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2.
Nat Commun ; 13(1): 1155, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1730286

ABSTRACT

Many locations around the world have used real-time estimates of the time-varying effective reproductive number ([Formula: see text]) of COVID-19 to provide evidence of transmission intensity to inform control strategies. Estimates of [Formula: see text] are typically based on statistical models applied to case counts and typically suffer lags of more than a week because of the latent period and reporting delays. Noting that viral loads tend to decline over time since illness onset, analysis of the distribution of viral loads among confirmed cases can provide insights into epidemic trajectory. Here, we analyzed viral load data on confirmed cases during two local epidemics in Hong Kong, identifying a strong correlation between temporal changes in the distribution of viral loads (measured by RT-qPCR cycle threshold values) and estimates of [Formula: see text] based on case counts. We demonstrate that cycle threshold values could be used to improve real-time [Formula: see text] estimation, enabling more timely tracking of epidemic dynamics.


Subject(s)
COVID-19/transmission , SARS-CoV-2 , Viral Load , Basic Reproduction Number/statistics & numerical data , COVID-19/epidemiology , COVID-19/virology , Computer Simulation , Computer Systems , Epidemics , Hong Kong/epidemiology , Humans , Models, Statistical , Pandemics , Viral Load/statistics & numerical data
3.
Viruses ; 14(2)2022 02 04.
Article in English | MEDLINE | ID: covidwho-1674823

ABSTRACT

Studies comparing SARS-CoV-2 nasopharyngeal (NP) viral load (VL) according to virus variant and host vaccination status have yielded inconsistent results. We conducted a single center prospective study between July and September 2021 at the drive-through testing center of the Toulouse University Hospital. We compared the NP VL of 3775 patients infected by the Delta (n = 3637) and Alpha (n = 138) variants, respectively. Patient's symptoms and vaccination status (2619 unvaccinated, 636 one dose and 520 two doses) were recorded. SARS-CoV-2 RNA testing and variant screening were assessed by using Thermo Fisher® TaqPath™ COVID-19 and ID solutions® ID™ SARS-CoV-2/VOC evolution Pentaplex assays. Delta SARS-CoV-2 infections were associated with higher VL than Alpha (coef = 0.68; p ≤ 0.01) independently of patient's vaccination status, symptoms, age and sex. This difference was higher for patients diagnosed late after symptom onset (coef = 0.88; p = 0.01) than for those diagnosed early (coef = 0.43; p = 0.03). Infections in vaccinated patients were associated with lower VL (coef = -0.18; p ≤ 0.01) independently of virus variant, symptom, age and sex. Our results suggest that Delta infections could lead to higher VL and for a longer period compared to Alpha infections. By effectively reducing the NP VL, vaccination could allow for limiting viral spread, even with the Delta variant.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , RNA, Viral/genetics , SARS-CoV-2/immunology , Vaccination/statistics & numerical data , Viral Load/immunology , Viral Load/statistics & numerical data , Adult , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Female , Hospitalization , Humans , Male , Nasopharynx/virology , Prospective Studies , SARS-CoV-2/genetics , Viral Load/methods , Young Adult
4.
Nat Microbiol ; 7(2): 277-288, 2022 02.
Article in English | MEDLINE | ID: covidwho-1616987

ABSTRACT

Associations between vaccine breakthrough cases and infection by different SARS coronavirus 2 (SARS-CoV-2) variants have remained largely unexplored. Here we analysed SARS-CoV-2 whole-genome sequences and viral loads from 1,373 persons with COVID-19 from the San Francisco Bay Area from 1 February to 30 June 2021, of which 125 (9.1%) were vaccine breakthrough infections. Vaccine breakthrough infections were more commonly associated with circulating antibody-resistant variants carrying ≥1 mutation associated with decreased antibody neutralization (L452R/Q, E484K/Q and/or F490S) than infections in unvaccinated individuals (78% versus 48%, P = 1.96 × 10-8). Differences in viral loads were non-significant between unvaccinated and fully vaccinated cases overall (P = 0.99) and according to lineage (P = 0.09-0.78). Symptomatic vaccine breakthrough infections had comparable viral loads (P = 0.64), whereas asymptomatic breakthrough infections had decreased viral loads (P = 0.023) compared with infections in unvaccinated individuals. In 5 cases with serial samples available for serologic analyses, vaccine breakthrough infections were found to be associated with low or undetectable neutralizing antibody levels attributable to an immunocompromised state or infection by an antibody-resistant lineage. Taken together, our results show that vaccine breakthrough infections are overrepresented by antibody-resistant SARS-CoV-2 variants, and that symptomatic breakthrough infections may be as efficient in spreading COVID-19 as unvaccinated infections, regardless of the infecting lineage.


