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4.
Biomed Pharmacother ; 164: 114997, 2023 Aug.
Article in English | MEDLINE | ID: covidwho-20241696

ABSTRACT

The SARS-CoV-2 pandemic made evident that there are only a few drugs against coronavirus. Here we aimed to identify a cost-effective antiviral with broad spectrum activity and high safety profile. Starting from a list of 116 drug candidates, we used molecular modelling tools to rank the 44 most promising inhibitors. Next, we tested their efficacy as antivirals against α and ß coronaviruses, such as the HCoV-229E and SARS-CoV-2 variants. Four drugs, OSW-1, U18666A, hydroxypropyl-ß-cyclodextrin (HßCD) and phytol, showed in vitro antiviral activity against HCoV-229E and SARS-CoV-2. The mechanism of action of these compounds was studied by transmission electron microscopy and by fusion assays measuring SARS-CoV-2 pseudoviral entry into target cells. Entry was inhibited by HßCD and U18666A, yet only HßCD inhibited SARS-CoV-2 replication in the pulmonary Calu-3 cells. Compared to the other cyclodextrins, ß-cyclodextrins were the most potent inhibitors, which interfered with viral fusion via cholesterol depletion. ß-cyclodextrins also prevented infection in a human nasal epithelium model ex vivo and had a prophylactic effect in the nasal epithelium of hamsters in vivo. All accumulated data point to ß-cyclodextrins as promising broad-spectrum antivirals against different SARS-CoV-2 variants and distant alphacoronaviruses. Given the wide use of ß-cyclodextrins for drug encapsulation and their high safety profile in humans, our results support their clinical testing as prophylactic antivirals.


Subject(s)
COVID-19 , Dermatologic Agents , beta-Cyclodextrins , Humans , SARS-CoV-2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , beta-Cyclodextrins/pharmacology , beta-Cyclodextrins/therapeutic use
5.
BMJ Open ; 13(6): e070489, 2023 Jun 09.
Article in English | MEDLINE | ID: covidwho-20241289

ABSTRACT

OBJECTIVES: This study investigated remdesivir's clinical use to provide direct evidence of effectiveness for a low-middle income Asian setting. DESIGN: A one-to-one propensity score matching retrospective cohort study. SETTING: A tertiary hospital with COVID-19 treatment facilities in Vietnam. PARTICIPANTS: A total of 310 patients in standard of care (SoC) group were matched with 310 patients in SoC+remdesivir (SoC+R) group. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was time to critical progression, defined as all-cause mortality or critical illness. The secondary outcomes were length of oxygen therapy/ventilation and need for invasive mechanical ventilation. Outcome reports were presented as HR, OR or effect difference with 95% CI. RESULTS: Patients receiving remdesivir had a lower risk for mortality or critical illness (HR=0.68, 95% CI 0.47 to 0.96, p=0.030). Remdesivir was not associated with a shorter length of oxygen therapy/ventilation (effect difference -0.17 days, 95% CI -1.29 to 0.96, p=0.774). The need for invasive mechanical ventilation was lower in SoC+R group (OR=0.57, 95% CI 0.38 to 0.86, p=0.007). CONCLUSIONS: This study's results showing remdesivir's benefits in non-critical patients with COVID-19 may be extrapolated to other similar low-middle income countries, allowing more regimens for limited resource areas and reducing poor outcomes and equity gap worldwide.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , COVID-19 Drug Treatment , Critical Illness , Retrospective Studies , Oxygen , Antiviral Agents/therapeutic use
6.
Vopr Virusol ; 67(6): 506-515, 2023 02 07.
Article in Russian | MEDLINE | ID: covidwho-20240619

