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.

Temporal trends and forecasting of COVID-19 hospitalisations and deaths in Scotland using a national real-time patient-level data platform: a statistical modelling study.

BACKGROUND: As the COVID-19 pandemic continues, national-level surveillance platforms with real-time individual person-level data are required to monitor and predict the epidemiological and clinical profile of COVID-19 and inform public health policy. We aimed to create a national dataset of patient-level data in Scotland to identify temporal trends and COVID-19 risk factors, and to develop a novel statistical prediction model to forecast COVID-19-related deaths and hospitalisations during the second wave. METHODS: We established a surveillance platform to monitor COVID-19 temporal trends using person-level primary care data (including age, sex, socioeconomic status, urban or rural residence, care home residence, and clinical risk factors) linked to data on SARS-CoV-2 RT-PCR tests, hospitalisations, and deaths for all individuals resident in Scotland who were registered with a general practice on Feb 23, 2020. A Cox proportional hazards model was used to estimate the association between clinical risk groups and time to hospitalisation and death. A survival prediction model derived from data from March 1 to June 23, 2020, was created to forecast hospital admissions and deaths from October to December, 2020. We fitted a generalised additive spline model to daily SARS-CoV-2 cases over the previous 10 weeks and used this to create a 28-day forecast of the number of daily cases. The age and risk group pattern of cases in the previous 3 weeks was then used to select a stratified sample of individuals from our cohort who had not previously tested positive, with future cases in each group sampled from a multinomial distribution. We then used their patient characteristics (including age, sex, comorbidities, and socioeconomic status) to predict their probability of hospitalisation or death. FINDINGS: Our cohort included 5 384 819 people, representing 98·6% of the entire estimated population residing in Scotland during 2020. Hospitalisation and death among those testing positive for SARS-CoV-2 between March 1 and June 23, 2020, were associated with several patient characteristics, including male sex (hospitalisation hazard ratio [HR] 1·47, 95% CI 1·38-1·57; death HR 1·62, 1·49-1·76) and various comorbidities, with the highest hospitalisation HR found for transplantation (4·53, 1·87-10·98) and the highest death HR for myoneural disease (2·33, 1·46-3·71). For those testing positive, there were decreasing temporal trends in hospitalisation and death rates. The proportion of positive tests among older age groups (>40 years) and those with at-risk comorbidities increased during October, 2020. On Nov 10, 2020, the projected number of hospitalisations for Dec 8, 2020 (28 days later) was 90 per day (95% prediction interval 55-125) and the projected number of deaths was 21 per day (12-29). INTERPRETATION: The estimated incidence of SARS-CoV-2 infection based on positive tests recorded in this unique data resource has provided forecasts of hospitalisation and death rates for the whole of Scotland. These findings were used by the Scottish Government to inform their response to reduce COVID-19-related morbidity and mortality. FUNDING: Medical Research Council, National Institute for Health Research Health Technology Assessment Programme, UK Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, Scottish Government Director General Health and Social Care.

SARS-CoV-2 screening among people living in homeless shelters in Brussels, Belgium.

BACKGROUND: Subgroups of precarious populations such as homeless people are more exposed to infection and at higher risk of developing severe forms of COVID-19 compared to the general population. Many of the recommended prevention measures, such as social distancing and self-isolation, are not feasible for a population living in shelters characterised by physical proximity and a high population density. The objective of the study was to describe SARS-CoV-2 infection prevalence in homeless shelters in Brussels (Belgium), and to identify risk factors and infection control practices associated with SARS-CoV-2 positivity rates. METHODS: A total of 1994 adults were tested by quantitative PCR tests in 52 shelters in Brussels (Belgium) between April and June, 2020, in collaboration with Doctors of the World. SARS-CoV-2 prevalence is here described site by site, and we identify risk factors associated with SARS-CoV-2 positivity rates. We also investigate associations between seropositivity and reported symptoms. RESULTS: We found an overall prevalence of 4.6% for the period, and a cluster of high rates of SARS-CoV-2 positivity (20-30% in two shelters). Among homeless people, being under 40 years of age (OR (CI95%) 2.3 (1.2-4.4), p = 0.02), having access to urgent medical care (AMU) (OR(CI95%): 2.4 (1.4-4.4)], p = 0.02), and sharing a room with someone who tested positive (OR(CI95%): 5.3 (2.9-9.9), p<0.0001) were factors associated with SARS-CoV-2 positivity rates. 93% of those who tested positive were asymptomatic. CONCLUSION: This study shows high rates of SARS-COV-2 infection positive tests in some shelters, with a high proportion of asymptomatic cases. The survey reveals how important testing and isolation measures are, together with actions taken by medical and social workers during the outbreak.

