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1.
Preprint | bioRxiv | ID: ppbiorxiv-447221

RESUMO

SARS-CoV-2 continues to circulate globally resulting in emergence of several variants of concern (VOC), including B.1.1.7 and B.1.351 that show increased transmissibility and enhanced resistance to antibody neutralization. In a K18-hACE2 transgenic mouse model, we demonstrate that Both B.1.1.7 and B.1.351 are 100 times more lethal than the original SARS-CoV-2 bearing 614D. Mice infected with B.1.1.7 and B.1.351 exhibited more severe lesions in internal organs than those infected with early SARS-CoV-2 strains bearing 614D or 614G. Infection of B.1.1.7 and B.1.351 also results in distinct tissue-specific cytokine signatures, significant D-dimer depositions in vital organs and less pulmonary hypoxia signaling before death as compared to the mice infected with early SARS-CoV-2 strains. However, K18-hACE2 mice with the pre-existing immunity from prior infection or immunization were resistant to the lethal reinfection of B.1.1.7 or B.1.351, despite having reduced neutralization titers against these VOC. Our study reveals distinguishing pathogenic patterns of B.1.1.7 and B.1.351 variants from those early SARS-CoV-2 strains in K18-hACE2 mice, which will help to inform potential medical interventions for combatting COVID-19.

2.
Preprint | medRxiv | ID: ppmedrxiv-21258422

RESUMO

ObjectivesIn a prospective healthcare worker (HCW) cohort, we assessed the risk of SARS-CoV-2 infection according to baseline serostatus. MethodsBaseline serologies were performed among HCW from 23 Swiss healthcare institutions between June and September 2020, before the second COVID-19 wave. Participants answered weekly electronic questionnaires covering information about nasopharyngeal swabs (PCR/rapid antigen tests) and symptoms compatible with Coronavirus Disease 2019 (COVID-19). Screening of symptomatic staff by nasopharyngeal swabs was routinely performed in participating facilities. We compared numbers of positive nasopharyngeal tests and occurrence of COVID-19 symptoms between HCW with and without anti-nucleocapsid antibodies. ResultsA total of 4818 HCW participated, whereof 144 (3%) were seropositive at baseline. We analysed 107820 questionnaires with a median follow-up of 7.9 months. Median number of answered questionnaires was similar (24 vs. 23 per person, P=0.83) between those with and without positive baseline serology. Among 2713 HCW with [≥]1 SARS-CoV-2 test during follow-up, 3/67 (4.5%) seropositive individuals reported a positive result (one of whom asymptomatic), compared to 547/2646 (20.7%) seronegative participants, 12 of whom asymptomatic (risk ratio [RR] 0.22; 95% confidence interval [CI] 0.07 to 0.66). Seropositive HCWs less frequently reported impaired olfaction/taste (6/144, 4.2% vs. 588/4674, 12.6%, RR 0.33, 95%-CI: 0.15-0.73), chills (19/144, 13.2% vs. 1040/4674, 22.3%, RR 0.59, 95%-CI: 0.39-0.90), and limb/muscle pain (28/144, 19.4% vs. 1335/4674, 28.6%, RR 0.68 95%-CI: 0.49-0.95). Impaired olfaction/taste and limb/muscle pain also discriminated best between positive and negative SARS-CoV-2 results. ConclusionsHaving SARS-CoV-2 anti-nucleocapsid antibodies provides almost 80% protection against SARS-CoV-2 re-infection for a period of at least eight months.