ABSTRACT

INTRODUCTION: The urgent problem of modern medicine is the fight against acute respiratory viral infections (ARVI). To combat ARVI, drugs of wide antiviral potency are needed, as well as immunomodulating drugs. Such antiviral and immunomodulatory effects has sodium deoxyribonucleate (DNA-Na) and its complex with iron (DNA-Na-Fe) developed on the basis of double-stranded DNA of natural origin. AIM OF THE STUDY: To assess antiviral and virucidal activity of DNA-Na and DNA-Na-Fe against viruses of different kingdoms and families. MATERIALS AND METHODS: Antiviral and virucidal activity of DNA-Na and DNA-Na-Fe was assessed in cell cultures infected with viruses. RESULTS AND DISCUSSION: DNA-Na and DNA-Na-Fe had antiviral activity against adenovirus at concentrations of 2501000 mcg/ml. Antiviral effect of both drugs was not detected in case of poliovirus. DNA-Na and DNA-Na-Fe had antiviral activity against coronavirus in all administration schemes. EC50 for DNA-Na ~ 2500 mcg/ml, for DNA-Na-Fe ~ 1000 mcg/ml. In cells treated with DNA-Na-Fe, secretion of following proinflammatory cytokines was detected: Interleukin (IL) 1, IL-2, IL-6, IL-18, interferon- (IFN-), IFN-, as well as anti-inflammatory cytokines: IL-4, IL-10, antagonist of IL-1 receptor. Evidently, DNA-Na and DNA-Na-Fe have antiviral effect, but mechanism of action does not seem to be associated with specific effect on viral replication. Presence of virucidal activity of drugs against representatives of Coronaviridae, Adenoviridae, Picornaviridae, Retroviridae, Herpesviridae in vitro test in range of 1.03.0 lg TCID50 was identified. CONCLUSION: Presence of simultaneous antiviral and virucidal activity of DNA-Na and DNA-Na-Fe against adeno- and coronaviruses shows their prospects for prevention and treatment of ARVI.


Subject(s)
Coronavirus Infections , Coronavirus , Herpesviridae , Respiratory Tract Infections , Virus Diseases , Humans , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Iron/pharmacology , Iron/therapeutic use , Sodium/pharmacology , Sodium/therapeutic use , Virus Diseases/drug therapy , Adenoviridae , Cytokines
7.
BMJ ; 381: 1001, 2023 05 10.
Article in English | MEDLINE | ID: covidwho-20240160
8.
Int J Mol Sci ; 24(11)2023 May 31.
Article in English | MEDLINE | ID: covidwho-20238922

ABSTRACT

Despite the fact that coronavirus disease 2019 (COVID-19) treatment and management are now considerably regulated, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still one of the leading causes of death in 2022. The availability of COVID-19 vaccines, FDA-approved antivirals, and monoclonal antibodies in low-income countries still poses an issue to be addressed. Natural products, particularly traditional Chinese medicines (TCMs) and medicinal plant extracts (or their active component), have challenged the dominance of drug repurposing and synthetic compound libraries in COVID-19 therapeutics. Their abundant resources and excellent antiviral performance make natural products a relatively cheap and readily available alternative for COVID-19 therapeutics. Here, we deliberately review the anti-SARS-CoV-2 mechanisms of the natural products, their potency (pharmacological profiles), and application strategies for COVID-19 intervention. In light of their advantages, this review is intended to acknowledge the potential of natural products as COVID-19 therapeutic candidates.


Subject(s)
Biological Products , COVID-19 , Humans , SARS-CoV-2 , COVID-19 Vaccines , Biological Products/pharmacology , Biological Products/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use
10.
Eur J Clin Microbiol Infect Dis ; 42(8): 951-958, 2023 Aug.
Article in English | MEDLINE | ID: covidwho-20238168

