Maternal and neonatal outcomes of French prospective multicenter cohort study COVIPREG during the first two COVID-19 waves.

BACKGROUND: SARS-CoV-2 infection on pregnant women was the subject of many questions since the COVID-19 pandemic. METHODS: We aim to assess maternal and neonatal outcomes of SARS-CoV-2 infection contracted during 2nd and 3rd trimesters of pregnancy during the first two COVID-19 waves across a prospective French multicenter cohort study. Patients were included between April 2020 and January 2021 in 10 maternity hospitals in Paris area with two groups (i) pregnant women with a positive SARS-CoV-2 nasopharyngeal RT-PCR between [14WG; 37WG[(symptomatic infection), (ii) pregnant women with a negative serology (or equivocal) at delivery and without a positive SARS-CoV-2 nasopharyngeal RT-PCR at any time during pregnancy (G2 group) MAIN FINDINGS: 2410 pregnant women were included, of whom 310 had a positive SARS-CoV-2 nasopharyngeal RT-PCR and 217 between [14WG; 37WG[. Most infections occurred between 28 and 37 weeks of gestation (56 %). Most patients could be managed as outpatients, while 23 % had to be hospitalized. Among women with a positive RT-PCR, multiparous women were over-represented (OR = 2.45[1.52;3.87]); were more likely to deliver before 37 weeks of gestation (OR = 2.19[1.44;3.24]) and overall cesarean deliveries were significantly increased (OR = 1.53[1.09;2.13]). CONCLUSIONS: This study highlights the maternal, obstetrical, and neonatal burden associated with SARS-CoV-2 infections during the first two pandemic waves before availability of vaccines. TRIAL REGISTRATION: NCT04355234 (registration date: 21/04/2020).

SARS-CoV-2 RT-PCR as a universal screening on planned admission in asymptomatic patients.

Universal screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on admission is reportedly beneficial in preventing nosocomial infections. However, some issues remain, including low positivity rate, cost, and time required for testing. We describe SARS-CoV-2 reverse transcription polymerase chain reaction (PCR) for universal screening in asymptomatic patients on planned admissions. In total, 14,574 patients were included between October 12, 2020, and June 23, 2022. The PCR-positive rate for the period was 0.44 % (64/14,574). The PCR positivity for the epidemic period by strain was 0.28 % (95 % confidence interval [CI] 0.12-0.56 %), 0.16 % (95 % CI 0.05-0.37 %), 0.21 % (95 % CI 0.09-0.41 %), and 0.9 % (95 % CI 0.65-1.2 %) for the wild-type strain, Alpha, Delta, and Omicron variants, respectively. The proportion of Ct values < 30 was higher in the first half of the epidemic (first vs. second, 29.4 % [95 % CI 16.9-44.8 %] vs. 16.7 % [95 % CI 6.0-28.5 %]), whereas that of Ct values ≥ 35 increased significantly in the second half (first vs. second, 32.4 % [95 % CI 19.3-47.8 %] vs. 70.0 % [95 % CI 53.5-83.4 %]). Of all positives, 50 % (32/64) had a coronavirus disease (COVID-19) history before PCR screening, with a median of 28 days (10-105) from COVID-19 onset or positive to PCR screening. PCR screening may help detect positives with high viral loads early in the epidemic for each mutant strain, with an increasing proportion of positives with low viral loads later in the epidemic. PCR testing may be unnecessary for recently diagnosed cases and patients in whom reinfection is unlikely.

Factores asociados a la positividad de la PCR para SARS-CoV-2 en menores de 15 años / Related PCR positivity factors for SARS-CoV-2 in children under 15 years of age / Fatores associados à positividade da PCR para SARS-CoV-2 em crianças menores de 15 anos de idade

