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1.
Medicine (Baltimore) ; 100(19): e25917, 2021 May 14.
Article in English | MEDLINE | ID: covidwho-2191007

ABSTRACT

ABSTRACT: The coronavirus disease (COVID-19) has become a global pandemic. Invasive mechanical ventilation is recommended for the management of patients with COVID-19 who have severe respiratory symptoms. However, various complications can develop after its use. The efficient and appropriate management of patients requires the identification of factors associated with an aggravation of COVID-19 respiratory symptoms to a degree where invasive mechanical ventilation becomes necessary, thereby enabling clinicians to prevent such ventilation. This retrospective study included 138 inpatients with COVID-19 at a tertiary hospital. We evaluated the differences in the demographic and clinical data between 27 patients who required invasive mechanical ventilation and 111 patients who did not. Multivariate logistic regression analysis indicated that the duration of fever, national early warning score (NEWS), and lactate dehydrogenase (LDH) levels on admission were significantly associated with invasive mechanical ventilation in this cohort. The optimal cut-off values were: fever duration ≥1 day (sensitivity 100.0%, specificity 54.95%), NEWS ≥7 (sensitivity 72.73%, specificity 92.52%), and LDH >810 mg/dL (sensitivity 56.0%, specificity 90.29%). These findings can assist in the early identification of patients who will require invasive mechanical ventilation. Further studies in larger patient populations are recommended to validate our findings.


Subject(s)
COVID-19/physiopathology , Early Warning Score , Respiration, Artificial/statistics & numerical data , Adult , Age Factors , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Female , Fever/physiopathology , Humans , Hydroxychloroquine/therapeutic use , L-Lactate Dehydrogenase/blood , Logistic Models , Male , Middle Aged , Pandemics , Real-Time Polymerase Chain Reaction , Republic of Korea , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2 , Sex Factors , Socioeconomic Factors , Tertiary Care Centers , Young Adult
3.
Rev. bras. promoç. saúde (Impr.) ; 34(1): 1-10, 17/02/2021.
Article in English, Portuguese | WHO COVID, LILACS (Americas) | ID: covidwho-2202502

ABSTRACT

Objetivo: Investigar a opinião de médicos brasileiros sobre o tratamento precoce da COVID-19 com hidroxicloroquina/ cloroquina e azitromicina em pacientes com suspeita clínica e sobre o tratamento com corticoterapia na fase inflamatória da doença. Métodos: Trata-se de uma pesquisa de opinião, com amostragem por conveniência, com médicos atuantes no Brasil. A coleta dos dados ocorreu no período de 26 de maio a 8 de junho de 2020 (13 dias), por meio de um formulário Google, disponibilizado publicamente nas redes sociais e aplicativos de comunicação. Realizou-se uma análise descritiva dos dados, teste de independência, teste T Student e modelo de regressão logística com análise multivariada. Resultados: A pesquisa contou com 1.020 médicos participantes, com média de 21,9 anos de formado. 72,4% dos participantes apresentaram-se a favor do tratamento precoce com hidroxicloroquina/cloroquina e azitromicina e 89,7% dos médicos apresentaram-se favoráveis ao uso da corticoterapia para o tratamento da fase inflamatória da COVID-19. Constatou-se também que participantes com maior idade, com residência médica, atuantes nas regiões Nordeste e Norte possuíam mais chances de serem favoráveis aos tratamentos. Por outro lado, profissionais especialistas em medicina intensiva, infectologia e pneumologia, além de atuantes nas unidades de terapia intensiva, mostraram-se mais desfavoráveis. Conclusão: A maioria dos médicos investigados nesta pesquisa de opinião mostrou-se a favor do tratamento precoce apresentado e do uso da corticoterapia no tratamento da COVID-19. Já os especialistas em medicina intensiva, infectologia e pneumologia e profissionais atuantes nas Unidades de Terapia Intensiva mostraram-se mais desfavoráveis.


