Molecular detection of SARS-CoV-2 being challenged by virus variation and asymptomatic infection

Coronavirus disease 2019(COVID-19)has been a pandemic for more than a year.With the expanding second wave of the pandemic in winter,the continuous evolution of SARS-CoV-2 has brought new issues,including the significance of virus mutations in infection and the detection of asymptomatic infection.In this review,we first introduced several major SARS-CoV-2 mutations since the COVID-19 outbreak and then mentioned the widely used molecular detection techniques to diagnose COVID-19,primarily focusing on their strengths and limitations.We further discussed the effects of viral genetic variation and asymptomatic infection on the molecular detection of SARS-CoV-2 infection.The review finally summarized useful insights into the molecular diagnosis of COVID-19 under the special situation being challenged by virus mutation and asymptomatic infection.

Visceral leishmaniasis: An immunological viewpoint on asymptomatic infections and post kala azar dermal leishmaniasis

Elimination of visceral leishmaniasis is a priority programme in Indian subcontinent.The World Health Organization has set a new target to eliminate kala-azar by the year 2020 as previous target elimination year(2015) has passed.The elimination programme has successfully curbed the rate of infection in endemic regions; however, there are still few challenges in its route.The current drug control regime is extremely limited and comprises only two(amphotericin B and miltefosine) drugs, which are also susceptible for parasites resistance.Moreover, these drugs do not produce sterile cure, and cured patients may develop post kala-azar dermal leishmaniasis even after a decade of cure leaving behind a potent source of parasitic reservoirs for further disease transmission.A significant proportion of endemic population remain seropositive but aymptomatic for many years without any clinical symptom that serve as latent parasitic reservoirs.The lack of tools to identify live parasites in asymptomatic infections and there association in disease transmission, parameters of sterile cure along with post kala-azar dermal leishmaniasis progression remain a major threat in its elimination.In this review, we discuss the potential of host immune inhibitory mechanisms to identify immune correlates of protective immunity to understand the mystery of asymptomatic infections, sterile cure and post kala azar dermal leishmaniasis.

Paying Attention to Special Populations:1 Case of COVID-19 Asymptomatic Infection with Positive Nucleic Acid and Negative Antibodies in Puerpera

As a newly emerged disease,COVID-19's in-depth understanding is still being explored.And also as the epidemic changes,various new situations will be encountered.Atypical patients have brought difficulties to our prevention and control of this disease.Among them,asymptomatic patients are a special category,and puerperae are a special population.What happens when a puerpera is infected with asymptomatic COVID-19?This study describes 1 case of COVID-19 asymptomatic infection with positive nucleic acid and negative antibodies in puerpera.The aim is to remind clinicians to take special cases seriously,such as puerperae and pregnant women,AIDS,and other immunocompromised patients.It may not be enough to rely solely on antibody detection,but more than two repeated nucleic acid tests are necessary,so that no suspicious patient can be easily let off.

Impact of asymptomatic infected individuals on epidemic transmission dynamics in multiplex networks with partial coupling

The theory of network science has attracted great interest of many researchers in the realm of biomathematics and public health,and numerous valuable epidemic models have been developed.In previous studies,it is common to set up a one-to-one correspondence between the nodes of a multi-layer network,ignoring the more complex situations in reality.In the present work,we explore this situation by setting up a partially coupled model of a two-layer network and investigating the impact of asymptomatic infected individuals on epidemics.We propose a self-discovery mechanism for asymptomatic infected individuals,taking into account situations such as nucleic acid testing in the community and individuals performing self-antigen testing during the epidemic.Considering these factors together,through the microscopic Markov chain approach(MMCA)and extensive Monte Carlo(MC)numerical simulations,we find that the greater the coupling between the networks,the more information dissemination is facilitated.In order to control the epidemics,more asymptomatic infected individuals should be made aware of their infection.Massive adoption of nucleic acid testing and individual adoption of antigenic self-testing can help to contain epidemic outbreaks.Meanwhile,the epidemic threshold of the proposed model is derived,and then miscellaneous factors affecting the epidemic threshold are also discussed.Current results are conducive to devising the prevention and control policies of pandemics.

Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing,China

Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease(COVID-19)and the evidence of person-to-person transmission.Limited data are available for asymptomatic infections.This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers.Epidemiological investigations were conducted among all close contacts of COVID-19 patients(or suspected patients)in Nanjing,Jiangsu Province,China,from Jan 28 to Feb 9,2020,both in clinic and in community.Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples.Their clinical records,laboratory assessments,and chest CT scans were reviewed.As a result,none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening.Five cases(20.8%)developed symptoms(fever,cough,fatigue,etc.)during hospitalization.Twelve(50.0%)cases showed typical CT images of ground-glass chest and 5(20.8%)presented stripe shadowing in the lungs.The remaining 7(29.2%)cases showed normal CT image and had no symptoms during hospitalization.These 7 cases were younger(median age:14.0 years;P=0.012)than the rest.None of the 24 cases developed severe COVID-19 pneumonia or died.The median communicable period,defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests,was 9.5 days(up to 21 days among the 24 asymptomatic cases).Through epidemiological investigation,we observed a typical asymptomatic transmission to the cohabiting family members,which even caused severe COVID-19 pneumonia.Overall,the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization.However,the communicable period could be up to three weeks and the communicated patients could develop severe illness.These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests.Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.

Epidemiological Analysis of Asymptomatic SARS-CoV-2 Novel Coronavirus Infection Cases in Yinchuan City of Ningxia

Objective:To analyze the epidemiological characteristics of asymptomatic SARS-CoV-2 novel coronavirus infection cases in Yinchuan City,Ningxia.Methods:Cases of asymptomatic SARSCoV-2 novel coronavirus infections discovered in Yinchuan City from February 2020 to April 2020 were taken as the research subjects,epidemiological and laboratory examination data were collected,and statistics and analysis were conducted.Results:Among the 10 cases of asymptomatic infection,6 were males and 4 were females,with an average age of(34.3±2.1)years;2 cases had a history of living in Hubei,8 cases had a history of close contact with confirmed cases;6 cases had no other underlying diseases while the other 4 cases were accompanied by one or more underlying diseases;6 cases were diagnosed as asymptomatic infection by serum-specific IgM antibody detection;4 cases were diagnosed as asymptomatic infection by throat swab testing;there were 4 cases with alanine base transferase level higher than the normal range,2 cases with aspartate aminotransferase level higher than the normal range,and 3 cases with D-dimer level out of the normal range.Conclusion:The asymptomatic SARS-CoV-2 novel coronavirus infection has certain clinical characteristics;it is infectious and has insidious characteristics.Even if medical observation is dismissed,monitoring is still needed to prevent the pandemic from rebounding.

Estimating the Level of Asymptomatic COVID-19 Infections in Northern Ireland in 2020

The identification and understanding of COVID-19 potential routes of transmission are fundamental to informing policies and strategies to successfully control the outbreak. Various studies highlighted asymptomatic infections as one of the silent drivers of the epidemic. An accurate estimation of the asymptomatic cases and the understanding of their contribution to the spread of the disease could enhance the effectiveness of current control strategies, mainly based on the symptom onset, to curb transmission. We investigate the dynamics of the COVID-19 epidemic in Northern Ireland during the period 1st March 25th to December 2020 to estimate the proportion of the asymptomatic infections in the country. We extended our previous model to include the stage of the asymptomatic infection, and we implement the corresponding deterministic model using a publicly available dataset. We partition the data into 11 sets over the period of study and fit the model parameters on the consecutive intervals using the cumulative number of confirmed positive cases for each interval. Moreover, we assess numerically the impacts of uncertainty in testing and we provide estimates of the reproduction numbers using the fitted parameters. We found that the proportion of asymptomatically infectious subpopulations, in Northern Ireland during the period of study, ranged between 5% and 25% of exposed individuals. Also, the estimate of the basic reproduction number, R0, is 3.3089. The lower and upper estimates for herd immunity are (0.6181, 0.7243) suggesting that around 70% of the population of Northern Ireland should acquire immunity via infection or vaccination, which is in line with estimates reported in other studies.

