Development and validation of a prediction model for severe respiratory failure in hospitalized patients with SARS-CoV-2 infection: a multicentre cohort study (PREDI-CO study)

ObjectivesWe aimed to develop and validate a risk score to predict severe respiratory failure (SRF) among patients hospitalized with coronavirus disease-2019 (COVID-19).MethodsWe performed a multicentre cohort study among hospitalized (>24 hours) patients diagnosed with COVID-19 from 22 February to 3 April 2020, at 11 Italian hospitals. Patients were divided into derivation and validation cohorts according to random sorting of hospitals. SRF was assessed from admission to hospital discharge and was defined as: Spo₂ <93% with 100% Fio₂, respiratory rate >30 breaths/min or respiratory distress. Multivariable logistic regression models were built to identify predictors of SRF, β-coefficients were used to develop a risk score. Trial Registration NCT04316949.ResultsWe analysed 1113 patients (644 derivation, 469 validation cohort). Mean (±SD) age was 65.7 (±15) years, 704 (63.3%) were male. SRF occurred in 189/644 (29%) and 187/469 (40%) patients in the derivation and validation cohorts, respectively. At multivariate analysis, risk factors for SRF in the derivation cohort assessed at hospitalization were age ≥70 years (OR 2.74; 95% CI 1.66–4.50), obesity (OR 4.62; 95% CI 2.78–7.70), body temperature ≥38°C (OR 1.73; 95% CI 1.30–2.29), respiratory rate ≥22 breaths/min (OR 3.75; 95% CI 2.01–7.01), lymphocytes ≤900 cells/mm³ (OR 2.69; 95% CI 1.60–4.51), creatinine ≥1 mg/dL (OR 2.38; 95% CI 1.59–3.56), C-reactive protein ≥10 mg/dL (OR 5.91; 95% CI 4.88–7.17) and lactate dehydrogenase ≥350 IU/L (OR 2.39; 95% CI 1.11–5.11). Assigning points to each variable, an individual risk score (PREDI-CO score) was obtained. Area under the receiver-operator curve was 0.89 (0.86–0.92). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 71.6% (65%–79%), 89.1% (86%–92%), 74% (67%–80%) and 89% (85%–91%), respectively. PREDI-CO score showed similar prognostic ability in the validation cohort: area under the receiver-operator curve 0.85 (0.81–0.88). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 80% (73%–85%), 76% (70%–81%), 69% (60%–74%) and 85% (80%–89%), respectively.ConclusionPREDI-CO score can be useful to allocate resources and prioritize treatments during the COVID-19 pandemic.     

Impact of dexamethasone on SARS-CoV-2 concentration kinetics and antibody response in hospitalized COVID-19 patients: results from a prospective observational study

ObjectivesDexamethasone has become the standard of care for severe coronavirus disease 2019 (COVID-19), but its virological impact is poorly understood. The objectives of this work were to characterize the kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) concentration in the upper respiratory tract (URT) and the antibody response in patients with (D⁺) and without (D^–) dexamethasone treatment.MethodsData and biosamples from hospitalized patients with severe COVID-19, enrolled between 4th March and 11th December 2020 in a prospective observational study, were analysed. SARS-CoV-2 virus concentration in serial URT samples was measured using RT-PCR. SARS-CoV-2-specific immunoglobulins A and G (IgA and IgG) were measured in serum samples using S1-ELISA.ResultsWe compared 101 immunocompetent patients who received dexamethasone (according to the inclusion criteria and dosage determined in the RECOVERY trial) to 93 immunocompetent patients with comparable disease severity from the first months of the pandemic, who had not been treated with dexamethasone or other glucocorticoids. We found no inter-group differences in virus concentration kinetics, duration of presence of viral loads >10⁶ viral copies/mL (D⁺ median 17 days (IQR 13–24), D^– 19 days (IQR 13–29)), or time from symptom onset until seroconversion (IgA: D⁺ median 11.5 days (IQR 11–12), D^– 14 days (IQR 11.5–15.75); IgG: D⁺ 13 days (IQR 12–14.5), D^– 12 days (IQR 11–15)).ConclusionDexamethasone does not appear to lead to a change in virus clearance or a delay in antibody response in immunocompetent patients hospitalized with severe COVID-19.     

