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3.
Clin Pharmacol Ther ; 108(4): 775-790, 2020 10.
Article in English | MEDLINE | ID: covidwho-833866

ABSTRACT

There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). However, this has not been accompanied by a comprehensive evaluation of the target plasma and lung concentrations of these drugs following approved dosing in humans. Accordingly, concentration 90% (EC90 ) values recalculated from in vitro anti-SARS-CoV-2 activity data was expressed as a ratio to the achievable maximum plasma concentration (Cmax ) at an approved dose in humans (Cmax /EC90 ratio). Only 14 of the 56 analyzed drugs achieved a Cmax /EC90 ratio above 1. A more in-depth assessment demonstrated that only nitazoxanide, nelfinavir, tipranavir (ritonavir-boosted), and sulfadoxine achieved plasma concentrations above their reported anti-SARS-CoV-2 activity across their entire approved dosing interval. An unbound lung to plasma tissue partition coefficient (Kp Ulung ) was also simulated to derive a lung Cmax /half-maximal effective concentration (EC50 ) as a better indicator of potential human efficacy. Hydroxychloroquine, chloroquine, mefloquine, atazanavir (ritonavir-boosted), tipranavir (ritonavir-boosted), ivermectin, azithromycin, and lopinavir (ritonavir-boosted) were all predicted to achieve lung concentrations over 10-fold higher than their reported EC50 . Nitazoxanide and sulfadoxine also exceeded their reported EC50 by 7.8-fold and 1.5-fold in lung, respectively. This analysis may be used to select potential candidates for further clinical testing, while deprioritizing compounds unlikely to attain target concentrations for antiviral activity. Future studies should focus on EC90 values and discuss findings in the context of achievable exposures in humans, especially within target compartments, such as the lungs, in order to maximize the potential for success of proposed human clinical trials.


Subject(s)
Antiviral Agents/administration & dosage , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Drug Delivery Systems/methods , Drug Repositioning/methods , Pneumonia, Viral/drug therapy , Antiviral Agents/blood , Coronavirus Infections/blood , Humans , Pandemics , Pneumonia, Viral/blood
4.
Antiviral Res ; 173: 104646, 2020 01.
Article in English | MEDLINE | ID: covidwho-829317

ABSTRACT

Human coronaviruses (HCoVs) are important pathogens that cause upper respiratory tract infections and have neuroinvasive abilities; however, little is known about the dynamic infection process of CoVs in vivo, and there are currently no specific antiviral drugs to prevent or treat HCoV infection. Here, we verified the replication ability and pathogenicity of a reporter HCoV-OC43 strain expressing Renilla luciferase (Rluc; rOC43-ns2DelRluc) in mice with different genetic backgrounds (C57BL/6 and BALB/c). Additionally, we monitored the spatial and temporal progression of HCoV-OC43 through the central nervous system (CNS) of live BALB/c mice after intranasal or intracerebral inoculation with rOC43-ns2DelRluc. We found that rOC43-ns2DelRluc was fatal to suckling mice after intranasal inoculation, and that viral titers and Rluc expression were detected in the brains and spinal cords of mice infected with rOC43-ns2DelRluc. Moreover, viral replication was initially observed in the brain by non-invasive bioluminescence imaging before the infection spread to the spinal cord of BALB/c mice, consistent with its tropism in the CNS. Furthermore, the Rluc readout correlated with the HCoV replication ability and protein expression, which allowed quantification of antiviral activity in live mice. Additionally, we validated that chloroquine strongly inhibited rOC43-ns2DelRluc replication in vivo. These results provide new insights into the temporal and spatial dissemination of HCoV-OC43 in the CNS, and our methods provide an extremely sensitive platform for evaluating the efficacy of antiviral therapies to treat neuroinvasive HCoVs in live mice.


Subject(s)
Central Nervous System/virology , Coronavirus Infections/virology , Coronavirus OC43, Human/physiology , Animals , Antiviral Agents/administration & dosage , Brain/diagnostic imaging , Brain/virology , Central Nervous System/diagnostic imaging , Chloroquine/administration & dosage , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/drug therapy , Coronavirus OC43, Human/genetics , Genes, Reporter , Humans , Luciferases, Renilla/genetics , Luciferases, Renilla/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Molecular Imaging , Virus Replication/drug effects
5.
Rev Peru Med Exp Salud Publica ; 37(2): 312-319, 2020.
Article in Spanish | MEDLINE | ID: covidwho-828017