Characteristics of a COVID-19 confirmed case series in primary care (COVID-19-PC project): a cross-sectional study.

BACKGROUND: To estimate the prevalence of symptoms and signs related to a COVID-19 case series confirmed by polymerase chain reaction (PCR) for SARS-CoV-2. Risk factors and the associated use of health services will also be analysed. METHODS: Observational, descriptive, retrospective case series study. The study was performed at two Primary Care Health Centres located in Madrid, Spain. The subjects studied were all PCR SARS-CoV-2 confirmed cases older than 18 years, diagnosed from the beginning of the community transmission (March 13) until April 15, 2020. We collected sociodemographic, clinical, health service utilization and clinical course variables during the following months. All data was gathered by their own attending physician, and electronic medical records were reviewed individually. STATISTICAL ANALYSIS: A descriptive analysis was carried out and a Poisson regression model was adjusted to study associated factors to Health Services use. RESULTS: Out of the 499 patients studied from two health centres, 55.1% were women and mean age was 58.2 (17.3). 25.1% were healthcare professionals. The most frequent symptoms recorded related to COVID-19 were cough (77.9%; CI 95% 46.5-93.4), fever (77.7%; CI95% 46.5-93.4) and dyspnoea (54.1%, CI95% 46.6-61.4). 60.7% were admitted to hospital. 64.5% first established contact with their primary care provider before going to the hospital, with a mean number of 11.4 Healthcare Providers Encounters with primary care during all the follow-up period. The number of visit-encounters with primary care was associated with being male [IRR 1.072 (1.013, 1.134)], disease severity {from mild respiratory infection [IRR 1.404 (1.095, 1.801)], up to bilateral pneumonia [IRR 1.852 (1.437,2.386)]}, and the need of a work leave [IRR 1.326 (1.244, 1.413]. CONCLUSION: Symptoms and risk factors in our case series are similar to those in other studies. There was a high number of patients with atypical unilateral or bilateral pneumonia. Care for COVID has required a high use of healthcare resources such as clinical encounters and work leaves.

Organizational aspects of pediatric anesthesia and surgery between two waves of Covid-19.

BACKGROUND: The initial wave of the Covid-19 pandemic has hit Italy, and Lombardy in particular, with violence, forcing to reshape all hospitals' activities; this happened even in pediatric hospitals, although the young population seemed initially spared from the disease. "Vittore Buzzi" Children's Hospital, which is a pediatric/maternal hospital located in Milan (Lombardy Region), had to stop elective procedures-with the exception of urgent/emergent ones-between February and May 2020 to leave space and resources to adults' care. We describe the challenges of reshaping the hospital's identity and structure, and restarting pediatric surgery and anesthesia, from May on, in the most hit area of the world, with the purpose to avoid and contain infections. Both patients and caregivers admitted to hospital have been tested for Sars-CoV-2 in every case. METHODS: Observational cohort study via review of clinical charts of patients undergoing surgery between 16th May and 30th September 2020, together with SARS-CoV -2 RT-PCR testing outcomes, and comparison to same period surgeries in 2019. RESULTS: An increase of approximately 70% in pediatric surgeries (OR 1.68 [1.33-2.13], P < .001) and a higher increase in the number of surgeries were reported (OR 1.75 (1.43-2.15), P < .001). Considering only urgent procedures, a significant difference in the distribution of the type of surgery was observed (Chi-squared P-value < .001). Sars-CoV-2-positive patients have been 0.8% of total number; 14% of these was discovered through caregiver's positivity. CONCLUSION: We describe our pathway for safe pediatric surgery and anesthesia and the importance of testing both patient and caregiver.