3.
Preprint | medRxiv | ID: ppmedrxiv-21258504

RESUMO

We developed an elaborated susceptible-infected-recovered (SIR) individual-based model (IBM) with pathogen strain drift, waning and cross immunity, implemented as a novel Java Runtime-Alterable-Model Platform (J-RAMP). This platform allows parameter values, process formulations, and scriptable runtime drivers to be easily added at the start of simulation. It includes facility for integration into the R statistical and other data analysis platforms. We selected a set of parameter values and process descriptions relevant to the current COVID-19 pandemic. These include pathogen-specific shedding, environmental persistence, host transmission and mortality, within-host pathogen mutation and replication, adaptive social distancing, and time dependent vaccine rate and strain valency specifications. Our simulations illustrate that if waning immunity outpaces vaccination rates, then vaccination rollouts may fail to contain the most transmissible strains. Our study highlights the need for adaptive vaccination rollouts, which depend on reliable real-time monitoring and surveillance of strain proliferation and reinfection data needed to ensure that vaccines target emerging strains and constrain escape mutations. Together with such data, our platform has the potential to inform the design of vaccination programs that extirpate rather than exacerbate local outbreaks. Finally, our RAMP concept promotes the development of highly flexible models that can be easily shared among researchers and policymakers not only addressing healthcare crises, but other types of environmental crises as well. Significance StatementEffective COVID-19 vaccine development has been unprecedented, but vaccinations are being delivered at contrasting rates across the globe. Here, using an innovative epidemiological Java runtime alterable modeling platform (J-RAMP), we demonstrate that seemingly reasonable vaccination programs may exacerbate rather than mitigate regional outbreaks when immune waning outpaces vaccinations and reinfection promotes escape mutations. Our simulations suggest that adaptive vaccination programs, requiring adequate strain and serology monitoring and surveillance, are needed to extirpate outbreaks. Our platform provides policymakers with an easy-to-use tool for designing effective vaccination programs. Our RAMP concept points the way to the development of highly flexible models that are easily shared among researchers and policymakers in all areas of systems analysis. ClassificationMajor: Biological Sciences; Minor: Biophysics and Computational Biology

4.
Preprint | medRxiv | ID: ppmedrxiv-21258414

RESUMO

Kidney transplant (KT) recipients with COVID-19 are at high risk of poor outcomes because of comorbidities and long-term immunosuppressive therapy (IST). There are little data on the effect of IST reduction and early graft function after COVID-19. We conducted a retrospective study on 45 consecutive KT recipients followed at the University Hospital of Modena who tested positive for COVID-19 by RT-PCR analysis. We detailed clinical management and outcomes of these patients. Median age of patients was 56.1 (interquartile range, [IQR] 47.3-61.1) years with a predominance of male (64.4%) and patients of Caucasian origin (91.1%). Kidney transplantation vintage was 10.1 (2.7-16) years, and more than half (55.6%) was on triple IST. Therapeutic management included antimetabolite (62.8%) and calcineurin inhibitor withdrawal (22.2%), and suspension of IST in severely ill patients. Of the 45 patients, 88.9% became symptomatic and 40% required hospitalization. Overall mortality accounted for 17.8% (n=8). There were no differences in outcomes between full- and reduced-dose IST at the end of follow-up. Overall, early graft function after COVID-19 showed a stable and unmodified kidney function in 95% of survivors. Risk factors for death were age (odds ratio [OR]: 1.19; 95% CI: 1.01-1.39), and years spent on immunosuppression (OR: 1.96; 95% CI: 0.38-10.03-4.9). One patient experienced symptomatic reinfection with COVID-19 after primary infection and anti-SARS-CoV-2 mRNA vaccine. COVID-19 impacted the graft and general survival of KT recipients. Short-term graft outcome after COVID-19 was favorable in most survivors. Age and transplantation vintage are independent predictors of death in our patients.

5.
Preprint | medRxiv | ID: ppmedrxiv-21258307

RESUMO

SARS-CoV-2 variants have emerged that escape neutralization and potentially impact vaccine efficacy. T cell responses play a role in protection from reinfection and severe disease, but the potential for spike mutations to affect T cell immunity is poorly studied. We assessed both neutralizing antibody and T cell responses in 44 South African COVID-19 patients infected either with B.1.351, now dominant in South Africa, or infected prior to its emergence ( first wave), to provide an overall measure of immune evasion. We show for the first time that robust spike-specific CD4 and CD8 T cell responses were detectable in B.1.351-infected patients, similar to first wave patients. Using peptides spanning only the B.1.351 mutated regions, we identified CD4 T cell responses targeting the wild type peptides in 12/22 (54.5%) first wave patients, all of whom failed to recognize corresponding B.1.351-mutated peptides (p=0.0005). However, responses to the mutated regions formed only a small proportion (15.7%) of the overall CD4 response, and few patients (3/44) mounted CD8 responses that targeted the mutated regions. First wave patients showed a 12.7 fold reduction in plasma neutralization of B.1.351. This study shows that despite loss of recognition of immunodominant CD4 epitope(s), overall CD4 and CD8 T cell responses to B.1.351 are preserved. These observations may explain why, despite substantial loss of neutralizing antibody activity against B.1.351, several vaccines have retained the ability to protect against severe COVID-19 disease. One Sentence SummaryT cell immunity to SARS-CoV-2 B.1.351 is preserved despite some loss of variant epitope recognition by CD4 T cells.