Introducción: la infección por SARS-CoV-2 en niños representa un porcentaje menor en la incidencia global de pacientes infectados por este virus. La prueba de reacción en cadena de polimerasa (PCR) para SARS-CoV-2 en muestra de secreciones nasofaríngeas es considerada como estándar de referencia, con niveles de sensibilidad y especificidad superiores a otras técnicas. Objetivo: describir las características de los pacientes menores de 15 años a los que se realizó PCR para SARS-CoV-2 en un prestador privado de salud del interior del país entre el 1° julio 2020 y el 30 de abril 2021. Analizar posibles factores asociados a la positividad de la prueba. Describir las características de los casos con PCR positiva Metodología: estudio observacional prospectivo con un análisis retrospectivo de tipo caso-control, a partir del seguimiento de una cohorte de menores de 15 años a los que se les realizó una prueba de PCR para SARS-CoV-2 en el período analizado, en un prestador integral de salud privado del interior del país. Se recabaron datos durante el seguimiento de los pacientes de acuerdo a un protocolo institucional que incluye: datos patronímicos, causa de la solicitud de la PCR, características del contacto, resultado de PCR y umbral de ciclo (CT), manifestaciones clínicas y evolución. Resultados: se solicitaron 2.361 PCR a menores de 15 años (15% del total de las PCR de la institución). Promedio de edad: 8,6 años (rango 7 días-14 años y 11 meses); 49% niñas y 51% varones. Motivo de solicitud de la prueba: 78,4% para estudio de contacto, 14,3% por síntomas sin noción de contacto y 7,3% previo a ingreso hospitalario (de urgencia o coordinación). Porcentaje de positividad de todo el período: 14,7%, con una importante variabilidad mensual (5,6% en diciembre y 27% en abril). La PCR fue positiva en 346 casos, con CT promedio de 27, y rango entre 16,8 y 37,3. No se encontraron diferencias estadísticas en relación a la edad y sexo entre casos positivos y negativos. Solo un caso fue PCR positivo previo al ingreso hospitalario (OR 0,03; IC 95% 0,004-0,22) y 20 de las 611 PCR solicitadas por contacto institucional (escolar, deportivo, etc.), siendo la diferencia estadísticamente significativa cuando el caso era mayor de 15 años (p 0,029). Del estudio retrospectivo de casos (PCR positiva) y controles (PCR negativa) surge una asociación estadísticamente significativa (p<0,000001) con la causa de solicitud por contacto en comparación con otra causa (OR 5,2; IC 95% 3,28-8,26), que el caso índice sea mayor de 15 años (OR 4,57 IC 95% 2,95 - 7,10) y que sea conviviente (OR 5,28 IC 95% 3,97 - 7,04). No hubo hospitalizaciones ni fallecimientos por COVID en la población analizada. Conclusiones: el testeo de niños y adolescentes en busca de COVID 19 continúa siendo una estrategia válida cuando existen síntomas sugestivos o contacto con un caso confirmado. En este estudio, los niños con antecedente de contacto con conviviente positivo, y mayor de 15 años, mostraron una mayor proporción de resultados positivos de PCR para SARS-CoV-2.

Introduction: the SARS-CoV-2 infection has shown a lower percentage in children compared to the global incidence of patients infected by this virus. The Polymerase Chain Reaction (PCR) test for SARS-CoV-2 in a sample of nasopharyngeal secretions is considered the reference standard test, and it has shown higher sensitivity and specificity levels than other techniques. Objective: describe the characteristics of patients under 15 years of age who underwent PCR for SARS-CoV-2 in a private health provider in the interior of the country between July 1, 2020 and April 30, 2021. Analyze possible factors linked to test positivity. Describe the characteristics of cases with positive PCR Methodology: prospective observational study with a retrospective case-control analysis based on the follow-up of a cohort of children under 15 years of age who underwent a PCR test for SARS-CoV-2 in the period analyzed, at a private health provider in the interior of Uruguay. Data were collected during patients' follow-up according to the institutional protocol that includes: personal data, reason for requesting the PCR, contact data, PCR result and cycle threshold (CT), clinical manifestations and evolution. Results: 2,361 PCRs were performed to children of under 15 years of age (15% of all PCRs in the institution). Average age 8.6 years (range 7 days - 14 years and 11 months); 49% girls and 51% boys. Reason for requesting the test: 78.4% due to previous contact, 14.3% due to symptoms without knowledge of contact and 7.3% prior to hospital admission (emergency or scheduled). Positivity percentage for the entire period 14.7% with significant monthly variability (5.6% in December and 27% in April). The PCR was positive in 346 cases, with a mean CT of 27, and a range between 16.8 and 37.3. No statistical differences were found regarding age and sex between positive and negative cases. Only 1 case was positive PCR prior to hospital admission (OR 0.03 95% CI 0.004 - 0.22) and 20 out of the 611 PCR were requested due to prior institutional contact (school, sports centers, etc.), the difference being statistically significant when the patient was older than 15 years (p 0.029). From the retrospective study of cases (PCR positive) and controls (PCR negative), a statistically significant link (p<0.000001) arose regarding: when the request resulted from a prior contact compared to other causes (OR 5.2 CI 95% 3.28-8.26), when the index case was older than 15 years of age (OR 4.57 95% CI 2.95-7.10) and when the patient and the contact had cohabited (OR 5.28 95% CI 3.97-7.04). There were no hospitalizations or deaths from COVID in the population analyzed. Conclusions: testing children and adolescents for COVID 19 continues to be a valid strategy in case of suggestive symptoms or contact with a confirmed positive case. In this study, children with a history of contact with a positive case, and older than 15 years, showed a higher proportion of positive PCR results for SARS-CoV-2.

