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1.
J Clin Microbiol ; 58(8)2020 Jul 23.
Article in English | MEDLINE | ID: covidwho-684350

ABSTRACT

Molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the gold standard for diagnosis of coronavirus disease 2019 (COVID-19), but the clinical performance of these tests is still poorly understood, particularly with regard to disease course, patient-specific factors, and viral shedding. From 10 March to 1 May 2020, NewYork-Presbyterian laboratories performed 27,377 SARS-CoV-2 molecular assays from 22,338 patients. Repeat testing was performed for 3,432 patients, of which 2,413 had initial negative and 802 had initial positive results. Repeat-tested patients were more likely to have severe disease and low viral loads. The negative predictive value of the first-day result among repeat-tested patients was 81.3% The clinical sensitivity of SARS-CoV-2 molecular assays was estimated between 58% and 96%, depending on the unknown number of false-negative results in single-tested patients. Conversion to negative was unlikely to occur before 15 to 20 days after initial testing or 20 to 30 days after the onset of symptoms, with 50% conversion occurring at 28 days after initial testing. Conversion from first-day negative to positive results increased linearly with each day of testing, reaching 25% probability in 20 days. Sixty patients fluctuated between positive and negative results over several weeks, suggesting that caution is needed when single-test results are acted upon. In summary, our study provides estimates of the clinical performance of SARS-CoV-2 molecular assays and suggests time frames for appropriate repeat testing, namely, 15 to 20 days after a positive test and the same day or next 2 days after a negative test for patients with high suspicion for COVID-19.


Subject(s)
Betacoronavirus/isolation & purification , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Diagnostic Tests, Routine/methods , Pneumonia, Viral/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus/genetics , Child , Child, Preschool , Coronavirus Infections/pathology , Coronavirus Infections/virology , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , New York , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Predictive Value of Tests , Sensitivity and Specificity , Viral Load , Young Adult
2.
Science ; 369(6499): 77-81, 2020 07 03.
Article in English | MEDLINE | ID: covidwho-667322

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines , Animals , Antibodies, Neutralizing/biosynthesis , Antibodies, Neutralizing/immunology , Antibodies, Viral/biosynthesis , Antibodies, Viral/immunology , Betacoronavirus/isolation & purification , Chlorocebus aethiops , Coronavirus Infections/immunology , Coronavirus Infections/virology , Dose-Response Relationship, Immunologic , Female , Immunogenicity, Vaccine , Immunoglobulin G/biosynthesis , Immunoglobulin G/blood , Immunoglobulin G/immunology , Macaca mulatta , Male , Mice , Mice, Inbred BALB C , Pilot Projects , Pneumonia, Viral/virology , Rats , Rats, Wistar , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunology , Vero Cells , Viral Load , Viral Vaccines/administration & dosage , Viral Vaccines/adverse effects , Viral Vaccines/immunology
4.
Infect Dis Poverty ; 9(1): 100, 2020 Jul 22.
Article in English | MEDLINE | ID: covidwho-662434

ABSTRACT

BACKGROUND: From the begging months of 2020 a severe acute respiratory syndrome coronavirus (SARS-CoV-2, also called 2019-nCoV) caused a devastating global outbreak. At present, the diagnosis of coronavirus disease 2019 (COVID-19) is made through a nasopharyngeal swab based on reverse transcription polymerase chain reaction (RT-PCR) technique. However, some recent studies suggested the possible role of oral fluids and saliva in the detection of SARS-CoV-2. The purpose of this scoping review is evaluating the available evidence regarding the efficacy of saliva as a diagnostic specimen in COVID-19 patients. METHODS: A systematic literature review of six databases (PubMed, Scopus, The Cochrane Central Register of Controlled Trials [CENTRAL], Science Direct, Web of Science and Google scholar) was carried out without any restrictions on date of publication to identify the reliability of saliva as a diagnostic specimen for detection of SARS-CoV-2 in suspected patients. RESULTS: Nine eligible articles were included in this review based on our described method. All the included studies are based on clinical surveys among patients with confirmed SARS-CoV-2 infection. Most of studies included in this review, reported that there is no statistically significant difference between nasopharyngeal or sputum specimens and saliva samples regarding viral load. CONCLUSIONS: Despite limitations of this study, the findings of this review suggest that the use of self-collected saliva as a non-invasive specimen has proper accuracy and reliability regarding detection of SARS-CoV-2 based on RT-PCR technique.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Saliva/virology , Viral Load , Humans , Pandemics , Reproducibility of Results
6.
Epidemiol Infect ; 148: e154, 2020 07 14.
Article in English | MEDLINE | ID: covidwho-650362

