The challenge of asymptomatic carriers of COVID-19: A rapid review of literature.

OBJECTIVES: To describe the epidemiological and sociodemographic characteristics of asymptomatic carriers reported in the literature, and to review the strategies used for diagnosis and control. METHODS: Systematic literature review approach. As inclusion criteria, all studies published between January 1 and June 26, 2020, conducted in humans, that reported people who remained asymptomatic of COVID-19. Descriptors were adapted to the interfaces of eight bibliographic databases were configured: PubMed, Ovid, SciELO, Ebsco, Scopus, LILACS, Epistemonikos and Embase. RESULTS: About 45% of the articles reported adult population, thirteen reported mixed population (adult and pediatric). 3 525 asymptomatic people were reported, with an average of 37,1 years [0.5-82 years]. Although the effectiveness of the control and prevention measures was not reported, the identification, isolation and follow-up of contacts stands out as a potential effective mechanism to prevent the transmission. CONCLUSIONS: The use of this information could be relevant to guide evidence-based public health policies and the protection of populations and the improvement of health care that contributes to stopping this pandemic.

Follow-up investigation of asymptomatic COVID-19 cases at diagnosis in Busan, Korea.

OBJECTIVES: The objective of the study was to conduct a follow-up investigation of 10 asymptomatic patients at diagnosis among the 98 confirmed coronavirus disease 2019 (COVID-19) cases reported in Busan between February 21, 2020 and March 13, 2020 to determine whether asymptomatic infection and transmission during asymptomatic period are possible. METHODS: The study analyzed 10 asymptomatic, confirmed COVID-19 cases to determine whether asymptomatic infection is possible. We conducted in-depth interviews with patients and guardians; interviews with primary physicians; review of medical records and drug utilization review (DUR) reports; and base station-based location tracking. RESULTS: Among the 98, confirmed COVID-19 cases reported in Busan, the study analyzed 10 (10.2%) asymptomatic patients at diagnosis. The results confirmed that two (2.0%) patients reported to be asymptomatic during the initial epidemiological investigation, but turned symptomatic before diagnosis as per the in-depth interview results. Four cases (4.0%) of early detection led to confirmed diagnosis during the incubation period and presentation of symptoms after diagnosis. In addition, the remaining four patients (4.0%), having no subjective symptoms nor specific findings on chest radiography and computed tomography, remained asymptomatic until the isolation order was lifted. With regard to whether transmission during the asymptomatic period is possible, it was found that one out of 23 household contacts of the confirmed patients was identified as an additional confirmed case after coming in close contact with an index patient during the presymptomatic period. CONCLUSIONS: Among the 98 confirmed cases, asymptomatic infection was confirmed in four cases (4.0%). In addition, there was one additional confirmed case in which the patient was a family member who came in close contact with an index patient during the incubation period, thereby confirming that transmission during the asymptomatic period is possible. The possibility of transmission during the asymptomatic period has been confirmed; therefore, it is necessary to review the measures for expanding contact tracing that is currently being applied starting one day prior to the onset of symptoms.

SARS-CoV-2 Infections and Presymptomatic Type 1 Diabetes Autoimmunity in Children and Adolescents From Colorado, USA, and Bavaria, Germany.

This study screens more than 50 000 youths in diverse populations of Colorado and Bavaria to assess whether previous SARS-CoV-2 infection was associated with autoimmunity, which predicts future type 1 diabetes.

Comparing pregnancy outcomes between symptomatic and asymptomatic COVID-19 positive unvaccinated women: Multicenter study in Saudi Arabia.