ABSTRACT

Disease caused by the new coronavirus (COVID-19) is characterized by fever, cough, and affection of the lower respiratory tract. It is associated with age, comorbidities and a weakened immune system. Typically, lymphopenias have been evidenced in severe cases and an excessive production of inflammatory cytokines (cytokine storm), which would explain the role of the hyperinflammatory response in the pathogenesis of COVID-19. Secondary inflammatory responses from virus reinfections may induce antibody-dependent enhancement (ADE), a viremic phenomenon that may be an alternative mechanism of cellular infection and should be considered when designing vaccines or immunotherapies involving the stimulation of neutralizing antibodies or the use of monoclonal antibodies. Currently, no vaccines or treatments demonstrate safety and efficacy in patients with COVID-19. However, the results from phase III clinical trials which involve the application of an mRNA (messenger ribonucleic acid) nucleic acid vaccine and an antiviral drug (remdisivir), are yet to be concluded. For the time being, the best measure to prevent the spread of COVID-19 is by implementing social isolation, this measure has been adopted by several countries as recommended by the World Health Organization (WHO).


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Social Isolation , Antiviral Agents/administration & dosage , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Cytokines/immunology , Humans , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Risk Factors , Viral Vaccines/administration & dosage
6.
Trials ; 21(1): 815, 2020 Sep 29.
Article in English | MEDLINE | ID: covidwho-803067

ABSTRACT

An unprecedented volume of research has been generated in response to the COVID-19 pandemic. However, there are risks of inefficient duplication and of important work being impeded if efforts are not synchronized. Excessive reliance on observational studies, which can be more rapidly conducted but are inevitably subject to measured and unmeasured confounders, can foil efforts to conduct rigorous randomized trials. These challenges are illustrated by recent global efforts to conduct clinical trials of post-exposure prophylaxis (PEP) as a strategy for preventing COVID-19. Innovative strategies are needed to help overcome these issues, including increasing communication between the Data Safety and Monitoring Committees (DSMCs) of similar trials. It is important to reinforce the primacy of high-quality trials in generating unbiased answers to pressing prevention and treatment questions about COVID-19.


Subject(s)
Antiviral Agents/administration & dosage , Betacoronavirus/drug effects , Clinical Trials Data Monitoring Committees/trends , Clinical Trials as Topic , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Post-Exposure Prophylaxis , Research Design/trends , Antiviral Agents/adverse effects , Betacoronavirus/pathogenicity , Cooperative Behavior , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Host-Pathogen Interactions , Humans , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Risk Factors , Time Factors , Treatment Outcome
8.
Clin Appl Thromb Hemost ; 26: 1076029620954911, 2020.
Article in English | MEDLINE | ID: covidwho-772058

ABSTRACT

Definitive pharmacological therapies for COVID-19 have yet to be identified. Several hundred trials are ongoing globally in the hope of a solution. However, nearly all treatments rely on systemic delivery but COVID-19 damages the lungs preferentially. The use of a targeted delivery approach is reviewed where engineered products are able to reach damaged lung tissue directly, which includes catheter-based and aerosol-based approaches. In this review we have outlined various target directed approaches which include microbubbles, extracellular vesicles including exosomes, adenosine nanoparticles, novel bio-objects, direct aerosol targeted pulmonary delivery and catheter-based drug delivery with reference to their relative effectiveness for the specific lesions. Currently several trials are ongoing to determine the effectiveness of such delivery systems alone and in conjunction with systemic therapies. Such approaches may prove to be very effective in the controlled and localized COVID-19 viral lesions in the lungs and potential sites. Moreover, localized delivery offered a safer delivery mode for such drugs which may have systemic adverse effects.


Subject(s)
Antiviral Agents/administration & dosage , Betacoronavirus , Coronavirus Infections/drug therapy , Pandemics , Pneumonia, Viral/drug therapy , Coronavirus Infections/epidemiology , Humans , Lung , Microtubules , Pneumonia, Viral/epidemiology
9.
JAMA ; 324(11): 1048-1057, 2020 09 15.
Article in English | MEDLINE | ID: covidwho-762932

ABSTRACT

Importance: Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown. Objective: To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment. Design, Setting, and Participants: Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020. Interventions: Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d. Main Outcomes and Measures: The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group. Results: Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care. Conclusions and Relevance: Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT04292730.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Administration, Intravenous , Aged , Alanine/administration & dosage , Alanine/adverse effects , Alanine/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Coronavirus Infections/mortality , Drug Administration Schedule , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Odds Ratio , Pandemics , Patient Acuity , Pneumonia, Viral/mortality , Treatment Outcome
10.
Pharmacol Res Perspect ; 8(5): e00653, 2020 10.
Article in English | MEDLINE | ID: covidwho-757850