Subject(s)
Antibodies, Viral/blood , COVID-19/epidemiology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Cohort Studies , Female , Genome, Viral , Humans , Male , Middle Aged , Mutation , Phylogeny , San Francisco/epidemiology , Vaccination , Viral Load/statistics & numerical data , Whole Genome Sequencing , Young Adult
5.
PLoS One ; 16(11): e0257979, 2021.
Article in English | MEDLINE | ID: covidwho-1526683

ABSTRACT

Public health interventions such as social distancing and mask wearing decrease the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they decrease the viral load of infected patients and whether changes in viral load impact mortality from coronavirus disease 2019 (COVID-19). We evaluated 6923 patients with COVID-19 at six New York City hospitals from March 15-May 14, 2020, corresponding with the implementation of public health interventions in March. We assessed changes in cycle threshold (CT) values from reverse transcription-polymerase chain reaction tests and in-hospital mortality and modeled the impact of viral load on mortality. Mean CT values increased between March and May, with the proportion of patients with high viral load decreasing from 47.7% to 7.8%. In-hospital mortality increased from 14.9% in March to 28.4% in early April, and then decreased to 8.7% by May. Patients with high viral loads had increased mortality compared to those with low viral loads (adjusted odds ratio 2.34). If viral load had not declined, an estimated 69 additional deaths would have occurred (5.8% higher mortality). SARS-CoV-2 viral load steadily declined among hospitalized patients in the setting of public health interventions, and this correlated with decreases in mortality.


Subject(s)
COVID-19/virology , Hospital Mortality/trends , Viral Load/statistics & numerical data , COVID-19/epidemiology , COVID-19/mortality , COVID-19 Nucleic Acid Testing/statistics & numerical data , Female , Humans , Male , New York , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity
6.
PLoS One ; 16(9): e0255981, 2021.
Article in English | MEDLINE | ID: covidwho-1416868

ABSTRACT

BACKGROUND: Hospitalization of patients infected with the severe acute respiratory syndrome virus 2 (SARS-CoV-2) have remained considerable worldwide. Patients often develop severe complications and have high mortality rates. The cycle threshold (Ct) value derived from nasopharyngeal swab samples using real time polymerase chain reaction (RT-PCR) may be a useful prognostic marker in hospitalized patients with SARS-CoV-2 infection, however, its role in predicting the course of the pandemic has not been evaluated thus far. METHODS: We conducted a retrospective cohort study which included all patients who had a nasopharyngeal sample positive for SARS-CoV-2 between April 4 -June 5, 2020. The Ct value was used to estimate the number of viral particles in a patient sample. The trend in initial viral load on admission on a population level was evaluated. Moreover, patient characteristics and outcomes stratified by viral load categories were compared and initial viral load was assessed as an independent predictor of intubation and in-hospital mortality. RESULTS: A total of 461 hospitalized patients met the inclusion criteria. This study consisted predominantly of acutely infected patients with a median of 4 days since symptom onset to PCR. As the severity of the pandemic eased, there was an increase in the percentage of samples in the low initial viral load category, coinciding with a decrease in deaths. Compared to an initial low viral load, a high initial viral load was an independent predictor of in-hospital mortality (OR 5.5, CI 3.1-9.7, p < 0.001) and intubation (OR 1.82 CI 1.07-3.11, p = 0.03), while an initial intermediate viral load was associated with increased risk of inpatient mortality (OR 1.9, CI 1.14-3.21, p = 0.015) but not with increased risk for intubation. CONCLUSION: The Ct value obtained from nasopharyngeal samples of hospitalized patients on admission may serve as a prognostic marker at an individual level and may help predict the course of the pandemic when evaluated at a population level.