ABSTRACT

Detection of SARS-CoV-2 RNA in serum, viremia, has been linked to disease severity and outcome. The kinetics of viremia in patients receiving remdesivir has not been thoroughly studied and could help predict treatment response and outcome. We investigated the kinetics of SARS-CoV-2 viremia and factors associated with baseline viremia, viral clearance and 30-day mortality in patients receiving remdesivir. An observational study including 378 hospitalised patients (median age 67 years, 67% male) sampled with serum SARS-CoV-2 RT-PCR within ± 24 h of initiation of remdesivir treatment. Baseline viremia was present in 206 (54%) patients with a median Ct value of 35.3 (IQR = 33.3-37.1). In patients with baseline viremia, the estimated probability of viral clearance was 72% by day 5. Ct values decreased significantly during remdesivir treatment for viremic patients, indicating an increase in viral load. In total, 44 patients (12%) died within 30 days, and mortality was significantly associated with viremia at baseline (OR = 2.45, p = 0.01) and lack of viral clearance by day 5 (OR = 4.8, p = < 0.01). Viral clearance was not associated with any individual risk factor. Viremia appears to be a prognostic marker before and during remedesivir treatment. The resolution of viremia was similar to patients not receiving remdesivir in other studies, and the decrease in Ct values during treatment questions the antiviral capacity of remdesivir in vivo. Prospective studies are warranted to confirm our findings.


Subject(s)
COVID-19 , Humans , Male , Aged , Female , SARS-CoV-2 , Kinetics , Viremia/drug therapy , RNA, Viral , COVID-19 Drug Treatment , Antiviral Agents/therapeutic use
11.
J Med Virol ; 95(6): e28863, 2023 06.
Article in English | MEDLINE | ID: covidwho-20238042

ABSTRACT

The ongoing COVID-19 has not only caused millions of deaths worldwide, but it has also led to economic recession and the collapse of public health systems. The vaccines and antivirals developed in response to the pandemic have improved the situation markedly; however, the pandemic is still not under control with recurring surges. Thus, it is still necessary to develop therapeutic agents. In our previous studies, we designed and synthesized a series of novel 2-anilinoquinazolin-4(3H)-one derivatives, and demonstrated inhibitory activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and MERS-CoV in vitro. We then conducted in vivo studies using modified compounds that are suitable for oral administration. These compounds demonstrated no toxicity in rats and inhibited viral entry. Here, we investigated the in vivo efficacy of these drug candidates against SARS-CoV-2. Three candidate drugs, 7-chloro-2-((3,5-dichlorophenyl)amino)quinazolin-4(3H)-one (1), N-(7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-N-(3,5-dichlorophenyl)acetamide (2), and N-(7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-N-(3,5-difluorophenyl)acetamide (3) were administered orally to hACE2 transgenic mice at a dose of 100 mg/kg. All three drugs improved survival rate and reduced the viral load in the lungs. These results show that the derivatives possess in vivo antiviral efficacy similar to that of molnupiravir, which is currently being used to treat COVID-19. Overall, our data suggest that 2-anilinoquinazolin-4(3H)-one derivatives are promising as potential oral antiviral drug candidates against SARS-CoV-2 infection.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , SARS-CoV-2 , Animals , Humans , Mice , Rats , Acetamides , Angiotensin-Converting Enzyme 2/genetics , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/genetics , COVID-19/therapy , Disease Models, Animal , Mice, Transgenic , Quinazolines/pharmacology , Quinazolines/therapeutic use , SARS-CoV-2/genetics
12.
Int J Mol Sci ; 24(11)2023 May 31.
Article in English | MEDLINE | ID: covidwho-20237382

ABSTRACT

The ongoing COVID-19 pandemic highlights the urgent need for effective antiviral agents and vaccines. Drug repositioning, which involves modifying existing drugs, offers a promising approach for expediting the development of novel therapeutics. In this study, we developed a new drug, MDB-MDB-601a-NM, by modifying the existing drug nafamostat (NM) with the incorporation of glycyrrhizic acid (GA). We assessed the pharmacokinetic profiles of MDB-601a-NM and nafamostat in Sprague-Dawley rats, revealing rapid clearance of nafamostat and sustained drug concentration of MDB-601a-NM after subcutaneous administration. Single-dose toxicity studies showed potential toxicity and persistent swelling at the injection site with high-dose administration of MDB-601a-NM. Furthermore, we evaluated the efficacy of MDB-601a-NM in protecting against SARS-CoV-2 infection using the K18 hACE-2 transgenic mouse model. Mice treated with 60 mg/kg and 100 mg/kg of MDB-601a-NM exhibited improved protectivity in terms of weight loss and survival rates compared to the nafamostat-treated group. Histopathological analysis revealed dose-dependent improvements in histopathological changes and enhanced inhibitory efficacy in MDB-601a-NM-treated groups. Notably, no viral replication was detected in the brain tissue when mice were treated with 60 mg/kg and 100 mg/kg of MDB-601a-NM. Our developed MDB-601a-NM, a modified Nafamostat with glycyrrhizic acid, shows improved protectivity against SARS-CoV-2 infection. Its sustained drug concentration after subcutaneous administration and dose-dependent improvements makes it a promising therapeutic option.