ABSTRACT

More than ten million patients worldwide have been diagnosed with coronavirus disease 19 (COVID-19) to date (WHO situation report, 1st July 2020). There is no vaccine to prevent infection with the causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), nor a cure. In the struggle to devise potentially useful therapeutics in record time, the repurposing of existing compounds is a key route of action. In this hypothesis paper, we argue that the bisbenzylisoquinoline and calcium channel blocker tetrandrine, originally extracted from the plant Stephania tetrandra and utilized in traditional Chinese medicine, may have potential in the treatment of COVID-19 and should be further investigated. We collate and review evidence for tetrandrine's putative mechanism of action in viral infection, specifically its recently discovered antagonism of the two-pore channel 2 (TPC2). While tetrandrine's particular history of use provides a very limited pharmacological dataset, there is a suggestion from the available evidence that it could be effective at doses used in clinical practice. We suggest that further research to investigate this possibility should be conducted.


Subject(s)
Antiviral Agents/administration & dosage , Benzylisoquinolines/administration & dosage , Betacoronavirus/drug effects , Calcium Channel Blockers/administration & dosage , Calcium Channels/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Animals , Antiviral Agents/adverse effects , Benzylisoquinolines/adverse effects , Betacoronavirus/pathogenicity , Calcium Channel Blockers/adverse effects , Calcium Channels/metabolism , Coronavirus Infections/diagnosis , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Drug Interactions , Host-Pathogen Interactions , Humans , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , Signal Transduction
11.
J Gastrointestin Liver Dis ; 29(3): 473-475, 2020 Sep 09.
Article in English | MEDLINE | ID: covidwho-761169
13.
Rev Peru Med Exp Salud Publica ; 37(2): 302-311, 2020.
Article in Spanish | MEDLINE | ID: covidwho-749299

ABSTRACT

During the first weeks of 2020, cases of SARS-CoV-2 began to be reported outside of China, with a rapid increase in cases and deaths worldwide. SARS-CoV-2 is a positive single-stranded RNA virus, encased in a lipid bilayer derived from the host cell membrane and consists of four structural proteins (S, M, E and N), plus a haemagglutinin-sterase. The binding of the S protein to the ECA2 receptor allows the entry of the virus into the host cell and is a potential therapeutic target. 81% of patients develop mild symptoms, 14% have severe symptoms and 5% require intensive care management. Fever is the most frequent symptom, followed by cough and dyspnea. Most patients do not present leukocytosis, but they do present lymphopenia with sputum cultures that do not show other pathogens. In lung biopsies of severe patients, the most noticeable finding is diffuse alveolar damage. Radiologically, ground glass and alveolar patterns are observed; the lesions being predominantly basal, subpleural, and posterior, with a multifocal peripheral distribution, more affecting the right lower lobe. There is a marked inflammatory response, up to the cytokine storm, in which anti-inflammatory treatment with pulse therapy with methylprednisolone would be indicated. Although there are no large-scale studies regarding the use of chloroquine / hydroxychloroquine, due to the global situation, its use has been authorized for its anti-SARS-CoV-2 and anti-inflammatory effect, which can be potentiated with the use of azithromycin.


Subject(s)
Coronavirus Infections/epidemiology , Inflammation/virology , Pneumonia, Viral/epidemiology , Anti-Inflammatory Agents/administration & dosage , Antiviral Agents/administration & dosage , Chloroquine/administration & dosage , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Humans , Hydroxychloroquine/administration & dosage , Inflammation/drug therapy , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/physiopathology
14.
J Nanobiotechnology ; 18(1): 125, 2020 Sep 05.
Article in English | MEDLINE | ID: covidwho-745681

ABSTRACT

Incidents of viral outbreaks have increased at an alarming rate over the past decades. The most recent human coronavirus known as COVID-19 (SARS-CoV-2) has already spread around the world and shown R0 values from 2.2 to 2.68. However, the ratio between mortality and number of infections seems to be lower in this case in comparison to other human coronaviruses (such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)). These outbreaks have tested the limits of healthcare systems and have posed serious questions about management using conventional therapies and diagnostic tools. In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis and treatment of COVID-19 and other viral infections. In this review, we discuss the use of nanotechnology for COVID-19 virus management by the development of nano-based materials, such as disinfectants, personal protective equipment, diagnostic systems and nanocarrier systems, for treatments and vaccine development, as well as the challenges and drawbacks that need addressing.


