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1.
Viruses ; 13(1)2020 12 30.
Article in English | MEDLINE | ID: covidwho-1073492

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), a lung disease that may progress to systemic organ involvement and in some cases, death. The identification of the earliest predictors of progressive lung disease would allow for therapeutic intervention in those cases. In an earlier clinical study, individuals with moderate COVID-19 were treated with either arbidol (ARB) or inhaled interferon (IFN)-α2b +/-ARB. IFN treatment resulted in accelerated viral clearance from the upper airways and in a reduction in the circulating levels of the inflammatory biomarkers IL-6 and C-reactive protein (CRP). We have extended the analysis of this study cohort to determine whether IFN treatment had a direct effect on virus-induced lung abnormalities and also to ascertain whether any clinical or immune parameters are associated with worsening of lung abnormalities. Evidence is provided that IFN-α2b treatment limits the development of lung abnormalities associated with COVID-19, as assessed by CT images. Clinical predictors associated with worsening of lung abnormalities include low CD8+ T cell numbers, low levels of circulating albumin, high numbers of platelets, and higher levels of circulating interleukin (IL)-10, IL-6, and C-reactive protein (CRP). Notably, in this study cohort, IFN treatment resulted in a higher percentage of CD8+ T cells, lower tumor necrosis factor (TNF)-α levels and, as reported earlier, lower IL-6 levels. Independent of treatment, age and circulating levels of albumin and CRP emerged as the strongest predictors of the severity of lung abnormalities.


Subject(s)
Antiviral Agents/therapeutic use , Interferon-alpha/therapeutic use , Lung/abnormalities , Administration, Inhalation , Antiviral Agents/administration & dosage , Biomarkers/blood , C-Reactive Protein , CD8-Positive T-Lymphocytes , China , Cohort Studies , Cytokines/immunology , Drug Therapy, Combination , Humans , Indoles/administration & dosage , Indoles/therapeutic use , Interferon-alpha/administration & dosage , Interleukin-10 , Interleukin-6 , Lung/diagnostic imaging , Lung/pathology , /drug effects
3.
J Interferon Cytokine Res ; 40(9): 438-442, 2020 09.
Article in English | MEDLINE | ID: covidwho-787046

ABSTRACT

A prospective observational study was conducted for assessing the therapeutic efficacy of interferon (IFN)-α2b in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first month after the coronavirus disease 2019 (COVID-19) outbreak began in Cuba. From March 11th to April 14th, 814 patients were confirmed SARS-CoV-2 positive in Cuba. Seven hundred sixty-one (93.4%) were treated with a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular administration of IFN-α2b (Heberon® Alpha R, Center for Genetic Engineering and Biotechnology, Havana, Cuba), 3 times per week, for 2 weeks. Fifty-three patients received the approved COVID protocol without IFN treatment. The proportion of patients discharged from hospital (without clinical and radiological symptoms and nondetectable virus by real-time polymerase chain reaction) was higher in the IFN-treated compared with the non-IFN treated group (95.4% vs. 26.1%, P < 0.01). The case fatality rate (CFR) for all patients was 2.95%, and for those patients who received IFN-α2b the CFR was reduced to 0.92. Intensive care was required for 82 patients (10.1%), 42 (5.5%) had been treated with IFN. This report provides preliminary evidence for the therapeutic effectiveness of IFN-α2b for COVID-19 and suggests that the use of Heberon Alpha R may contribute to complete recovery of patients.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Interferon-alpha/therapeutic use , Pneumonia, Viral/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Chloroquine/therapeutic use , Coronavirus Infections/mortality , Cuba , Drug Therapy, Combination , Female , Humans , Infant , Lopinavir/therapeutic use , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Prospective Studies , Ritonavir/therapeutic use , Young Adult
4.
Nature ; 586(7830): 560-566, 2020 10.
Article in English | MEDLINE | ID: covidwho-733515