The latest research progress in asymptomatic and pre-symptomatic patients with COVID-19

The asymptomatic and pre-symptomatic infections of coronavirus disease 2019(COVID-19)has no perceptible clinical symptoms and signs,and it is not easy to be detected. The transmission of the virus carried by asymptomatic and pre-symptomatic patients is insidious,which brings great challenges to the control of the epidemic. Due to the length of the incubation period,some studies have failed to distinguish between asymptomatic and pre-symptomatic infections,resulting in a higher proportion of asymptomatic infections. This article reviews the latest research progress of characteristics,transmission,detection and control of asymptomatic and pre-symptomatic infection.

Research progress on detection methods of the asymptomatic COVID- 19 infected persons

The global pandemic of COVID-19 has brought great harm and challenges to many countries and regions around the world.The majority of COVID-19 patients have typical clinical manifestations,but the number of asymptomatic infections is increasing as COVID-19 research continues and SARS-CoV-2 testing improves.Many asymptomatic COVID-19 patients with no obvious clinical symptoms are able to transmit the virus to others due to the presence of SARS-CoV-2 in their bodies,thus greatly accelerating the worldwide pandemic and posing great difficulty and threat to global epidemic prevention and control.Therefore,early detection and identification of asymptomatic infected persons through various testing methods are effective measures to control the COVID-19 pandemic.This article will provide a brief review of the available methods and techniques for detecting asymptomatic COVID-19 patients.

Congenital Cytomegalovirus Infection and Maternal Varicella during Pregnancy.Is There a Coincidence?A Case Report

Background: Co-infections may represent substantial diagnostic and treatment challenges. Aim: To the better of our knowledge, we describe the first case in the literature of congenital Cytomegalovirus (CMV) infection following maternal CMV non primary infection contemporary to varicella during pregnancy. Case Presentation: A pregnant woman had a varicella during her pregnancy. Congenital CMV infection was fortuitously discovered in the neonate owing to a universal CMV screening. Retrospective analysis of maternal serums during pregnancy showed CMV reactivation. We aim to highlight that CMV reactivation could be due to varicella and discuss if it could facilitate the transplacental transmission of CMV. Conclusion: This case report emphasizes neonatal CMV screening, and warns against dual maternal infection especially because this may be at particular risk of transmission to the fetus.

The Nongenomic Effects of Progesterone in Repressing iNOS Activation through P38MAPK Pathways in Gonococci-Infected Polymorphonuclear Leukocytes and the Clinical Significance

Progesterone has nongenomic effects on inducible nitric oxide synthase(iNOS),which is mediated by mitogen activated protein kinase(MAPK)pathways.This effect is supposed to have some potential association with asymptomatic gonococcal infections in women by immunological depression.In this study,polymorphonuclear leukocytes(PMNs)challenged by gonococci were used to study the nongenomic effects of progesterone.The activation of iNOS was assessed by measuring [3H] L-arginine converses to [3H] L-citrulline,and t...

Asymptomatic stage of human immunodeficiency virus infection is the optimal timing for its management with Traditional Chinese Medicine

Acquired immune deficiency syndrome(AIDS) is a worldwide public health problem and an incurable disease.The roles of Traditional Chinese Medicine(TCM) on AIDS had been recognized and accepted by more and more people.Being a relatively long period,to initiate combination antiretroviral therapy(cART) for the asymptomatic human immunodeficiency virus(HIV) infection patient is not consensus.According to TCM theory,not only the imbalance of Yin and Yang but also the disharmony of internal body function and external natural environment had occurred in the body of the patient,the imbalance and the disharmony should be adjusted by the means of the treatment based on the patters identified among the symptoms in terms of TCM.We aimed to analyze the feature of patients with asymptomatic infection,and compare the advantages and disadvantages of the usage of cART for asymptomatic infection,explored the possible mechanism underlying TCM treatment of the asymptomatic infection,by reviewing the TCM treatment progress on asymptomatic HIV infection.

Necessary problems in re-emergence of COVID-19

The ongoing pandemic of coronavirus disease 2019 poses a great threat to human beings.Although numerous patients have recovered,re-positive cases have been reported in several countries.Till now,we still know very little about the disease and its pathogen severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Therefore,more attention should be paid to the following aspects,such as postdischarge surveillance,asymptomatic infection,re-evaluation of influenza-like symptoms,and dynamic monitoring of genomic mutation of SARS-CoV-2.