Introdução: a infecção por SARS-CoV-2 em crianças representa um percentual menor do que na incidência global de pacientes infectados por esse vírus. O teste de reação em cadeia da polimerase (PCR) para SARS-CoV-2 em uma amostra de secreções nasofaríngeas é considerado o padrão de referência, com níveis de sensibilidade e especificidade mais elevados do que outras técnicas. Objetivo: descrever as características dos pacientes menores de 15 anos de idade que realizaram PCR para SARS-CoV-2 em uma prestadora de saúde privada do interior do país entre 1º de julho de 2020 e 30 de abril de 2021. Analisar possíveis fatores associados à positividade do teste. Descrever as características dos casos com PCR positivo. Metodologia: estudo observacional prospectivo com análise retrospectiva caso-controle a partir do acompanhamento de uma coorte de crianças menores de 15 anos que realizaram teste de PCR para SARS-CoV 2 no período analisado, em uma assistência médica de saúde no interior do país. Os dados foram coletados durante o acompanhamento dos pacientes de acordo com o protocolo institucional e incluíram: informação pessoal, motivo da solicitação do PCR, características do contato, resultado do PCR e limiar de ciclo (CT), manifestações clínicas e evolução. Resultados: foram solicitados 2.361 PCRs de menores de 15 anos (15% do total de PCRs da instituição). Idade média 8,6 anos (variação 7 dias - 14 anos e 11 meses); 49% meninas e 51% meninos. Motivo do pedido do exame: 78,4% por estudo de contato, 14,3% por sintomas sem conhecimento de contato e 7,3% antes da internação (por emergência ou coordenação). Porcentagem de positividade para todo o período 14,7% com significativa variabilidade mensal (5,6% em dezembro e 27% em abril). O PCR foi positivo em 346 casos, com média de TC de 27 e variação entre 16,8 e 37,3. Não foram encontradas diferenças estatísticas em relação à idade e sexo entre os casos positivos e negativos. Apenas 1 caso foi PCR positivo antes da admissão hospitalar (OR 0,03 IC 95% 0,004 - 0,22) e 20 dos 611 PCR solicitados por contato institucional (escola, centros de esportes, etc.), sendo a diferença estatisticamente significativa para os casos que tinham mais de 15 anos de idade (p 0,029). Do estudo retrospectivo de casos (PCR positivo) e controles (PCR negativo), emergiu uma associação estatisticamente significativa (p <0,000001) quando: a causa da solicitação do teste tinha sido um contato positivo prévio em relação a outra causa (OR 5,2 IC 95% 3,28 - 8,26), e quando o caso índice era mais velho do que 15 anos (OR 4,57 IC 95% 2,95 - 7,10) ou coabitava com o paciente (OR 5,28 IC 95% 3,97 - 7,04). Não houve internações ou óbitos por COVID na população analisada. Conclusões: a testagem de crianças e adolescentes em busca de COVID-19 continua sendo uma estratégia válida quando há sintomas sugestivos ou contato com um caso positivo confirmado. Neste estudo, crianças com histórico de contato com casos positivos na mesma casa e mais velhos do que 15 anos de idade apresentaram maior proporção de resultados positivos de PCR para SARS-CoV-2.

Distinct Outcomes in COVID-19 Patients with Positive or Negative RT-PCR Test.

Identification of the SARS-CoV-2 virus by RT-PCR from a nasopharyngeal swab sample is a common test for diagnosing COVID-19. However, some patients present clinical, laboratorial, and radiological evidence of COVID-19 infection with negative RT-PCR result(s). Thus, we assessed whether positive results were associated with intubation and mortality. This study was conducted in a Brazilian tertiary hospital from March to August of 2020. All patients had clinical, laboratory, and radiological diagnosis of COVID-19. They were divided into two groups: positive (+) RT-PCR group, with 2292 participants, and negative (-) RT-PCR group, with 706 participants. Patients with negative RT-PCR testing and an alternative most probable diagnosis were excluded from the study. The RT-PCR(+) group presented increased risk of intensive care unit (ICU) admission, mechanical ventilation, length of hospital stay, and 28-day mortality, when compared to the RT-PCR(-) group. A positive SARS-CoV-2 RT-PCR result was independently associated with intubation and 28 day in-hospital mortality. Accordingly, we concluded that patients with a COVID-19 diagnosis based on clinical data, despite a negative RT-PCR test from nasopharyngeal samples, presented more favorable outcomes than patients with positive RT-PCR test(s).

Performances of rapid and connected salivary RT-LAMP diagnostic test for SARS-CoV-2 infection in ambulatory screening.

