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1.
Viruses ; 16(5)2024 04 26.
Article in English | MEDLINE | ID: mdl-38793562

ABSTRACT

The skin is a complex tissue that provides a strong physical barrier against invading pathogens. Despite this, many viruses can access the skin and successfully replicate in either the epidermal keratinocytes or dermal immune cells. In this review, we provide an overview of the antiviral T cell biology responding to cutaneous viral infections and how these responses differ depending on the cellular targets of infection. Much of our mechanistic understanding of T cell surveillance of cutaneous infection has been gained from murine models of poxvirus and herpesvirus infection. However, we also discuss other viral infections, including flaviviruses and papillomaviruses, in which the cutaneous T cell response has been less extensively studied. In addition to the mechanisms of successful T cell control of cutaneous viral infection, we highlight knowledge gaps and future directions with possible impact on human health.


Subject(s)
Skin Diseases, Viral , Skin , T-Lymphocytes , Humans , Animals , T-Lymphocytes/immunology , Skin Diseases, Viral/immunology , Skin Diseases, Viral/virology , Skin/virology , Skin/immunology , Mice , Immunologic Surveillance , Virus Diseases/immunology
2.
J Cutan Pathol ; 51(8): 565-571, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38654546

ABSTRACT

Cytomegalovirus (CMV) infection is common and often self-limited. Reactivation results in a variety of disease presentations, especially in the setting of immunocompromise. While cutaneous manifestations of systemic CMV infection are rare, dermatologic manifestations of CMV are increasingly reported with a wide morphologic spectrum clinically. Three male patients, with untreated human immunodeficiency virus (HIV), penile lichenoid dermatitis treated with long-term topical and intralesional corticosteroids, and metastatic Merkel cell carcinoma on immune checkpoint inhibitor therapy, each presented with isolated cutaneous ulcers. The ulcers were located on the perianal skin, glans of the penis, and distal thumb. In each case, nonspecific histopathologic features were seen. However, very rare dermal cytomegalic cells with nuclear and cytoplasmic inclusions were present and highlighted with an immunohistochemical stain for CMV. Isolated ulcers due to CMV infection may occur in the setting of systemic or localized immunosuppression. A high index of suspicion is needed upon histopathologic evaluation, as few cytomegalic cells may be present and accurate diagnosis is crucial for prompt and appropriate clinical management.


Subject(s)
Cytomegalovirus Infections , Humans , Cytomegalovirus Infections/pathology , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/virology , Male , Middle Aged , Cytomegalovirus/isolation & purification , Aged , Skin Ulcer/pathology , Skin Ulcer/virology , Skin Ulcer/diagnosis , Immunocompromised Host , HIV Infections/complications , HIV Infections/diagnosis , Skin Diseases, Viral/pathology , Skin Diseases, Viral/diagnosis , Skin Diseases, Viral/virology
5.
Actas dermo-sifiliogr. (Ed. impr.) ; 114(4): 318-326, abr. 2023. ilus, tab
Article in Spanish | IBECS | ID: ibc-218984

ABSTRACT

MPOX es una enfermedad zoonótica emergente que se ha propagado rápidamente por todo el mundo y que ha sido declarada por la OMS como una emergencia de salud pública de interés internacional. Esta es una revisión no sistemática de los aspectos clínicos, epidemiológicos, diagnósticos y terapéuticos más relevantes para el dermatólogo. En el brote actual, la transmisión durante las relaciones sexuales es la principal forma de contagio como resultado del contacto físico cercano. Si bien los casos iniciales se informaron en hombres que tienen sexo con hombres, cualquier persona en contacto cercano con personas o fómites infectados está en riesgo. El pródromo clásico puede ser subclínico y la erupción puede ser sutil. Las complicaciones son frecuentes, pero el requerimiento de hospitalización es infrecuente. El diagnóstico definitivo se realiza mediante PCR de las lesiones mucocutáneas. Actualmente no existen tratamientos específicos, y el tratamiento sintomático es el pilar terapéutico (AU)


