Stronger impact of COVID-19 in nursing homes of a French Region during the second pandemic wave

Objectives Quantify the effects of characteristics of nursing homes and their surrounding on the spread of COVID-19 outbreaks and assess the changes in resident protection between the first two waves (March 1 to July 31 and August 1 to December 31, 2020). Design An observational study was carried out on data on COVID-19 outbreaks extracted from a database that monitored the spread of the virus in nursing homes. Setting and participants The study concerned all 937 nursing homes with > 10 beds in Auvergne-Rhône-Alpes Region, France. Methods The rate of nursing homes with at least one outbreak and the cumulative number of deaths were modeled for each wave. Results During the second (vs. the first wave), the proportion of nursing homes that reported at least one outbreak was higher (70% vs. 56%) and the cumulative number of deaths more than twofold (3348 vs. 1590). The outbreak rate was significantly lower in public hospital-associated nursing homes than in private for-profit ones. During the second wave, it was lower in public and private not-for-profit nursing homes than in private for-profit ones. During the first wave, the probability of outbreak and the mean number of deaths increased with the number of beds (p < 0.001). During the second wave, the probability of outbreak remained stable in > 80-bed institutions and, under proportionality assumption, the mean number of death was less than expected in > 100-bed institutions. The outbreak rate and the cumulative number of deaths increased significantly with the increase in the incidence of hospitalization for COVID-19 in the surrounding populations. Conclusions and implications The outbreak in the nursing homes was stronger during the second than the first wave despite better preparedness and higher availabilities of tests and protective equipment. Insufficient staffing, inadequate rooming, and suboptimal functioning should find solutions before future epidemics.

Additional value of chest CT AI-based quantification of lung involvement in predicting death and ICU admission for COVID-19 patients.

Objectives: We evaluated the contribution of lung lesion quantification on chest CT using a clinical Artificial Intelligence (AI) software in predicting death and intensive care units (ICU) admission for COVID-19 patients. Methods: For 349 patients with positive COVID-19-PCR test that underwent a chest CT scan at admittance or during hospitalization, we applied the AI for lung and lung lesion segmentation to obtain lesion volume (LV), and LV/Total Lung Volume (TLV) ratio. ROC analysis was used to extract the best CT criterion in predicting death and ICU admission. Two prognostic models using multivariate logistic regressions were constructed to predict each outcome and were compared using AUC values. The first model ("Clinical") was based on patients' characteristics and clinical symptoms only. The second model ("Clinical+LV/TLV") included also the best CT criterion. Results: LV/TLV ratio demonstrated best performance for both outcomes; AUC of 67.8% (95% CI: 59.5 - 76.1) and 81.1% (95% CI: 75.7 - 86.5) respectively. Regarding death prediction, AUC values were 76.2% (95% CI: 69.9 - 82.6) and 79.9% (95%IC: 74.4 - 85.5) for the "Clinical" and the "Clinical+LV/TLV" models respectively, showing significant performance increase (+ 3.7%; p-value<0.001) when adding LV/TLV ratio. Similarly, for ICU admission prediction, AUC values were 74.9% (IC 95%: 69.2 - 80.6) and 84.8% (IC 95%: 80.4 - 89.2) respectively corresponding to significant performance increase (+ 10%: p-value<0.001). Conclusions: Using a clinical AI software to quantify the COVID-19 lung involvement on chest CT, combined with clinical variables, allows better prediction of death and ICU admission.

Evaluation of commercial Anti-SARS-CoV-2 neutralizing antibody assays in seropositive subjects.

The virus neutralization test (VNT) is the reference for the assessment of the functional ability of neutralizing antibodies (NAb) to block SARS-CoV-2 entry into cells. New competitive immunoassays measuring antibodies preventing interaction between the spike protein and its cellular receptor are proposed as surrogate VNT (sVNT). We tested three commercial sVNT (a qualitative immunochromatographic test and two quantitative immunoassays named YHLO and TECO) together with a conventional anti-spike IgG assay (bioMérieux) in comparison with an in-house plaque reduction neutralization test (PRNT50) using the original 19A strain and different variants of concern (VOC), on a panel of 306 sera from naturally-infected or vaccinated patients. The qualitative test was rapidly discarded because of poor sensitivity and specificity. Areas under the curve of YHLO and TECO assays were, respectively, 85.83 and 84.07 (p-value >0.05) using a positivity threshold of 20 for PRNT50, and 95.63 and 90.35 (p-value =0.02) using a threshold of 80. However, the performances of YHLO and bioMérieux were very close for both thresholds, demonstrating the absence of added value of sVNT compared to a conventional assay for the evaluation of the presence of NAb in seropositive subjects. In addition, the PRNT50 assay showed a reduction of NAb titers towards different VOC in comparison to the 19A strain that could not be appreciated by the commercial tests. Despite the good correlation between the anti-spike antibody titer and the titer of NAb by PRNT50, our results highlight the difficulty to distinguish true NAb among the anti-RBD antibodies with commercial user-friendly immunoassays.