INTRODUCTION: COVID-19 infection in pregnancy ranges from asymptomatic infection to severe disease. However, the maternal and pregnancy outcomes are primarily favorable. Acute Respiratory Illness (ARI) score is a Visual Triage Checklist for Acute Respiratory symptoms created by the ministry of health of Saudi Arabia 12 to screen the patient for acute respiratory infection with MERS-CoV. It has been used during the COVID-19 pandemic to identify suspected cases and place patients in isolation precautions if the score is≥ 4. METHOD: This study is a cross-sectional study of all pregnant women who tested positive for COVID-19 in four medical centers located in four different cities in Saudi Arabia. The study period was from 1/3/2020 until 31/10/2020. Outcomes investigated were the prevalence of COVID infection in pregnant women at the time of delivery. Rate of asymptomatic disease, different maternal and pregnancy outcomes. Women were divided into symptomatic and asymptomatic groups according to the ARI score. The two groups were compared in maternal, perinatal, and neonatal outcomes. Furthermore, the cohort was divided according to maternal age into two groups: women of advanced maternal age ≥ 35 years and younger. The two groups were compared in maternal, perinatal, and neonatal outcomes RESULTS: During the study period, 9573 women gave birth at KAMCs, and 402 pregnant women were identified as COVID positive. Out of all COVID-positive women, only 394 women gave birth at KAMCs. The screening for COVID infection differed between the centers, but the testing was the same by the Nasopharyngeal polymerase chain reaction (PCR) swab. In Riyadh, screening was based on ARI scoring at the beginning of the pandemic. Then, it became universal. In Jeddah, the screening was based on ARI scoring. Any woman who scored four or more was labeled as suspected, and she was tested. Finally, in Madinah and Dammam, the screening was universal throughout the study. The prevalence of COVID-19 infection among women who gave birth at KAMCs was 4.2% (402/9573). (CI 3.8-4.6%). At the time of diagnosis, most women (62%) were asymptomatic. The most common symptoms were cough and shortness of breath. Twenty-two women (5.5%) had Pneumonia, and five women (1.3%) needed admission to Intensive care units (ICU). One woman died due to respiratory failure. When pregnancy outcomes were compared between symptomatic and asymptomatic women, pregnancy in symptomatic women was more likely to be complicated by Abortion (6 versus 2% p-value 0.00), fetal death (3 versus 1.3%), and cesarean delivery (30.8 versus 22.4%, p-value 0.001). COVID-positive pregnant women of advanced maternal age (AMA) were more likely to be symptomatic, have Abortion (5 versus 1%, p-value 0.01), and have Preterm delivery (17 versus 11% p-value 0.01) than younger women. In addition, neonatal death was more common in AMA COVID-positive women than younger (4 versus 0%), regardless of COVID-related symptoms. CONCLUSION: Most of the COVID-infected pregnant women are asymptomatic. Therefore, the ARI scoring system does not help to triage patients. Symptomatic women, especially those older than 35, tend to have a higher maternal and pregnancy complication rate.

Evaluation of the SARS-CoV-2 positivity ratio and upper respiratory tract viral load among asymptomatic individuals screened before hospitalization or surgery in Flanders, Belgium.

INTRODUCTION: The incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections in the Belgian community is mainly estimated based on test results of patients with coronavirus disease (COVID-19)-like symptoms. The aim of this study was to investigate the evolution of the SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) positivity ratio and distribution of viral loads within a cohort of asymptomatic patients screened prior hospitalization or surgery, stratified by age category. MATERIALS/METHODS: We retrospectively studied data on SARS-CoV-2 real-time RT-PCR detection in respiratory tract samples of asymptomatic patients screened pre-hospitalization or pre-surgery in nine Belgian hospitals located in Flanders over a 12-month period (1 April 2020-31 March 2021). RESULTS: In total, 255925 SARS-CoV-2 RT-PCR test results and 2421 positive results for which a viral load was reported, were included in this study. An unweighted overall SARS-CoV-2 real-time RT-PCR positivity ratio of 1.27% was observed with strong spatiotemporal differences. SARS-CoV-2 circulated predominantly in 80+ year old individuals across all time periods except between the first and second COVID-19 wave and in 20-30 year old individuals before the second COVID-19 wave. In contrast to the first wave, a significantly higher positivity ratio was observed for the 20-40 age group in addition to the 80+ age group compared to the other age groups during the second wave. The median viral load follows a similar temporal evolution as the positivity rate with an increase ahead of the second wave and highest viral loads observed for 80+ year old individuals. CONCLUSION: There was a high SARS-CoV-2 circulation among asymptomatic patients with a predominance and highest viral loads observed in the elderly. Moreover, ahead of the second COVID-19 wave an increase in median viral load was noted with the highest overall positivity ratio observed in 20-30 year old individuals, indicating they could have been the hidden drivers of this wave.