In the context of social events reopening and economic relaunch, sanitary surveillance of SARS-CoV-2 infection is still required. Here, we evaluated the diagnostic performances of a rapid, extraction-free and connected reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay on saliva. Nasopharyngeal (NP) swabs and saliva from 443 outpatients were collected simultaneously and tested by reverse-transcription quantitative PCR (RT-qPCR) as reference standard test. Seventy-one individuals (16.0%) were positive by NP and/or salivary RT-qPCR. Sensitivity and specificity of salivary RT-LAMP were 85.9% (95%CI 77.8-94.0%) and 99.5% (98.7-100%), respectively. Performances were similar for symptomatic and asymptomatic participants. Moreover, SARS-CoV-2 genetic variants were analyzed and no dominant mutation in RT-LAMP primer region was observed during the period of the study. We demonstrated that this RT-LAMP test on self-collected saliva is reliable for SARS-CoV-2 detection. This simple connected test with optional automatic results transfer to health authorities is unique and opens the way to secure professional and social events in actual context of economics restart.

Clinical, anamnestic, and sociodemographic predictors of positive SARS-CoV-2 testing in children: A cross sectional study in a tertiary hospital in Italy.

OBJECTIVES: We aimed to identify clinical, anamnestic, and sociodemographic characteristics associated with a positive swab for SARS-CoV2, and to provide a predictive score to identify at risk population in children aged 2-14 years attending school and tested for clinical symptoms of COVID-19. DESIGN: Cross sectional study. SETTING: Outpatient clinic of the IRCCS Burlo Garofolo, a maternal and child health tertiary care hospital and research centre in Italy. DATA COLLECTION AND ANALYSIS: Data were collected through a predefined form, filled out by parents, and gathered information on sociodemographic characteristics, and specific symptoms, which were analysed to determine their association with a positive SARS-CoV-2 swab. The regression coefficients of the variables included in the multivariate analysis were further used in the calculation of a predictive score of the positive or negative test. RESULTS: Between September 20th and December 23rd 2020, from 1484 children included in the study, 127 (8.6%) tested positive. In the multivariate analysis, the variables retained by the model were the presence of contact with a cohabiting, non-cohabiting or unspecified symptomatic case (respectively OR 37.2, 95% CI 20.1-68.7; 5.1, 95% CI 2.7-9.6; 15.6, 95% CI 7.3-33.2); female sex (OR 1.49, 95% CI 1.0-2.3); age (6-10 years old: OR 3.2, 95% CI 1.7-6.1 p<0.001; >10 years old: OR 4.8, 95% CI 2.7-8.8 p<0.001); fever (OR 3.9, 95% CI 2.3-6.4); chills (OR 1.9, 95% CI 1.1-3.3); headache (OR 1.45, 95% CI 0.9-2.4); ageusia (OR 1.3, 95% CI 0.5-4.0); sore throat (OR 0.48, 95% CI 0.3-0.8); earache (OR 0.4, 95% CI 0.1-1.3); rhinorrhoea (OR 0.8, 95% CI 0.5-1.3); and diarrhoea (OR 0.52, 95% CI 0.2-1.1). The predictive score based on these variables generated 93% sensitivity and 99% negative predictive value. CONCLUSIONS: The timely identification of SARS-CoV2 cases among children is useful to reduce the dissemination of the disease and its related burden. The predictive score may be adopted in a public health perspective to rapidly identify at risk children.

Automatic system for high-throughput and high-sensitivity diagnosis of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had severe consequences for health and the global economy. To control the transmission, there is an urgent demand for early diagnosis and treatment in the general population. In the present study, an automatic system for SARS-CoV-2 diagnosis is designed and built to deliver high specification, high sensitivity, and high throughput with minimal workforce involvement. The system, set up with cross-priming amplification (CPA) rather than conventional reverse transcription-polymerase chain reaction (RT-PCR), was evaluated using more than 1000 real-world samples for direct comparison. This fully automated robotic system performed SARS-CoV-2 nucleic acid-based diagnosis with 192 samples in under 180 min at 100 copies per reaction in a "specimen in data out" manner. This throughput translates to a daily screening capacity of 800-1000 in an assembly-line manner with limited workforce involvement. The sensitivity of this device could be further improved using a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based assay, which opens the door to mixed samples, potentially include SARS-CoV-2 variants screening in extensively scaled testing for fighting COVID-19.

Increased complications in patients who test COVID-19 positive after elective surgery and implications for pre and postoperative screening.