Mpox is an emerging zoonotic disease that has spread rapidly around the world. It has been declared a public health emergency of international concern by the World Health Organization. This review is an update for dermatologists on the epidemiology, clinical presentation, diagnosis, and treatment of Mpox. The primary mode of transmission in the current outbreak is close physical contact during sexual activity. Although most of the initial cases were reported in men who have sex with men, anyone who has close contact with an infected person or contaminated fomites is at risk. Classic prodromal features of Mpox include subclinical manifestations and a mild rash. Complications are common but rarely require hospitalization. Polymerase chain reaction analysis of mucocutaneous lesions is the test of choice for a definitive diagnosis. In the absence of specific treatments, management focuses on symptomatic relief (AU)


Subject(s)
Humans , Male , Mpox (monkeypox)/transmission , Skin Diseases, Viral/transmission , Mpox (monkeypox)/diagnosis , Skin Diseases, Viral/diagnosis , Sexual and Gender Minorities , Homosexuality, Male , Risk Factors
6.
Actas dermo-sifiliogr. (Ed. impr.) ; 114(4): t318-t326, abr. 2023. ilus, tab
Article in English | IBECS | ID: ibc-218985

ABSTRACT

Mpox is an emerging zoonotic disease that has spread rapidly around the world. It has been declared a public health emergency of international concern by the World Health Organization. This review is an update for dermatologists on the epidemiology, clinical presentation, diagnosis, and treatment of Mpox. The primary mode of transmission in the current outbreak is close physical contact during sexual activity. Although most of the initial cases were reported in men who have sex with men, anyone who has close contact with an infected person or contaminated fomites is at risk. Classic prodromal features of Mpox include subclinical manifestations and a mild rash. Complications are common but rarely require hospitalization. Polymerase chain reaction analysis of mucocutaneous lesions is the test of choice for a definitive diagnosis. In the absence of specific treatments, management focuses on symptomatic relief (AU)


MPOX es una enfermedad zoonótica emergente que se ha propagado rápidamente por todo el mundo y que ha sido declarada por la OMS como una emergencia de salud pública de interés internacional. Esta es una revisión no sistemática de los aspectos clínicos, epidemiológicos, diagnósticos y terapéuticos más relevantes para el dermatólogo. En el brote actual, la transmisión durante las relaciones sexuales es la principal forma de contagio como resultado del contacto físico cercano. Si bien los casos iniciales se informaron en hombres que tienen sexo con hombres, cualquier persona en contacto cercano con personas o fómites infectados está en riesgo. El pródromo clásico puede ser subclínico y la erupción puede ser sutil. Las complicaciones son frecuentes, pero el requerimiento de hospitalización es infrecuente. El diagnóstico definitivo se realiza mediante PCR de las lesiones mucocutáneas. Actualmente no existen tratamientos específicos, y el tratamiento sintomático es el pilar terapéutico (AU)


Subject(s)
Humans , Male , Mpox (monkeypox)/transmission , Skin Diseases, Viral/transmission , Mpox (monkeypox)/diagnosis , Skin Diseases, Viral/diagnosis , Homosexuality, Male , Risk Factors , Sexual and Gender Minorities
7.
Vet Dermatol ; 34(4): 367-370, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36941227

ABSTRACT

A raised plaque that contained histological evidence of papillomavirus infection and sequences from a novel papillomavirus type developed close to the ear canal of a 14-year-old West Highland white terrier. The plaque was excised, and further plaques developed within the same area of pinna.


Une plaque virale à papillomavirus confirmée histologiquement contenant des séquences d'un un nouveau type de papillomavirus se sont développées à proximité du conduit auditif d'un West Highland White âgé de 14 ans. La plaque a été retirée chirurgicalement et d'autres plaques se sont développées dans la même zone du pavillon.


Una placa elevada que contenía evidencia histológica de infección por papilomavirus y secuencias de un nuevo tipo de papilomavirus se desarrolló cerca del canal auditivo de un West Highland White Terrier de 14 años. Se extirpó la placa y se desarrollaron más placas dentro de la misma área del pabellón auricular.


