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.     

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.     

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.     

The impact of COVID-19 on liver injury in various age

The coronavirus disease 2019 (COVID-19) disease was first detected in December 2019 in Wuhan, China. This disease is currently one of the most important global health problems. The novel coronavirus COVID-19 is a respiratory illness, that has caused a deadly pandemic that is spreading rapidly around the world. It is not only a respiratory system virus that causes severe lung disease, but also a systemic disease agent that can affect all systems. People with COVID-19 disease usually have respiratory signs, however, the liver disorder is not an uncommon presentation. In addition, many studies around the world have revealed that the liver is injured to various degrees in patients with severe acute respiratory syndrome coronavirus 2 disease. This review mainly focuses on the impact of COVID-19 on Liver Injury at various ages.     

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.     

COVID-19 and geographical area of origin

ObjectivesTo describe and compare the main clinical characteristics and outcome measures in hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) according to geographical area of origin.MethodsA retrospective analysis of patients hospitalized with confirmed COVID-19 at a referral centre in Madrid, Spain, during March–May 2020 was performed. Recorded variables (age, gender, intensive care unit (ICU) admission, outcome), and geographical area of origin were compared for Europeans and non-Europeans (Latin Americans, Asians and Africans).ResultsIn total, 2345 patients with confirmed COVID-19 hospitalized during the study period were included in the study. Of these, 1956 (83.4%) were European and 389 (16.6%) were non-European (of whom over 90%, 354/389, were Latin American). Non-Europeans were significantly younger than Europeans (mean 54 (SD 13.5) versus 70.4 (SD 15.1) years, p < 0.001); the majority were male (1420/2345, 60.6%), with no significant differences in gender between Europeans and non-Europeans (1197/1956 (61.2%) male in the European group versus 223/389 (57.3%) male in the non-European group, p 0.15). In-hospital mortality overall was higher in Europeans (443/1956, 22.7%) than in non-Europeans (40/389, 10.3%) (p < 0.001), but there were no significant differences when adjusted for age/gender (OR 1.27, 95% CI 0.86–1.88). Non-Europeans were more frequently admitted to ICU (71/389, 18.3%) compared with Europeans (187/1956, 9.6%) (p < 0.001) and a difference in ICU admission rate was also found when adjusted for age/gender (OR 1.43, 95% CI 1.03–1.98).ConclusionsNo significant differences in mortality were observed between Europeans and non-Europeans (mainly Latin Americans), but an increase in ICU admission rate was found in non-Europeans.     

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.     

Rectally shed SARS-CoV-2 in COVID-19 inpatients is consistently lower than respiratory shedding and lacks infectivity

ObjectivesAssessment of whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been propagated during intestinal passage and infectivity is conserved when shed rectally by hospitalized individuals.MethodsAn exploratory cohort study including 28 inpatients with coronavirus disease 2019 with estimation of RNA levels by RT-PCR and of viral infectivity by culturing of viral material sampled concomitantly and identically from pharynx and rectum.ResultsSARS-CoV-2 RNA was detected more frequently (91%, 30/33 versus 42%, 14/33, p <0.0001) and at higher concentrations (median levels 2 190 186 IU/mL versus 13 014 IU/mL, p <0.0001) in the pharyngeal swabs than in the rectal swabs. For all sample pairs (n = 33) the rectal swabs contained undetectable or lower SARS-CoV-2 RNA concentrations than their paired pharyngeal swabs. Replicative virus was found in 37% (11/30) of the PCR-positive pharyngeal swabs, whereas none of the PCR-positive rectal swabs could be cultured (0%, 0/14) despite containing SARS-CoV-2 RNA concentrations up to 1 544 691 IU/mL.ConclusionsOur data draw into question whether SARS-CoV-2 is transmitted readily from faeces.     

A compendium answering 150 questions on COVID-19 and SARS-CoV-2

In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID-19). This disease, caused by the severe acute respiratory syndrome–related coronavirus 2 (SARS-CoV-2), has developed into a pandemic. To date, it has resulted in ~9 million confirmed cases and caused almost 500 000 related deaths worldwide. Unequivocally, the COVID-19 pandemic is the gravest health and socioeconomic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence-based medical advice on SARS-CoV-2 and COVID-19. Although the majority of the patients show a very mild, self-limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID-19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a “cytokine storm” leading to acute respiratory distress syndrome, endothelitis, thromboembolic complications, and multiorgan failure. The epidemiologic features of COVID-19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID-19–related topics should be based on more coordinated high-quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS-CoV-2, COVID-19, and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development, and epidemiology. A total of 150 questions were answered by experts in the field providing a comprehensive and practical overview of COVID-19 and allergic disease.     

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.     

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.     

Impact of COVID-19 on Pregnancy

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is an emerging disease. There has been a rapid increase in cases and deaths since it was identified in Wuhan, China, in early December 2019, with over 4,000,000 cases of COVID-19 including at least 250,000 deaths worldwide as of May 2020. However, limited data about the clinical characteristics of pregnant women with COVID-19 have been reported. Given the maternal physiologic and immune function changes during pregnancy, pregnant women may be at a higher risk of being infected with SARS-CoV-2 and developing more complicated clinical events. Information on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) may provide insights into the effects of COVID-19''s during pregnancy. Even though SARS and MERS have been associated with miscarriage, intrauterine death, fetal growth restriction and high case fatality rates, the clinical course of COVID-19 pneumonia in pregnant women has been reported to be similar to that in non-pregnant women. In addition, pregnant women do not appear to be at a higher risk of catching COVID-19 or suffering from more severe disease than other adults of similar age.Moreover, there is currently no evidence that the virus can be transmitted to the fetus during pregnancy or during childbirth. Babies and young children are also known to only experience mild forms of COVID-19. The aims of this systematic review were to summarize the possible symptoms, treatments, and pregnancy outcomes of women infected with COVID-19 during pregnancy.     

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.     

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.