Modeling the Prevalence of Asymptomatic COVID-19 Infections in the Chinese Mainland

Recently,considerable efforts have been focused on intensifying the screening process for asymptomatic COVID-19 cases in the ChineseMainland,especially for up to 10 million citizens living in Wuhan City by nucleic acid testing.However,a high percentage of domestic asymptomatic cases did not develop into symptomatic ones,which is abnormal and has drawn considerable public attention.Here,we aimed to investigate the prevalence of COVID-19 infections in the Chinese Mainland from a statistical perspective,as it is of referential significance for other regions.By conservatively assuming a development time lag from pre-symptomatic(i.e.,referring to the infected cases that were screened before the COVID-19 symptom onset)to symptomatic as an incubation time of 5.2 days,our results indicated that 92.5%of those tested in Wuhan City,China,and 95.1%of those tested in the Chinese Mainland should have COVID-19 syndrome onset,which was extremely higher than their corresponding practical percentages of 0.8%and 3.3%,respectively.We propose that a certain false positive rate may exist if large-scale nucleic acid screening tests for asymptomatic cases are conducted in common communities with a low incidence rate.Despite adopting relatively high-sensitivity,high-specificity detection kits,we estimated a very low prevalence of COVID-19 infections,ranging from 10
6 to 10
4 in both Wuhan City and the Chinese Mainland.Thus,the prevalence rate of asymptomatic infections in China had been at a very low level.Furthermore,given the lower prevalence of the infection,close examination of the data for false positive results is necessary to minimize social and economic impacts.

Long-term asymptomatic SARS-CoV-2 infection associated with deficiency on multiple immune cells

The immune responses and the function of immune cells among asymptomatic severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)infection cases,especially in immuno‐compromised individuals,remain largely unknown.Here we present a case of asymptomatic SARS‐CoV‐2 infection that lasted for at least 67 days.The patient has administrated Thymalfasin as 1.6 mg per dose every other day from Day 45 to 70,plus 200 mg per dose Arbidol antiviral therapy three doses per day from Day 48 to 57.Throughout the infection,no anti‐SARS‐CoV‐2 specific IgM or IgG antibodies were detected.Instead,the patient showed either a low percentage or an absolute number of non‐classical monocytes,dendritic cells(DCs),CD4^(+)T cells,and regulatory T cells(Tregs),which may account for the clinical feature and absence of antibody response.This case may shed new light on the outbreak management related to control/prevention,treatment,and vaccination of SARS‐CoV‐2 and other virus infections in immunocompromised individuals.

Clinical characteristics of 290 foreign-imported cases infected with SARS-CoV-2 in Chengdu, China

Objective:To analyze the epidemiological and clinical characteristics of foreign-imported patients infected with SARS-CoV-2 in Chengdu City.Methods:A total of 290 foreign-imported patients infected with SARS-CoV-2 and discharged from Public Health Clinical Center of Chengdu were included in our study,they were divided into asymptomatic infection group(131 cases)and confirmed cases group(159 cases)in order to compare the epidemiology,clinical characteristics and laboratory tests between two groups.Multi-factor logistic regression analysis was used to investigate the influence factors of becoming a dominant infection after infected with SARS-CoV-2.Results:Among the 290 cases aged from 2 months to 68 years old,83.4%were males,62.1%came from Asia,and 43.8%were complicated with fatty liver disease,the age group of 14-49 years old had the largest number(247 cases).80.5%confirmed case group cases were general type,there was only 1 severe patient.Hospital stays in asymptomatic infection group was shorter than that in confirmed cases group,lymphocyte count,CD4+T count,CD8+T count,CD4+T/CD8+T creatine kinase in two groups half a month after discharge were relatively lower than those on admission,and alanine aminotransferase,aspartate aminotransferase,albumin,lactate dehydrogenase,creatine kinase isoenzyme were relatively higher than those on admission(P<0.05).Logistic regression analysis showed that increased age,decreased lymphocyte count on admission and increased lactate dehydrogenase on admission were associated with dominant infection.Chest CT of 13 general type cases indicated an increase in lesions compared with that at discharge and 3 of them had re-detectable positive RNA test.Conclusion:The majority of foreign-imported cases in Chengdu are mainly from Asia,fewer of them are severe patients.In the early stage of recovery,some SARS-CoV-2 infected patients still have intermittent viral replication.Early isolation and early treatment of imported patients is not only conducive to epidemic prevention and control,but also may change the natural course of the disease.