Subject(s)
COVID-19/diagnosis , Hospitalization/statistics & numerical data , Nasopharynx/virology , SARS-CoV-2/genetics , Viral Load/genetics , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19/virology , Female , Humans , Male , Middle Aged , Pandemics/prevention & control , Real-Time Polymerase Chain Reaction/methods , Retrospective Studies , SARS-CoV-2/physiology , Severity of Illness Index , Viral Load/statistics & numerical data , Young Adult
7.
Laryngoscope ; 131(10): 2312-2318, 2021 10.
Article in English | MEDLINE | ID: covidwho-1318729

ABSTRACT

OBJECTIVES/HYPOTHESIS: The aim of this study was to evaluate the correlations between the severity and duration of olfactory dysfunctions (OD), assessed with psychophysical tests, and the viral load on the rhino-pharyngeal swab determined with a direct method, in patients affected by coronavirus disease 2019 (COVID-19). STUDY DESIGN: Prospective cohort study. METHODS: Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and determination of the normalized viral load on nasopharyngeal swab within 10 days of the clinical onset of COVID-19. RESULTS: Sixty COVID-19 patients were included in this study. On psychophysical testing, 12 patients (20% of the cohort) presented with anosmia, 11 (18.3%) severe hyposmia, 13 (18.3%) moderate hyposmia, and 10 (16.7%) mild hyposmia with an overall prevalence of OD of 76.7%. The overall median olfactory score was 50 (interquartile range [IQR] 30-72.5) with no significant differences between clinical severity subgroups. The median normalized viral load detected in the series was 2.56E+06 viral copies/106 copies of human beta-2microglobulin mRNA present in the sample (IQR 3.17E+04-1.58E+07) without any significant correlations with COVID-19 severity. The correlation between viral load and olfactory scores at baseline (R2  = 0.0007; P = .844) and 60-day follow-up (R2  = 0.0077; P = .519) was weak and not significant. CONCLUSIONS: The presence of OD does not seem to be useful in identifying subjects at risk for being super-spreaders or who is at risk of developing long-term OD. Similarly, the pathogenesis of OD is probably related to individual factors rather than to viral load and activity. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2312-2318, 2021.


Subject(s)
Anosmia/diagnosis , COVID-19/complications , SARS-CoV-2/physiology , Severity of Illness Index , Viral Load/statistics & numerical data , Aged , Anosmia/virology , COVID-19/virology , Female , Humans , Male , Middle Aged , Prevalence , Prospective Studies
8.
BMC Infect Dis ; 21(1): 688, 2021 Jul 16.
Article in English | MEDLINE | ID: covidwho-1314252

ABSTRACT

BACKGROUND: Being able to use COVID-19 RT-PCR Ct values as simple clinical markers of disease outcome or prognosis would allow for the easy and proactive identification and triaging of high-risk cases. This study's objective was thus to explore whether a correlation exists between COVID-19 viral loads, as indicated by RT-PCR Ct values, and disease severity, as indicated by respiratory indices. RESULTS: A multi-centre cross-sectional retrospective study was conducted, using data obtained from Bahrain's National COVID-19 Task force's centralised database. The study period ranged from May 2, 2020 to July 31, 2020. A multivariable logistic regression was used to assess for a correlation using data from a total of 1057 admitted COVID-19 cases. The covariates adjusted for included sex, age, presentation, and comorbidities. In our cohort, Ct value showed no statistical significance for an association with requirement for oxygenation on admission (Odds ratio 1.046; 95%CI 0.999 to 1.096, p = 0.054). CONCLUSION: Viral load, as indicated by Ct values, did not seem to be associated with requirement for oxygenation on admission in our cohort. We postulate however that time since onset of symptom may have acted as an unaccounted-for confounder. As such, RT-PCR Ct values may not be a useful prognostic clinical tool in isolation.


Subject(s)
COVID-19/diagnosis , COVID-19/pathology , SARS-CoV-2/physiology , Viral Load/physiology , Adult , Aged , Bahrain/epidemiology , COVID-19/epidemiology , COVID-19/virology , Cohort Studies , Comorbidity , Cross-Sectional Studies , Female , Hospitalization/statistics & numerical data , Humans , Lung/pathology , Lung/virology , Male , Middle Aged , Prognosis , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Serologic Tests , Severity of Illness Index , Viral Load/statistics & numerical data
9.
Virol J ; 18(1): 40, 2021 02 18.
Article in English | MEDLINE | ID: covidwho-1092409