ABSTRACT

Coronaviruses are prone to transmission to new host species, as recently demonstrated by the spread to humans of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic1. Small animal models that recapitulate SARS-CoV-2 disease are needed urgently for rapid evaluation of medical countermeasures2,3. SARS-CoV-2 cannot infect wild-type laboratory mice owing to inefficient interactions between the viral spike protein and the mouse orthologue of the human receptor, angiotensin-converting enzyme 2 (ACE2)4. Here we used reverse genetics5 to remodel the interaction between SARS-CoV-2 spike protein and mouse ACE2 and designed mouse-adapted SARS-CoV-2 (SARS-CoV-2 MA), a recombinant virus that can use mouse ACE2 for entry into cells. SARS-CoV-2 MA was able to replicate in the upper and lower airways of both young adult and aged BALB/c mice. SARS-CoV-2 MA caused more severe disease in aged mice, and exhibited more clinically relevant phenotypes than those seen in Hfh4-ACE2 transgenic mice, which express human ACE2 under the control of the Hfh4 (also known as Foxj1) promoter. We demonstrate the utility of this model using vaccine-challenge studies in immune-competent mice with native expression of mouse ACE2. Finally, we show that the clinical candidate interferon-λ1a (IFN-λ1a) potently inhibits SARS-CoV-2 replication in primary human airway epithelial cells in vitro-both prophylactic and therapeutic administration of IFN-λ1a diminished SARS-CoV-2 replication in mice. In summary, the mouse-adapted SARS-CoV-2 MA model demonstrates age-related disease pathogenesis and supports the clinical use of pegylated IFN-λ1a as a treatment for human COVID-196.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/prevention & control , Disease Models, Animal , Interferons/pharmacology , Interferons/therapeutic use , Interleukins/pharmacology , Interleukins/therapeutic use , Pandemics/prevention & control , Pneumonia, Viral/drug therapy , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , Aging/immunology , Animals , Betacoronavirus/drug effects , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Female , Forkhead Transcription Factors/genetics , Humans , Interferon-alpha/administration & dosage , Interferon-alpha/pharmacology , Interferon-alpha/therapeutic use , Interferons/administration & dosage , Interleukins/administration & dosage , Male , Mice , Mice, Inbred BALB C , Mice, Transgenic , Models, Molecular , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/genetics , Pneumonia, Viral/immunology , Receptors, Virus/genetics , Receptors, Virus/metabolism
6.
Eur J Clin Microbiol Infect Dis ; 39(12): 2211-2223, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-696275

ABSTRACT

Since the outbreak of novel coronavirus infection pneumonia in Wuhan City, China, in late 2019, such cases have been gradually reported in other parts of China and abroad. Children have become susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of their immature immune function. As the outbreak has progressed, more cases of novel coronavirus infection/pneumonia in children have been reported. Compared with adults, the impact of SARS-CoV-2 infection in children is less severe, with a lower incidence and susceptibility in children, which results in fewer children being tested, thereby underestimating the actual number of infections. Therefore, strengthening the diagnosis of the disease is particularly important for children, and early and clear diagnosis can determine treatment strategies and reduce the harm caused by the disease to children. According to the Novel Coronavirus Infection Pneumonia Diagnosis and Treatment Standards (trial version 7) issued by National Health Committee and the latest diagnosis and treatment strategies for novel coronavirus infection pneumonia in children, this review summarizes current strategies on diagnosis and treatment of SARS-CoV-2 infection in children.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/genetics , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , RNA, Viral/blood , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Asymptomatic Diseases , Betacoronavirus/pathogenicity , Biomarkers/blood , Child , Coronavirus Infections/transmission , Coronavirus Infections/virology , Cough/diagnosis , Drug Combinations , Early Diagnosis , Fever/diagnosis , Humans , Hydroxychloroquine/therapeutic use , Interferon-alpha/therapeutic use , Lopinavir/therapeutic use , Pandemics , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Practice Guidelines as Topic , RNA, Viral/genetics , Ribavirin/therapeutic use , Ritonavir/therapeutic use , Severity of Illness Index , Tomography, X-Ray Computed
7.
Immun Inflamm Dis ; 8(4): 506-511, 2020 12.
Article in English | MEDLINE | ID: covidwho-691247