SARS-CoV-2 new infections among health-care workers after the first dose of the BNT162b2 mRNA COVID-19 vaccine. A hospital-wide cohort study

ObjectivesTo evaluate the effect of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on the incidence of new SARS-CoV-2 infections in health-care workers (HCW).MethodsThe evolution of the incident rate of microbiologically confirmed SARS-CoV-2 infection in a cohort of 2590 HCW after BNT162b2 mRNA SARS-CoV-2 vaccination, compared with the rate in the community (n = 170 513) was evaluated by mixed Poisson regression models.ResultsA total of 1820 HCW (70.3% of total) received the first dose of the BNT162b2 mRNA vaccine between 10 January and 16 January 2021, and 296 (11.4%) received it the following week. All of them completed vaccination 3 weeks later. Incidence rates of SARS-CoV-2 infection after the first dose of mRNA SARS-CoV-2 vaccine declined by 71% (Incidence Rate Ratio (IRR) 0.286, 95% CI 0.174–0.468; p < 0.001) and by 97% (IRR 0.03, 95% CI 0.013–0.068; p < 0.001) after the second dose, compared with the perivaccine time. SARS-CoV-2 incidence rates in the community (with a negligible vaccination rate) had a much lower decline: 2% (IRR 0.984, 95% CI 0.943–1.028; p 0.47) and 61% (IRR 0.390, 95% CI 0.375–0.406; p < 0.001) for equivalent periods. Adjusting for the decline in the community, the reduction in the incident rates among HCW were 73% (IRR 0.272, 95% CI 0.164–0.451 p < 0.001) after the first dose of the vaccine and 92% (IRR 0.176, 95% CI 0.033–0.174; p < 0.001) after the second dose.ConclusionsmRNA SARS-CoV-2 vaccination is associated with a dramatic decline in new SARS-CoV-2 infection among HCW, even before the administration of the second dose of the vaccine.     

Seroprevalence of severe acute respiratory syndrome coronavirus 2 in Slovenia: results of two rounds of a nationwide population study on a probability-based sample,challenges and lessons learned

ObjectivesSeroprevalence surveys provide crucial information on cumulative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure. This Slovenian nationwide population study is the first longitudinal 6-month serosurvey using probability-based samples across all age categories.MethodsEach participant supplied two blood samples: 1316 samples in April 2020 (first round) and 1211 in October/November 2020 (second round). The first-round sera were tested using Euroimmun Anti-SARS-CoV-2 ELISA IgG (ELISA) and, because of uncertain estimates, were retested using Elecsys Anti-SARS-CoV-2 (Elecsys-N) and Elecsys Anti-SARS-CoV-2 S (Elecsys-S). The second-round sera were concomitantly tested using Elecsys-N/Elecsys-S.ResultsThe populations of both rounds matched the overall population (n = 3000), with minor settlement type and age differences. The first-round seroprevalence corrected for the ELISA manufacturer's specificity was 2.78% (95% highest density interval [HDI] 1.81%–3.80%), corrected using pooled ELISA specificity calculated from published data 0.93% (95% CI 0.00%–2.65%), and based on Elecsys-N/Elecsys-S results 0.87% (95% HDI 0.40%–1.38%). The second-round unadjusted lower limit of seroprevalence on 11 November 2020 was 4.06% (95% HDI 2.97%–5.16%) and on 3 October 2020, unadjusted upper limit was 4.29% (95% HDI 3.18%–5.47%).ConclusionsSARS-CoV-2 seroprevalence in Slovenia increased four-fold from late April to October/November 2020, mainly due to a devastating second wave. Significant logistic/methodological challenges accompanied both rounds. The main lessons learned were a need for caution when relying on manufacturer-generated assay evaluation data, the importance of multiple manufacturer-independent assay performance assessments, the need for concomitant use of highly-specific serological assays targeting different SARS-CoV-2 proteins in serosurveys conducted in low-prevalence settings or during epidemic exponential growth and the usefulness of a Bayesian approach for overcoming complex methodological challenges.     

