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1.
MAbs ; 13(1): 1919285, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34074219

RESUMEN

The newly emerging variants of SARS-CoV-2 from South Africa (B.1.351/501Y.V2) and Brazil (P.1/501Y.V3) have led to a higher infection rate and reinfection of COVID-19 patients. We found that the mutations K417N, E484K, and N501Y within the receptor-binding domains (RBDs) of the virus could confer ~2-fold higher binding affinity to the human receptor, angiotensin converting enzyme 2 (ACE2), compared to the wildtype RBD. The mutated version of RBD also completely abolishes the binding of bamlanivimab, a therapeutic antibody, in vitro. Detailed analysis shows that the ~10-fold gain of binding affinity between ACE2 and Y501-RBD, which also exits in the high contagious variant B.1.1.7/501Y.V1 from the United Kingdom, is compromised by additional introduction of the K417/N/T mutation. Mutation of E484K leads to the loss of bamlanivimab binding to RBD, although this mutation does not affect the binding between RBD and ACE2.


Asunto(s)
Anticuerpos Monoclonales Humanizados/metabolismo , Antivirales/metabolismo , COVID-19/virología , Mutación , SARS-CoV-2/metabolismo , Enzima Convertidora de Angiotensina 2/metabolismo , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Sitios de Unión , COVID-19/diagnóstico , COVID-19/tratamiento farmacológico , Interacciones Huésped-Patógeno , Humanos , Simulación del Acoplamiento Molecular , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Receptores Virales/metabolismo , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/genética
2.
Biochim Biophys Acta Mol Basis Dis ; : 166198, 2021 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-34118406

RESUMEN

Some maternal infections, contracted before or during pregnancy, can be transmitted to the fetus, during gestation (congenital infection), during labor and childbirth (perinatal infection) and through breastfeeding (postnatal infection). The agents responsible for these infections can be viruses, bacteria, protozoa, fungi. Among the viruses most frequently responsible for congenital infections are Cytomegalovirus (CMV), Herpes simplex 1-2, Herpes virus 6, Varicella zoster. Moreover Hepatitis B and C virus, HIV, Parvovirus B19 and non-polio Enteroviruses when contracted during pregnancy may involve the fetus or newborn at birth. Recently, new viruses have emerged, SARS-Cov-2 and Zika virus, of which we do not yet fully know the characteristics and pathogenic power when contracted during pregnancy. Viral infections in pregnancy can damage the fetus (spontaneous abortion, fetal death, intrauterine growth retardation) or the newborn (congenital anomalies, organ diseases with sequelae of different severity). Some risk factors specifically influence the incidence of transmission to the fetus: the timing of the infection in pregnancy, the order of the infection, primary or reinfection or chronic, the duration of membrane rupture, type of delivery, socio-economic conditions and breastfeeding. Frequently infected neonates, symptomatic at birth, have worse outcomes than asymptomatic. Many asymptomatic babies develop long term neurosensory outcomes. The way in which the virus interacts with the maternal immune system, the maternal-fetal interface and the placenta explain these results and also the differences that are observed from time to time in the fetal-neonatal outcomes of maternal infections. The maternal immune system undergoes functional adaptation during pregnancy, once thought as physiological immunosuppression. This adaptation, crucial for generating a balance between maternal immunity and fetus, is necessary to promote and support the pregnancy itself and the growth of the fetus. When this adaptation is upset by the viral infection, the balance is broken, and the infection can spread and lead to the adverse outcomes previously described. In this review we will describe the main viral harmful infections in pregnancy and the potential mechanisms of the damages on the fetus and newborn.

3.
Virus Res ; : 198473, 2021 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-34118360

RESUMEN

The Coronavirus Disease 2019 (COVID-19) is the first known pandemic caused by a coronavirus. Its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appears to be capable of infecting different mammalian species. Recent detections of this virus in pet, zoo, wild, and farm animals have compelled inquiry regarding the zoonotic (animal-to-human) and reverse zoonotic (human-to-animal) transmissibility of SARS-CoV-2 with the potential of COVID-19 pandemic evolving into a panzootic. It is important to monitor the global spread of disease and to assess the significance of genomic changes to support prevention and control efforts during a pandemic. An understanding of the SARS-CoV-2 epidemiology provides opportunities to prevent the risk of repeated re-infection of humans and requires a robust One Health-based investigation. This review paper describes the known properties and the existing gaps in scientific knowledge about the zoonotic and reverse zoonotic transmissibility of the novel virus SARS-CoV-2 and the COVID-19 disease it causes.