Uma placa elevada apresentando evidências histopatológicas de infecção por papilomavírus e sequências de um novo tipo de papilomavírus surgiu próximo ao conduto auditivo de um West Highland White Terrier de 14 anos de idade. A placa foi removida e outras placas se desenvolveram na mesma área da orelha.


Subject(s)
Dog Diseases , Papillomavirus Infections , Skin Diseases, Viral , Dogs , Animals , Papillomavirus Infections/diagnosis , Papillomavirus Infections/veterinary , Papillomavirus Infections/pathology , Dog Diseases/pathology , DNA, Viral , Skin Diseases, Viral/diagnosis , Skin Diseases, Viral/veterinary , Skin Diseases, Viral/pathology , Papillomaviridae/genetics
9.
J Eur Acad Dermatol Venereol ; 36(9): 1648-1659, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35535625

ABSTRACT

BACKGROUND: Populations around the world are rapidly ageing. The profile of skin diseases in the elderly is likely to present unique demands on the healthcare system. OBJECTIVES: To provide current data on the burden of skin diseases in Singaporean patients and identify differences in the pattern of skin diseases between elderly patients and the rest of the population. METHODS: This was a retrospective cohort study of 858 117 patients who attended the National Skin Centre between 2004 and 2018. Prevalence was calculated by grouping International Classification of Diseases codes into different categories of skin conditions based on Global Burden of Disease and American Academy of Dermatology classifications. Years lost to disability (YLDs) and disability-adjusted life years (DALYs) were calculated to report the morbidity and mortality of skin diseases. Differences of each skin condition between age groups were compared. RESULTS: The three most prevalent dermatoses across all age groups were dermatitis (33.3%), acne vulgaris (8.3%) and viral skin diseases (7.5%). The top three most common skin conditions among the elderly were dermatitis (37.7%), viral skin diseases (6.2%) and fungal skin diseases (4.3%). Decubitus ulcers, keratinocyte carcinomas and scabies represented a significant proportion of YLD per 100 000 in the elderly (P < 0.001). Malignant melanomas, keratinocyte carcinomas, cellulitis, pyoderma and decubitus ulcers contributed to high DALYs in patients aged 70-80 years. CONCLUSION: Aligning health systems with specific healthcare needs will reduce the disproportionately high burden of skin disease observed in the elderly.


Subject(s)
Carcinoma , Dermatitis , Pressure Ulcer , Skin Diseases, Viral , Aged , Cohort Studies , Global Health , Humans , Prevalence , Quality-Adjusted Life Years , Retrospective Studies , Singapore/epidemiology
10.
Sci Rep ; 12(1): 1641, 2022 01 31.
Article in English | MEDLINE | ID: mdl-35102178

ABSTRACT

H84T BanLec is a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses. H84T BanLec dimers bind glycoproteins containing high-mannose N-glycans on the virion envelope, blocking attachment, entry, uncoating, and spread. It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. Human skin was obtained from reduction mammoplasties and prepared for culture. Skin was infected and cultured up to 14 days. H84T BanLec prevented VZV, HCMV and HSV-1 spread in skin at 10 µM in the culture medium, and also exhibited dose-dependent antiviral effects. Additionally, H84T BanLec arrested virus spread when treatment was delayed. Histopathology of HCMV-infected skin showed no overt toxicity when H84T BanLec was present in the media. In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. This is the first demonstration of H84T BanLec effectiveness against DNA viruses. H84T BanLec may have additional unexplored activity against other, clinically relevant, glycosylated viruses.