ABSTRACT

BACKGROUND: The 2019 novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) is driving a novel atypical pneumonia (coronavirus disease 2019 [COVID-19]) outbreak in Wuhan, causing huge public health challenges both in China and globally. Limited data are available for information and prognosis on COVID-19 patients with pre-existing chronic kidney disease. CASE PRESENTATION: Here we described the clinical characteristics and outcomes from two patients-a female aged 40-year-old and an 83-year-old male-who were subjected to SARS-CoV-2 infection, with history of chronic renal insufficiency. The female was admitted for dry cough and shortness of breath and the male was admitted for fever. The thorax computed tomography revealed patchy consolidation and ground-glass opacity in both scattered lobes and the throat swab sample for coronavirus nucleic acid was positive. They were diagnosed with COVID-19 and their renal function became progressively worse after infection with COVID-19. After symptomatic support treatment, in both the patients, renal function was obviously restored, and both recovered from this pneumonia and conformed to the discharge criteria. CONCLUSION: SARS-CoV-2 infection may aggravate renal function impairment. It is crucial to monitor changes of renal function in patients with COVID-19, especially those with primary kidney disease. Kidney protection interventions should be taken as early as possible, thereby improving the prognosis of patients with COVID-19.


Subject(s)
Acute Kidney Injury/etiology , Betacoronavirus/pathogenicity , Coronavirus Infections/complications , Pneumonia, Viral/complications , Acute Kidney Injury/blood , Acute Kidney Injury/diagnosis , Acute Kidney Injury/therapy , Adult , Aged, 80 and over , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Creatinine/blood , Female , Humans , Interferon-alpha/therapeutic use , Lung/diagnostic imaging , Male , Methylprednisolone/therapeutic use , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , RNA, Viral/isolation & purification , Recombinant Proteins/therapeutic use , Renal Replacement Therapy , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome
8.
Cell Host Microbe ; 28(3): 455-464.e2, 2020 09 09.
Article in English | MEDLINE | ID: covidwho-654072

ABSTRACT

Interferons (IFNs) are widely used in treating coronavirus disease 2019 (COVID-19) patients. However, a recent report of ACE2, the host factor mediating SARS-Cov-2 infection, identifying it as interferon-stimulated raised considerable safety concern. To examine the association between the use and timing of IFN-α2b and clinical outcomes, we analyzed in a retrospective multicenter cohort study of 446 COVID-19 patients in Hubei, China. Regression models estimated that early administration (≤5 days after admission) of IFN-α2b was associated with reduced in-hospital mortality in comparison with no admission of IFN-α2b, whereas late administration of IFN-α2b was associated with increased mortality. Among survivors, early IFN-α2b was not associated with hospital discharge or computed tomography (CT) scan improvement, whereas late IFN-α2b was associated with delayed recovery. Additionally, early IFN-α2b and umifenovir alone or together were associated with reduced mortality and accelerated recovery in comparison with treatment with lopinavir/ritonavir (LPV/r) alone. We concluded that administration of IFN-α2b during the early stage of COVID-19 could induce favorable clinical responses.


Subject(s)
Antiviral Agents/administration & dosage , Betacoronavirus , Coronavirus Infections/drug therapy , Interferon-alpha/therapeutic use , Pneumonia, Viral/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Child , China/epidemiology , Cohort Studies , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Drug Therapy, Combination , Female , Hospital Mortality , Host Microbial Interactions/drug effects , Humans , Indoles/administration & dosage , Interferon-alpha/administration & dosage , Length of Stay , Lopinavir/administration & dosage , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Retrospective Studies , Ritonavir/administration & dosage , Treatment Outcome , Young Adult
9.
Cytokine Growth Factor Rev ; 54: 43-50, 2020 08.
Article in English | MEDLINE | ID: covidwho-634065