BACKGROUND: The COVID-19 pandemic has necessitated the adoption of protocols to minimize risk of periprocedural complications associated with SARS-CoV-2 infection. This typically involves a preoperative symptom screen and nasal swab RT-PCR test for viral RNA. Asymptomatic patients with a negative COVID-19 test are cleared for surgery. However, little is known about the rate of postoperative COVID-19 positivity among elective surgical patients, risk factors for this group and rate of complications. METHODS: This prospective multicenter study included all patients undergoing elective surgery at 170 Veterans Health Administration (VA) hospitals across the United States. Patients were divided into groups based on first positive COVID-19 test within 30 days after surgery (COVID[-/+]), before surgery (COVID[+/-]) or negative throughout (COVID[-/-]). The cumulative incidence, risk factors for and complications of COVID[-/+], were estimated using univariate analysis, exact matching, and multivariable regression. RESULTS: Between March 1 and December 1, 2020 90,093 patients underwent elective surgery. Of these, 60,853 met inclusion criteria, of which 310 (0.5%) were in the COVID[-/+] group. Adjusted multivariable logistic regression identified female sex, end stage renal disease, chronic obstructive pulmonary disease, congestive heart failure, cancer, cirrhosis, and undergoing neurosurgical procedures as risk factors for being in the COVID[-/+] group. After matching on current procedural terminology code and month of procedure, multivariable Poisson regression estimated the complication rate ratio for the COVID[-/+] group vs. COVID[-/-] to be 8.4 (C.I. 4.9-14.4) for pulmonary complications, 3.0 (2.2, 4.1) for major complications, and 2.6 (1.9, 3.4) for any complication. DISCUSSION: Despite preoperative COVID-19 screening, there remains a risk of COVID infection within 30 days after elective surgery. This risk is increased for patients with a high comorbidity burden and those undergoing neurosurgical procedures. Higher intensity preoperative screening and closer postoperative monitoring is warranted in such patients because they have a significantly elevated risk of postoperative complications.

Clinical Utility of COVID-19 Real Time-Polymerase Chain Reaction Testing of Ocular Tissues of Non-COVID-19 Cornea Donors Deemed Suitable for Corneal Retrieval and Transplantation.

PURPOSE: The purpose of this study was to evaluate the prevalence of SARS-CoV-2 in human postmortem ocular tissues of asymptomatic donors and its implications on our eye banking protocols. METHODS: The expression of SARS-CoV-2 RNA was assessed by reverse transcription-polymerase chain reaction in corneal rims and conjunctival tissues from 100 donors who were found suitable for transplantation as per the donor screening guidelines of the Global Alliance of Eye Bank Associations. The donor's clinical history and cause of death were assessed for secondary analysis. RESULTS: Of 200 ocular tissues (100 corneal and 100 conjunctival) from the same 1 eye of 100 surgical-intended donors, between September 2020 and April 2021, the overall positivity rate for SARS-CoV-2 was ∼1% (2/200). Both the ocular samples that tested positive were conjunctival biopsies (2/100, 2%), whereas corneal samples were negative (0/100, 0%) in both donors. The causes of donor death were trauma in 51 donors, suicide in 33, cardiac arrest in 7, electric shock in 5, metabolic cause in 2, malignancy in 1, and snake bite in 1. None of the donors had a medical history suggestive of COVID infection or possible contact. None of the recipients from the donors were reported to have any systemic adverse event after keratoplasty until the follow-up of 6 weeks. CONCLUSIONS: The overall prevalence of SARS-CoV-2 was 1% (2% for conjunctival and 0% for corneal samples, P value = 0.5) in the donors who were found suitable for cornea recovery and transplantation. The findings of exceptionally low positive rates in our samples validate the criticality of history-based donor screening and do not support the necessity of postmortem PCR testing as a criterion for procurement and subsequent use for corneal transplantation.

Final efficacy analysis, interim safety analysis, and immunogenicity of a single dose of recombinant novel coronavirus vaccine (adenovirus type 5 vector) in adults 18 years and older: an international, multicentre, randomised, double-blinded, placebo-controlled phase 3 trial.