Early antibody response in health-care professionals after two doses of SARS-CoV-2 mRNA vaccine (BNT162b2)

ObjectivesData on the immune response after two doses of BNT162b2 are so far limited. Previously infected individuals were excluded from pivotal clinical trials and the optimum dose regimen in this population has not been clearly studied. The CRO-VAX HCP study aims to investigate the early antibody response in a population of health-care professionals having received two doses of the BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine.MethodsThe CRO-VAX HCP study is a multicentre, prospective, interventional study conducted in several sites in Belgium. The study included 231 health-care professional volunteers who received the two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine. Of these, 73 were previously infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 158 were uninfected and seronegative. In the first group, blood samples were collected at baseline and after 2, 4, 7, 10, 14, 21 and 28 days. In the second group, samples were obtained at baseline and after 14 and 28 days. Antibodies against the SARS-CoV-2 nucleocapsid and the receptor binding domain of the S1 subunit of the spike protein were measured in all individuals at different time-points.ResultsIn uninfected individuals, 95.5% (95% CI 91.0%–98.2%) developed anti-spike antibodies after 14 days and a 24.9-fold rise (95% CI 21.4%–28.9%) in antibody titre was observed after the second dose. In previously infected individuals, peak antibody response was reached after 7 days (i.e. 6347 U/mL) and the second dose did not lead to significantly higher antibody titres (i.e. 8856–11 911 U/mL). Antibody titres were higher in previously infected individuals.ConclusionsThis study supports the concept that a single dose of BNT162b2 would be sufficient in previously infected individuals.     

High-speed large-scale automated isolation of SARS-CoV-2 from clinical samples using miniaturized co-culture coupled to high-content screening

ObjectivesA novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the current coronavirus disease 2019 global pandemic. Only a few laboratories routinely isolate the virus, which is because the current co-culture strategy is highly time-consuming and requires a biosafety level 3 laboratory. This work aimed to develop a new high-throughput isolation strategy using novel technologies for rapid and automated isolation of SARS-CoV-2.MethodsWe used an automated microscope based on high-content screening (HCS), and we applied specific image analysis algorithms targeting cytopathic effects of SARS-CoV-2 on Vero E6 cells. A randomized panel of 104 samples, including 72 that tested positive by RT-PCR and 32 that tested negative, were processed with our HCS strategy and were compared with the classical isolation procedure.ResultsThe isolation rate was 43% (31/72) with both strategies on RT-PCR-positive samples and was correlated with the initial RNA viral load in the samples, in which we obtained a positivity threshold of 27 Ct. Co-culture delays were shorter with the HCS strategy, where 80% (25/31) of the positive samples were recovered by the third day of co-culture, compared with only 26% (8/30) with the classic strategy. Moreover, only the HCS strategy allowed us to recover all the positive samples (31 with HCS versus 27 with classic strategy) after 1 week of co-culture.ConclusionsThis system allows the rapid and automated screening of clinical samples with minimal operator workload, which reduces the risk of contamination and paves the way for future applications in clinical microbiology, such as large-scale drug susceptibility testing.     

Prevalence and impact factors of recurrent positive SARS-CoV-2 detection in 599 hospitalized COVID-19 patients

ObjectivesRepeat-positive tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals with coronavirus disease 2019 (COVID-19) were common. We aimed to investigate the rate and risk factors of recurrent positive detection of SARS-CoV-2 in hospitalized individuals with COVID-19.MethodsOropharyngeal and nasopharyngeal swabs (n = 3513) were collected to detect SARS-CoV-2 during the hospitalization. We analysed the recurrent positive rate after consecutive negative results and its relationship to demographic characteristics.ResultsAmong 599 enrolled individuals with COVID-19, the median time for viral RNA shedding was 24 days (interquartile range 19–33 days). The positive rates of RT-PCR were 35.9% (215/599), 17.0% (65/383) and 12.4% (23/185) after one, two and three consecutive negative RT-PCR test results, respectively. Medians of Ct values of initial positive test, rebound positive test after two consecutive negative results, and rebound positive after three consecutive negative results were 28.8, 32.8 and 36.1, respectively. Compared with male patients, females had a significantly higher rate of recurrent positive RT-PCR after three consecutive negative results (18.2%, 18/99, versus 5.8%, 5/86; p 0.013). Older individuals (≥55 years) had a significantly higher rate of recurrent positive RT-PCR after one negative result (42.3%, 165/390, versus 23.9%, 50/209; p < 0.001). Nasopharyngeal swab tests produced a higher positive rate than oropharyngeal swab tests (37.3%, 152/408, versus 35.8%, 1111/3105).ConclusionOur study revealed the prevalence and dynamic characteristics of recurrent positive RT-PCR to SARS-CoV-2. We showed that around 17.0% (65/383) of patients tested positive for SARS-CoV-2 after two consecutive negative results. Patients with a rebound positive RT-PCR test had a low viral load. Older age and being female were risk factors for recurrent positive results.     