Variability of cycle threshold values in an external quality assessment scheme for detection of the SARS-CoV-2 virus genome by RT-PCR.

OBJECTIVES: The qualitative results of SARS-CoV-2 specific real-time reverse transcription (RT) PCR are used for initial diagnosis and follow-up of Covid-19 patients and asymptomatic virus carriers. However, clinical decision-making and health management policies often are based additionally on cycle threshold (Ct) values (i.e., quantitative results) to guide patient care, segregation and discharge management of individuals testing positive. Therefore, an analysis of inter-protocol variability is needed to assess the comparability of the quantitative results. METHODS: Ct values reported in a SARS-CoV-2 virus genome detection external quality assessment challenge were analyzed. Three positive and two negative samples were distributed to participating test laboratories. Qualitative results (positive/negative) and quantitative results (Ct values) were assessed. RESULTS: A total of 66 laboratories participated, contributing results from 101 distinct test systems and reporting Ct values for a total of 92 different protocols. In all three positive samples, the means of the Ct values for the E-, N-, S-, RdRp-, and ORF1ab-genes varied by less than two cycles. However, 7.7% of reported results deviated by more than ±4.0 (maximum 18.0) cycles from the respective individual means. These larger deviations appear to be systematic errors. CONCLUSIONS: In an attempt to use PCR diagnostics beyond the identification of infected individuals, laboratories are frequently requested to report Ct values along with a qualitative result. This study highlights the limitations of interpreting Ct values from the various SARS-CoV genome detection protocols and suggests that standardization is necessary in the reporting of Ct values with respect to the target gene.

SARS-CoV-2 antibody detection in skilled nursing facility residents.

OBJECTIVE: To describe the frequency and timing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody detection in a convenience sample of skilled nursing facility (SNF) residents with and without confirmed SARS-CoV-2 infection. DESIGN: Retrospective analysis of SNF electronic health records. SETTING: Qualitative SARS-CoV-2 antibody test results were available from 81 SNFs in 16 states. PARTICIPANTS: Six hundred and sixty nine SNF residents who underwent both polymerase chain reaction (PCR) and antibody testing for SARS-CoV-2. MEASUREMENTS: Presence of SARS-CoV-2 antibodies following the first positive PCR test for confirmed cases, or first PCR test for non-cases. RESULTS: Among 397 residents with PCR-confirmed infection, antibodies were detected in 4 of 7 (57.1%) tested within 7-14 days of their first positive PCR test; in 44 of 47 (93.6%) tested within 15-30 days; in 182 of 219 (83.1%) tested within 31-60 days; and in 110 of 124 (88.7%) tested after 60 days. Among 272 PCR negative residents, antibodies were detected in 2 of 9 (22.2%) tested within 7-14 days of their first PCR test; in 41 of 81 (50.6%) tested within 15-30 days; in 65 of 148 (43.9%) tested within 31-60 days; and in 9 of 34 (26.5%) tested after 60 days. No significant differences in baseline resident characteristics or symptoms were observed between those with versus without antibodies. CONCLUSIONS: These findings suggest that vulnerable older adults can mount an antibody response to SARS-CoV-2, and that antibodies are most likely to be detected within 15-30 days of diagnosis. That antibodies were detected in a large proportion of residents with no confirmed SARS-CoV-2 infection highlights the complexity of identifying who is infected in real time. Frequent surveillance and diagnostic testing based on low thresholds of clinical suspicion for symptoms and/or exposure will remain critical to inform strategies designed to mitigate outbreaks in SNFs while community SARS-CoV-2 prevalence remains high.

An Observational Laboratory-Based Assessment of SARS-CoV-2 Molecular Diagnostics in Benin, Western Africa.