4.
Acta Virol ; 65(2): 115-126, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34130463

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) devastation on the central nervous system (CNS) is ascertained by the present clinical findings and the noticeable signs and symptoms. The CNS involvement of the virus is not trivial; although the brain has highly protective systems, the virus has ways to breach them with a destructive potential. For successful entry of the virus, different possible routes with favorable mechanisms are used. The SARS-CoV-2 invasion induces a mechanism of both the innate and adaptive immune response to control virus replication and removal from the CNS tissues. The cytokine storm and autoimmune response during the immunological events result in demyelination, damage of resident cells and neurons, cerebrovascular thrombosis, and dysregulation of neuro signaling pathways. Furthermore, hypoxia and toxemia accelerate the neurological destruction process. The acute attributions on psychology due to inflammation is a hallmark of CNS involved pathogenesis; nevertheless, the productivity, durability, and longevity of virus-specific lymphocytes are the vital indicators for complete removal of viral antigen and in combat against reinfection of the CNS. Keywords: CNS invasion; immune response; cytokine storm; demyelination; mental status.

6.
Med Hypotheses ; 152: 110619, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-34102600

RESUMEN

Sars Cov-2, the pathogen which belongs to the beta coronavirus family that is responsible for COVID-19, uses Angiotensin Converting Enzyme 2 (ACE2) as a receptor, which is responsible for controlling the actions of renin-angiotensin system (RAS). Sars Cov-2 - ACE2 binding leads to a RAS mediated immune response, which targets especially lungs to form ARDS, which in turn, is the most important cause of mortality in COVID-19. CD8+ T cell response dominates over CD4+ T cell response and natural killer cell dysfunction also leads to CD4+ cell dysfunction in COVID-19; this immune dysregulation leads to inappropriate (ARDS) and inadequate (low or quickly waning antibodies) responses to the disease and unfortunately, prepares the patients for re-infections. The peripheral anergy seen in chronic sarcoidosis has much resemblance to COVID-19; CD8+ T cell accumulation is also responsible for inadequate reaction to tuberculin and antigenic stimulus. This article, based on the similarity of COVID-19 and sarcoidosis, discusses a combination of the therapeutic strategy of the tetanus-diphtheria vaccine and dual RAS inhibition, alongside with hydroxychloroquine and antiviral agents, as a solution to overcome the problems described above.

7.
Results Phys ; : 104433, 2021 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-34123716

RESUMEN

We propose and study an epidemiological model on a social network that takes into account heterogeneity of the population and different vaccination strategies. In particular, we study how the COVID-19 epidemics evolves and how it is contained by different vaccination scenarios by taking into account data showing that older people, as well as individuals with comorbidities and poor metabolic health, and people coming from economically depressed areas with lower quality of life in general, are more likely to develop severe COVID-19 symptoms, and quicker loss of immunity and are therefore more prone to reinfection. Our results reveal that the structure and the spatial arrangement of subpopulations are important epidemiological determinants. In a healthier society the disease spreads more rapidly but the consequences are less disastrous as in a society with more prevalent chronic comorbidities. If individuals with poor health are segregated within one community, the epidemic outcome is less favorable. Moreover, we show that, contrary to currently widely adopted vaccination policies, prioritizing elderly and other higher-risk groups is beneficial only if the supply of vaccine is high. If, however, the vaccination availability is limited, and if the demographic distribution across the social network is homogeneous, better epidemic outcomes are achieved if healthy people are vaccinated first. Only when higher-risk groups are segregated, like in elderly homes, their prioritization will lead to lower COVID-19 related deaths. Accordingly, young and healthy individuals should view vaccine uptake as not only protecting them, but perhaps even more so protecting the more vulnerable socio-demographic groups.