BACKGROUND: The Ad5-nCoV vaccine is a single-dose adenovirus type 5 (Ad5) vectored vaccine expressing the SARS-CoV-2 spike protein that was well-tolerated and immunogenic in phase 1 and 2 studies. In this study, we report results on the final efficacy and interim safety analyses of the phase 3 trial. METHODS: This double-blind, randomised, international, placebo-controlled, endpoint-case driven, phase 3, clinical trial enrolled adults aged 18 years older at study centres in Argentina, Chile, Mexico, Pakistan, and Russia. Participants were eligible for the study if they had no unstable or severe underlying medical or psychiatric conditions; had no history of a laboratory-confirmed SARS-CoV-2 infection; were not pregnant or breastfeeding; and had no previous receipt of an adenovirus-vectored, coronavirus, or SARS-CoV-2 vaccine. After informed consent was obtained, 25 mL of whole blood was withdrawn from all eligible participants who were randomised in a 1:1 ratio to receive a single intramuscular dose of 0·5 mL placebo or a 0·5 mL dose of 5 × 1010 viral particle (vp)/mL Ad5-nCoV vaccine; study staff and participants were blinded to treatment allocation. All participants were contacted weekly by email, telephone, or text message to self-report any symptoms of COVID-19 illness, and laboratory testing for SARS-CoV-2 was done for all participants with any symptoms. The primary efficacy objective evaluated Ad5-nCoV in preventing symptomatic, PCR-confirmed COVID-19 infection occurring at least 28 days after vaccination in all participants who were at least 28 days postvaccination on Jan 15, 2021. The primary safety objective evaluated the incidence of any serious adverse events or medically attended adverse events postvaccination in all participants who received a study injection. This trial is closed for enrolment and is registered with ClinicalTrials.gov (NCT04526990). FINDINGS: Study enrolment began on Sept 22, 2020, in Pakistan, Nov 6, 2020, in Mexico, Dec 2, 2020, in Russia and Chile, and Dec 17, 2020, in Argentina; 150 endpoint cases were reached on Jan 15, 2021, triggering the final primary efficacy analysis. One dose of Ad5-nCoV showed a 57·5% (95% CI 39·7-70·0, p=0·0026) efficacy against symptomatic, PCR-confirmed, COVID-19 infection at 28 days or more postvaccination (21 250 participants; 45 days median duration of follow-up [IQR 36-58]). In the primary safety analysis undertaken at the time of the efficacy analysis (36 717 participants), there was no significant difference in the incidence of serious adverse events (14 [0·1%] of 18 363 Ad5-nCoV recipients and 10 [0·1%] of 18 354 placebo recipients, p=0·54) or medically attended adverse events (442 [2·4%] of 18 363 Ad5-nCoV recipients and 411 [2·2%] of 18 354 placebo recipients, p=0·30) between the Ad5-nCoV or placebo groups, or any serious adverse events considered related to the study product (none in both Ad5-nCoV and placebo recipients). In the extended safety cohort, 1004 (63·5%) of 1582 of Ad5-nCoV recipients and 729 (46·4%) of 1572 placebo recipients reported a solicited systemic adverse event (p<0·0001), of which headache was the most common (699 [44%] of Ad5-nCoV recipients and 481 [30·6%] of placebo recipients; p<0·0001). 971 (61·3%) of 1584 Ad5-nCoV recipients and 314 (20·0%) of 1573 placebo recipients reported an injection-site adverse event (p<0·0001), of which pain at the injection site was the most frequent; reported by 939 (59%) Ad5-nCoV recipients and 303 (19%) placebo recipients. INTERPRETATION: One dose of Ad5-nCoV is efficacious and safe in healthy adults aged 18 years and older. FUNDING: CanSino Biologics and the Beijing Institute of Biotechnology.

Differences in age distribution in first and second waves of COVID-19 in eastern Uttar Pradesh, India.

Comparison of first and second waves of Coronavirus disease (COVID-19) showed varied differences including the peak and time distribution. Contrary to published reports of comparing two waves in India wherein the younger age group was affected more in the second wave in India; a secondary data analysis of around 0.5 million real-time reverse transcription-polymerase chain reaction tests conducted in COVID-19 diagnostic laboratory in eastern Uttar Pradesh, India showed an increase in positivity rate in older age groups in the second wave. The positivity rate among symptomatic cases was found to be three times higher in second wave compare to the first wave. Higher positivity rates were seen across older age groups, with a shift of 11 years in the mean age of positivity in the second wave compared to the first.

Changes in SARS-CoV-2 viral load and mortality during the initial wave of the pandemic in New York City.

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.

COVID-19 Community Transmission and Super Spreaders in Rural Villages from Manabi Province in the Coastal Region of Ecuador Assessed by Massive Testing of Community-Dwelling Population.

Neglected rural communities in Latin America are highly vulnerable to COVID-19 due to a poor health infrastructure and limited access to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis. Manabí is a province of the Coastal Region of Ecuador characterized by a high prevalence of rural population living under poverty conditions. In the current study, we present the retrospective analysis of the results of a massive SARS-CoV-2 testing operation in nonhospitalized populations from Manabí carried out from August to September 2020. A total of 4,003 people from 15 cantons were tested for SARS-CoV-2 by reverse-transcriptase quantitative polymerase chain reaction, resulting in an overall infection rate of 16.13% for SARS-CoV-2, with several communities > 30%. Moreover, 29 SARS-CoV-2 super-spreader community-dwelling individuals with viral loads above 108 copies/mL were found. These results support that uncontrolled COVID-19 community transmission was happening in Manabí during the first semester of COVID-19 pandemic. This report endorses the utility of massive SARS-CoV-2 testing among asymptomatic population for control and surveillance of COVID-19.

SARS-CoV-2 infection in central North Carolina: Protocol for a population-based longitudinal cohort study and preliminary participant results.