6.
Preprint | medRxiv | ID: ppmedrxiv-21258073

RESUMO

Assessment of humoral immunity to SARS-CoV-2 and other infectious agents is typically restricted to detecting antigen-specific antibody in the serum. Rarely does immune monitoring entail assessment of the memory B cell compartment itself, although it is these cells that engage in secondary antibody responses capable of mediating immune protection when pre-existing antibodies fail to prevent re-infection. There are few techniques that are capable of detecting rare antigen-specific B cells while also providing information regarding their precursory frequency, class/subclass usage and functional affinity. In theory, the ELISPOT/FluoroSpot (collectively ImmunoSpot) assay platform is ideally-suited for antigen- specific B cell assessments since it provides this information at single-cell resolution for individual antibody-secreting cells (ASC). Here, we tested the hypothesis that antigen coating efficiency could be universally improved across a diverse set of viral antigens if the standard direct (non-specific, low affinity) antigen absorption to the membrane was substituted by high affinity capture. Specifically, we report an enhancement in assay sensitivity and a reduction in required protein concentrations through the capture of recombinant proteins via their encoded hexahistidine (6XHis) affinity tag. Affinity tag antigen coating enabled detection of SARS-CoV-2 Spike receptor binding domain (RBD)-reactive ASC, and also significantly improved assay performance using additional control antigens. Collectively, establishment of a universal antigen coating approach streamlines characterization of the memory B cell compartment after SARS-CoV-2 infection or COVID-19 vaccinations, and facilitates high-throughput immune monitoring efforts of large donor cohorts in general.

8.
J Infect Dis ; 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34107025

RESUMO

A 77-year-old-male (Case R) who had had a previous diagnosis of mild COVID-19 episode, was hospitalized 35 days later. On Day 23 post-admission, he developed a second COVID-19 episode, now severe, and finally died. Initially, Case R COVID-19 recurrence was interpreted as a reinfection due to the exposure to a SARS-CoV-2 RT-PCR-positive room-mate. However, whole-genome-sequencing indicated that case R recurrence corresponded to a reactivation of the strain involved in his first episode. Case R reactivation had major consequences, leading to a more severe episode, and causing a subsequent transmission to another two hospitalized patients, one of them with fatal outcome.

9.
MAbs ; 13(1): 1919285, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34074219

RESUMO

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.


Assuntos
Anticorpos Monoclonais Humanizados/metabolismo , Antivirais/metabolismo , COVID-19/virologia , Mutação , SARS-CoV-2/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Sítios de Ligação , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , Interações Hospedeiro-Patógeno , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Receptores Virais/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética
10.
Biochim Biophys Acta Mol Basis Dis ; : 166198, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34118406

RESUMO

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.

11.
Viral Immunol ; 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34101517

RESUMO

Coronavirus disease 2019 (COVID-19) is a worldwide emergency that has affected millions of populations in developed and underdeveloped countries. To our surprise, many people have been tested positive twice. Few cases of true reinfections involved genetic alterations in the virus. Appearance of multiple positive tests may be due to human errors or remnant genetic material, but genetic modification in virus represents very serious issue of controlling this pandemic. It is the need of the day that all the gaps and deficiencies, represented by variable response of adaptive immune system toward this infection, be filled and rectified. We have discussed reinfections with variable outcomes along with the possible reasons for variable response. Phenomena such as T cell memory, absence of cross-reactive immunity, T cell exhaustion, drawbacks pertaining to neutralizing antibodies, and immune enhancement are crucial areas by which adaptive immune response can weaken considerably. Earlier and stronger herd immunity is also at the mercy of strong adaptive immune system to avoid future pandemics by the same microorganism. Likewise, consequences of this phenomenon should also be considered during vaccine development as resources worth billions are being used and staked. Many countries have entered the second/third waves of COVID-19. Therefore, we need to come up with ways toward uniform strengthening of adaptive immune response to fight off this pandemic. Also, to develop and maintain constant resistance to severe acute respiratory syndrome coronavirus (SARS-CoV-2), the mentioned weakened links in the chain of adaptive immunity may be explored to keep viral invasion and physiological damage to minimum.

12.
Viruses ; 13(5)2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066205

RESUMO

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.

13.
Viruses ; 13(5)2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067128

RESUMO

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.

14.
Viruses ; 13(6)2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073577

RESUMO

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.


