HIV-1/immunology , Humans , Immunocompromised Host/immunology , Immunocompromised Host/physiology , Lymphopenia/pathology , Middle Aged , Treatment Outcome
9.
J Mol Cell Biol ; 13(4): 259-268, 2021 08 04.
Article in English | MEDLINE | ID: covidwho-1147985

ABSTRACT

Viruses hijack host functions to invade their target cells and spread to new cells. Specifically, viruses learned to usurp liquid‒liquid phase separation (LLPS), a newly exploited mechanism, used by the cell to concentrate enzymes to accelerate and confine a wide variety of cellular processes. LLPS gives rise to actual membraneless organelles (MLOs), which do not only increase reaction rates but also act as a filter to select molecules to be retained or to be excluded from the liquid droplet. This is exactly what seems to happen with the condensation of SARS-CoV-2 nucleocapsid protein to favor the packaging of intact viral genomes, excluding viral subgenomic or host cellular RNAs. Another older pandemic virus, HIV-1, also takes advantage of LLPS in the host cell during the viral cycle. Recent discoveries highlighted that HIV-1 RNA genome condensates in nuclear MLOs accompanied by specific host and viral proteins, breaking the dogma of retroviruses that limited viral synthesis exclusively to the cytoplasmic compartment. Intriguing fundamental properties of viral/host LLPS remain still unclear. Future studies will contribute to deeply understanding the role of pathogen-induced MLOs in the epidemic invasion of pandemic viruses.


Subject(s)
HIV-1/physiology , Organelles/metabolism , SARS-CoV-2/physiology , COVID-19/pathology , COVID-19/virology , HIV Infections/pathology , HIV Infections/virology , HIV-1/genetics , HIV-1/isolation & purification , Host-Pathogen Interactions , Humans , Nucleocapsid Proteins/metabolism , RNA, Viral/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Virus Replication
10.
Rev Med Virol ; 31(6): e2228, 2021 11.
Article in English | MEDLINE | ID: covidwho-1126517

ABSTRACT

Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used as antiviral agents for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. We performed a systematic review to examine whether prior clinical studies that compared the effects of CQ and HCQ to a control for the treatment of non-SARS-CoV2 infection supported the use of these agents in the present SARS-CoV2 outbreak. PubMed, EMBASE, Scopus and Web of Science (PROSPERO CRD42020183429) were searched from inception through 2 April 2020 without language restrictions. Of 1766 retrieved reports, 18 studies met our inclusion criteria, including 17 prospective controlled studies and one retrospective study. CQ or HCQ were compared to control for the treatment of infectious mononucleosis (EBV, n = 4), warts (human papillomavirus, n = 2), chronic HIV infection (n = 6), acute chikungunya infection (n = 1), acute dengue virus infection (n = 2), chronic HCV (n = 2), and as preventive measures for influenza infection (n = 1). Survival was not evaluated in any study. For HIV, the virus that was most investigated, while two early studies suggested HCQ reduced viral levels, four subsequent ones did not, and in two of these CQ or HCQ increased viral levels and reduced CD4 counts. Overall, three studies concluded CQ or HCQ were effective; four concluded further research was needed to assess the treatments' effectiveness; and 11 concluded that treatment was ineffective or potentially harmful. Prior controlled clinical trials with CQ and HCQ for non-SARS-CoV2 viral infections do not support these agents' use for the SARS-CoV2 outbreak.