Subject(s)
Antiviral Agents/pharmacology , Cytomegalovirus/drug effects , Herpesviridae Infections/drug therapy , Herpesvirus 1, Human/drug effects , Herpesvirus 3, Human/drug effects , Plant Lectins/pharmacology , Skin Diseases, Viral/drug therapy , Skin/virology , Animals , Chlorocebus aethiops , Cytomegalovirus/growth & development , Herpesviridae Infections/virology , Herpesvirus 1, Human/growth & development , Herpesvirus 3, Human/growth & development , Mice, Nude , Musa/genetics , Plant Lectins/genetics , Skin Diseases, Viral/virology , Tissue Culture Techniques , Vero Cells , Virus Replication/drug effects
11.
Dermatol Clin ; 39(4): 487-503, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34556240

ABSTRACT

Coronavirus disease 2019 (COVID-19), an emergent disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the globe since its discovery in December 2019. Although first appreciated to cause pneumonia, numerous organ systems are now known to be involved. The objective of this article is to review the broad spectrum of cutaneous manifestations reported in association with SARS-CoV-2 infection. The most commonly reported cutaneous manifestations associated with COVID-19 infection include pernio (chilblain)-like acral lesions, morbilliform (exanthematous) rash, urticaria, vesicular (varicella-like) eruptions, and vaso-occlusive lesions (livedo racemosa, retiform purpura). It is important to consider SARS-CoV-2 infection in the differential diagnosis of a patient presenting with these lesions in the appropriate clinical context, as cutaneous manifestations may be present in otherwise asymptomatic individuals, or present before developing other symptoms of infection. With increased access to diagnostic testing, we are beginning to understand the utility and limitations of currently available assays.


Subject(s)
COVID-19/epidemiology , Skin Diseases, Viral/epidemiology , COVID-19/pathology , Comorbidity , Exanthema/epidemiology , Humans , Purpura/epidemiology , SARS-CoV-2 , Skin/pathology , Skin Diseases, Viral/pathology , Urticaria/epidemiology
12.
Dermatol Clin ; 39(4): 505-519, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34556241

ABSTRACT

Children are a unique subset of patients in relation to the COVID-19 pandemic, often presenting asymptomatically, mildly, or atypically. Manifestations of the skin may be a primary (or the only) presenting sign. Recognizing cutaneous manifestations of COVID-19 in the pediatric population is important to guiding precautions, testing, and management for patients and close contacts. Whereas some dermatologic signs in children overlap with those in adults, other skin findings are reported with higher frequency in children and may be clues to multisystemic sequelae. This article describes presentation, pathophysiologic theories, and management strategies for cutaneous manifestations of COVID-19 in children.


Subject(s)
COVID-19/complications , COVID-19/diagnosis , Skin Diseases, Viral/etiology , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/diagnosis , COVID-19 Testing/statistics & numerical data , Child , Humans , Skin Diseases, Viral/diagnosis
15.
Cutis ; 107(4): 209-215, 2021 Apr.
Article in English | MEDLINE | ID: mdl-34096848

ABSTRACT

Cutaneous manifestations of COVID-19-SARS-CoV-2-are common and varied. Morbilliform, vesicular, and urticarial eruptions may be nonspecific initial features of the disease. Chilblainlike lesions on the fingers or toes typically occur as part of a resolution phase, signifying a milder course, whereas livedoid lesions and retiform purpura are associated with coaguloapthy and more severe disease. Additionally, a severe Kawasaki-like multisystem inflammatory syndrome rarely is seen in children. This diverse range of cutaneous manifestations in COVID-19 reflects a spectrum of host immunologic responses to SARS-CoV-2 and may inform disease pathophysiology.


Subject(s)
COVID-19/complications , Severity of Illness Index , Skin Diseases/diagnosis , Skin Diseases/etiology , COVID-19/epidemiology , COVID-19 Testing , Dermatology , Exanthema/diagnosis , Exanthema/etiology , Female , Humans , Male , Purpura/diagnosis , Purpura/etiology , Skin/pathology , Skin Diseases/virology , Skin Diseases, Viral/diagnosis , Skin Diseases, Viral/etiology , Urticaria/diagnosis , Urticaria/etiology
16.
Am J Clin Dermatol ; 22(4): 523-540, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34008162