ABSTRACT

Coronavirus disease 2019 (COVID-19) first emerged in late 2019 in China. At the time of writing, its causative agent SARS-CoV-2 has spread worldwide infecting over 9 million individuals and causing more than 460,000 deaths. In the absence of vaccines, we are facing the dramatic challenge of controlling COVID-19 pandemic. Among currently available drugs, type I Interferons (IFN-I) - mainly IFN-α and ß -represent ideal candidates given their direct and immune-mediated antiviral effects and the long record of clinical use. However, the best modalities of using these cytokines in SARS-CoV-2 infected patients is a matter of debate. Here, we discuss how we can exploit the current knowledge on IFN-I system to tailor the most promising dosing, timing and route of administration of IFN-I to the disease stage, with the final aim of making these cytokines a valuable therapeutic strategy in today's fight against COVID-19 pandemic.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/prevention & control , Interferon-alpha/therapeutic use , Interferon-beta/therapeutic use , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Humans , Immunotherapy/methods , Secondary Prevention/methods
10.
Front Immunol ; 11: 1061, 2020.
Article in English | MEDLINE | ID: covidwho-612905

ABSTRACT

The global pandemic of COVID-19 cases caused by infection with SARS-CoV-2 is ongoing, with no approved antiviral intervention. We describe here the effects of treatment with interferon (IFN)-α2b in a cohort of confirmed COVID-19 cases in Wuhan, China. In this uncontrolled, exploratory study, 77 adults hospitalized with confirmed COVID-19 were treated with either nebulized IFN-α2b (5 mU b.i.d.), arbidol (200 mg t.i.d.) or a combination of IFN-α2b plus arbidol. Serial SARS-CoV-2 testing along with hematological measurements, including cell counts, blood biochemistry and serum cytokine levels, and temperature and blood oxygen saturation levels, were recorded for each patient during their hospital stay. Treatment with IFN-α2b with or without arbidol significantly reduced the duration of detectable virus in the upper respiratory tract and in parallel reduced duration of elevated blood levels for the inflammatory markers IL-6 and CRP. These findings suggest that IFN-α2b should be further investigated as a therapy in COVID-19 cases.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Interferon-alpha/therapeutic use , Pneumonia, Viral/drug therapy , Adult , Age Factors , Aged , Aged, 80 and over , Biomarkers/blood , China , Cohort Studies , Comorbidity , Coronavirus Infections/blood , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Cytokines/blood , Drug Therapy, Combination , Female , Humans , Indoles/therapeutic use , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Sex Factors
11.
mSphere ; 5(3)2020 05 13.
Article in English | MEDLINE | ID: covidwho-260573

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2, or SARS-CoV-2) is the cause of the respiratory infection known as COVID-19. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce increased levels of a variety of T-helper 1 (Th1) and inflammatory cytokines and chemokines, including interleukin-1 (IL-1), IL-6, CCL2 protein, and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 symptoms and severity. This report briefly describes the following four unconventional but commercially accessible immunomodulatory agents that can be employed in clinical trials to evaluate their effectiveness at alleviating disease symptoms and severity: low-dose oral interferon alpha, microdose DNA, low-dose thimerosal, and phytocannabinoids.


Subject(s)
Cannabinoids/therapeutic use , Coronavirus Infections/drug therapy , DNA/therapeutic use , Immunomodulation , Interferon-alpha/therapeutic use , Pneumonia, Viral/drug therapy , Thimerosal/therapeutic use , Betacoronavirus , Cytokines/immunology , Humans , Pandemics , Phytochemicals/therapeutic use
12.
Cytokine Growth Factor Rev ; 53: 38-42, 2020 06.
Article in English | MEDLINE | ID: covidwho-116329