ABSTRACT

There is limited information concerning the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in aerosols deposited on environmental surfaces and the effectiveness of infection prevention and control procedures on eliminating SARS-CoV-2 contamination in hospital settings. We examined the concentration of SARS-CoV-2 in aerosol samples and on environmental surfaces in a hospital designated for treating severe COVID-19 patients. Aerosol samples were collected by a microbial air sampler, and environmental surfaces were sampled using sterile premoistened swabs at multiple sites. Ninety surface swabs and 135 aerosol samples were collected. Only two swabs, sampled from the inside of a patient's mask, were positive for SARS-CoV-2 RNA. All other swabs and aerosol samples were negative for the virus. Our study indicated that strict implementation of infection prevention and control procedures was highly effective in eliminating aerosol and environmental borne SARS-CoV-2 RNA thereby reducing the risk of cross-infection in hospitals.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Cross Infection/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/virology , RNA, Viral/isolation & purification , Viral Load , Aerosols , Betacoronavirus/genetics , Coronavirus Infections/transmission , Cross Infection/transmission , Cross Infection/virology , Environment , Environmental Microbiology , Hospitals, University , Humans , Masks/virology , Pneumonia, Viral/transmission
7.
Nat Commun ; 11(1): 3572, 2020 07 14.
Article in English | MEDLINE | ID: covidwho-647071

ABSTRACT

SARS-CoV-2 outbreak is the first pandemic of the century. SARS-CoV-2 infection is transmitted through droplets; other transmission routes are hypothesized but not confirmed. So far, it is unclear whether and how SARS-CoV-2 can be transmitted from the mother to the fetus. We demonstrate the transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise. The transmission is confirmed by comprehensive virological and pathological investigations. In detail, SARS-CoV-2 causes: (1) maternal viremia, (2) placental infection demonstrated by immunohistochemistry and very high viral load; placental inflammation, as shown by histological examination and immunohistochemistry, and (3) neonatal viremia following placental infection. The neonate is studied clinically, through imaging, and followed up. The neonate presented with neurological manifestations, similar to those described in adult patients.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , Infectious Disease Transmission, Vertical , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Pregnancy Complications, Infectious/virology , Vasculitis, Central Nervous System/virology , Betacoronavirus , Coronavirus Infections/pathology , Female , Humans , Infant, Newborn , Male , Maternal-Fetal Exchange/physiology , Mothers , Pandemics , Placenta/pathology , Placenta/virology , Pneumonia, Viral/pathology , Pregnancy , Viral Load , Viremia/transmission , Young Adult
9.
Virologie (Montrouge) ; 24(3): 142-146, 2020 06 01.
Article in English | MEDLINE | ID: covidwho-639711

ABSTRACT

The emerging coronavirus called SARS-CoV-2 has spread rapidly around the world. Responsible for severe pneumonitis (Covid-19), there are also doubts concerning a possible mother-to-fetal transmission of this virus. Current data are patchy and obtained from small groups of patients. They tend to support the idea that the mother-to-fetal transmission of SARS-CoV-2 is very rare, but the period between infection and childbirth was often very short and may not allow sufficient replication to consider transplacental passage. Here, we reviewed the existing virological data and those remaining to explore. Thus, the natural history of SARS-CoV-2 infection in pregnant women and the risk of transmission in utero is not yet fully understood and defined. Four months from the emergence of this virus, it is therefore reasonable to wait for the results of specific studies on larger cohorts which, to be conclusive, must meet the best scientific criteria.