Information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread in Africa is limited by insufficient diagnostic capacity. Here, we assessed the coronavirus disease (COVID-19)-related diagnostic workload during the onset of the pandemic in the central laboratory of Benin, Western Africa; characterized 12 SARS-CoV-2 genomes from returning travelers; and validated the Da An RT-PCR-based diagnostic kit that is widely used across Africa. We found a 15-fold increase in the monthly laboratory workload due to COVID-19, dealt with at the cost of routine activities. Genomic surveillance showed near-simultaneous introduction of distinct SARS-CoV-2 lineages termed A.4 and B.1, including the D614G spike protein variant potentially associated with higher transmissibility from travelers from six different European and African countries during March-April 2020. We decoded the target regions within the ORF1ab and N genes of the Da An dual-target kit by MinION-based amplicon sequencing. Despite relatively high similarity between SARS-CoV-2 and endemic human coronaviruses (HCoVs) within the ORF1ab target domain, no cross-detection of high-titered cell culture supernatants of HCoVs was observed, suggesting high analytical specificity. The Da An kit was highly sensitive, detecting 3.2 to 9.0 copies of target-specific in vitro transcripts/reaction. Although discrepant test results were observed in low-titered clinical samples, clinical sensitivity of the Da An kit was at least comparable to that of commercial kits from affluent settings. In sum, virologic diagnostics are achievable in a resource-limited setting, but unprecedented pressure resulting from COVID-19-related diagnostics requires rapid and sustainable support of national and supranational stakeholders addressing limited laboratory capacity.IMPORTANCE Months after the start of the COVID-19 pandemic, case numbers from Africa are surprisingly low, potentially because the number of SARS-CoV-2 tests performed in Africa is lower than in other regions. Here, we show an overload of COVID-19-related diagnostics in the central laboratory of Benin, Western Africa, with a stagnating average number of positive samples irrespective of daily sample counts. SARS-CoV-2 genomic surveillance confirmed a high genomic diversity in Benin introduced by travelers returning from Europe and other African countries, including early circulation of the D614G spike mutation associated with potentially higher transmissibility. We validated a widely used RT-PCR kit donated by the Chinese Jack Ma Foundation and confirmed high analytical specificity and clinical sensitivity equivalent to tests used in affluent settings. Our assessment shows that although achievable in an African setting, the burden from COVID-19-related diagnostics on national reference laboratories is very high.

COVID-19 among the inhabitants of the slums in the city of Buenos Aires: a population-based study.

OBJECTIVE: To summarise the unfolding of the COVID-19 epidemic among slum dwellers and different social strata in the city of Buenos Aires during the first 20 weeks after the first reported case. DESIGN: Observational study using a time-series analysis. Natural experiment in a big city. SETTING: Population of the city of Buenos Aires and the integrated health reporting system records of positive RT-PCR for COVID-19 tests. PARTICIPANTS: Records from the Argentine Integrated Health Reporting System for all persons with suspected and RT-PCR-confirmed diagnosis of COVID-19 between 31 January and 14 July 2020. OUTCOMES: To estimate the effects of living in a slum on the standardised incidence rate of COVID-19, corrected Poisson regression models were used. Additionally, the impact of socioeconomic status was performed using an ecological analysis at the community level. RESULTS: A total of 114 052 people were tested for symptoms related with COVID-19. Of these, 39 039 (34.2%) were RT-PCR positive. The incidence rates for COVID-19 towards the end of the 20th week were 160 (155 to 165) per 100 000 people among the inhabitants who did not reside in the slums (n=2 841 997) and 708 (674 to 642) among slums dwellers (n=233 749). Compared with the better-off socioeconomic quintile (1.00), there was a linear gradient on incidence rates: 1.36 (1.25 to 1.46), 1.61 (1.49 to 1.74), 1.86 (1.72 to 2.01), 2.94 (2.74 to 3.16) from Q2 to Q5, respectively. Slum dwellers were associated with an incidence rate of 14.3 (13.4 to 15.4). CONCLUSIONS: The distribution of the epidemic is socially conditioned. Slum dwellers are at a much higher risk than the rest of the community. Slum dwellers should not be considered just another risk category but an entirely different reality that requires policies tailored to their needs.