Assuntos
Anticorpos Neutralizantes/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Animais , Anticorpos Antivirais/imunologia , COVID-19/diagnóstico , COVID-19/virologia , Chlorocebus aethiops , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Humanos , Imunoglobulina G/imunologia , Cinética , Testes de Neutralização , Fosfoproteínas/imunologia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia , Células Vero
15.
Results Phys ; : 104433, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34123716

RESUMO

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.

16.
Preprint | medRxiv | ID: ppmedrxiv-21256915

RESUMO

BackgroundIn the absence of genome sequencing, two positive molecular SARS-CoV-2 tests separated by negative tests, prolonged time, and symptom resolution remain the best surrogate measure of possible re-infection. MethodsUsing a large electronic health record database, we characterized clinical and testing data for 23 patients with repeatedly positive SARS-CoV-2 PCR test results [≥]60 days apart, separated by [≥]2 consecutive negative test results. Prevalence of chronic medical conditions, symptoms and severe outcomes related to COVID-19 illness were ascertained. ResultsMedian age was 64.5 years, 40% were Black, and 39% were female. 83% smoked within the prior year, 61% were overweight/obese, 83% had immune compromising conditions, and 96% had [≥]2 comorbidities. Median interval between the two positive tests was 77 days. Among the 19 patients with 60-89 days between positive tests, 17 (89%) exhibited symptoms or clinical manifestations indicative of COVID-19 at the time of the second positive test and 14 (74%) were hospitalized at the second positive test. Of the four patients with [≥]90 days between two positive tests, two had mild or no symptoms at the second positive test and one, an immune compromised patient, had a brief hospitalization at the first diagnosis, followed by ICU admission at the second diagnosis three months later. ConclusionsOur study demonstrated a high prevalence of immune compromise, comorbidities, obesity and smoking among patients with repeatedly positive SARS-CoV-2 tests. Despite limitations, including lack of semi-quantitative estimates of viral load, these data may help prioritize suspected cases of reinfection for investigation and continued surveillance. ImportanceComprehensive characterization of clinical and SARS-CoV-2 testing data for patients with repeatedly positive SARS-CoV-2 tests can help prioritize suspected cases of reinfection for investigation in the absence of sequencing data and for continued surveillance for potential long-term health consequences of SARS-CoV-2 infection.

17.
PLoS One ; 16(6): e0251159, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34115768

RESUMO

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.

18.
mSphere ; : e0050721, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34133199

RESUMO

Epidemiological studies have revealed the emergence of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC), including the lineage B.1.1.7 that is rapidly replacing old variants. The B.1.1.7 variant has been linked to increased morbidity rates, transmissibility, and potentially mortality. To assess viral fitness in vivo and to address whether the B.1.1.7 variant is capable of immune escape, we conducted infection and reinfection studies in naive and convalescent Syrian hamsters (>10 months old). Nasal wash samples from hamsters infected by a B.1.1.7 variant exhibited slightly higher viral RNA levels but lower infectious titers than those from B.1 (G614) variant-infected hamsters, and the two variants induced comparable lung pathologies in hamsters. Despite a sporadic and transient low-level infection in the nasal cavity, convalescent hamsters that had recovered from a previous USA-WA1 isolate (D614) infection displayed no observable clinical signs or lung pathology following B.1.1.7 rechallenge. Altogether, our study did not find that the B.1.1.7 variant significantly differs from the B.1 variant in pathogenicity in Syrian hamsters and that a heterologous natural infection-induced immunity confers protection against a secondary challenge by the B1.1.7 variant. IMPORTANCE The rapid emergence of several variants of concern of SARS-CoV-2 calls for evaluations of viral fitness and pathogenicity in animal models in order to understand the mechanism of enhanced transmission and the possible increases in morbidity and mortality rates. Here, we demonstrated that immunity naturally acquired through a prior infection with the first-wave variant does confer nearly complete protection against the B.1.1.7 variant in Syrian hamsters upon reexposure. Strikingly, although the B.1.1.7 variant appears to replicate to a higher level in the nose than the ancestral B.1 variant, it does not induce more severe lung pathology in hamsters.

20.
Med Hypotheses ; 152: 110619, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34102600

RESUMO

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.


Assuntos
COVID-19 , Sarcoidose , Tétano , Toxoide Diftérico , Humanos , Peptidil Dipeptidase A/metabolismo , Sistema Renina-Angiotensina , SARS-CoV-2
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