Subject(s)
Betacoronavirus , Coronavirus Infections/transmission , Infectious Disease Transmission, Vertical , Pneumonia, Viral/transmission , Pregnancy Complications, Infectious , Betacoronavirus/physiology , Coronavirus Infections/virology , Female , Fetal Diseases/virology , Humans , Infant, Newborn , Pandemics , Placenta/virology , Pneumonia, Viral/virology , Pregnancy , Viral Load , Viral Tropism
11.
Cent Eur J Public Health ; 28(2): 161-162, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-615012

ABSTRACT

The mandatory face mask wearing was implemented in the Czech Republic and Slovakia shortly after the COVID-19 outbreak in Central Europe. So far, the number of COVID-19-associated deaths per 100,000 individuals is far lower in these countries as compared with other neighbouring or close countries. The use of face masks in public may not protect the general public from contracting the virus, however, presumptively decreases the viral load and contributes to a favourable clinical outcome in COVID-19 disease. A certain time is required for antigen-specific T cells and B cells to fully develop. Obligatory face mask wearing in public favours the virus transmission through oral mucosa and/or conjunctival epithelium, which enables the adaptive immune responses to evolve. In the case of inhalation of high loads of SARS-CoV-2, the time for the development of fully protective adaptive immune responses seems to be insufficient. Then, a less specific and more damaging innate immune response prevails.


Subject(s)
Coronavirus Infections/prevention & control , Masks , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Czech Republic/epidemiology , Humans , Personal Protective Equipment , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Protective Clothing , Slovakia/epidemiology , Viral Load
12.
Trials ; 21(1): 485, 2020 Jun 05.
Article in English | MEDLINE | ID: covidwho-617180