Subject(s)
Betacoronavirus , Coronavirus Infections , Nanotechnology/methods , Pandemics , Pneumonia, Viral , Antiviral Agents/administration & dosage , Betacoronavirus/isolation & purification , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Disinfection/methods , Drug Carriers , Drug Delivery Systems , Humans , Nanostructures/administration & dosage , Personal Protective Equipment , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Viral Vaccines/administration & dosage
16.
Adv Healthc Mater ; 9(19): e2000979, 2020 10.
Article in English | MEDLINE | ID: covidwho-743611

ABSTRACT

Researchers, engineers, and medical doctors are made aware of the severity of the COVID-19 infection and act quickly against the coronavirus SARS-CoV-2 using a large variety of tools. In this review, a panoply of nanoscience and nanotechnology approaches show how these disciplines can help the medical, technical, and scientific communities to fight the pandemic, highlighting the development of nanomaterials for detection, sanitation, therapies, and vaccines. SARS-CoV-2, which can be regarded as a functional core-shell nanoparticle (NP), can interact with diverse materials in its vicinity and remains attached for variable times while preserving its bioactivity. These studies are critical for the appropriate use of controlled disinfection systems. Other nanotechnological approaches are also decisive for the development of improved novel testing and diagnosis kits of coronavirus that are urgently required. Therapeutics are based on nanotechnology strategies as well and focus on antiviral drug design and on new nanoarchitectured vaccines. A brief overview on patented work is presented that emphasizes nanotechnology applied to coronaviruses. Finally, some comments are made on patents of the initial technological responses to COVID-19 that have already been put in practice.


Subject(s)
Betacoronavirus , Coronavirus Infections , Nanotechnology/methods , Pandemics , Pneumonia, Viral , Antiviral Agents/administration & dosage , Betacoronavirus/chemistry , Betacoronavirus/ultrastructure , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Disinfection/methods , Humans , Nanoparticles/chemistry , Nanoparticles/ultrastructure , Nanostructures/chemistry , Nanotechnology/legislation & jurisprudence , Pandemics/prevention & control , Patents as Topic , Pneumonia, Viral/diagnosis , Pneumonia, Viral/prevention & control , Pneumonia, Viral/therapy , Surface Properties , Viral Vaccines/administration & dosage
17.
Rev Peru Med Exp Salud Publica ; 37(2): 320-326, 2020.
Article in Spanish | MEDLINE | ID: covidwho-740609

ABSTRACT

The Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) of the Seguro Social de Salud (EsSalud) has completed seven brief reports by means of rapid reviews of evidence regarding the potentially effective therapies against SARS-CoV-2 in order to provide current and relevant information for decision makers, clinicians, researchers and the academic community in Peru. The therapeutic agents evaluated were chloroquine/hydroxychloroquine, lopinavir/ritonavir, tocilizumab, oseltamivir, interferon, atazanavir and anti SARS-CoV-2 serum. Evidence identification included the review of PubMed and Cochrane Library electronic databases. Additionally, manual search was carried out on websites from groups dedicated to research and education on health, as well as in the main specialized societies or institutions, such as, the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC). Furthermore, in order to reduce publication bias, the websites: www.clinicaltrials.gov and http://apps.who.int/trialsearch were searched to identify in-progress or unpublished clinical trials. Finally, a "snowball" strategy was performed by reviewing the reference lists of the systematic reviews, primary studies and selected narrative reviews to identify relevant information. The latest review (March 27, 2020) showed that there is no evidence to recommend any medication for patients´ treatment with COVID-19. More evidence, preferably high-quality randomized clinical trials, is needed for decision-making against SARS-CoV-2.


Subject(s)
Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Antiviral Agents/administration & dosage , Coronavirus Infections/virology , Humans , Pandemics , Peru , Pneumonia, Viral/virology , Treatment Outcome
18.
Cien Saude Colet ; 25(9): 3413-3419, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-740430

ABSTRACT

When Covid-19 emerged in December last year, there was no vaccine nor was there specific effective treatment for this fast-spreading and life-threatening viral respiratory infection. Clinical trials were planned and are in progress to investigate whether drugs used for influenza, HIV and other viruses, and also anthelmintics (ivermectin, nitazoxanide, niclosamide), and antimalarials (chloroquine, hydroxychloroquine) showing antiviral activity in in vitro assays, are effective and safe for Covid-19. So far there is no convincing evidence that these antiviral and antiparasitic drugs are of any benefit for Covid-19. Notwithsanding the absence of evidence of clinical efficacy, these drugs are widely used outside of clinical trials (off label) for prophylaxis and treatment of this viral infection. The rationale behind the prescription of macrolide antibiotics (azithromycin) for Covid-19 is obscure as well. The widespread prescription and use of drugs of unproven efficacy and safety for Covid-19 is at odds with the rational use of medicines, a cornerstone principle of pharmacotherapy advanced by WHO in 1985. This irrational use of drugs is cause for concern because some of them are associated with serious heart disorders and deaths.