Addressing the COVID-19 pandemic challenges for operational adaptations of a cluster randomized controlled trial on dengue vector control in Malaysia.

INTRODUCTION: The COVID-19 pandemic placed an unprecedented overload on healthcare system globally. With all medical resources being dedicated to contain the spread of the disease, the pandemic may have impacted the burden of other infectious diseases such as dengue, particularly in countries endemic for dengue fever. Indeed, the co-occurrence of COVID-19 made dengue diagnosis challenging because of some shared clinical manifestations between the two pathogens. Furthermore, the sudden emergence and novelty of this global public health crisis has forced the suspension or slow-down of several research trials due to the lack of sufficient knowledge on how to handle the continuity of research trials during the pandemic. We report on challenges we have faced during the COVID-19 pandemic and measures that were implemented to continue the iDEM project (intervention for Dengue Epidemiology in Malaysia). METHODS: This randomized controlled trial aims to assess the effectiveness of Integrated Vector Management (IVM) on the incidence of dengue in urban Malaysia by combining: targeted outdoor residual spraying (TORS), deployment of auto-dissemination devices (ADDs), and active community engagement (CE). Our operational activities started on February 10, 2020, a few weeks before the implementation of non-pharmaceutical interventions to contain the spread of COVID-19 in Malaysia. RESULTS: The three main issues affecting the continuity of the trial were: ensuring the safety of field workers during the interventions; ensuring the planned turnover of TORS application and ADD deployment and services; and maintaining the CE activities as far as possible. CONCLUSIONS: Even though the pandemic has created monumental challenges, we ensured the safety of field workers by providing complete personal protective equipment and regular COVID-19 testing. Albeit with delay, we maintained the planned interval time between TORS application and ADDs services by overlapping the intervention cycles instead of having them in a sequential scheme. CE activities continued remotely through several channels (e.g., phone calls and text messages). Sustained efforts of the management team, significant involvement of the Malaysian Ministry of Health and a quick and smart adaptation of the trial organisation according to the pandemic situation were the main factors that allowed the successful continuation of our research. TRIAL REGISTRATION: Trial registration number: ISRCTN-81915073 . Date of registration: 17/04/2020, 'Retrospectively registered'.

Evaluation of Commercial Anti-SARS-CoV-2 Antibody Assays and Comparison of Standardized Titers in Vaccinated Health Care Workers.

With the availability of vaccines, commercial assays detecting anti-severe acute respiratory syndrome coronavirus-2 antibodies (Ab) evolved toward quantitative assays directed to the spike glycoprotein or its receptor binding domain (RBD). The main objective of the present study was to compare the Ab titers obtained with quantitative commercial binding Ab assays, after one dose (convalescent individuals) or two doses (naive individuals) of vaccine, in health care workers (HCW). Antibody titers were measured in 255 sera (from 150 HCW) with five quantitative immunoassays (Abbott RBD IgG II quant, bioMérieux RBD IgG, DiaSorin Trimeric spike IgG, Siemens Healthineers RBD IgG, Wantai RBD IgG). One qualitative total antibody anti-RBD detection assay (Wantai) was used to detect previous infection before vaccination. The results are presented in binding Ab units (BAU)/mL after application, when possible, of a conversion factor provided by the manufacturers and established from a World Health Organization internal standard. There was a 100% seroconversion with all assays evaluated after two doses of vaccine. With assays allowing BAU/mL correction, Ab titers were correlated (Pearson correlation coefficient, ρ, range: 0.85-0.94). The titer differences varied by a mean of 10.6% between Siemens and bioMérieux assays to 60.9% between Abbott and DiaSorin assays. These results underline the importance of BAU conversion for the comparison of Ab titer obtained with the different quantitative assays. However, significant differences persist, notably, between kits detecting Ab against the different antigens. A true standardization of the assays would be to include the International Standard in the calibration of each assay to express the results in IU/mL.

COVID-19 outbreaks in nursing homes: A strong link with the coronavirus spread in the surrounding population, France, March to July 2020.