ABSTRACT

Viral venereal diseases remain difficult to treat. Human papilloma virus (HPV) and herpes simplex virus (HSV) are two common viral venereal diseases. HPV infections are characterized by anogenital warts and less commonly by premalignant or malignant lesions. HSV infections classically present as grouped vesicles on an erythematous base with associated burning or pain; however, immunosuppressed patients may have atypical presentations with nodular or ulcerative lesions. This review discusses the epidemiology, diagnosis, and management of anogenital HPV and HSV infections with an emphasis on treatment modalities for the practicing dermatologist. Diagnosis of these diseases typically relies on clinical assessment, although multiple diagnostic techniques can be utilized and are recommended when diagnosis is uncertain or evaluating an individual with increased risk of malignancy. Management of HPV and HSV infections involves appropriate counseling, screening, and multiple treatment techniques. Particularly for HPV infections, a practitioner may need to use a combination of techniques to achieve the desired outcome.


Subject(s)
Herpesviridae Infections/diagnosis , Papillomavirus Infections/diagnosis , Sexually Transmitted Diseases, Viral/diagnosis , Skin Diseases, Viral/diagnosis , Alphapapillomavirus/isolation & purification , Combined Modality Therapy/methods , Combined Modality Therapy/standards , Counseling/standards , Dermatology/methods , Dermatology/standards , Herpesviridae/isolation & purification , Herpesviridae Infections/epidemiology , Herpesviridae Infections/therapy , Herpesviridae Infections/transmission , Humans , Mass Screening/standards , Papillomavirus Infections/epidemiology , Papillomavirus Infections/therapy , Papillomavirus Infections/transmission , Practice Guidelines as Topic , Prevalence , Risk Factors , Sexually Transmitted Diseases, Viral/epidemiology , Sexually Transmitted Diseases, Viral/therapy , Sexually Transmitted Diseases, Viral/transmission , Skin/pathology , Skin/virology , Skin Diseases, Viral/epidemiology , Skin Diseases, Viral/therapy , Skin Diseases, Viral/transmission
17.
Front Immunol ; 12: 662234, 2021.
Article in English | MEDLINE | ID: mdl-34012447

ABSTRACT

Herpes simplex virus type 1 (HSV-1) infection is highly prevalent in humans, with approximately two-thirds of the world population living with this virus. However, only a fraction of those carrying HSV-1, which elicits lifelong infections, are symptomatic. HSV-1 mainly causes lesions in the skin and mucosae but reaches the termini of sensory neurons innervating these tissues and travels in a retrograde manner to the neuron cell body where it establishes persistent infection and remains in a latent state until reactivated by different stimuli. When productive reactivations occur, the virus travels back along axons to the primary infection site, where new rounds of replication are initiated in the skin, in recurrent or secondary infections. During this process, new neuron infections occur. Noteworthy, the mechanisms underlying viral reactivations and the exit of latency are somewhat poorly understood and may be regulated by a crosstalk between the infected neurons and components of the immune system. Here, we review and discuss the immune responses that occur at the skin during primary and recurrent infections by HSV-1, as well as at the interphase of latently-infected neurons. Moreover, we discuss the implications of neuronal signals over the priming and migration of immune cells in the context of HSV-1 infection.


Subject(s)
Epithelial Cells/metabolism , Herpes Simplex/immunology , Herpesvirus 1, Human/immunology , Sensory Receptor Cells/metabolism , Skin Diseases, Viral/immunology , Animals , Cell Culture Techniques , Epithelial Cells/immunology , Gene Expression Regulation, Viral , Herpesvirus 1, Human/genetics , Humans , Mice , Sensory Receptor Cells/immunology , Virus Activation , Virus Latency , Virus Replication
18.
Medicine (Baltimore) ; 100(18): e25706, 2021 May 07.
Article in English | MEDLINE | ID: mdl-33950953