Characterization of Specific Humoral Immunity in Asymptomatic SARS-CoV-2 Infection

The outbreak of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in December 2019 caused a huge blow to both global public health and global economy.At the early stage of the coronavirus disease 2019(COVID-19)epidemic,asymptomatic individuals with SARS-CoV-2 infection were ignored,without appropriate identification and isolation.However,asymptomatic individuals proved to comprise a high proportion of all SARS-CoV-2-infected individuals,which greatly contributed to the rapid and wide spread of this disease.In this review,we summarize the latest advances in epidemiological characteristics,diagnostic assessment methods,factors related to the establishment of SARS-CoV-2 asymptomatic infection,as well as humoral immune features after SARS-CoV-2 infection or vaccination in asymptomatic individuals,which would contribute to effective control of ongoing COVID-19 epidemic.

Recent progress on rapid diagnosis of COVID-19 by point-of-care testing platforms

The outbreak of COVID-19 has drawn great attention around the world.SARS-CoV-2 is a highly infectious virus with occult transmission by many mutations and a long incubation period.In particular,the emergence of asymptomatic infections has made the epidemic even more severe.Therefore,early diagnosis and timely management of suspected cases are essential measures to control the spread of the virus.Developing simple,portable,and accurate diagnostic techniques for SARS-CoV-2 is the key to epidemic prevention.The advantages of point-of-care testing technology make it play an increasingly important role in viral detection and screening.This review summarizes the point-of-care testing platforms developed by nucleic acid detection,immunological detection,and nanomaterial-based biosensors detection.Furthermore,this paper provides a prospect for designing future highly accurate,cheap,and convenient SARS-CoV-2 diagnostic technology.

Demand for longer quarantine period among common and uncommon COVID-19 infections: a scoping review

Background:As one of the non-pharmacological interventions to control the transmission of COVID-19,determining the quarantine duration is mainly based on the accurate estimates of the incubation period.However,patients with coarse information of the exposure date,as well as infections other than the symptomatic,were not taken into account in previously published studies.Thus,by using the statistical method dealing with the interval-censored data,we assessed the quarantine duration for both common and uncommon infections.The latter type includes the presymptomatic,the asymptomatic and the recurrent test positive patients.Methods:As of 10 December 2020,information on cases have been collected from the English and Chinese databases,including Pubmed,Google scholar,CNKI(China National Knowledge Infrastructure)and Wanfang.Official websites and medias were also searched as data sources.All data were transformed into doubly interval-censored and the accelerated failure time model was applied.By estimating the incubation period and the time-to-event distribution of worldwide COVID-19 patients,we obtain the large percentiles for determining and suggesting the quarantine policies.For symptomatic and presymptomatic COVID-19 patients,the incubation time is the duration from exposure to symptom onset.For the asymptomatic,we substitute the date of first positive result of nucleic acid testing for that of symptom onset.Furthermore,the time from hospital discharge or getting negative test result to the positive recurrence has been calculated for recurrent positive patients.Results:A total of 1920 laboratory confirmed COVID-19 cases were included.Among all uncommon infections,34.1%(n=55)of them developed symptoms or were identified beyond fourteen days.Based on all collected cases,the 95th and 99th percentiles were estimated to be 16.2 days(95%Cl 15.5-17.0)and 22.9 days(21.7-24.3)respectively.Besides,we got similar estimates based on merely symptomatic and presymptomatic infections as 15.1 days(14.4-15.7)and 21.1 days(20.0-22.2).Conclusions:There are a certain number of infected people who require longer quarantine duration.Our findings well support the current practice of the extended active monitoring.To further prevent possible transmissions induced and facilitated by such infectious outliers after the 14-days quarantine,properly prolonging the quarantine duration could be prudent for high-risk scenarios and in regions with insufficient test resources.