ABSTRACT

BACKGROUND: Acute respiratory tract infections (ARTIs) causes high amounts of morbidity and mortality worldwide every year. Human metapneumovirus (HMPV) is a major pathogen of ARTIs in children. In this study, we aimed to investigate the epidemiology and genotypic diversity of HMPV in children hospitalized with ARTIs in Beijing, China. METHODS: Hospitalized children aged < 14 years with ARTIs were enrolled from April 2017 to March 2018; nasopharyngeal aspirates were collected and subjected to real-time polymerase chain reaction tests for HMPV. HMPV-positive samples were genotyped based on a partial N gene. Whole genome sequences were determined for samples with high viral loads. RESULTS: 4.08% (52/1276) enrolled paediatric patients were identified as having HMPV infection. The epidemic season is winter and early spring, children aged ≤ 4 years were more susceptible to HMPV infection (47/52, 90.38%). The co-infection rate were 36.54% (19/52), the most common co-infected virus were influenza and respiratory syncytial virus. The main diagnoses of HMPV infection were pneumonia (29/52, 55.77%) and bronchitis (23/52, 44.23%), while the main clinical manifestations were cough, fever, rhinorrhoea, and sneeze. Among 48 HMPV-positive specimens, A2b (19/48, 39.58%) and B1 (26/48, 54.17%) were the main epidemic subtypes. Patients with HMPV genotype A infection had a higher viral load compared to genotype B patients (6.07 vs. 5.37 log10 RNA copies/ml). Five complete sequences of HMPV were obtained. This is the first report of a whole genome sequence of HMPV-B1 isolated in China. CONCLUSIONS: HMPV is an important respiratory pathogen in paediatric patients. Cases of HMPV infection could burden hospitals in the epidemic season. HMPV viral loads and genotypes have no correlation with co-infection or clinical characteristics.


Subject(s)
Genetic Variation , Genotype , Metapneumovirus/genetics , Paramyxoviridae Infections/epidemiology , Respiratory Tract Infections/epidemiology , Acute Disease/epidemiology , Adolescent , Beijing/epidemiology , Child , Child, Preschool , Coinfection/epidemiology , Coinfection/virology , Female , Hospitalization/statistics & numerical data , Humans , Infant , Male , Metapneumovirus/classification , Metapneumovirus/pathogenicity , Nasopharynx/virology , Paramyxoviridae Infections/virology , Respiratory Tract Infections/virology , Viral Load/statistics & numerical data
10.
J R Soc Interface ; 18(176): 20200916, 2021 03.
Article in English | MEDLINE | ID: covidwho-1161023

ABSTRACT

Epidemiological data about SARS-CoV-2 spread indicate that the virus is not transmitted uniformly in the population. The transmission tends to be more effective in select settings that involve exposure to relatively high viral dose, such as in crowded indoor settings, assisted living facilities, prisons or food processing plants. To explore the effect on infection dynamics, we describe a new mathematical model where transmission can occur (i) in the community at large, characterized by low-dose exposure and mostly mild disease, and (ii) in so-called transmission hot zones, characterized by high-dose exposure that can be associated with more severe disease. The model yields different types of epidemiological dynamics, depending on the relative importance of hot zone and community transmission. Interesting dynamics occur if the rate of virus release/deposition from severely infected people is larger than that of mildly infected individuals. Under this assumption, we find that successful infection spread can hinge upon high-dose hot zone transmission, yet the majority of infections are predicted to occur in the community at large with mild disease. In this regime, residual hot zone transmission can account for continued virus spread during community lockdowns, and the suppression of hot zones after community interventions are relaxed can cause a prolonged lack of infection resurgence following the reopening of society. This gives rise to the notion that targeted interventions specifically reducing virus transmission in the hot zones have the potential to suppress overall infection spread, including in the community at large. Epidemiological trends in the USA and Europe are interpreted in light of this model.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Models, Biological , Pandemics , SARS-CoV-2 , Basic Reproduction Number/statistics & numerical data , COVID-19/virology , Computer Simulation , Humans , Mathematical Concepts , Pandemics/prevention & control , Pandemics/statistics & numerical data , Quarantine , Viral Load/statistics & numerical data
11.
Epidemics ; 35: 100454, 2021 06.
Article in English | MEDLINE | ID: covidwho-1135321