SARS-CoV-2 infection: the environmental endurance of the virus can be influenced by the increase of temperature

ObjectivesTo evaluate whether the increase of temperature can influence the environmental endurance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsVirus was inoculated on a plastic surface and harvested at predefined time-points in parallel at 20°C–25°C (room temperature; RT) and at 28°C (June temperature; JT). Samples were tested by TCID₅₀ titres on Vero cells.ResultsOur results confirm that fomite transmission of the emerging SARS-CoV-2 is possible: the virus reserved its ability to infect cells for up to 84 hours at both RT and JT on a plastic surface, with TCID₅₀ viral titres of 0.67 and 0.25 log₁₀, respectively. At RT, an important reduction in the viral titre, from 4 log₁₀ to 3 log₁₀ TCID₅₀, was observed during the first 24–36 hours. At JT, the same decay was observed more rapidly (between 8 and 12 hours), The rate of viral inactivation by D-value was 24.74 hours at RT and 12.21 hours at JT.ConclusionsThis remarkable difference between the two temperatures suggests that virus vitality can be influenced by the environmental temperature and that the hot season could reduce the probability of COVID-19 transmission.     

Monitoring the SARS-CoV-2 pandemic: screening algorithm with single nucleotide polymorphism detection for the rapid identification of established and emerging variants

ObjectivesTo evaluate a testing algorithm for the rapid identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that includes the use of PCR-based targeted single nucleotide polymorphism (SNP) detection assays preceded by a multiplex PCR sensitive to S-Gene Target Failure (SGTF).MethodsPCR SNP assays targeting SARS-CoV-2 S-gene mutations ΔH69–V70, L452R, E484K, N501Y, H655Y and P681R using melting curve analysis were performed on 567 samples in which SARS-CoV-2 viral RNA was detected by a multiplex PCR. Viral whole-genome sequencing (WGS) was performed to confirm the presence of SNPs and to identify the Pangolin lineage. Additionally, 1133 SARS-CoV-2 positive samples with SGTF were further assessed by WGS to determine the presence of ΔH69–V70.ResultsThe N501Y-specific assay (n = 567) had an overall percentage agreement (OPA) of 98.5%. The ΔH69-V70-specific (n = 178) and E484K-specific (n = 401) assays had OPA of 96.6% and 99.7%, respectively. Assessment of H655Y (n = 139) yielded a 100.0% concordance when applied in the proposed algorithm. The L452R-specific (n = 67) and P681R-specific (n = 62) assays had an OPA of 98.2% and 98.1%, respectively. The proposed algorithm identified six variants of concern/interest (VOC/VOI)—Alpha (n = 149), Beta (n = 65), Gamma (n = 86), Delta (n = 49), Eta (n = 6), Kappa (n = 6)—and 205 non-VOC/VOI strains—including the variants under monitoring B.1.214.2 (n = 43) and B.1.1.318 (n = 18) and Epsilon (n = 1). An excellent concordance was observed for the identification of all SARS-CoV-2 lineages evaluated.ConclusionsWe present a flexible testing algorithm for the rapid detection of current and emerging SARS-CoV-2 VOC/VOIs, which can be easily adapted based on the local endemicity of specific variants.     