ABSTRACT

Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/pathology , Cytokine Release Syndrome/pathology , Cytokines/blood , Multiple Organ Failure/mortality , Pneumonia, Viral/pathology , Adrenal Cortex Hormones/therapeutic use , Antibodies, Monoclonal/therapeutic use , Continuous Renal Replacement Therapy/methods , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Cytokine Release Syndrome/drug therapy , Cytokines/biosynthesis , Female , Humans , Interferon-alpha/therapeutic use , Male , Multiple Organ Failure/immunology , Multiple Organ Failure/pathology , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Polyethylene Glycols/therapeutic use , Recombinant Proteins/therapeutic use , Retrospective Studies
13.
Drug Discov Ther ; 14(2): 67-72, 2020 May 06.
Article in English | MEDLINE | ID: covidwho-116944

ABSTRACT

The virus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is currently affecting more than 200 countries and territories worldwide. It has been declared as pandemic by World Health Organization (WHO) and the whole world is suffering from corona virus disease 2019 (COVID-19). Currently, no treatment for SARS-CoV-2 are approved because of lack of evidence, but a number of clinical trials are in process and we are expecting fruitful results very soon. This review focuses on various approaches of treatment and few of the most recent clinical trials carried out in this field.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus , Chloroquine/therapeutic use , Clinical Trials as Topic , Coronavirus Infections/drug therapy , Darunavir/therapeutic use , Drug Combinations , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Indoles/therapeutic use , Interferon-alpha/therapeutic use , Interferon-beta/therapeutic use , Lopinavir/therapeutic use , Pandemics , Pyrazines/therapeutic use , Ritonavir/therapeutic use
14.
J Chin Med Assoc ; 83(6): 534-536, 2020 06.
Article in English | MEDLINE | ID: covidwho-33814

ABSTRACT

The emerging outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 continues to spread all over the world. Agents or vaccines of proven efficacy to treat or prevent human coronavirus infection are in urgent need and are being investigated vigorously worldwide. This review summarizes the current evidence of potential therapeutic agents, such as lopinavir/ritonavir, remdesivir, favipiravir, chloroquine, hydroxychloroquine, interferon, ribavirin, tocilizumab, and sarilumab. More clinical trials are being conducted for further confirmation of the efficacy and safety of these agents in treating COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Clinical Trials as Topic , Drug Combinations , Humans , Hydroxychloroquine/therapeutic use , Interferon-alpha/therapeutic use , Lopinavir/therapeutic use , Pandemics , Ritonavir/therapeutic use
15.
Inflamm Res ; 69(6): 599-606, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-17695

ABSTRACT

OBJECTIVE: This study aims to evaluate the correlation between viral clearance and blood biochemical index of 94 discharged patients with COVID-19 infection in Shenzhen Third People's Hospital, enrolled from Jan 5 to Feb 13, 2020. METHODS: The clinical and laboratory findings were extracted from the electronic medical records of the patients. The data were analysed and reviewed by a trained team of physicians. Information on clinical signs and symptoms, medical treatment, virus clearance, and laboratory parameters including interleukin 6 (IL-6) and C-reactive protein were collected. RESULTS: COVID-19 mRNA clearance ratio was identified significantly correlated with the decline of serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Furthermore, COVID-19 mRNA clearance time was positively correlated with the length of hospital stay in patients treated with either IFN-α + lopinavir/ritonavir or IFN-α + lopinavir/ritonavir + ribavirin. CONCLUSIONS: Therapeutic regimens of IFN-α + lopinavir/ritonavir and IFN-α + lopinavir/ritonavir + ribavirin might be beneficial for treatment of COVID-19. Serum LDH or CK decline may predict a favorable response to treatment of COVID-19 infection.


Subject(s)
Coronavirus Infections/blood , Coronavirus Infections/virology , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Adolescent , Adult , Aged , Child , Child, Preschool , China , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Creatine Kinase/blood , Drug Combinations , Humans , Interferon-alpha/therapeutic use , L-Lactate Dehydrogenase/blood , Lopinavir/therapeutic use , Middle Aged , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/physiopathology , Polymerase Chain Reaction , RNA, Viral/analysis , Retrospective Studies , Ritonavir/therapeutic use , Young Adult
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