ABSTRACT

The incubation period, or the time from infection to symptom onset, of COVID-19 has usually been estimated by using data collected through interviews with cases and their contacts. However, this estimation is influenced by uncertainty in the cases' recall of exposure time. We propose a novel method that uses viral load data collected over time since hospitalization, hindcasting the timing of infection with a mathematical model for viral dynamics. As an example, we used reported data on viral load for 30 hospitalized patients from multiple countries (Singapore, China, Germany, and Korea) and estimated the incubation period. The median, 2.5, and 97.5 percentiles of the incubation period were 5.85 days (95 % CI: 5.05, 6.77), 2.65 days (2.04, 3.41), and 12.99 days (9.98, 16.79), respectively, which are comparable to the values estimated in previous studies. Using viral load to estimate the incubation period might be a useful approach, especially when it is impractical to directly observe the infection event.


Subject(s)
COVID-19/transmission , Infectious Disease Incubation Period , Viral Load/statistics & numerical data , Adult , COVID-19/virology , China , Hospitalization , Humans , Male , Models, Theoretical , SARS-CoV-2
13.
J Gen Virol ; 102(3)2021 03.
Article in English | MEDLINE | ID: covidwho-1015423

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), presents a challenge to laboratorians and healthcare workers around the world. Handling of biological samples from individuals infected with the SARS-CoV-2 virus requires strict biosafety measures. Within the laboratory, non-propagative work with samples containing the virus requires, at minimum, Biosafety Level-2 (BSL-2) techniques and facilities. Therefore, handling of SARS-CoV-2 samples remains a major concern in areas and conditions where biosafety for specimen handling is difficult to maintain, such as in rural laboratories or austere field testing sites. Inactivation through physical or chemical means can reduce the risk of handling live virus and increase testing ability especially in low-resource settings due to easier and faster sample processing. Herein we assess several chemical and physical inactivation techniques employed against SARS-CoV-2 isolates from Cambodia. This data demonstrates that all chemical (AVL, inactivating sample buffer and formaldehyde) and heat-treatment (56 and 98 °C) methods tested completely inactivated viral loads of up to 5 log10.


Subject(s)
COVID-19/virology , Containment of Biohazards , SARS-CoV-2 , Specimen Handling , Virus Inactivation , Animals , Cambodia , Cells, Cultured , Chlorocebus aethiops , Hot Temperature , Humans , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Viral Load/drug effects , Viral Load/statistics & numerical data , Virus Inactivation/drug effects
14.
J Infect Dis ; 223(7): 1132-1138, 2021 04 08.
Article in English | MEDLINE | ID: covidwho-1003585

ABSTRACT

BACKGROUND: There is limited information on the association between upper respiratory tract (URT) viral loads, host factors, and disease severity in SARS-CoV-2-infected patients. METHODS: We studied 1122 patients (mean age, 46 years) diagnosed by polymerase chain reaction (PCR). URT viral load, measured by PCR cycle threshold, was categorized as high, moderate, or low. RESULTS: There were 336 (29.9%) patients with comorbidities; 309 patients (27.5%) had high, 316 (28.2%) moderate, and 497 (44.3%) low viral load. In univariate analyses, compared to patients with moderate or low viral load, patients with high viral load were older, more often had comorbidities, developed Symptomatic disease (COVID-19), were intubated, and died. Patients with high viral load had longer stay in intensive care unit and longer intubation compared to patients with low viral load (P values < .05 for all comparisons). Patients with chronic cardiovascular disease, hypertension, chronic pulmonary disease, immunosuppression, obesity, and chronic neurological disease more often had high viral load (P value < .05 for all comparisons). In multivariate analysis high viral load was associated with COVID-19. Level of viral load was not associated with any other outcome. CONCLUSIONS: URT viral load could be used to identify patients at higher risk for morbidity or severe outcome.


Subject(s)
COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Severity of Illness Index , Viral Load/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/therapy , COVID-19/virology , COVID-19 Nucleic Acid Testing/statistics & numerical data , Child , Child, Preschool , Comorbidity , Female , Humans , Infant , Infant, Newborn , Intensive Care Units/statistics & numerical data , Intubation, Intratracheal/statistics & numerical data , Length of Stay/statistics & numerical data , Male , Middle Aged , Nasopharynx/virology , Oropharynx/virology , Prospective Studies , Respiration, Artificial/statistics & numerical data , Young Adult
15.
Am J Trop Med Hyg ; 104(2): 540-545, 2020 Dec 23.
Article in English | MEDLINE | ID: covidwho-1000466