ABSTRACT

OBJECTIVES: The hypothesis of the study is that treatment with hydroxychloroquine sulphate in hospitalised patients with coronavirus disease 2019 (Covid-19) is safe and will accelerate the virological clearance rate for patients with moderately severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) when compared to standard care. Furthermore, we hypothesize that early treatment with hydroxychloroquine sulphate is associated with more rapid resolve of clinical symptoms as assessed by the National Early Warning Score 2 (NEWS2), decreased admission rate to intensive care units and mortality, and improvement in protein biomarker profiles (C-reactive protein, markers of renal and hepatic injury, and established cardiac biomarkers like cardiac troponin and B-type natriuretic peptide). TRIAL DESIGN: The study is a two-arm, open label, pragmatic randomised controlled group sequential adaptive trial designed to assess the effect on viral loads and clinical outcome of hydroxychloroquine sulphate therapy in addition to standard care compared to standard care alone in patients with established Covid-19. By utilizing resources already paid for by the hospitals (physicians and nurses in daily clinical practice), this pragmatic trial can include a larger number of patients over a short period of time and at a lower cost than studies utilizing traditional randomized controlled trial designs with an external study organization. The pragmatic approach will enable swift initiation of randomisation and allocation to treatment. PARTICIPANTS: Patients will be recruited from all inpatients at Akershus University Hospital, Lørenskog, Norway. Electronic real-time surveillance of laboratory reports from the Department of Microbiology will be examined regularly for SARS-CoV-2 positive subjects. All of the following conditions must apply to the prospective patient at screening prior to inclusion: (1) Hospitalisation; (2) Adults 18 years or older; (3) Moderately severe Covid-19 disease (NEWS2 of 6 or less); (4) SARS-CoV-2 positive nasopharyngeal swab; (5) Expected time of hospitalisation > 48 hours; and (6) Signed informed consent must be obtained and documented according to Good Clinical Practice guidelines of the International Conference on Harmonization, and national/local regulations. Patients will be excluded from participation in the study if they meet any of the following criteria: (1) Requiring intensive care unit admission at screening; (2) History of psoriasis; (3) Known adverse reaction to hydroxychloroquine sulphate; (4) Pregnancy; or (5) Prolonged corrected QT interval (>450 ms). Clinical data, including standard hospital biochemistry, medical therapy, vital signs, NEWS2, and microbiology results (including blood culture results and reverse transcriptase polymerase chain reaction [RT-PCR] for other upper airway viruses), will be automatically extracted from the hospital electronic records and merged with the study specific database. INTERVENTION AND COMPARATOR: Included patients will be randomised in a 1:1 ratio to (1) standard care with the addition of 400 mg hydroxychloroquine sulphate (PlaquenilTM) twice daily for seven days or (2) standard care alone. MAIN OUTCOMES: The primary endpoint of the study is the rate of decline in SARS-CoV-2 viral load in oropharyngeal samples as assessed by RT-PCR in samples collected at baseline, 48 and 96 hours after randomization and administration of drug for the intervention arm. Secondary endpoints include change in NEWS2 at 96 hours after randomisation, admission to intensive care unit, mortality (in-hospital, and at 30 and 90 days), duration of hospital admission, clinical status on a 7-point ordinal scale 14 days after randomization ([1] Death [2] Hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation [3] Hospitalised, on non-invasive ventilation or high flow oxygen devices [4] Hospitalized, requiring supplemental oxygen [5] Hospitalised, not requiring supplemental oxygen [6] Not hospitalized, but unable to resume normal activities [7] Not hospitalised, with resumption of normal activities), and improvement in protein biomarker profiles (C-reactive protein, markers of renal and hepatic injury, and established cardiac biomarkers like cardiac troponin and B-type natriuretic peptide) at 96 hours after randomization. RANDOMISATION: Eligible patients will be allocated in a 1:1 ratio, using a computer randomisation procedure. The allocation sequence has been prepared by an independent statistician. BLINDING (MASKING): Open label randomised controlled pragmatic trial without blinding, no active or placebo control. The virologist assessing viral load in the oropharyngeal samples and the statistician responsible for analysis of the data will be blinded to the treatment allocation for the statistical analyses. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): This is a group sequential adaptive trial where analyses are planned after 51, 101, 151 and 202 completed patients, with a maximum sample size of 202 patients (101 patients allocated to intervention and standard care and 101 patients allocated to standard care alone). TRIAL STATUS: Protocol version 1.3 (March 26, 2020). Recruitment of first patient on March 26, 2020, and 51 patients were included as per April 28, 2020. Study recruitment is anticipated to be completed by July 2020. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04316377. Trial registered March 20, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Pragmatic Clinical Trials as Topic , Coronavirus Infections/virology , Female , Hospitalization , Humans , Male , Norway , Pandemics , Pneumonia, Viral/virology , Research Design , Viral Load
13.
Sci Immunol ; 5(48)2020 06 26.
Article in English | MEDLINE | ID: covidwho-617063

ABSTRACT

SARS-CoV-2 has been identified as the causative agent of a global outbreak of respiratory tract disease (COVID-19). In some patients the infection results in moderate to severe acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation. High serum levels of IL-6, IL-10 and an immune hyperresponsiveness referred to as a 'cytokine storm' have been associated with poor clinical outcome. Despite the large numbers of COVID-19 cases and deaths, information on the phenotype and kinetics of SARS-CoV-2-specific T cells is limited. Here, we studied 10 COVID-19 patients who required admission to an intensive care unit and detected SARS-CoV-2-specific CD4+ and CD8+ T cells in 10 out of 10 and 8 out of 10 patients, respectively. We also detected low levels of SARS-CoV-2-reactive T cells in 2 out of 10 healthy controls not previously exposed to SARS-CoV-2, which is indicative of cross-reactivity due to past infection with 'common cold' coronaviruses. The strongest T-cell responses were directed to the spike (S) surface glycoprotein, and SARS-CoV-2-specific T cells predominantly produced effector and Th1 cytokines, although Th2 and Th17 cytokines were also detected. Furthermore, we studied T-cell kinetics and showed that SARS-CoV-2-specific T cells are present relatively early and increase over time. Collectively, these data shed light on the potential variations in T-cell responses as a function of disease severity, an issue that is key to understanding the potential role of immunopathology in the disease, and also inform vaccine design and evaluation.