Subject(s)
COVID-19 , SARS-CoV-2 , Rats , Humans , Animals , Mice , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Glycyrrhizic Acid/pharmacology , Glycyrrhizic Acid/therapeutic use , Pandemics , Disease Models, Animal , Rats, Sprague-Dawley
13.
J Antimicrob Chemother ; 78(7): 1644-1648, 2023 07 05.
Article in English | MEDLINE | ID: covidwho-20237061

ABSTRACT

OBJECTIVES: Immunocompromised patients have an increased risk of severe or prolonged COVID-19. Currently available drugs are registered to treat COVID-19 during the first 5 to 7 days after symptom onset. Data on the effectivity in immunocompromised patients with chronic non-resolving COVID-19 are urgently needed. Here, we report the outcome of patients treated with nirmatrelvir/ritonavir together with high-titer convalescent plasma (CP) in six immunocompromised patients with non-resolving COVID-19. METHODS: Immunocompromised patients with persisting COVID-19 (positive PCR with Ct values <30 for ≥20 days) received off-label therapy with nirmatrelvir/ritonavir. It was combined with CP containing BA.5 neutralizing titers of ≥1/640 whenever available. Follow-up was done by PCR and sequencing on nasopharyngeal swabs on a weekly basis until viral genome was undetectable consecutively. RESULTS: Five immunocompromised patients were treated with high-titer CP and 5 days of nirmatrelvir/ritonavir. One patient received nirmatrelvir/ritonavir monotherapy. Median duration of SARS-CoV-2 PCR positivity was 70 (range 20-231) days before nirmatrelvir/ritonavir treatment. In four patients receiving combination therapy, no viral genome of SARS-CoV-2 was detected on day 7 and 14 after treatment while the patient receiving nirmatrelvir/ritonavir monotherapy, the day 7 Ct value increased to 34 and viral genome was undetectable thereafter. Treatment was unsuccessful in one patient. In this patient, sequencing after nirmatrelvir/ritonavir treatment did not show protease gene mutations. CONCLUSIONS: In immunocompromised patients with non-resolving COVID-19, the combination of nirmatrelvir/ritonavir and CP may be an effective treatment. Larger prospective studies are needed to confirm these preliminary results and should compare different treatment durations.


Subject(s)
COVID-19 , Humans , COVID-19/therapy , Ritonavir/therapeutic use , SARS-CoV-2 , COVID-19 Drug Treatment , COVID-19 Serotherapy , Immunocompromised Host , Antiviral Agents/therapeutic use
14.
Aust J Gen Pract ; 52(6): 345-357, 2023 06.
Article in English | MEDLINE | ID: covidwho-20237045

ABSTRACT

BACKGROUND: Patient harm resulting from drug interactions between conventional and traditional or complementary medicines (CM) are avoidable. OBJECTIVE: To provide a clinical overview of a selection of CM interactions with drugs commonly used in Australian general practice or in the management of COVID-19. DISCUSSION: Many herb constituents are substrates for cytochrome P450 enzymes, and inducers and/or inhibitors of transporters such as P-glycoprotein. Hypericum perforatum (St John's Wort), Hydrastis canadensis (golden seal), Ginkgo biloba (ginkgo) and Allium sativum (garlic) are reported to interact with many drugs. Simultaneous administration of certain anti-viral drugs with zinc compounds and several herbs should also be avoided. Preventing and identifying unwanted CM-drug interactions in primary care requires vigilance, access to CM-drug interaction checkers and excellent communication skills. Potential risks from interactions should be balanced against the potential benefits of continuing the drug and/or CM and involve shared decision making.