9.
PLoS One ; 16(6): e0251159, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34115768

RESUMEN

OBJECTIVES: To quantify SARS-CoV2 IgG antibody titers over time and assess the longevity of the immune response in a multi-ethnic population setting. SETTING: This prospective study was conducted in a tertiary hospital in Abu Dhabi city, UAE, among COVID-19 confirmed patients. The virus-specific IgG were measured quantitatively in serum samples from the patients during three visits over a period of 6 months. Serum IgG levels ≥15 AU/ml was used to define a positive response. PARTICIPANTS: 113 patients were analyzed at first visit, with a mean (SD) age of participants of 45.9 (11.8) years 87.5% of the patients were men. 63 and 27 participants had data available for visits 2 and 3, respectively. PRIMARY OUTCOME: Change in SARS-CoV2 IgG antibody titers over the visits. RESULTS: No mortality or re-infection were reported. 69% of the patients developed positive IgG response within the first month after the onset of symptoms. The levels of IgG showed a consistent increase during the first three months with a peak level during the third month. Increasing trend in the levels of IgG were observed in 82.5%, 55.6% and 70.4% of patients between visit 1 to visit 2, visit 2 to visit 3, and from visit 1 to visit 3, respectively. Furthermore, about 64.3% of the patients showed sustained increase in IgG response for more than 120 days. CONCLUSIONS: Our study indicates a sustained and prolonged positive immune response in COVID-19 recovered patients. The consistent rise in antibody and positive levels of IgG titers within the first 5 months suggest that immunization is possible, and the chances of reinfection minimal.

10.
Emerg Microbes Infect ; : 1-20, 2021 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-34120579

RESUMEN

The circulation of SARS-CoV-2 has resulted in the emergence of variants of concern (VOCs). It is currently unclear whether previous infection with SARS-CoV-2 provides protection against reinfection with VOCs. Here, we show that low dose aerosol exposure to hCoV-19/human/USA/WA-CDC-WA1/2020 (WA1, lineage A), resulted in a productive mild infection. In contrast, low dose of SARS-CoV-2 via fomites did not result in productive infection in the majority of exposed hamsters and these animals remained non-seroconverted. After recovery, hamsters were re-exposed to hCoV-19/South African/KRISP-K005325/2020 (VOC B.1.351) via an intranasal challenge. Seroconverted rechallenged animals did not lose weight and shed virus for 3 days. They had little infectious virus and no pathology in the lungs. In contrast, shedding, weight loss and extensive pulmonary pathology caused by B.1.351 replication was observed in the non-seroconverted animals. The rechallenged seroconverted animals did not transmit virus to naïve sentinels via direct contact transmission, in contrast to the non-seroconverted animals. Reinfection with B.1.351 triggered an anamnestic response that boosted not only neutralizing titers against lineage A, but also titers against B.1.351. Our results confirm that aerosol exposure is a more efficient infection route than fomite exposure. Furthermore, initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351 but prevents disease and onward transmission. These data suggest that previous SARS-CoV-2 exposure induces partial protective immunity. The reinfection generated a broadly neutralizing humoral response capable of effectively neutralizing B.1.351 while maintaining its ability to neutralize the virus to which the initial response was directed against.

11.
Viruses ; 13(6)2021 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-34073577

RESUMEN

Increasing evidence suggests that some newly emerged SARS-CoV-2 variants of concern (VoCs) resist neutralization by antibodies elicited by the early-pandemic wild-type virus. We applied neutralization tests to paired recoveree sera (n = 38) using clinical isolates representing the first wave (D614G), VoC1, and VoC2 lineages (B.1.1.7 and B 1.351). Neutralizing antibodies inhibited contemporary and VoC1 lineages, whereas inhibition of VoC2 was reduced 8-fold, with 50% of sera failing to show neutralization. These results provide evidence for the increased potential of VoC2 to reinfect previously SARS-CoV-infected individuals. The kinetics of NAbs in different patients showed similar decline against all variants, with generally low initial anti-B.1.351 responses becoming undetectable, but with anti-B.1.1.7 NAbs remaining detectable (>20) for months after acute infection.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , COVID-19/inmunología , SARS-CoV-2/inmunología , Animales , Anticuerpos Antivirales/inmunología , COVID-19/diagnóstico , COVID-19/virología , Chlorocebus aethiops , Proteínas de la Nucleocápside de Coronavirus/inmunología , Humanos , Inmunoglobulina G/inmunología , Cinética , Pruebas de Neutralización , Fosfoproteínas/inmunología , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Glicoproteína de la Espiga del Coronavirus/inmunología , Células Vero
13.
Rev Bras Epidemiol ; 24: e210022, 2021.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-34105594