Public health surveillance systems likely underestimate the true prevalence and incidence of SARS-CoV-2 infection due to limited access to testing and the high proportion of subclinical infections in community-based settings. This ongoing prospective, observational study aimed to generate accurate estimates of the prevalence and incidence of, and risk factors for, SARS-CoV-2 infection among residents of a central North Carolina county. From this cohort, we collected survey data and nasal swabs every two weeks and venous blood specimens every month. Nasal swabs were tested for the presence of SARS-CoV-2 virus (evidence of active infection), and serum specimens for SARS-CoV-2-specific antibodies (evidence of prior infection). As of June 23, 2021, we have enrolled a total of 153 participants from a county with an estimated 76,285 total residents. The anticipated study duration is at least 24 months, pending the evolution of the pandemic. Study data are being shared on a monthly basis with North Carolina state health authorities and future analyses aim to compare study data to state-wide metrics over time. Overall, the use of a probability-based sampling design and a well-characterized cohort will enable collection of critical data that can be used in planning and policy decisions for North Carolina and may be informative for other states with similar demographic characteristics.

Molecular testing and analysis of disease spreading during the emergence of COVID-19 in Macaé, the Brazilian National Capital of Oil.

The Brazilian strategy to overcome the spread of COVID-19 has been particularly criticized due to the lack of a national coordinating effort and an appropriate testing program. Here, a successful approach to control the spread of COVID-19 transmission is described by the engagement of public (university and governance) and private sectors (hospitals and oil companies) in Macaé, state of Rio de Janeiro, Brazil, a city known as the National Oil Capital. In 2020 between the 17th and 38th epidemiological week, over two percent of the 206,728 citizens were subjected to symptom analysis and RT-qPCR testing by the Federal University of Rio de Janeiro, with positive individuals being notified up to 48 h after swab collection. Geocodification and spatial cluster analysis were used to limit COVID-19 spreading in Macaé. Within the first semester after the outbreak of COVID-19 in Brazil, Macaé recorded 1.8% of fatalities associated with COVID-19 up to the 38th epidemiological week, which was at least five times lower than the state capital (10.6%). Overall, considering the successful experience of this joint effort of private and public engagement in Macaé, our data suggest that the development of a similar strategy countrywise could have contributed to a better control of the COVID-19 spread in Brazil. Quarantine decree by the local administration, comprehensive molecular testing coupled to scientific analysis of COVID-19 spreading, prevented the catastrophic consequences of the pandemic as seen in other populous cities within the state of Rio de Janeiro and elsewhere in Brazil.

SARS-CoV-2 vaccine breakthrough infections with the alpha variant are asymptomatic or mildly symptomatic among health care workers.

Vaccine breakthrough SARS-CoV-2 infection has been monitored in 3720 healthcare workers receiving 2 doses of BNT162b2. SARS-CoV-2 infection is detected in 33 subjects, with a 100-day cumulative incidence of 0.93%. Vaccine protection against acquisition of SARS-CoV-2 infection is 83% (95%CI: 58-93%) in the overall population and 93% (95%CI: 69-99%) in SARS-CoV-2-experienced subjects, when compared with a non-vaccinated control group from the same Institution, in which SARS-CoV-2 infection occurs in 20/346 subjects (100-day cumulative incidence: 5.78%). The infection is symptomatic in 16 (48%) vaccinated subjects vs 17 (85%) controls (p = 0.01). All analyzed patients, in whom the amount of viral RNA was sufficient for genome sequencing, results infected by the alpha variant. Antibody and T-cell responses are not reduced in subjects with breakthrough infection. Evidence of virus transmission, determined by contact tracing, is observed in two (6.1%) cases. This real-world data support the protective effect of BNT162b2 vaccine. A triple antigenic exposure, such as two-dose vaccine schedule in experienced subjects, may confer a higher protection.

Predictive usefulness of RT-PCR testing in different patterns of Covid-19 symptomatology: analysis of a French cohort of 12,810 outpatients.

Reverse transcriptase polymerase chain reaction (RT-PCR) is a key tool to diagnose Covid-19. Yet it may not be the most efficient test in all patients. In this paper, we develop a clinical strategy for prescribing RT-PCR to patients based on data from COVIDOM, a French cohort of 54,000 patients with clinically suspected Covid-19, including 12,810 patients tested by RT-PCR. We use a machine-learning algorithm (decision tree) in order to predict RT-PCR results based on the clinical presentation. We show that symptoms alone are sufficient to predict RT-PCR outcome with a mean average precision of 86%. We identify combinations of symptoms that are predictive of RT-PCR positivity (90% for anosmia/ageusia) or negativity (only 30% of RT-PCR+ for a subgroup with cardiopulmonary symptoms): in both cases, RT-PCR provides little added diagnostic value. We propose a prescribing strategy based on clinical presentation that can improve the global efficiency of RT-PCR testing.