Subject(s)
COVID-19 , Garlic , Humans , Pharmaceutical Preparations , Herb-Drug Interactions , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Australia , Primary Health Care
15.
RNA Biol ; 20(1): 272-280, 2023 01.
Article in English | MEDLINE | ID: covidwho-20236945

ABSTRACT

RNA interference (RNAi) offers an efficient way to repress genes of interest, and it is widely used in research settings. Clinical applications emerged more recently, with 5 approved siRNAs (the RNA guides of the RNAi effector complex) against human diseases. The development of siRNAs against the SARS-CoV-2 virus could therefore provide the basis of novel COVID-19 treatments, while being easily adaptable to future variants or to other, unrelated viruses. Because the biochemistry of RNAi is very precisely described, it is now possible to design siRNAs with high predicted activity and specificity using only computational tools. While previous siRNA design algorithms tended to rely on simplistic strategies (raising fully complementary siRNAs against targets of interest), our approach uses the most up-to-date mechanistic description of RNAi to allow mismatches at tolerable positions and to force them at beneficial positions, while optimizing siRNA duplex asymmetry. Our pipeline proposes 8 siRNAs against SARS-CoV-2, and ex vivo assessment confirms the high antiviral activity of 6 out of 8 siRNAs, also achieving excellent variant coverage (with several 3-siRNA combinations recognizing each correctly-sequenced variant as of September2022). Our approach is easily generalizable to other viruses as long as avariant genome database is available. With siRNA delivery procedures being currently improved, RNAi could therefore become an efficient and versatile antiviral therapeutic strategy.


Subject(s)
COVID-19 , Viruses , Humans , RNA, Small Interfering/genetics , SARS-CoV-2/genetics , COVID-19/genetics , RNA Interference , Viruses/genetics , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use
16.
Adv Ther ; 40(8): 3525-3542, 2023 Aug.
Article in English | MEDLINE | ID: covidwho-20236924

ABSTRACT

INTRODUCTION: During the recent coronavirus disease 2019 (COVID-19) pandemic, preferences for factors associated with vaccines have been evaluated. Three oral antiviral drugs have been approved in Japan for patients with mild-to-moderate I COVID-19 symptoms. Although preferences for the drugs may also depend on various factors, these have not been fully evaluated. METHODS: A conjoint analysis was performed based on an online survey in August 2022 to estimate the intangible costs of factors associated with oral antiviral drugs for COVID-19. Respondents were individuals aged 20-69 across Japan. The attributes included the company (Japanese/foreign) that developed the drug, formulation and size of the drug, frequency of administration per day, number of tablets/capsules per dose, number of days until no longer infectious to others, and out-of-pocket expenses. A logistic regression model was applied to estimate the utility of each level for each attribute. The intangible costs were calculated by comparing the utility to the out-of-pocket attribute. RESULTS: Responses were collected from 11,303 participants. The difference between levels was the largest for companies that developed a drug; the intangible costs were JPY 5390 higher for the foreign company than for the Japanese company. The next largest difference was in the number of days until one is no longer infectious. For the same formulation, the intangible cost was lower for small sizes than large sizes. For similar-sized tablets and capsules, the intangible cost was lower for tablets than capsules. These tendencies were similar regardless of COVID-19 infection history and the presence of risk factors for severe COVID-19 in the respondents. CONCLUSION: Intangible costs for factors associated with oral antiviral drugs among the Japanese population were estimated. The results may change as the number of people with a history of COVID-19 infection increases and significant progress is made regarding treatments.