BACKGROUND: Worldwide, COVID-19 outbreaks in nursing homes have often been sudden and massive. The study investigated the role SARS-CoV-2 virus spread in nearby population plays in introducing the disease in nursing homes. MATERIAL AND METHODS: This was carried out through modelling the occurrences of first cases in each of 943 nursing homes of Auvergne-Rhône-Alpes French Region over the first epidemic wave (March-July, 2020). The cumulative probabilities of COVID-19 outbreak in the nursing homes and those of hospitalization for the disease in the population were modelled in each of the twelve Départements of the Region over period March-July 2020. This allowed estimating the duration of the active outbreak period, the dates and heights of the peaks of outbreak probabilities in nursing homes, and the dates and heights of the peaks of hospitalization probabilities in the population. Spearman coefficient estimated the correlation between the two peak series. RESULTS: The cumulative proportion of nursing homes with COVID-19 outbreaks was 52% (490/943; range: 22-70% acc. Département). The active outbreak period in the nursing homes lasted 11 to 21 days (acc. Département) and ended before lockdown end. Spearman correlation between outbreak probability peaks in nursing homes and hospitalization probability peaks in the population (surrogate of the incidence peaks) was estimated at 0.71 (95% CI: [0.66; 0.78]). CONCLUSION: The modelling highlighted a strong correlation between the outbreak in nursing homes and the external pressure of the disease. It indicated that avoiding disease outbreaks in nursing homes requires a tight control of virus spread in the surrounding populations.

Open-label randomized controlled trial of ultra-low tidal ventilation without extracorporeal circulation in patients with COVID-19 pneumonia and moderate to severe ARDS: study protocol for the VT4COVID trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe complication of COVID-19 pneumonia, with a mortality rate amounting to 34-50% in moderate and severe ARDS, and is associated with prolonged duration of invasive mechanical ventilation. Such as in non-COVID ARDS, harmful mechanical ventilation settings might be associated with worse outcomes. Reducing the tidal volume down to 4 mL kg-1 of predicted body weight (PBW) to provide ultra-low tidal volume ventilation (ULTV) is an appealing technique to minimize ventilator-inducted lung injury. Furthermore, in the context of a worldwide pandemic, it does not require any additional material and consumables and may be applied in low- to middle-income countries. We hypothesized that ULTV without extracorporeal circulation is a credible option to reduce COVID-19-related ARDS mortality and duration of mechanical ventilation. METHODS: The VT4COVID study is a randomized, multi-centric prospective open-labeled, controlled superiority trial. Adult patients admitted in the intensive care unit with COVID-19-related mild to severe ARDS defined by a PaO2/FiO2 ratio ≤ 150 mmHg under invasive mechanical ventilation for less than 48 h, and consent to participate to the study will be eligible. Patients will be randomized into two balanced parallels groups, at a 1:1 ratio. The control group will be ventilated with protective ventilation settings (tidal volume 6 mL kg-1 PBW), and the intervention group will be ventilated with ULTV (tidal volume 4 mL kg-1 PBW). The primary outcome is a composite score based on 90-day all-cause mortality as a prioritized criterion and the number of ventilator-free days at day 60 after inclusion. The randomization list will be stratified by site of recruitment and generated using random blocks of sizes 4 and 6. Data will be analyzed using intention-to-treat principles. DISCUSSION: The purpose of this manuscript is to provide primary publication of study protocol to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency. Enrollment of patients in the study is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT04349618 . Registered on April 16, 2020.

The COVID-19 pandemic is deepening the health crisis in South Kivu, Democratic Republic of Congo.

OBJECTIVE: The outbreak of coronavirus disease 2019 (COVID-19) in South Kivu, Democratic Republic of Congo raised concerns regarding additional morbidity and mortality. Updating these indicators before a second wave is essential in order to prepare for additional help. METHODS: From mid-May to mid-December 2020, weekly surveys were undertaken in sampled streets from 10 health areas to quantify the use of barrier measures, and interview pedestrians about sickness and deaths in their households. Crude death rates (CDRs) were estimated. RESULTS: Minimal use or no use of face masks was observed in at least half of the streets. From May to December 2020, the number of suspected cases of COVID-19 increased six-fold (P < 0.05). Of deaths within 30 days preceding the interviews, 20% were considered to be related to COVID-19. The monthly CDRs at the beginning and end of the study were approximately 5 and 25 per 1000 population, respectively (P < 0.05); that is, annual CDRs of 60 and 260 per 1000 population, respectively. Thus, during the first wave, the estimated mortality rate increased by 50% compared with previous years, and increased at least four-fold by the end of 2020. CONCLUSION: Despite possible overestimations, the excess mortality in South Kivu is extremely concerning. This crisis calls for a rapid response and increased humanitarian assistance.

Assessment of serological techniques for screening patients for COVID-19 (COVID-SER): a prospective, multicentric study.