Feasibility of a surveillance programme based on gargle samples and pool testing to prevent SARS-CoV-2 outbreaks in schools.

School closures have a negative impact on physical and mental well-being, and education, of children and adolescents. A surveillance programme to detect asymptomatic SARS-CoV-2 infection could allow schools to remain open, while protecting the vulnerable. We assessed the feasibility of a programme employing gargle samples and pool testing of individually extracted RNA using rRT-qPCR in a primary and a secondary school in Germany, based on programme logistics and acceptance. Twice a week, five participants per class were selected to provide samples, using an algorithm weighted by a risk-based priority score to increase likelihood of case detection. The positive response rate was 54.8% (550 of 1003 pupils). Logistics evaluation revealed the rate-limiting steps: completing the regular pre-test questionnaire and handing in the samples. Acceptance questionnaire responses indicated strong support for research into developing a surveillance programme and a positive evaluation of gargle tests. Participation was voluntary. As not all pupils participated, individual reminders could lead to participant identification. School-wide implementation of the programme for infection monitoring purposes would enable reminders to be given to all school pupils to address these steps, without compromising participant anonymity. Such a programme would provide a feasible means to monitor asymptomatic respiratory tract infection in schools.

Antigen-detection in the diagnosis of SARS-CoV-2 infection: interim guidance, 6 October 2021

Diagnostic testing for SARS-CoV-2 is a critical component to the overall prevention and control strategy for COVID-19. Countries should have a national testing strategy in place with clear objectives that can be adapted according to changes in the epidemiological situation, available resources and tools, and country-specific context. It is critical that all SARSCoV-2 testing is linked to public health actions to ensure appropriate clinical care and support and to carry out contact tracing to break chains of transmission. Since the early days of the SARS-CoV-2 pandemic, laboratories have been using nucleic acid amplification tests (NAATs), such as real time reverse transcription polymerase chain reaction (rRT-PCR) assays, to detect SARS-CoV-2, the virus that causes COVID-19. Since mid-2020, less expensive and faster diagnostic tests that detect antigens specific for SARS-CoV-2 infection have become commercially available, and several have achieved WHO Emergency use listing. Antigen-detecting diagnostic tests are designed to directly identify SARS-CoV-2 proteins produced by replicating virus in respiratory secretions (or oral fluid/saliva) and have been developed as both laboratory-based tests and rapid diagnostic tests (RDTs) intended for near-patient use. The diagnostic development landscape is dynamic, with over two hundred tests for SARS-CoV-2 antigen detection on the market, of which 85% can be delivered at the point of care and the other 15% for use on high throughput machines in laboratory-based settings.

Serological Testing Reveals the Hidden COVID-19 Burden among Health Care Workers Experiencing a SARS-CoV-2 Nosocomial Outbreak.

We describe the results of testing health care workers, from a tertiary care hospital in Japan that had experienced a coronavirus disease 2019 (COVID-19) outbreak during the first peak of the pandemic, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody seroconversion. Using two chemiluminescent immunoassays and a confirmatory surrogate virus neutralization test, serological testing revealed that a surprising 42% of overlooked COVID-19 diagnoses (27/64 cases) occurred when case detection relied solely on SARS-CoV-2 nucleic acid amplification testing (NAAT). Our results suggest that the NAAT-positive population is only the tip of the iceberg and the portion left undetected might potentially have led to silent transmissions and triggered the spread. A questionnaire-based risk assessment was further indicative of exposures to specific aerosol-generating procedures (i.e., noninvasive ventilation and airway suctioning) having mediated transmission and served as the origins of the outbreak. Our observations are supportive of a multitiered testing approach, including the use of serological diagnostics, in order to accomplish exhaustive case detection along the whole COVID-19 spectrum. IMPORTANCE We describe the results of testing frontline health care workers, from a hospital in Japan that had experienced a COVID-19 outbreak, for SARS-CoV-2-specific antibodies. Antibody testing revealed that a surprising 42% of overlooked COVID-19 diagnoses occurred when case detection relied solely on PCR-based viral detection. COVID-19 clusters have been continuously striking the health care system around the globe. Our findings illustrate that such clusters are lined with hidden infections eluding detection with diagnostic PCR and that the cluster burden in total is more immense than actually recognized. The mainstays of diagnosing infectious diseases, including COVID-19, generally consist of two approaches, one aiming to detect molecular fragments of the invading pathogen and the other to measure immune responses of the host. Considering antibody testing as one trustworthy option to test our way through the pandemic can aid in the exhaustive case detection of COVID-19 patients with variable presentations.