ABSTRACT

Controversy exists in the literature regarding the possible prognostic implications of the nasopharyngeal SARS-CoV-2 viral load. We carried out a retrospective observational study of 169 patients, 96 (58.9%) of whom had a high viral load and the remaining had a low viral load. Compared with patients with a low viral load, patients with a high viral load did not exhibit differences regarding preexisting cardiovascular risk factors or comorbidities. There were no differences in symptoms, vital signs, or laboratory tests in either group, except for the maximum cardiac troponin I (cTnI), which was higher in the group with a higher viral load (24 [interquartile range 9.5-58.5] versus 8.5 [interquartile range 3-22.5] ng/L, P = 0.007). There were no differences in the need for hospital admission, admission to the intensive care unit, or the need for mechanical ventilation in clinical management. In-hospital mortality was greater in patients who had a higher viral load than in those with low viral load (24% versus 10.4%, P = 0.029). High viral loads were associated with in-hospital mortality in the binary logistic regression analysis (odds ratio: 2.701, 95% Charlson Index (CI): 1.084-6.725, P = 0.033). However, in an analysis adjusted for age, gender, CI, and cTnI, viral load was no longer a predictor of mortality. In conclusion, an elevated nasopharyngeal viral load was not a determinant of in-hospital mortality in patients with COVID-19, as much as age, comorbidity, and myocardial damage determined by elevated cTnI are.


Subject(s)
COVID-19/mortality , COVID-19/virology , Hospital Mortality , Hospitals, University/statistics & numerical data , Viral Load/statistics & numerical data , Aged , Comorbidity , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Nasopharynx/virology , Prognosis , Retrospective Studies
16.
Laryngoscope ; 131(5): E1677-E1682, 2021 05.
Article in English | MEDLINE | ID: covidwho-888104

ABSTRACT

OBJECTIVES/HYPOTHESIS: The emergence of a new coronavirus strain (SARS-CoV-2) in December 2019 from China led to a global pandemic. The lack of herd immunity against this virus and the possibility of viral spread from asymptomatic individuals is still a major challenge for the prevention of viral transmission. The aim of this study was to evaluate the presence of the virus in different bodily secretions as a potential source of viral spread among patients infected with SARS-CoV-2. STUDY DESIGN: Cross Sectional Study. METHODS: The study included 38 COVID-19 patients with a positive real-time polymerase chain reaction (RT-PCR) test result for SARS-CoV-2, obtained from the combined nasopharyngeal-oropharyngeal swab samples. Saliva, tear, and cerumen samples were taken from the patients within 72 hours of the first RT-PCR test. SARS-CoV-2 N1 and N2 gene regions were studied with single-step RT-PCR in all samples. RESULTS: Among the studied samples, the highest positivity rate was in saliva (76.3%) followed by tears (55.3%) and cerumen (39.5%). Viral load in saliva was also significantly higher compared to tears and cerumen (P < .001), while there was no significant difference between tears and cerumen. Higher viral load in combined nasopharyngeal-oropharyngeal swab samples was associated with higher viral load in tears, but not in saliva or cerumen. Half of the saliva, tear, and cerumen samples obtained from asymptomatic patients contained SARS-CoV-2 genome. CONCLUSIONS: The virus was detected in the saliva, tears, and cerumen samples of both symptomatic and asymptomatic patients. The potential role of these bodily fluids on viral spread needs to be studied. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1677-E1682, 2021.


Subject(s)
Cerumen/virology , SARS-CoV-2/isolation & purification , Saliva/virology , Tears/virology , Adult , Aged , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/transmission , COVID-19/virology , COVID-19 Testing/methods , China/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Nasopharynx/virology , Oropharynx/virology , Real-Time Polymerase Chain Reaction/methods , SARS-CoV-2/genetics , Viral Load/statistics & numerical data
17.
Trials ; 21(1): 875, 2020 Oct 22.
Article in English | MEDLINE | ID: covidwho-886002