Subject(s)
COVID-19 , Humans , Antiviral Agents/therapeutic use , Japan , Capsules , Health Expenditures , Ritonavir
18.
Mar Biotechnol (NY) ; 25(3): 415-427, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-20236354

ABSTRACT

COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which mainly affects the respiratory system. It has been declared as a "pandemic" in March 2020 by the World Health Organization due to the high spreading rate. SARS-CoV-2 binds with the angiotensin-converting enzyme 2 (ACE2) receptors on the cell surface which leads to the downregulation of ACE2 and upregulation of angiotensin-converting enzyme (ACE) receptors. The elevated level of cytokines and ACE receptors leads to the severity of SARS-CoV-2 infection. Due to the limited availability of vaccines and recurrent attacks of COVID-19 mainly in low-income countries, it is important to search for natural remedies to prevent or treat COVID-19 infection. Marine seaweeds are a rich source of bioactive compounds such as phlorotannins; fucoidan; carotenoids; omega-3 and omega-6 fatty acids; vitamins B12, D, and C; and minerals including zinc and selenium that exhibit antioxidant, antiviral, and anti-inflammatory activities. Furthermore, bioactive compounds present in marine seaweeds have the ability to inhibit ACEs by inducing ACE2 which exhibits anti-inflammatory effects in COVID-19. Correspondingly, soluble dietary fibers present in seaweeds are served as prebiotics by generating short-chain fatty acids through fermentation. Hence, seaweeds can be utilized to reduce the gastrointestinal infections associated with SARS-CoV-2 infection.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use
19.
Int J Mol Sci ; 24(10)2023 May 16.
Article in English | MEDLINE | ID: covidwho-20236306

ABSTRACT

Since the beginning of the COVID-19 pandemic, the scientific community has focused on prophylactic vaccine development. In parallel, the experience of the pharmacotherapy of this disease has increased. Due to the declining protective capacity of vaccines against new strains, as well as increased knowledge about the structure and biology of the pathogen, control of the disease has shifted to the focus of antiviral drug development over the past year. Clinical data on safety and efficacy of antivirals acting at various stages of the virus life cycle has been published. In this review, we summarize mechanisms and clinical efficacy of antiviral therapy of COVID-19 with drugs based on plasma of convalescents, monoclonal antibodies, interferons, fusion inhibitors, nucleoside analogs, and protease inhibitors. The current status of the drugs described is also summarized in relation to the official clinical guidelines for the treatment of COVID-19. In addition, here we describe innovative drugs whose antiviral effect is provided by antisense oligonucleotides targeting the SARS-CoV-2 genome. Analysis of laboratory and clinical data suggests that current antivirals successfully combat broad spectra of emerging strains of SARS-CoV-2 providing reliable defense against COVID-19.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Pandemics/prevention & control , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Interferons/therapeutic use
20.
J Antimicrob Chemother ; 78(7): 1683-1688, 2023 07 05.
Article in English | MEDLINE | ID: covidwho-20234435

ABSTRACT

OBJECTIVES: To assess and compare subsequent hospital admissions within 30 days for patients after receiving a prescription for either oral nirmatrelvir/ritonavir or oral molnupiravir. METHODS: We conducted a retrospective review of 3207 high-risk, non-hospitalized adult COVID-19 patients who received a prescription for molnupiravir (n = 209) or nirmatrelvir/ritonavir (n = 2998) at an academic medical centre in New York City from April to December 2022. Variables including age, vaccination status, high-risk conditions and demographic factors were pulled from the electronic medical record. We used multivariable logistic regression to adjust for potential confounding variables. RESULTS: All-cause 30 day hospitalization was not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (1.4% versus 1.9%, P value = 0.55). The association between COVID-related hospitalization and medication was also not significant (0.7%versus 0.5%, P value = 0.99). Patients who received molnupiravir were more likely to have more underlying high-risk conditions. After adjusting for potential confounders, the odds of all-cause hospitalizations were not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (OR = 1.16, 95% CI: 0.4-3.3, P value = 0.79). CONCLUSIONS: These data provide additional evidence to support molnupiravir as a suitable alternative when other COVID-19 antivirals cannot be given.


Subject(s)
COVID-19 , Outpatients , Adult , Humans , Ritonavir/therapeutic use , COVID-19 Drug Treatment , Prescriptions , Antiviral Agents/therapeutic use
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