Objective: To investigate the opinion of Brazilian physicians on the early treatment of COVID-19 with hydroxychloroquine/ chloroquine and azithromycin in patients with clinical suspicion and on the treatment with corticosteroid therapy in the inflammatory stage of the disease. Methods: This is an opinion survey conducted with a convenient sample of physicians working in Brazil. Data were collected from May 26 to June 8, 2020 (13 days) through Google forms made publicly available on social media and chat applications. Data underwent descriptive analysis, independence test, Student t-test, and a logistic regression model using multivariate analysis. Results: The survey included 1020 physicians with a mean of 21.9 years since graduation. 72.4% of the participants were in favor of early treatment with hydroxychloroquine/chloroquine and azithromycin and 89.7% of the physicians were in favor of using corticosteroid therapy to treat the inflammatory stage of COVID-19. We also observed that older participants, those who completed medical residency, and those working in the Northeast and North regions were more likely to be in favor of the treatments. On the other hand, professionals specialized in intensive care medicine, infectious diseases and pneumology and working in intensive care units were more opposed. Conclusion: Most physicians in this opinion survey were in favor of the early treatment presented and the use of corticosteroid therapy in the treatment of COVID-19. But specialists in intensive care medicine, infectious diseases and pulmonology, and professionals working in Intensive Care Units were more opposed to them.


Objetivo: Investigar la opinión de médicos brasileños sobre el tratamiento precoz de la COVID-19 con la hidroxicloroquina/ cloroquina y la azitromicina en pacientes con sospecha clínica y bajo el tratamiento de corticoterapia en la fase inflamatoria de la enfermedad. Métodos: Se trata de una investigación de opinión con la muestra de conveniencia realizada con médicos de Brasil. La recogida de datos se dio en el periodo entre 26 de mayo y 8 de junio de 2020 (13 días) a través de un formulario Google que ha estado disponible públicamente en las redes sociales y los aplicativos de comunicación. Se realizó un análisis descriptivo de los datos, la prueba de independencia, la prueba T Student y el modelo de regresión logística con el análisis multivariado. Resultados: La investigación tuvo 1.020 médicos participantes, con la media de 21,9 años de término del grado. El 72,4% de los participantes se presentaron a favor del tratamiento precoz con la hidroxicloroquina/cloroquina y la azitromicina y el 89,7% de los médicos se presentaron favorables a la utilización de la corticoterapia para el tratamiento de la fase inflamatoria de la COVID-19. Se constató también que los participantes de más edad, con el curso de residencia medica y que eran de las regiones Noreste y Norte del país eran más favorables a los tratamientos. Los profesionales especialistas de la medicina intensiva, la infectologia y la neumología, además de actuaren en las unidades de cuidados intensivos parecieron más desfavorables. Conclusión: La mayoría de los médicos investigados de esa investigación de opinión se mostró favorable al tratamiento precoz presentado y a la utilización de la corticoterapia para el tratamiento de la COVID-19. Los especialistas de la medicina intensiva, la infectología y la neumología y los profesionales de las Unidades de Cuidados Intensivos se presentaron más desfavorables a los tratamientos.


Subject(s)
Adrenal Cortex Hormones , Coronavirus Infections , Drug Therapy , Hydroxychloroquine
4.
Lancet ; 399(10339): 1941-1953, 2022 05 21.
Article in English | MEDLINE | ID: covidwho-2159958

ABSTRACT

BACKGROUND: The Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-ß1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date. METHODS: Solidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-ß1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948. FINDINGS: Between March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82-1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89-1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76-0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46-1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76-0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77-1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75-0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings. INTERPRETATION: Remdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both). FUNDING: WHO.


Subject(s)
Antiviral Agents , COVID-19 , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adult , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Hydroxychloroquine/therapeutic use , Interferon beta-1a/therapeutic use , Lopinavir/therapeutic use , Oxygen/administration & dosage , Randomized Controlled Trials as Topic , Treatment Outcome , World Health Organization
6.
Ther Drug Monit ; 42(3): 360-368, 2020 06.
Article in English | MEDLINE | ID: covidwho-2152206