Subject(s)
Chikungunya Fever/drug therapy , Chloroquine/therapeutic use , HIV Infections/drug therapy , Hepatitis C, Chronic/drug therapy , Hydroxychloroquine/therapeutic use , Infectious Mononucleosis/drug therapy , Severe Dengue/drug therapy , Warts/drug therapy , Alphapapillomavirus/drug effects , Alphapapillomavirus/immunology , Alphapapillomavirus/pathogenicity , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Chikungunya Fever/immunology , Chikungunya Fever/pathology , Chikungunya Fever/virology , Chikungunya virus/drug effects , Chikungunya virus/immunology , Chikungunya virus/pathogenicity , Dengue Virus/drug effects , Dengue Virus/immunology , Dengue Virus/pathogenicity , HIV/drug effects , HIV/immunology , HIV/pathogenicity , HIV Infections/immunology , HIV Infections/pathology , HIV Infections/virology , Hepacivirus/drug effects , Hepacivirus/immunology , Hepacivirus/pathogenicity , Hepatitis C, Chronic/immunology , Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/virology , Herpesvirus 4, Human/drug effects , Herpesvirus 4, Human/immunology , Herpesvirus 4, Human/pathogenicity , Humans , Infectious Mononucleosis/immunology , Infectious Mononucleosis/pathology , Infectious Mononucleosis/virology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severe Dengue/immunology , Severe Dengue/pathology , Severe Dengue/virology , Treatment Outcome , Warts/immunology , Warts/pathology , Warts/virology
11.
Front Immunol ; 11: 596631, 2020.
Article in English | MEDLINE | ID: covidwho-1004678

ABSTRACT

COVID-19 is a distinctive infection characterized by elevated inter-human transmission and presenting from absence of symptoms to severe cytokine storm that can lead to dismal prognosis. Like for HIV, lymphopenia and drastic reduction of CD4+ T cell counts in COVID-19 patients have been linked with poor clinical outcome. As CD4+ T cells play a critical role in orchestrating responses against viral infections, important lessons can be drawn by comparing T cell response in COVID-19 and in HIV infection and by studying HIV-infected patients who became infected by SARS-CoV-2. We critically reviewed host characteristics and hyper-inflammatory response in these two viral infections to have a better insight on the large difference in clinical outcome in persons being infected by SARS-CoV-2. The better understanding of mechanism of T cell dysfunction will contribute to the development of targeted therapy against severe COVID-19 and will help to rationally design vaccine involving T cell response for the long-term control of viral infection.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , COVID-19/immunology , HIV Infections/immunology , Lymphopenia/pathology , SARS-CoV-2/immunology , CD4 Lymphocyte Count , CD8-Positive T-Lymphocytes/immunology , COVID-19/pathology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Cytokines/blood , Dysbiosis/pathology , Gastrointestinal Microbiome/physiology , HIV Infections/pathology , Humans , Tight Junctions/pathology
12.
Molecules ; 25(21)2020 Oct 22.
Article in English | MEDLINE | ID: covidwho-983187

ABSTRACT

Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , HIV Infections/drug therapy , Hepatitis C, Chronic/drug therapy , Herpes Simplex/drug therapy , Influenza, Human/drug therapy , Phytochemicals/therapeutic use , Pneumonia, Viral/drug therapy , Antiviral Agents/chemistry , Antiviral Agents/classification , Antiviral Agents/isolation & purification , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/virology , Drug Discovery , HIV/drug effects , HIV/pathogenicity , HIV/physiology , HIV Infections/pathology , HIV Infections/virology , Hepacivirus/drug effects , Hepacivirus/pathogenicity , Hepacivirus/physiology , Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/virology , Herpes Simplex/pathology , Herpes Simplex/virology , Humans , Influenza, Human/pathology , Influenza, Human/virology , Orthomyxoviridae/drug effects , Orthomyxoviridae/pathogenicity , Orthomyxoviridae/physiology , Pandemics , Phytochemicals/chemistry , Phytochemicals/classification , Phytochemicals/isolation & purification , Plants, Medicinal , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS-CoV-2 , Simplexvirus/drug effects , Simplexvirus/pathogenicity , Simplexvirus/physiology , Virus Internalization/drug effects , Virus Replication/drug effects
13.
J Korean Med Sci ; 35(39): e358, 2020 Oct 12.
Article in English | MEDLINE | ID: covidwho-853915