RESUMEN

This article discusses the epidemic situation of Covid-19 in Brazil, in the face of the emergence of a new strain called P.1, which is more transmissible and may be associated with reinfection. Given the collapse of hospital care in Manaus in January 2021 and the results of three recent preprints, each that reports increased transmissibility of the P.1 variant, we propose some urgent measures. Genomic surveillance based on multi-step diagnostics, starting with RT-PCR type tests and up to sequencing, should be established. Efforts to identify reinfections associated with this variant and the update of its definition in protocols should be prioritized, and studies on the efficacy of currently available vaccines in Brazil concerning the new variant should be conducted. We also propose improving the Brazilian health surveillance system such that genomic surveillance is coordinated and thereby better able to respond to future emergencies in a more timely fashion. We call on the public agents involved in health surveillance to share data and information regarding the epidemic in a clear, fast and transparent way. Finally, we propose a greater engagement in inter-institutional cooperation of all those involved in the response and production of knowledge about the pandemic in our country.


Asunto(s)
COVID-19 , SARS-CoV-2 , Brasil/epidemiología , Urgencias Médicas , Humanos , Salud Pública
14.
Int J Infect Dis ; 2021 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-34107326

RESUMEN

We report a case of reinfection by SARS-CoV-2 with the second virus harboring amino acid changes in the Spike protein (141-143del, D215A, ins215AGY, L452R, D614 G), orf1a, helicase, orf3a, and Nucleocapside. The virus associated with the reinfection, from an endemic lineage containing the S:L452R immune escape mutation, was circulating in Panama at the time.

15.
Medicina (Kaunas) ; 57(5)2021 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-34063699

RESUMEN

Since the onset of the COVID-19 pandemic, there have been multiple questions regarding reinfections associated with SARS-CoV-2. Healthcare workers on duty, due to overexposure in environments where there are more cases of COVID-19, are more prone to become infected by this virus. Here, we report 4 cases that meet the definition of clinical reinfection by SARS-CoV-2, as well as a literature review on this subject; all occurred in healthcare workers in Acapulco Guerrero, Mexico who provide their services in a hospital that cares for patients with COVID-19. The time between the manifestation of the first and second infection for each case was 134, 129, 107 and 82 days, all patients presented symptomatology in both events. The time between remission of the first infection and onset of second infection was 108, 109, 78 and 67 days for each case, while the time to confirmation by reverse transcription polymerase chain reaction (RT-PCR) between infections was 134, 124, 106 and 77 days. In two of the four cases the reinfection resulted in a more severe case, while in the remaining two cases the manifestation of symptoms and complications was similar to that presented in the first infection. Given this scenario, greater care is needed in the management of the pandemic caused by SARS-CoV-2 to protect healthcare workers and the general public from risks and complications caused by a possible reinfection by SARS-CoV-2.


Asunto(s)
COVID-19 , SARS-CoV-2 , Personal de Salud , Humanos , México/epidemiología , Pandemias , Reinfección
16.
Viruses ; 13(5)2021 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-34066205

RESUMEN

This study describes a case of SARS-CoV-2 reinfection confirmed by whole-genome sequencing in a healthy physician who had been working in a COVID-19 hospital in Italy since the beginning of the pandemic. Nasopharyngeal swabs were obtained from the patient at each presentation as part of routine surveillance. Nucleic acid amplification testing was performed on the two samples to confirm SARS-CoV-2 infection, and serological tests were used to detect SARS-CoV-2 IgG antibodies. Comparative genome analysis with whole-genome sequencing was performed on nasopharyngeal swabs collected during the two episodes of COVID-19. The first COVID-19 episode was in March 2020, and the second was in January 2021. Both SARS-CoV-2 infections presented with mild symptoms, and seroconversion for SARS-CoV-2 IgG was documented. Genomic analysis showed that the viral genome from the first infection belonged to the lineage B.1.1.74, while that from the second infection to the lineage B.1.177. Epidemiological, clinical, serological, and genomic analyses confirmed that the second episode of SARS-CoV-2 infection in the healthcare worker met the qualifications for "best evidence" for reinfection. Further studies are urgently needed to assess the frequency of such a worrisome occurrence, particularly in the light of the recent diffusion of SARS-CoV-2 variants of concern.