ABSTRACT

BACKGROUND: COVID-19 is a novel infectious disease caused by the severe acute respiratory distress (SARS)-coronavirus-2 (SARS-CoV-2). Several therapeutic options are currently emerging but none with universal consensus or proven efficacy. Solid organ transplant recipients are perceived to be at increased risk of severe COVID-19 because of their immunosuppressed conditions due to chronic use of immunosuppressive drugs (ISDs). It is therefore likely that solid organ transplant recipients will be treated with these experimental antivirals. METHODS: This article is not intended to provide a systematic literature review on investigational treatments tested against COVID-19; rather, the authors aim to provide recommendations for therapeutic drug monitoring of ISDs in transplant recipients infected with SARS-CoV-2 based on a review of existing data in the literature. RESULTS: Management of drug-drug interactions between investigational anti-SARS-CoV-2 drugs and immunosuppressants is a complex task for the clinician. Adequate immunosuppression is necessary to prevent graft rejection while, if critically ill, the patient may benefit from pharmacotherapeutic interventions directed at limiting SARS-CoV-2 viral replication. Maintaining ISD concentrations within the desired therapeutic range requires a highly individualized approach that is complicated by the pandemic context and lack of hindsight. CONCLUSIONS: With this article, the authors inform the clinician about the potential interactions of experimental COVID-19 treatments with ISDs used in transplantation. Recommendations regarding therapeutic drug monitoring and dose adjustments in the context of COVID-19 are provided.


Subject(s)
Antiviral Agents/adverse effects , Coronavirus Infections/drug therapy , Drug Monitoring , Immunosuppressive Agents/adverse effects , Pneumonia, Viral/drug therapy , Transplant Recipients , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antibodies, Monoclonal, Humanized , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , Drug Interactions , Glucocorticoids , Humans , Hydroxychloroquine , Immunosuppressive Agents/therapeutic use , Pandemics , Protease Inhibitors , SARS-CoV-2
7.
PLoS One ; 17(11): e0277807, 2022.
Article in English | MEDLINE | ID: covidwho-2140664

ABSTRACT

BACKGROUND: The emergence of COVID-19 overwhelmed tuberculosis (TB) prevention and control, resulting in a decrease in TB detection rate and an increase in TB deaths. Furthermore, the temporary immunosuppressive effects, lung inflammation, and the corticosteroids used to treat COVID-19, may play a direct role in immunosuppression, leading to reactivation of either previous infection or latent TB or the development of new TB. Thus, the aim of this study was to review TB incidence in individuals who recovered from COVID-19. METHODS: We conducted a systematic search of available databases for previously published studies that reported TB in COVID-19 survivors. The PRISMA checklist was used to guide the review, and the JBI checklist was used to evaluate the study's quality. The descriptive data were summarized. RESULTS: Data were extracted from 21 studies conducted in 13 countries having 33 cases. The median age was 44 years (range; 13.5-80), and more than half (18, 54.5%) were males. Twelve patients immigrated from TB endemic settings. All 17 patients assessed for HIV were seronegative, and all 11 patients assessed for BCG vaccination status were vaccinated. The majority (20, 69%) of patients had some type of comorbidity with diabetes (12/29) and hypertension (9/29) being the most common. Four patients (30.77%) had a history of TB. Corticosteroids were used to treat COVID-19 in 62.5% (10) of individuals. Dexamethasone, remdesivir, azithromycin, hydroxychloroquine, and enoxaparin were the most commonly used drugs to treat COVID-19. The most common TB symptoms were fever, cough, weight loss, dyspnea, and fatigue. Twenty, eleven, and two patients developed pulmonary, extrapulmonary, and disseminated/miliary TB respectively. It may take up to seven months after COVID-19 recovery to develop tuberculosis. Data on the final treatment outcome was found for 24 patients, and five patients died during the anti-TB treatment period. CONCLUSION: Tuberculosis after recovering from COVID-19 is becoming more common, potentially leading to a TB outbreak in the post-COVID-19 era. The immunosuppressive nature of the disease and its treatment modalities may contribute to post COVID-19 TB. Thus, we recommend a further study with a large sample size. Furthermore, we recommend feasibility studies to assess and treat latent TB in COVID-19 patients residing in TB endemic counties since treatment of latent TB is done only in TB non-endemic countries.


Subject(s)
COVID-19 , Latent Tuberculosis , Tuberculosis, Miliary , Male , Humans , Adult , Female , COVID-19/epidemiology , Hydroxychloroquine , Azithromycin
9.
Environ Sci Pollut Res Int ; 28(30): 40431-40444, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-2113716

ABSTRACT

The outbreak of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the entire world with its infectious spread and mortality rate. The severe cases of coronavirus disease 2019 (COVID-19) are characterized by hypoxia and acute respiratory distress syndrome. In the absence of any specific treatment, just the preventive and supportive care options are available. Therefore, much focus is given to assess the available therapeutic options not only to avoid acute respiratory failure and hypoxia but also to reduce the viral load to control the severity of the disease. The antimalarial drug hydroxychloroquine (HCQ) is among the much-discussed drugs for the treatment and management of COVID-19 patients. This article reviews the therapeutic potential of HCQ in the treatment of COVID-19 based on the available in vitro and clinical evidence, current status of registered HCQ-based clinical trials investigating therapeutic options for COVID-19, and environmental implications of HCQ.