Subject(s)
Betacoronavirus/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Coronavirus Infections/immunology , Phenotype , Pneumonia, Viral/immunology , Respiratory Distress Syndrome, Adult/immunology , Aged , Cells, Cultured , Coronavirus Infections/blood , Coronavirus Infections/virology , Cytokines/metabolism , Female , Humans , Immunologic Memory , Kinetics , Longitudinal Studies , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Respiratory Distress Syndrome, Adult/blood , Respiratory Distress Syndrome, Adult/virology , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology , Viral Load/immunology
14.
Tidsskr Nor Laegeforen ; 140(9)2020 06 16.
Article in English, Norwegian | MEDLINE | ID: covidwho-608543

ABSTRACT

BACKGROUND: The diagnosis of COVID-19 is made by detection of SARS-CoV-2 RNA by reverse transcription polymerase chain reaction (RT-PCR). Studies have shown a percentage of up to 30 % false negative results. CASE PRESENTATION: A previously healthy man in his late thirties was admitted to the hospital after 3-5 days of suffering chest pain, dyspnoea and abdominal discomfort. He had hypoxic respiratory failure and required oxygen therapy. The routine nasopharyngeal swab for PCR was negative at days 5 and 7 after onset of symptoms. A specimen obtained from bronchoalveolar lavage on day 8 was positive. INTERPRETATION: This case report shows us that even in the early course of SARS-Cov-2 infection, when the viral load in the upper respiratory tract has been shown to be at its highest, there might be false negative tests. It also emphasises the importance of including other clinical measures before discontinuation of isolation.


Subject(s)
Betacoronavirus , Coronavirus Infections , Nasopharynx , Pandemics , Pneumonia, Viral , Adult , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , False Negative Reactions , Humans , Male , Nasopharynx/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Viral Load
15.
Signal Transduct Target Ther ; 5(1): 100, 2020 06 19.
Article in English | MEDLINE | ID: covidwho-606785
16.
Virol J ; 17(1): 80, 2020 06 19.
Article in English | MEDLINE | ID: covidwho-606695

ABSTRACT

BACKGROUND: Convalescent plasma (CP) transfusion was reported to be effective in treating critically ill patients with COVID-19, and hydroxychloroquine could potently inhibit SARS-CoV-2 in vitro. Herein, we reported a case receiving combination therapy with CP transfusion and hydroxychloroquine for the first time. CASE PRESENTATION: Laboratory findings showed high lactic acid level (2.1 mmol/L) and C-reactive protein (CRP, 48.8 mg/L), and low white blood cell count (1.96 × 109/L) in a 65-year-old Chinese man, who was diagnosed with severe COVID-19. CP was intravenously given twice, and hydroxychloroquine was orally administrated for a week (0.2 g, three times a day). The lactic acid and C-reactive protein levels remained high (2.1 mmol/L and 73.23 mg/L, respectively), while the arterial oxyhemoglobin saturation decreased to 86% with a low oxygenation index (OI, 76 mmHg) on day 4 after CP transfusion. His temperature returned to normal and the OI ascended above 300 on day 11. Moreover, the RNA test remained positive in throat swab, and computed tomography revealed severe pulmonary lesions on day 11 after admission. CONCLUSION: These findings suggested that the effectiveness of combination therapy with CP and hydroxychloroquine may be non-optimal, and specific therapy needs to be explored.