ABSTRACT

ABSTRACT: Enteroviruses is a group of positive single-stranded RNA viruses ubiquitous in the environment, which is a causative agent of epidemic diseases in children and infants. But data on neonates are still limited. The present study aimed to describe the clinical characteristics of enterovirus infection in neonates and arise the awareness of this disease to general public.Between March 2018 and September 2019, data from all of the neonates diagnosed with enterovirus infection were collected and analyzed from neonatal intensive care unit of Zhangzhou Hospital in Fujian, China.A total of 23 neonates were enrolled. All of them presented with fever (100%), and some with rashes (39.1%). The incidence of aseptic meningitis was high (91.3%), but only a small proportion (28.6%) presented with cerebrospinal fluid (CSF) leukocytosis. The positive value for nucleic acid detection in CSF was significantly higher than throat swab (91.3% vs 43.5%, P = .007). Five of the infected neonates presented with aseptic meningitis (23.8%) underwent brain magnetic resonance imaging examination and no craniocerebral injuries were found. Subsequent follow-ups were performed in 15 of them (71.4%) and no neurological sequelae was found.Aseptic meningitis is a common type of enterovirus infection in neonates with a benign course. Nucleic acid detection of CSF has an important diagnostic value. Febrile neonates would be suggested to screen for enterovirus infection in addition to complete septic workup. An unnecessary initiation or earlier cessation of antibiotics could be considered in enterovirus infection, but that indications still need further studies to guarantee the safety.


Subject(s)
Enterovirus Infections/epidemiology , Enterovirus/isolation & purification , Fever/epidemiology , Meningitis, Aseptic/epidemiology , Meningitis, Viral/epidemiology , Brain/diagnostic imaging , China/epidemiology , Enterovirus/genetics , Enterovirus Infections/cerebrospinal fluid , Enterovirus Infections/diagnosis , Enterovirus Infections/virology , Exanthema/cerebrospinal fluid , Exanthema/diagnosis , Exanthema/epidemiology , Exanthema/virology , Female , Fever/cerebrospinal fluid , Fever/diagnosis , Fever/virology , Humans , Incidence , Infant, Newborn , Intensive Care Units, Neonatal/statistics & numerical data , Magnetic Resonance Imaging , Male , Meningitis, Aseptic/cerebrospinal fluid , Meningitis, Aseptic/diagnosis , Meningitis, Aseptic/virology , Meningitis, Viral/cerebrospinal fluid , Meningitis, Viral/diagnosis , Meningitis, Viral/virology , Pharynx/virology , RNA, Viral/cerebrospinal fluid , RNA, Viral/isolation & purification , Retrospective Studies , Skin Diseases, Viral/cerebrospinal fluid , Skin Diseases, Viral/epidemiology , Skin Diseases, Viral/virology
20.
São Paulo med. j ; 139(2): 186-189, Mar.-Apr. 2021. tab, graf
Article in English | LILACS | ID: biblio-1181004

ABSTRACT

ABSTRACT CONTEXT: Various skin manifestations have been reported in coronavirus disease. It may be difficult to determine the etiology of these lesions in view of the increased frequency of handwashing during the pandemic, along with occurrences of irritant contact dermatitis and allergic contact dermatitis due to disinfectant use; usage of herbal medicine and supplements to strengthen the immune system; and urticarial or maculopapular drug eruptions due to COVID-19 treatment. The variety of associated skin manifestations seen with COVID-19 makes it challenging to identify virus-specific skin manifestations. Petechiae, purpura, acrocyanosis and necrotic and non-necrotic purpura, which can be considered as manifestations of vascular involvement on the skin, have been reported. CASE REPORT: Here, we report a case of eruptive cherry angiomas, which was thought to have developed due to COVID-19, with a papulovesicular rash on distal extremities that progressed over time to reticular purpura. CONCLUSION: The case presented had a papulovesicular rash at the onset, which evolved to retiform purpura, and eruptive cherry angiomas were observed. It should be kept in mind that dermatological signs may vary in patients with COVID-19.


Subject(s)
Humans , Male , Female , Middle Aged , Purpura/virology , Skin/virology , Skin Diseases, Viral/virology , Exanthema/virology , COVID-19/complications , COVID-19/virology , Hemangioma/virology , Skin/drug effects , Skin/pathology , Treatment Outcome , Skin Diseases, Viral/diagnosis , Skin Diseases, Viral/therapy , COVID-19 Testing , SARS-CoV-2 , COVID-19/drug therapy , COVID-19/therapy
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