Usefulness of lung ultrasound for selecting asymptomatic older patients with COVID 19 pneumonia.

Clinical and prognostic differences between symptomatic and asymptomatic older patients with COVID-19 are of great interest since frail patients often show atypical presentation of illness. Lung Ultrasound (LUS) has been proven to be a reliable tool for detecting early-phase COVID-19 pneumonic alterations. The current prospective bicentric study aimed to compare LUS score and 3-month overall mortality between asymptomatic and symptomatic older patients with COVID-19, according to frailty status. Patients were stratified according to LUS score tertiles and Clinical Frailty Scale categories. Survival rate was assessed by telephone interviews 3 months after discharge. 64 symptomatic (24 women, aged 80.0 ± 10.8 years) and 46 asymptomatic (31 women, aged 84.3 ± 8.8 years) were consecutively enrolled. LUS score resulted an independent predictor of 3-month mortality [OR 2.27 (CI95% 1.09-4.8), p = 0.03], and the highest mortality rate was observed in symptomatic and asymptomatic pre-frail and frail patients (70.6% and 66.7%, respectively) with greater LUS abnormalities (3rd tertile). In conclusion, LUS identified an acute interstitial lung involvement in most of the older asymptomatic patients. Mortality rate progressively increased according to clinical frailty and LUS score degree, resulting a reliable prognostic tool in both symptomatic and asymptomatic patients.

Asymptomatic individuals can increase the final epidemic size under adaptive human behavior.

Infections produced by non-symptomatic (pre-symptomatic and asymptomatic) individuals have been identified as major drivers of COVID-19 transmission. Non-symptomatic individuals, unaware of the infection risk they pose to others, may perceive themselves-and be perceived by others-as not presenting a risk of infection. Yet, many epidemiological models currently in use do not include a behavioral component, and do not address the potential consequences of risk misperception. To study the impact of behavioral adaptations to the perceived infection risk, we use a mathematical model that incorporates the behavioral decisions of individuals, based on a projection of the system's future state over a finite planning horizon. We found that individuals' risk misperception in the presence of non-symptomatic individuals may increase or reduce the final epidemic size. Moreover, under behavioral response the impact of non-symptomatic infections is modulated by symptomatic individuals' behavior. Finally, we found that there is an optimal planning horizon that minimizes the final epidemic size.

Screening Students and Staff for Asymptomatic Coronavirus Disease 2019 in Chicago Schools.

OBJECTIVES: To assess rates of asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positivity in K-8 schools with risk mitigation procedures in place, and to evaluate SARS-CoV-2 transmission in school and household contacts of these positive individuals. STUDY DESIGN: In this prospective observational study, screening testing for SARS-CoV-2 was performed by oropharyngeal swabbing and polymerase chain reaction (PCR) analysis in students and staff at K-8 private schools in high-risk Chicago ZIP codes. New coronavirus disease 2019 (COVID-19) diagnoses or symptoms among participants, household contacts, and nonparticipants in each school were queried. RESULTS: Among 11 K-8 private schools across 8 Chicago ZIP codes, 468 participants (346 students, 122 staff members) underwent screening testing. At the first school, 17 participants (36%) tested positive, but epidemiologic investigation suggested against in-school transmission. Only 5 participants in the subsequent 10 schools tested positive for an overall 4.7% positivity rate (1.2% excluding school 1). All but 1 positive test among in-person students had high PCR cycle threshold values, suggesting very low SARS-CoV-2 viral loads. In all schools, no additional students, staff, or household contacts reported new diagnoses or symptoms of COVID-19 during the 2 weeks following screening testing. CONCLUSIONS: We identified infrequent asymptomatic COVID-19 in schools in high-risk Chicago communities and did not identify transmission among school staff, students, or their household contacts. These data suggest that COVID-19 mitigation procedures, including masking and physical distancing, are effective in preventing transmission of COVID-19 in schools. These results may inform future strategies for screening testing in K-8 schools.

[Transmission of SARS-CoV-2 through contact with a SARS-CoV-2-infected individual in the presymptomatic or asymptomatic state in Japan: A case series].