ABSTRACT

OBJECTIVES: The primary objective is to demonstrate that COVID-19 convalescent plasma (CCP) prevents progression to severe pneumonia in elderly COVID-19 pneumonia patients with chronic comorbidities. Secondary objectives are to demonstrate that CCP decreases the viral load in nasopharyngeal swabs and increases the anti-SARS-CoV-2 antibody titre in recipients. TRIAL DESIGN: This is a randomized, open-label, parallel group, phase II/III study with a superiority framework. The trial starts with a screening phase II designed with two-tailed alpha=0.2. In case of positive results, the trial will proceed in a formally comparative phase III (alpha=0.05). PARTICIPANTS: Adult patients with confirmed or suspected COVID-19 who are at risk according to CDC definition are eligible. Inclusion criteria are all the following: age ≥ 65; pneumonia at CT scan; PaO2/FiO2 ≥300 mmHg; presence of one or more comorbidities; signed informed consent. Exclusion criteria are one of the following: age < 65; PaO2/FiO2 < 300 mmHg; pending cardiopulmonary arrest; refusal to blood product transfusions; severe IgA deficiency; any life-threatening comorbidity or any other medical condition which, in the opinion of the investigator, makes the patient unsuitable for inclusion. The trial is being conducted at three reference COVID-19 centres in the middle of Italy. INTERVENTION AND COMPARATOR: Intervention: COVID-19 Convalescent Plasma (CCP) in addition to standard therapy. Patients receive three doses (200 ml/day on 3 consecutive days) of ABO matched CCP. Comparator: Standard therapy MAIN OUTCOMES: A. Primary outcome for Phase II: Proportion of patients without progression in severity of pulmonary disease, defined as worsening of 2 points in the ordinal scale of WHO by day 14. B. Primary outcome for Phase III: Proportion of patients without progression in severity of pulmonary disease, defined as worsening of 2 points in the ordinal scale of WHO by day 14. Secondary outcomes for Phase III: Decreased viral load on nasopharyngeal swab at days 6, 9 and 14; Decreased viremia at days 6 and 9; Increased antibody titer against SARS-CoV2 at days 30 and 60; Proportion of patients with negative of SARS-CoV2 nasopharyngeal swab at day 30; Length of hospital stay; Mortality rate at day 28; Total plasma related adverse event (day 60); Total non-plasma related adverse events (day 60); Severe adverse events (SAE) (day 60). RANDOMISATION: Treatment allocation is randomized with a ratio 1:1 in both phase II and phase III. Randomization sequences will be generated at Fondazione Policlinico Gemelli IRCCS through the RedCap web application. Randomized stratification is performed according to age (under/over 80 years), and sex. BLINDING (MASKING): None, this is an open-label trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Phase II: 114 patients (57 per arm). Phase III: 182 patients (91 per arm) TRIAL STATUS: The trial recruitment started on May 27, 2020. The anticipated date of recruitment completion is April 30, 2021. The protocol version is 2 (May 10, 2020). TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov (May 5, 2020). The Identifier number is NCT04374526 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/genetics , Blood Transfusion/methods , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Aged , Aged, 80 and over , Betacoronavirus/immunology , COVID-19 , Comorbidity , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Disease Progression , Female , Humans , Immunization, Passive/adverse effects , Immunization, Passive/methods , Informed Consent/ethics , Italy/epidemiology , Male , Mortality/trends , Pandemics , Pneumonia/diagnostic imaging , Pneumonia/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2 , Tomography, X-Ray Computed/methods , Viral Load/immunology , Viral Load/statistics & numerical data
18.
Appl Physiol Nutr Metab ; 46(1): 10-26, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-639400

ABSTRACT

Holder pasteurization (62.5 °C, 30 min) of human milk is thought to reduce the risk of transmitting viruses to an infant. Some viruses may be secreted into milk - others may be contaminants. The effect of thermal pasteurization on viruses in human milk has yet to be rigorously reviewed. The objective of this study is to characterize the effect of common pasteurization techniques on viruses in human milk and non-human milk matrices. Databases (MEDLINE, Embase, Web of Science) were searched from inception to April 20th, 2020, for primary research articles assessing the impact of pasteurization on viral load or detection of live virus. Reviews were excluded, as were studies lacking quantitative measurements or those assessing pasteurization as a component of a larger process. Overall, of 65 131 reports identified, 109 studies were included. Pasteurization of human milk at a minimum temperature of 56-60 °C is effective at reducing detectable live virus. In cell culture media or plasma, coronaviruses (e.g., SARS-CoV, SARS-CoV-2, MERS-CoV) are highly susceptible to heating at ≥56 °C. Although pasteurization parameters and matrices reported vary, all viruses studied, except parvoviruses, were susceptible to thermal killing. Future research important for the study of novel viruses should standardize pasteurization protocols and should test inactivation in human milk. Novelty In all matrices, including human milk, pasteurization at 62.5 °C was generally sufficient to reduce surviving viral load by several logs or to below the limit of detection. Holder pasteurization (62.5 °C, 30 min) of human milk should be sufficient to inactivate nonheat resistant viruses, including coronaviruses, if present.