ABSTRACT

Although some comorbidities, such as diabetes mellitus, lung disease, and chronic kidney disease, are known as risk factors for poor clinical outcome in patients with coronavirus disease 2019 (COVID-19), it is unknown if human immunodeficiency virus (HIV) patients with COVID-19 would have poor prognosis than others. Rare cases of HIV patients with COVID-19 have been reported. As of May 25th, 2020, over 11,000 patients have been diagnosed with COVID-19 and over 13,000 are living with HIV in Korea. Here, we present the first HIV patient with COVID-19 in Korea. The 29-year-old Korean man had been taking Genvoya® regularly for seven years and HIV was well suppressed with CD4 counts of 555/mm³. He had mild symptoms of sore throat, dry cough, loss of taste and smell. He received hydroxychloroquine while Genvoya® was continued. Pneumonia diagnosed in chest computed tomography improved without oxygen supplementation. He was discharged on hospital day 31. HIV patients are considered as immunocompromised, but this case suggests that well controlled HIV patients have satisfactory prognosis following proper medical care.


Subject(s)
Coronavirus Infections/diagnosis , HIV Infections/pathology , Pneumonia, Viral/diagnosis , Adult , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , CD4 Lymphocyte Count , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , HIV Infections/complications , Humans , Hydroxychloroquine/therapeutic use , Male , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Prognosis , RNA, Viral/genetics , RNA, Viral/metabolism , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Tomography, X-Ray Computed
14.
Int J Infect Dis ; 101: 243-246, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-796902

ABSTRACT

Despite measures put in place to curb the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across South Africa, there has been a rapid spread which caused extensive morbidity and mortality. Whilst there is currently increased COVID-19 associated death, autopsies on COVID positive individuals are not routinely performed. An autopsy was performed on a 19 years old African patient who was recently diagnosed with human immunodeficiency virus (HIV). He presented with clinical features suggestive of SARS-CoV-2, which he subsequently tested positive for. Important histopathological findings included diffuse alveolar damage and fibrin thrombi. No superimposed infections were noted. The cause of death was attributed to COVID-19. We report the first autopsy case of an HIV-infected individual with COVID-19 as the cause of death.


Subject(s)
COVID-19/pathology , Adult , Autopsy , COVID-19/etiology , COVID-19/mortality , COVID-19/virology , Fatal Outcome , HIV Infections/pathology , HIV-1/physiology , Humans , Lung/pathology , Lung/virology , Male , Pandemics , SARS-CoV-2 , South Africa , Young Adult
15.
Sci Adv ; 6(35): eaba7910, 2020 08.
Article in English | MEDLINE | ID: covidwho-760200

ABSTRACT

Targeting a universal host protein exploited by most viruses would be a game-changing strategy that offers broad-spectrum solution and rapid pandemic control including the current COVID-19. Here, we found a common YxxØ-motif of multiple viruses that exploits host AP2M1 for intracellular trafficking. A library chemical, N-(p-amylcinnamoyl)anthranilic acid (ACA), was identified to interrupt AP2M1-virus interaction and exhibit potent antiviral efficacy against a number of viruses in vitro and in vivo, including the influenza A viruses (IAVs), Zika virus (ZIKV), human immunodeficiency virus, and coronaviruses including MERS-CoV and SARS-CoV-2. YxxØ mutation, AP2M1 depletion, or disruption by ACA causes incorrect localization of viral proteins, which is exemplified by the failure of nuclear import of IAV nucleoprotein and diminished endoplasmic reticulum localization of ZIKV-NS3 and enterovirus-A71-2C proteins, thereby suppressing viral replication. Our study reveals an evolutionarily conserved mechanism of protein-protein interaction between host and virus that can serve as a broad-spectrum antiviral target.