Objectives　There is little evidence supporting the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from presymptomatic or asymptomatic SARS-CoV-2-infected individuals in Japan, where the incidence of SARS-CoV-2 infection is lower than that in other developed countries. This study aimed to determine whether SARS-CoV-2 transmission can occur from presymptomatic or asymptomatic SARS-CoV-2-infected individuals.Methods　We surveyed all directors of Japanese public health centers for index cases and secondary patients who possibly contracted SARS-CoV-2 infection from a presymptomatic or asymptomatic SARS-CoV-2-infected individual who came under their care before June 20, 2020. The professional staff at the centers routinely perform contact tracing of infected persons based on the guidelines of the Infection Control Act. Four authors independently reviewed reports of 9 index cases of SARS-CoV-2-infected individuals with 17 secondary patients from 8 prefectures and examined the cases to determine whether transmission from a SARS-CoV-2-infected individual in the presymptomatic or asymptomatic state occurred.Results　We reported 7 index cases with 13 secondary patients. 1) An elderly woman acquired SARS-CoV-2 infection from her sustained asymptomatic granddaughter at home, 2) 4 guests and 1 accompanying child waiting at a hair salon acquired infection from the presymptomatic female hair stylist, 3) 2 inpatients acquired infection from a presymptomatic nurse while providing nursing care in close contact, 4) an elderly couple acquired SARS-CoV-2 infection from their presymptomatic relative who was in the 50s during household care at their home, 5) a man acquired SARS-CoV-2 infection from a presymptomatic adult neighbor in an enclosed space with poor ventilation, 6) a presymptomatic man had transmitted infection to another man at a coffee shop while having a discussion on business, and 7) a man in his 50s acquired SARS-CoV-2 infection from a presymptomatic man during 50 minutes of close contact at their office and in a car. These secondary patients had no other likely routes of infection. The interval between the date of symptom onset in the presymptomatic index case and the secondary patient ranged from 2 to 6 days. The incidence rates at the time these infections occurred in the corresponding prefectures ranged from 0.00 to 6.56 cases/1 million person-days.Conclusion　We report the first case of SARS-CoV-2 transmission from a sustained asymptomatic index case in Japan. All secondary patients came into close contact with presymptomatic index cases in areas with poor ventilation.

Silent Hypoxemia in Patients with COVID-19 Pneumonia: A Review.

During the coronavirus disease 2019 (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, patients presented with COVID-19 pneumonia of varying severity. The phenomenon of severe hypoxemia without signs of respiratory distress is also known as silent or hidden hypoxemia. Although silent hypoxemia is not unique to pneumonia due to SARS-CoV-2 infection, this phenomenon is now recognized to be associated with severe COVID-19 pneumonia. Proper management of critically ill patients is the key to reducing mortality. Herein, we summarize the possible and rare factors contributing to silent hypoxemia in patients with COVID-19. Microvascular thrombosis causes dead space ventilation in the lungs, and the flow of pulmonary capillaries is reduced, which leads to an imbalance in the V/Q ratio. The dissociation curve of oxyhemoglobin shifts to the left and limits the release of oxygen to the tissue. SARS-CoV-2 interferes with the synthesis of hemoglobin and reduces the ability to carry oxygen. The accumulation of endogenous carbon monoxide and carboxyhemoglobin will reduce the total oxygen carrying capacity and interfere with pulse oxygen saturation readings. There are also some non-specific factors that cause the difference between pulse oximetry and oxygen partial pressure. We propose some potentially more effective clinical alternatives and recommendations for optimizing the clinical management processes of patients with COVID-19. This review aims to describe the prevalence of silent hypoxemia in COVID-19 pneumonia, to provide an update on what is known of the pathophysiology, and to highlight the importance of diagnosing silent hypoxemia in patients with COVID-19 pneumonia.

Prehospital characteristics of COVID-19 patients in Helsinki - experience of the first wave of the pandemic.