Subject(s)
Milk, Human/virology , Milk/virology , Pasteurization/methods , Viral Load/statistics & numerical data , Animals , Humans
19.
Microbes Infect ; 22(10): 617-621, 2020.
Article in English | MEDLINE | ID: covidwho-745971

ABSTRACT

RT-PCRs to detect SARS-CoV-2 RNA is key to manage the COVID-19 pandemic. We analyzed SARS-CoV-2 viral loads from 22'323 RT-PCR results according to samples types, gender, age, and health units. Viral load did not show any difference across age and appears to be a poor predictor of disease outcome. SARS-CoV-2 viral load showed similar high viral loads than the one observed for RSV and influenza B. The importance of viral load to predict contagiousness and to assess disease progression is discussed.


Subject(s)
COVID-19/virology , Coronavirus Infections/virology , SARS-CoV-2/isolation & purification , Viral Load/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing , Child , Child, Preschool , Coronavirus Infections/diagnosis , Disease Progression , Female , Humans , Infant , Infant, Newborn , Influenza B virus/isolation & purification , Influenza, Human/virology , Male , Middle Aged , Pandemics , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/isolation & purification , Serologic Tests/methods , Switzerland/epidemiology
20.
JAMA Cardiol ; 5(11): 1281-1285, 2020 11 01.
Article in English | MEDLINE | ID: covidwho-676377

ABSTRACT

Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be documented in various tissues, but the frequency of cardiac involvement as well as possible consequences are unknown. Objective: To evaluate the presence of SARS-CoV-2 in the myocardial tissue from autopsy cases and to document a possible cardiac response to that infection. Design, Setting, and Participants: This cohort study used data from consecutive autopsy cases from Germany between April 8 and April 18, 2020. All patients had tested positive for SARS-CoV-2 in pharyngeal swab tests. Exposures: Patients who died of coronavirus disease 2019. Main Outcomes and Measures: Incidence of SARS-CoV-2 positivity in cardiac tissue as well as CD3+, CD45+, and CD68+ cells in the myocardium and gene expression of tumor necrosis growth factor α, interferon γ, chemokine ligand 5, as well as interleukin-6, -8, and -18. Results: Cardiac tissue from 39 consecutive autopsy cases were included. The median (interquartile range) age of patients was 85 (78-89) years, and 23 (59.0%) were women. SARS-CoV-2 could be documented in 24 of 39 patients (61.5%). Viral load above 1000 copies per µg RNA could be documented in 16 of 39 patients (41.0%). A cytokine response panel consisting of 6 proinflammatory genes was increased in those 16 patients compared with 15 patients without any SARS-CoV-2 in the heart. Comparison of 15 patients without cardiac infection with 16 patients with more than 1000 copies revealed no inflammatory cell infiltrates or differences in leukocyte numbers per high power field. Conclusions and Relevance: In this analysis of autopsy cases, viral presence within the myocardium could be documented. While a response to this infection could be reported in cases with higher virus load vs no virus infection, this was not associated with an influx of inflammatory cells. Future investigations should focus on evaluating the long-term consequences of this cardiac involvement.


Subject(s)
Autopsy/methods , COVID-19/complications , Cardiovascular Infections/etiology , SARS-CoV-2/genetics , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Cardiovascular Infections/metabolism , Cardiovascular Infections/virology , Chemokines/metabolism , Cohort Studies , Female , Germany/epidemiology , Humans , Incidence , Interferon-gamma/metabolism , Interleukin-18/metabolism , Interleukin-6/metabolism , Interleukin-8/metabolism , Male , Myocarditis/etiology , Myocarditis/metabolism , Myocarditis/virology , Myocardium/immunology , Myocardium/metabolism , Pandemics , Peptide Fragments/metabolism , SARS-CoV-2/isolation & purification , Tumor Necrosis Factor-alpha/metabolism , Viral Load/statistics & numerical data
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