Subject(s)
Adaptor Proteins, Vesicular Transport/metabolism , Antiviral Agents/pharmacology , Cinnamates/pharmacology , Coronavirus Infections/drug therapy , HIV Infections/drug therapy , Influenza, Human/drug therapy , Pneumonia, Viral/drug therapy , ortho-Aminobenzoates/pharmacology , A549 Cells , Animals , Betacoronavirus/drug effects , Binding Sites/genetics , COVID-19 , Cell Line, Tumor , Chlorocebus aethiops , Coronavirus Infections/pathology , Dogs , HEK293 Cells , HIV Infections/pathology , HIV-1/drug effects , Host-Pathogen Interactions/drug effects , Humans , Influenza A virus/drug effects , Influenza, Human/pathology , Madin Darby Canine Kidney Cells , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Middle East Respiratory Syndrome Coronavirus/drug effects , Pandemics , Pneumonia, Viral/pathology , Protein Binding/genetics , Protein Transport/drug effects , RNA, Viral/genetics , Receptor, Interferon alpha-beta/genetics , SARS-CoV-2 , Transforming Growth Factor beta1/metabolism , Vero Cells , Virus Replication/drug effects , Zika Virus/drug effects , Zika Virus Infection/pathology
16.
Rev Med Virol ; 31(1): 1-12, 2021 01.
Article in English | MEDLINE | ID: covidwho-739642

ABSTRACT

BACKGROUND AND SETTING: Little is known about SARS-CoV-2 impact on some vulnerable subgroups, such as people living with HIV/AIDS (PLWHA). In our study we reviewed the current knowledge on SARS-CoV-2 cases in PLWHA. METHODS: A systematic review was conducted by searching the MEDLINE, EMBASE and Google Scholar databases. Studies reporting data on PLWHA affected by SARS-CoV-2 were considered for inclusion. The aim of this study was the systematic characterization of cases of SARS-CoV-2 infection among PLWHA, particularly focusing on age, clinical findings at diagnosis, radiological features, therapeutic management and clinical outcomes. RESULTS: Twenty three relevant articles were identified, which reported 164 adults with both HIV and SARS-CoV-2 infection. Of those, the large majority were males (120/142, 84.5%), often with one or more comorbidities. Fifteen cases needed intensive care treatment and 16 died. For each group, respectively three patients had underlying comorbidities. There were no studies on children. The included studies were mostly retrospective or case series/reports (19 studies). The overall risk of bias was moderate, due to the study types and characteristics. CONCLUSION: It is still unclear if HIV infection may influence SARS-CoV-2 infection and disease course, however some PLWHA and particularly males affected by ARV-related complications may be at greater risk of severe Covid-19 course.


Subject(s)
COVID-19/pathology , HIV Infections/pathology , Adolescent , Adult , Aged , COVID-19/epidemiology , Child , Comorbidity , Female , HIV Infections/epidemiology , Humans , Male , Middle Aged , Risk , SARS-CoV-2 , Young Adult
18.
Infection ; 48(5): 681-686, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-232706

ABSTRACT

INTRODUCTION: Data on people living with human immunodeficiency virus (PLWH) in the current SARS-CoV-2 pandemic are still scarce. This case series of 33 PLWH patients with COVID-19 reveals symptoms and outcome in this special population. METHODS: Retrospective analysis of anonymized data including age, gender, HIV-associated parameters, symptoms, and outcome. RESULTS: Three out of 32 patients with documented outcomes died (9%). 91% of the patients recovered and 76% have been classified as mild cases. All patients were on antiretroviral treatment, of them 22 on tenofovir-containing regimen and 4 on the protease inhibitor darunavir. CONCLUSIONS: This preliminary case series does not support excess morbidity and mortality among symptomatic COVID-19 PLWH and with viral suppression on ART. SARS-CoV-2 infections may occur during boosted darunavir-based and/or on tenofovir-containing ART.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/virology , Darunavir/therapeutic use , HIV Infections/virology , HIV/pathogenicity , Pneumonia, Viral/virology , Tenofovir/therapeutic use , Adult , Antiretroviral Therapy, Highly Active , Betacoronavirus/drug effects , Betacoronavirus/immunology , COVID-19 , Coinfection , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Coronavirus Infections/pathology , Female , HIV/drug effects , HIV/immunology , HIV Infections/drug therapy , HIV Infections/mortality , HIV Infections/pathology , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Survival Analysis , Viral Load/drug effects
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