BACKGROUND: There is a lack of knowledge how patients with COVID-19 disease differ from patients with similar signs or symptoms (but who will have a diagnosis other than COVID-19) in the prehospital setting. The aim of this study was to compare the characteristics of these two patient groups met by the emergency medical services. METHODS: All prehospital patients after the World Health Organisation (WHO) pandemic declaration 11.3.2020 until 30.6.2020 were recruited for the study. The patients were screened using modified WHO criteria for suspected COVID-19. Data from the electronic prehospital patient reporting system were linked with hospital laboratory results to check the laboratory confirmation for COVID-19. For comparison, we divided the patients into two groups: screening- and laboratory-positive patients with a hospital diagnosis of COVID-19 and screening-positive but laboratory-negative patients who eventually received a different diagnosis in hospital. RESULTS: A total of 4157 prehospital patients fulfilled the criteria for suspected COVID-19 infection during the study period. Five-hundred-thirty-six (12.9%) of the suspected cases received a laboratory confirmation for COVID-19. The proportion of positive cases in relation to suspected ones peaked during the first 2 weeks after the declaration of the pandemic. In the comparison of laboratory-positive and laboratory-negative cases, there were clinically insignificant differences between the groups in age, tympanic temperature, systolic blood pressure, heart rate, on-scene time, urgency category of the call and mode of transportation. Foreign-language-speakers were overrepresented amongst the positive cases over native language speakers (26,6% vs. 7,4%, p < 0,001). The number of cases in which no signs or symptoms of COVID-19 disease were reported, but patients turned out to have a positive test result was 125 (0,3% of the whole EMS patient population and 11,9% of all verified COVID-19 patients encountered by the EMS). CONCLUSIONS: In a sample of suspected COVID-19 patients, the laboratory-positive and laboratory-negative patients were clinically indistinguishable from each other during the prehospital assessment. Foreign-language-speakers had a high likelihood of having Covid-19. The modified WHO criteria still form the basis of screening of suspected COVID-19 patients in the prehospital setting.

A novel automated SARS-CoV-2 saliva PCR test protects a global asymptomatic workforce.

Regular PCR testing of nasopharyngeal swabs from symptomatic individuals for SARS-CoV-2 virus has become the established method by which health services are managing the COVID-19 pandemic. Businesses such as AstraZeneca have also prioritised voluntary asymptomatic testing to keep workplaces safe and maintain supply of essential medicines to patients. We describe the development of an internal automated SARS-CoV-2 testing programme including the transformative introduction of saliva as an alternative sample type.

Detecting infected asymptomatic cases in a stochastic model for spread of Covid-19: the case of Argentina.

We have studied the dynamic evolution of the Covid-19 pandemic in Argentina. The marked heterogeneity in population density and the very extensive geography of the country becomes a challenge itself. Standard compartment models fail when they are implemented in the Argentina case. We extended a previous successful model to describe the geographical spread of the AH1N1 influenza epidemic of 2009 in two essential ways: we added a stochastic local mobility mechanism, and we introduced a new compartment in order to take into account the isolation of infected asymptomatic detected people. Two fundamental parameters drive the dynamics: the time elapsed between contagious and isolation of infected individuals ([Formula: see text]) and the ratio of people isolated over the total infected ones (p). The evolution is more sensitive to the [Formula: see text]parameter. The model not only reproduces the real data but also predicts the second wave before the former vanishes. This effect is intrinsic of extensive countries with heterogeneous population density and interconnection.The model presented has proven to be a reliable predictor of the effects of public policies as, for instance, the unavoidable vaccination campaigns starting at present in the world an particularly in Argentina.

Pitfall of Universal Pre-Admission Screening for SARS-CoV-2 in a Low Prevalence Country.

It is unclear whether universal PCR screening for SARS-CoV-2 in asymptomatic individuals prior to admission is useful. From April to December 2020, the positive rate of universal pre-admission screening was 0.005% (4/76,521) in a tertiary care hospital in Korea. The positive rates were not different between the periods (period 1 (daily new patients of <1 per million inhabitants) vs. period 2 (1-8.3 per million inhabitants) vs. period 3 (10.3 to 20 per million inhabitants); P = 0.45). Universal pre-admission screening for SARS-CoV-2 had a lower positive rate than that of symptom-based screening (0.005% vs. 0.049% (53/109,257), p < 0.001). In addition, seven patients with negative pre-admission test results had subsequent positive PCR during hospitalization, and four patients had secondary transmission. Universal pre-admission PCR screening may not be practical in settings of low prevalence of COVID-19, and negative PCR results at admission should not serve as a basis for underestimating the risk of nosocomial spread from asymptomatic patients.