17.
Viruses ; 13(5)2021 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-34067128

RESUMEN

The future prevalence and virulence of SARS-CoV-2 is uncertain. Some emerging pathogens become avirulent as populations approach herd immunity. Although not all viruses follow this path, the fact that the seasonal coronaviruses are benign gives some hope. We develop a general mathematical model to predict when the interplay among three factors, correlation of severity in consecutive infections, population heterogeneity in susceptibility due to age, and reduced severity due to partial immunity, will promote avirulence as SARS-CoV-2 becomes endemic. Each of these components has the potential to limit severe, high-shedding cases over time under the right circumstances, but in combination they can rapidly reduce the frequency of more severe and infectious manifestation of disease over a wide range of conditions. As more reinfections are captured in data over the next several years, these models will help to test if COVID-19 severity is beginning to attenuate in the ways our model predicts, and to predict the disease.

19.
Wiad Lek ; 74(5): 1125-1129, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34090276

RESUMEN

OBJECTIVE: The aim: To determine the level of public awareness of COVID-19 and information needs, as well as level of public confidence in both official information on COVID-19 and to develop recommendations for communication policy on longer-term awareness in pandemic settings COVID-19, using principles of behavioral economics. PATIENTS AND METHODS: Materials and methods: 4 focus group interviews were conducted in residents of Ukraine, with a total quantity of 48 people aged 16-70 years questioned and an anonymous questionnaire was conducted in 1,700 respondents, representing the adult population aged 18 years and older from all over Ukraine. The representative error of the study with probability of 0.95 does not exceed 4%. The processing of questionnaires was carried out by SDU Center of Social Researches (SDUCSR) employees, using the OSA program. RESULTS: Results: 28.5% of respondents believe that politicians and media underestimate the danger of the COVID-19 epidemic, while other 28.1% believe that politicians and media adequately assess its danger. 18.9% of respondents are sure that the danger is exaggerated. As much as 24.5% of Ukrainian respondents could not decide on such assessment. The most common sources of information about disease/treatment are Internet and social media. Traditional media and relatives/acquaints who endured the COVID-19 also gain population`s confidence. A family doctor is the least popular source of information. 42.1% of respondents do not trust official information on the number of infected people and severity of the disease, and another 40% are not sure whether they should trust or not. Only 17.9% of respondents trust official information. CONCLUSION: Conclusions: Within informing the society about public health in conditions of a COVID-19 pandemic it is better to provide communication strategy for various target audiences: for youth which is inclined to underestimate threats of epidemic and obtains information on social networks; for people of a retirement age (as risk group) who lack information because they use only traditional media (mainly TV); for women who need psychological support to decrease in level of stress in the family more often and also to overcome the negative post-stressful situations (connected with the death of the family/relatives); for men who are inclined to neglect their own health, etc.; for the people who have endured COVID-19 to prevent possible reinfection in them.


Asunto(s)
COVID-19 , Economía del Comportamiento , Adolescente , Adulto , Femenino , Humanos , Masculino , Pandemias , SARS-CoV-2 , Ucrania
20.
Viruses ; 13(6)2021 05 29.
Artículo en Inglés | MEDLINE | ID: mdl-34072390

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), continues to wreak havoc, threatening the public health services and imposing economic collapse worldwide. Tailoring public health responses to the SARS-CoV-2 pandemic depends on understanding the mechanism of viral replication, disease pathogenesis, accurately identifying acute infections, and mapping the spreading risk of hotspots across the globe. However, effective identification and isolation of persons with asymptomatic and mild SARS-CoV-2 infections remain the major obstacles to efforts in controlling the SARS-CoV-2 spread and hence the pandemic. Understanding the mechanism of persistent viral shedding, reinfection, and the post-acute sequalae of SARS-CoV-2 infection (PASC) is crucial in our efforts to combat the pandemic and provide better care and rehabilitation to survivors. Here, we present a living literature review (January 2020 through 15 March 2021) on SARS-CoV-2 viral persistence, reinfection, and PASC. We also highlight potential areas of research to uncover putative links between viral persistence, intra-host evolution, host immune status, and protective immunity to guide and direct future basic science and clinical research priorities.

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