INTRODUCTION: The COVID-19 pandemic caused by SARS-CoV-2 threatens global public health, and there is an urgent public health need to assess acquired immunity to SARS-CoV-2. Serological tests might provide results that can be complementary to or confirm suspected COVID-19 cases and reveal previous infection. The performance of serological assays (sensitivity and specificity) has to be evaluated before their use in the general population. The neutralisation capacity of the produced antibodies also has to be evaluated. METHODS AND ANALYSIS: We set up a prospective, multicentric clinical study to evaluate the performance of serological kits among a population of healthcare workers presenting mild symptoms suggestive of SARS-CoV-2 infection. Four hundred symptomatic healthcare workers will be included in the COVID-SER study. The values obtained from a control cohort included during the prepandemic time will be used as reference. A workflow was set up to study serological response to SARS-CoV-2 infection and to evaluate antibody neutralisation capacity in patients with a confirmed SARS-CoV-2 infection. The sensitivity and specificity of the tests will be assessed using molecular detection of the virus as a reference. The measurement of IgM and IgG antibodies will be performed once per week for 6 consecutive weeks and then at 6, 12, 18, 24 and 36 months after the diagnosis. The kinetics of IgM and IgG will determine the optimal period to perform serological testing. The proportion of false negative PCR tests in symptomatic subjects will be determined on the basis of subsequent seroconversions. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France) (ID RCB 2020-A00932-37). Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04341142.

A dashboard for monitoring preventive measures in response to COVID-19 outbreak in the Democratic Republic of Congo.

BACKGROUND: In most health areas, an information system is necessary for an effective fight against COVID-19. Current methods for surveillance of diseases with epidemic potential do not include monitoring the adherence to preventive measures. Furthermore, modern data collection methods depend often on technologies (e.g., cameras or drones) that are hardly available in low-income countries. Simpler solutions could be just as effective. METHODS: A dashboard was used over a whole week to monitor preventive measures in Bukavu (DRC) by mid-May 2020. It was designed to collect from street passers-by information on the adherence to barrier measures, the level of awareness of these measures, the opinion on their usefulness, and the health status of people in the households. RESULTS: Creating a dashboard and collecting the necessary data proved feasible. The use of barrier measures was very limited and that of masks practically nil despite repeated recommendations from the health authorities. The end of each day was the worst moment due to clearly insufficient distancing. Barrier measures were significantly more used in areas where they were best known and most acknowledged. At the time of the study, there were few sick people and only rare severe cases were attributed to COVID-19. CONCLUSIONS: Creating COVID-19 situation dashboards in limited-resource metropoles is feasible. They give real-time access to data that help fight the epidemic. The findings of this pilot study call for a rapid community awareness actions to back national media-based prevention campaigns.

Chest CT for rapid triage of patients in multiple emergency departments during COVID-19 epidemic: experience report from a large French university hospital.

OBJECTIVES: To assess the diagnostic performances of chest CT for triage of patients in multiple emergency departments during COVID-19 epidemic, in comparison with reverse transcription polymerase chain reaction (RT-PCR) test. METHOD: From March 3 to April 4, 2020, 694 consecutive patients from three emergency departments of a large university hospital, for which a hospitalization was planned whatever the reasons, i.e., COVID- or non-COVID-related, underwent a chest CT and one or several RT-PCR tests. Chest CTs were rated as "Surely COVID+," "Possible COVID+," or "COVID-" by experienced radiologists. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using the final RT-PCR test as standard of reference. The delays for CT reports and RT-PCR results were recorded and compared. RESULTS: Among the 694 patients, 287 were positive on the final RT-PCR exam. Concerning the 694 chest CT, 308 were rated as "Surely COVID+", 34 as "Possible COVID+," and 352 as "COVID-." When considering only the "Surely COVID+" CT as positive, accuracy, sensitivity, specificity, PPV, and NPV reached 88.9%, 90.2%, 88%, 84.1%, and 92.7%, respectively, with respect to final RT-PCR test. The mean delay for CT reports was three times shorter than for RT-PCR results (187 ± 148 min versus 573 ± 327 min, p < 0.0001). CONCLUSION: During COVID-19 epidemic phase, chest CT is a rapid and most probably an adequately reliable tool to refer patients requiring hospitalization to the COVID+ or COVID- hospital units, when response times for virological tests are too long. KEY POINTS: • In a large university hospital in Lyon, France, the accuracy, sensitivity, specificity, PPV, and NPV of chest CT for COVID-19 reached 88.9%, 90.2%, 88%, 84.1%, and 92.7%, respectively, using RT-PCR as standard of reference. • The mean delay for CT reports was three times shorter than for RT-PCR results (187 ± 148 min versus 573 ± 327 min, p < 0.0001). • Due to high accuracy of chest CT for COVID-19 and shorter time for CT reports than RT-PCR results, chest CT can be used to orient patients suspected to be positive towards the COVID+ unit to decrease congestion in the emergency departments.