Subject(s)
Blood Component Transfusion/methods , Coronavirus Infections/therapy , Hydroxychloroquine/administration & dosage , Pneumonia, Viral/therapy , Administration, Oral , Aged , Antibodies, Neutralizing/administration & dosage , Antibodies, Viral/administration & dosage , Betacoronavirus/isolation & purification , C-Reactive Protein/metabolism , Coronavirus Infections/blood , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/virology , Humans , Immunization, Passive/methods , Lactic Acid/blood , Leukocyte Count , Male , Oxyhemoglobins , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Viral Load
17.
Drug Des Devel Ther ; 14: 2159-2164, 2020.
Article in English | MEDLINE | ID: covidwho-600590

ABSTRACT

Objective: This study aimed to evaluate the fundamental characteristics of coronavirus disease (COVID-19) clinical trials registered in China. Methods: COVID-19 clinical trials registered in China were analyzed from databases on ChiCTR and ClinicalTrials.gov. The study designs, samples, primary end points, and intervention measures were evaluated. Results: In total, 262 intervention clinical trials were retrieved on March 10, 2020. Overall, 181 (69.1%) trials involved two groups, 200 (76.3%) trials were randomized parallel trials, 24 (9.2%) trials were double blind, and 60.3% of trials included ≤100 participants. Sixty (22.9%) trials considered symptom improvement as the primary endpoint and 43 (16.4%) trials considered the rate or time at which the subjects became virus-free as the primary endpoint. Of 262 intervention studies, chemical drugs and biological products were studied in 105 (40.1%) intervention studies, of which antiviral drugs accounted for 15.3% and malaria drugs accounted for 8.4% of the studies. Among all trials, 27.9% of the studies used traditional Chinese medicine (TCM), 10.3% used cell therapy, and 5.0% used plasma therapy. Conclusion: This study is the first snapshot of the landscape of COVID-19 clinical trials registered in China and provided the basic features of clinical trial designs for the treatment and prevention of COVID-19 to offer useful information to guide future clinical trials on COVID-19 in other countries.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Clinical Trials as Topic , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Research Design/trends , Antiviral Agents/adverse effects , Betacoronavirus/pathogenicity , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/virology , Host-Pathogen Interactions , Humans , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Remission Induction , Time Factors , Treatment Outcome , Viral Load/trends
18.
J Pediatric Infect Dis Soc ; 9(3): 370-372, 2020 Jul 13.
Article in English | MEDLINE | ID: covidwho-597839

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected from at least 1 buccal specimen in 9 of 11 coronavirus disease 2019 (COVID-19)-infected children (81.8%). Viral loads in buccal specimens were substantially lower than those in nasopharyngeal specimens. Buccal swabs are not good as COVID-19 screening specimens in children.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Mouth Mucosa/virology , Pneumonia, Viral/diagnosis , Cheek , Child , Child, Preschool , Coronavirus Infections/virology , Humans , Infant , Nasopharynx/virology , Pandemics , Pneumonia, Viral/virology , Real-Time Polymerase Chain Reaction , Saliva/virology , Viral Load
19.
Int J Infect Dis ; 97: 290-292, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-597415

ABSTRACT

A relationship between the infecting dose and the risk of disease severity has not been demonstrated for SARS-CoV-2 infection. Here, we report three clusters of individuals that were potentially exposed to distinct inoculum in Madrid. Overall each group developed divergent clinical forms of COVID-19. Our data support that a greater viral inoculum at the time of SARS-CoV-2 exposure might determine a higher risk of severe COVID-19.


Subject(s)
Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Viral Load , Adult , Aged , Aged, 80 and over , Betacoronavirus , Coronavirus Infections/epidemiology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Spain/epidemiology , Time Factors , Virulence
20.
Viruses ; 12(6)2020 06 10.
Article in English | MEDLINE | ID: covidwho-592405

ABSTRACT

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-ß1b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC50 at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Animals , Antigens, Viral/immunology , Betacoronavirus/immunology , Betacoronavirus/metabolism , Chlorocebus aethiops , Coronavirus Infections/virology , Humans , Interferons/metabolism , Lipogenesis/drug effects , Pandemics , Pneumonia, Viral/virology , Signal Transduction/drug effects , Vero Cells , Viral Load/drug effects , Viral Plaque Assay , Virus Replication/drug effects
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