Epidemiological and clinical features of asymptomatic patients with SARS-CoV-2 infection

Few studies reported the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients with completely asymptomatic throughout the disease course. We investigated the epidemiological and clinical features of patients infected by SARS-CoV-2 without any symptoms. Patients with confirmed SARS-CoV-2 infection were retrospectively recruited. The demographic characteristics, clinical data, treatment, and outcomes of SARS-CoV-2 infected patients without any symptoms were analyzed. Fifteen (4.4%) of 342 SARS-CoV-2 infected patients did not develop any symptom during the course of the disease. The median time from exposure to diagnosis was 7.0 days (interquartile range [IQR]: 1.0-15.0 days). Of the 15 patients, 14 patients were diagnosed by tested positive for SARS-CoV-2 in throat swabs, while one patient was only tested positive for SARS-CoV-2 in anal swabs. During hospitalization, only 1 (6.7%) patient developed lymphopenia. Abnormalities of chest computed tomography examinations were detected in 8 (53.4%) patients on admission. As of 8 March 2020, all patients have been discharged. The median time of SARS-CoV-2 tested negative from admission was 7.0 days (IQR: 4.0-9.0 days). Patients without any symptoms but with SARS-CoV-2 exposure should be closely monitored and tested for SARS-CoV-2 both in anal and throat swabs to excluded the infection. Asymptomatic patients infected by SARS-CoV-2 have favorable outcomes.     

不同人群中SARS-CoV-2抗体检测的作用价值

目的:探讨新型冠状病毒（severe acute respiratory syndrome coronavirus 2,SARS-CoV-2）特异性IgM和IgG抗体检测应用于不同人群新型冠状病毒肺炎（corona virus disease 2019,COVID-19）诊断和筛查的作用价值。方法:回顾性分析2020年...     

Self-testing for the detection of SARS-CoV-2 infection with rapid antigen tests for people with suspected COVID-19 in the community

ObjectivesTo evaluate the performance of nasal mid-turbinate self-testing using rapid antigen detection tests (RDT) for persons with suspected coronavirus disease 2019 (COVID-19) in the community. Self-testing for COVID-19 infection with lateral flow assay severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RDT, provides rapid results and could enable frequent and extensive testing in the community, thereby improving the control of SARS-CoV-2.MethodsParticipants visiting a municipal SARS-CoV-2 testing centre, received self-testing kits containing either the BD Veritor System (BD-RDT) or Roche SARS-CoV-2 antigen detection test (Roche-RDT). Oro-nasopharyngeal swabs were collected from the participants for quantitative RT-PCR (qRT-PCR) testing. As a proxy for contagiousness, viral culture was performed on a selection of qRT-PCR positive samples to determine the Ct-value at which the chance of a positive culture dropped below 0.5 (Ct-value cut-off). Sensitivity and specificity of self-testing were compared to qRT-PCR with a Ct-value below the Ct value cut-off. Determinants independently associated with a false-negative self-test result were determined.ResultsA total of 3201 participants were included (BD-RDT n = 1595; Roche-RDT n = 1606). Sensitivity and specificity of self-testing compared with the qRT-PCR results with a Ct-value below the Ct-value cut-off were 78.4% (95% CI 73.2%–83.5%) and 99.4% (95% CI 99.1%–99.7%), respectively. A higher age was independently associated with a false-negative self-testing result with an odds ratio of 1.024 (95% CI 1.003–1.044).ConclusionsSelf-testing using currently available RDT has a high specificity and relatively high sensitivity to identify individuals with a high probability of contagiousness.     

2020年北京市大兴区新型冠状病毒肺炎疫情流行特征分析

目的:分析2020年北京市大兴区报告的新型冠状病毒肺炎（coronavirus disease 2019,COVID-19）病例的流行病学特征,为大兴区进一步做好COVID-19疫情防控提供依据。方法:收集2020年报告的大兴区COVID-19病例的流行病学调查信息,采用描述性流行病学方法对病例进行人群、时间和空间分布...     