Subject(s)
COVID-19 , Coronavirus Infections , Antiviral Agents , COVID-19/drug therapy , Coronavirus Infections/drug therapy , Humans , Hydroxychloroquine/therapeutic use , SARS-CoV-2
15.
Turk J Ophthalmol ; 52(5): 324-330, 2022 10 28.
Article in English | MEDLINE | ID: covidwho-2100078

ABSTRACT

Objectives: Retinal vascular complications have been described in patients with coronavirus disease 2019 (COVID-19). This study aimed to analyze retinal microvascular changes and their correlations with clinical findings. Materials and Methods: This case-controlled study was conducted in a university hospital. The right eyes of 52 otherwise healthy patients recovered from COVID-19 and 42 healthy controls were examined with optical coherence tomography angiography. Mann-Whitney U test was used to compare vessel density (VD) and foveal avascular zone (FAZ) parameters. Associations with treatment choices, pneumonia, and laboratory findings were analyzed. Results: Twenty-nine patients (56%) and 18 healthy controls (43%) were men. Mean age of the COVID-19 group was 39.00±13.04 years. Twenty-two patients had pneumonia, 18 (35%) received hydroxychloroquine (HCQ), 17 (33%) received HCQ plus low-molecular-weight heparin (LMWH), and 10 (19%) received favipiravir. The patient group had lower parafoveal VD in the superficial capillary plexus (SCP) and lower parafoveal VD and perifoveal VD in the deep capillary plexus (DCP) than controls (p=0.003, p=0.004, p=0.001). FAZ area did not differ significantly (p=0.953). Perifoveal VD in the DCP was also significantly lower in the HCQ+LMWH group than the HCQ group (p=0.020) and in the presence of pneumonia (p=0.040). C-reactive protein (CRP) and ferritin levels were negatively correlated with perifoveal VD in the DCP (r=-0.445, p=0.023; r=-0.451, p=0.040). Ferritin was also negatively correlated with parafoveal VD in the SCP (r=-0.532, p=0.013). Conclusion: Parafoveal and perifoveal VD was found to be lower in the COVID-19 group. Presence of pneumonia, need for LMWH prophylaxis, and levels of CRP and ferritin were found to be negatively associated with retinal VD. Large-scale studies are needed to evaluate the clinical importance.


Subject(s)
COVID-19 , Tomography, Optical Coherence , Male , Humans , Adult , Middle Aged , Female , Tomography, Optical Coherence/methods , Fluorescein Angiography/methods , Fovea Centralis , COVID-19/complications , Heparin, Low-Molecular-Weight , Hydroxychloroquine/therapeutic use , Ferritins
16.
Trials ; 23(1): 273, 2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-2098437

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a heterogeneous outcome in individuals from remaining asymptomatic to death. In a majority of cases, mild symptoms are present that do not require hospitalization and can be successfully treated in the outpatient setting, though symptoms may persist for a long duration. We hypothesize that drugs suitable for decentralized study in outpatients will have efficacy among infected outpatients METHODS: The TREAT NOW platform is designed to accommodate testing multiple agents with the ability to incorporate new agents in the future. TREAT NOW is an adaptive, blinded, multi-center, placebo-controlled superiority randomized clinical trial which started with two active therapies (hydroxychloroquine and lopinavir/ritonavir) and placebo, with the hydroxychloroquine arm dropped shortly after enrollment began due to external evidence. Each arm has a target enrollment of 300 participants who will be randomly assigned in an equal allocation to receive either an active therapy or placebo twice daily for 14 days with daily electronic surveys collected over days 1 through 16 and on day 29 to evaluate symptoms and a modified COVID-19 ordinal outcome scale. Participants are enrolled remotely by telephone and consented with a digital interface, study drug is overnight mailed to study participants, and data collection occurs electronically without in-person interactions. DISCUSSION: If effective treatments for COVID-19 can be identified for individuals in the outpatient setting before they advance to severe disease, it will prevent progression to more severe disease, reduce the need for hospitalization, and shorten the duration of symptoms. The novel decentralized, "no touch" approach used by the TREAT NOW platform has distinction advantages over traditional in-person trials to reach broader populations and perform study procedures in a pragmatic yet rigorous manner. TRIAL REGISTRATION: ClinicalTrials.gov NCT04372628. Registered on April 30, 2020. First posted on May 4, 2020.