Subject(s)
Coronavirus Infections/drug therapy , Off-Label Use , Pneumonia, Viral/drug therapy , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Coronavirus Infections/virology , Humans , Inappropriate Prescribing/statistics & numerical data , Pandemics , Pneumonia, Viral/virology , Practice Patterns, Physicians'/standards
19.
Cien Saude Colet ; 25(9): 3517-3554, 2020 Sep.
Article in English, Portuguese | MEDLINE | ID: covidwho-740424

ABSTRACT

This work aimed to evaluate the effects of drug therapies for coronavirus infections. Rapid systematic review with search in the MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov and International Clinical Trials Registry Platform databases. Thirty-six studies evaluating alternative drugs against SARS, SARS-CoV-2 and MERS were included. Most of the included studies were conducted in China with an observational design for the treatment of COVID-19. The most studied treatments were with antimalarials and antivirals. In antimalarial, the meta-analysis of two studies with 180 participants did not identify the benefit of hydroxychloroquine concerning the negative viral load via real-time polymerase chain reaction, and the use of antivirals compared to standard care was similar regarding outcomes. The available scientific evidence is preliminary and of low methodological quality, which suggests caution when interpreting its results. Research that evaluates comparative efficacy in randomized, controlled clinical trials, with adequate follow-up time and with the methods properly disclosed and subject to scientific peer review is required. A periodic update of this review is recommended.


Subject(s)
Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Antimalarials/administration & dosage , Antiviral Agents/administration & dosage , Betacoronavirus/drug effects , Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Humans , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Pandemics , Pneumonia, Viral/virology , Randomized Controlled Trials as Topic , SARS Virus/drug effects , SARS Virus/isolation & purification , Severe Acute Respiratory Syndrome/virology
20.
Medicine (Baltimore) ; 99(35): e21810, 2020 Aug 28.
Article in English | MEDLINE | ID: covidwho-740205

ABSTRACT

RATIONALE: The clinical manifestations of the SARS-CoV-2 infection are mainly respiratory but the virus can cause a variety of symptoms. Dermatological findings are less well-characterized. Data is scarce on their timing, type and correlation with the immune response. PATIENT CONCERNS: We present the case of SARS-CoV-2 infection in a previously healthy woman who presented with respiratory symptoms and developed anosmia, diarrhea, and an erythematous maculo-papular rash on day 15 from symptom onset. DIAGNOSIS: The nasopharyngeal swab tested by real time PCR for COVID-19 was positive. We interpreted this as a viral exanthema likely caused by an immune response to SARS-CoV-2 nucleotides. INTERVENTIONS: She was treated with Hydroxychloroquine, Azithromycin and Lopinavir/Ritonavir, and the rash with topical corticosteroids. OUTCOMES: All symptoms resolved except for anosmia which persisted for 6 weeks. At the 4- and 6-weeks follow-up the IgG titers for SARS-CoV-2 were high. LESSONS: We must consider that SARS-CoV-2 has a multi-organ tropism. In our case, the SARS-CoV-2 infection had lung, nasopharyngeal, neurological, digestive, and skin manifestations. Identifying the different manifestations is useful for understanding the extent of SARS-CoV-2 infection. We not only present a rare manifestation but also suggest that cutaneous manifestations may correlate with immunity.


Subject(s)
Azithromycin/administration & dosage , Betacoronavirus , Coronavirus Infections , Exanthema , Glucocorticoids/administration & dosage , Hydroxychloroquine/administration & dosage , Lopinavir/administration & dosage , Pandemics , Pneumonia, Viral , Ritonavir/administration & dosage , Administration, Topical , Adult , Antiviral Agents/administration & dosage , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Drug Combinations , Exanthema/diagnosis , Exanthema/drug therapy , Exanthema/etiology , Exanthema/immunology , Female , Humans , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Symptom Assessment/methods , Treatment Outcome
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