Clinical outcomes in COVID-19 patients infected with different SARS-CoV-2 variants in Marseille,France

ObjectivesTo compare the clinical and epidemiological aspects associated with different predominant lineages circulating in Marseille from March 2020 to January 2021.MethodsIn this single-centre retrospective cohort study, characteristics of patients infected with four different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were documented from medical files. The outcome was the occurrence of clinical failure, defined as hospitalization (for outpatients), transfer to the intensive care unit (inpatients) and death (all).ResultsA total of 254 patients were infected with clade 20A (20AS), 85 with Marseille-1 (M1V), 190 with Marseille-4 (M4V) and 211 with N501Y (N501YV) variants. 20AS presented a bell-shaped epidemiological curve and nearly disappeared around May 2020. M1V reached a very weak peak, then disappeared after six weeks. M4V appeared in July presented an atypical wave form for 7 months. N501YV has only recently appeared. Compared with 20AS, patients infected with M1V were less likely to report dyspnoea (adjusted odds ratio (OR) 0.50, p 0.04), rhinitis (aOR 0.57, p 0.04) and to be hospitalized (aOR 0.22, p 0.002). Patients infected with M4V were more likely to report fever than those with 20AS and M1V (aOR 2.49, p < 0.0001 and aOR 2.30, p 0.007, respectively) and to be hospitalized than those with M1V (aOR 4.81, p 0.003). Patients infected with N501YV reported lower rate of rhinitis (aOR 0.50, p 0.001) and anosmia (aOR 0.57, p 0.02), compared with those infected with 20AS. A lower rate of hospitalization was associated with N501YV infection compared with 20AS and M4V (aOR 0.33, p < 0.0001 and aOR 0.27, p < 0.0001, respectively).ConclusionsThe four lineages have presentations that differ from one another, epidemiologically and clinically. This supports SARS-CoV-2 genomic surveillance through next-generation sequencing.     

Remdesivir use in the coronavirus disease 2019 pandemic: A mini-review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative viral pathogen of coronavirus disease 2019 (COVID-19), appears to have various clinical presentations and may result in severe respiratory failure. The global SARS-CoV-2-associated viral pneumonia pandemic was first reported in December 2019 in China. Based on known pharmacological mechanisms, many therapeutic drugs have been repurposed to target SARS-CoV-2. Among these drugs, remdesivir appears to be the currently most promising according to several clinical trials and reports of compassionate use. In this mini-review, we summarize the current evidence on the efficacy and challenges of remdesivir for the treatment of coronavirus disease 2019 (COVID-19).     

Use of an antiviral mouthwash as a barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: a multicentre,randomized, double-blind controlled trial

ObjectivesTo determine if commercially available mouthwash with β-cyclodextrin and citrox (bioflavonoids) (CDCM) could decrease the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) salivary viral load.MethodsIn this randomized controlled trial, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive patients aged 18–85 years with asymptomatic to mild coronavirus disease 2019 (COVID-19) symptoms for <8 days were recruited. A total of 176 eligible patients were randomly assigned (1:1) to CDCM or placebo. Three rinses daily were performed for 7 days. Saliva sampling was performed on day 1 at 09.00 (T1), 13.00 (T2) and 18.00 (T3). On the following 6 days, one sample was taken at 15.00. Quantitative RT-PCR was used to detect SARS-CoV-2.ResultsThe intention-to-treat analysis demonstrated that, over the course of 1 day, CDCM was significantly more effective than placebo 4 hours after the first dose (p 0.036), with a median percentage (log₁₀ copies/mL) decrease T1–T2 of –12.58% (IQR –29.55% to –0.16%). The second dose maintained the low median value for the CDCM (3.08 log₁₀ copies/mL; IQR 0–4.19), compared with placebo (3.31 log₁₀ copies/mL; IQR 1.18–4.75). At day 7, there was still a greater median percentage (log₁₀ copies/mL) decrease in salivary viral load over time in the CDCM group (–58.62%; IQR –100% to –34.36%) compared with the placebo group (–50.62%; IQR –100% to –27.66%). These results were confirmed by the per-protocol analysis.ConclusionsThis trial supports the relevance of using CDCM on day 1 (4 hours after the initial dose) to reduce the SARS-CoV-2 viral load in saliva. For long-term effect (7 days), CDMC appears to provide a modest benefit compared with placebo in reducing viral load in saliva.