Subject(s)
COVID-19 , Antiviral Agents/adverse effects , COVID-19/drug therapy , Hospitalization , Humans , Hydroxychloroquine/adverse effects , Outpatients , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
19.
Med Trop Sante Int ; 2(3)2022 09 30.
Article in French | MEDLINE | ID: covidwho-2091754

ABSTRACT

The authors report on their experience of managing COVID-19 at the Regional hospital of Lambaréné, capital of the Moyen-Ogooué province in central Gabon.The infectious diseases department was the referral and follow-up site for COVID-19, with an intervention team to follow up outpatients. The department followed national recommendations for overall management with mild cases receiving vitamin therapy, moderate cases hydroxychloroquine and azithromycin, severe cases azithromycin, another antibiotic and oxygen.Over 1 year in 2020, 495 cases (RT-PCR +) were recruited; 92 were hospitalized (comorbidities or severe signs). The average duration of hospitalization was 21 +/- 3 days.These 92 cases are composed of 38 mild cases all cured by symptomatic treatments; 32 moderate cases treated and cured; and 26 severe cases treated with azithromycin plus a second antibiotic with 24 cured without sequelae, 1 with sequelae and 1 death (co-infected with HIV).The 399 cases followed up in the outpatient department all recovered and are distributed as follows: 199 asymptomatic and without co-morbidity, untreated; 102 with mild signs under vitamins; 98 with moderate signs treated with azithromycin + HCHQ + vitamins.In total, all 495 cases recovered without sequelae except for 1 patient with sequelae and 1 death; 199 received no treatment. However, 6 deaths occurred before the diagnosis was made. This strategy encountered difficulties in terms of overloading the carers and feeding the patients.


Subject(s)
COVID-19 , Hydroxychloroquine , Humans , Hydroxychloroquine/therapeutic use , SARS-CoV-2 , Azithromycin/therapeutic use , Gabon , Treatment Outcome , Hospitals , Anti-Bacterial Agents/therapeutic use , Vitamins , Oxygen
20.
Med J Aust ; 217 Suppl 9: S7-S13, 2022 Nov 06.
Article in English | MEDLINE | ID: covidwho-2090766

ABSTRACT

Early treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can prevent hospitalisation and death in patients with coronavirus disease 2019 (COVID-19) who have one or more risk factors for serious COVID-19 progression. While early treatment presents a range of logistical challenges, clinicians are nevertheless aided by a growing number of approved medications for early treatment of COVID-19. Medications include drugs that inhibit SARS-CoV-2 viral replication, anti-SARS-CoV-2 monoclonal antibody formulations that provide passive immunisation, and immunomodulatory drugs that suppress the body's inflammatory response. Several drugs with different modes of action are approved in Australia for early treatment of COVID-19, including nirmatrelvir plus ritonavir, molnupiravir, and monoclonal antibody formulations. Although these drugs are recommended, clinicians are encouraged to remain up to date on current indications, contraindications and the clinical efficacy of these drugs against SARS-CoV-2 variants currently circulating in communities. Other treatments, including hydroxychloroquine, ivermectin and dietary supplements, have been popularised but are not recommended for early treatment of COVID-19. As new drugs and new data on use of existing approved drugs become available, clinicians face a growing challenge in determining the optimal treatments from the array of options. As it stands, early treatment of COVID-19 needs to be individualised depending on age, pregnancy status, existing medications, and renal and liver disease status. Future treatments in development might have roles in patients with lower risk profiles and in reducing transmission as we learn to live with SARS-CoV-2.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Humans , Pregnancy , Female , SARS-CoV-2 , COVID-19/drug therapy , Hydroxychloroquine/therapeutic use , Antibodies, Viral , Antibodies, Monoclonal , Antiviral Agents/therapeutic use
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