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1.
Artículo en Inglés | MEDLINE | ID: mdl-33037944

RESUMEN

Can a patient diagnosed with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) be infected again? This question is still unsolved. We tried to analyze local and literature cases with a positive respiratory swab after recovery. We collected data from symptomatic patients diagnosed with SARS-CoV-2 infection in the Italian Umbria Region that, after recovery, were again positive for SARS-CoV-2 in respiratory tract specimens. Samples were also assessed for infectivity in vitro. A systematic review of similar cases reported in the literature was performed. The study population was composed of 9 patients during a 4-month study period. Among the new positive samples, six were inoculated in Vero-E6 cells and showed no growth and negative molecular test in culture supernatants. All patients were positive for IgG against SARS-CoV-2 nucleoprotein and/or S protein. Conducting a review of the literature, 1350 similar cases have been found. The presumptive reactivation occurred in 34.5 days on average (standard deviation, SD, 18.7 days) after COVID-19 onset, when the 5.6% of patients presented fever and the 27.6% symptoms. The outcome was favorable in 96.7% of patients, while the 1.1% of them were still hospitalized at the time of data collection and the 2.1% died. Several hypotheses have been formulated to explain new positive respiratory samples after confirmed negativity. According to this study, the phenomenon seems to be due to the prolonged detection of SARS-CoV-2 RNA traces in respiratory samples of recovered patients. The failure of the virus to replicate in vitro suggests its inability to replicate in vivo.

2.
Science ; 2020 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-33055131

RESUMEN

Reinfection, seasonality, and viral competition will shape endemic transmission patterns.

3.
Lancet Microbe ; 2020 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-33015652

RESUMEN

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The proportion of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can be detected up to 3 months after symptom resolution. We investigated both seroconversion and PCR positivity in a large cohort of convalescent serum donors in the New York City (NY, USA) region. Methods: In this observational study, we ran an outreach programme in the New York City area. We recruited participants via the REDCap (Vanderbilt University, Nashville, TN, USA) online survey response. Individuals with confirmed or suspected SARS-CoV-2 infection were screened via PCR for presence of viral genome and via ELISA for presence of anti-SARS-CoV-2 spike antibodies. One-way ANOVA and Fisher's exact test were used to measure the association of age, gender, symptom duration, and days from symptom onset and resolution with positive antibody results. Findings: Between March 26 and April 10, 2020, we measured SARS-CoV-2 antibody titres in 1343 people. Of the 624 participants with confirmed SARS-CoV-2 infection who had serologies done after 4 weeks, all but three seroconverted to the SARS-CoV-2 spike protein, whereas 269 (37%) of 719 participants with suspected SARS-CoV-2 infection seroconverted. PCR positivity was detected up to 28 days from symptom resolution. Interpretation: Most patients with confirmed COVID-19 seroconvert, potentially providing immunity to reinfection. We also report that in a large proportion of individuals, viral genome can be detected via PCR in the upper respiratory tract for weeks after symptom resolution, but it is unclear whether this signal represents infectious virus. Analysis of our large cohort suggests that most patients with mild COVID-19 seroconvert 4 weeks after illness, and raises questions about the use of PCR to clear positive individuals. Funding: None.

4.
medRxiv ; 2020 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-33052361

RESUMEN

BACKGROUND: SARS-CoV-2-specific antibodies may protect from reinfection and disease, providing the rationale for administration of plasma containing SARS-CoV-2 neutralizing antibodies (nAb) as a treatment for COVID-19. The clinical factors and laboratory assays to streamline plasma donor selection, and the durability of nAb responses, are incompletely understood. METHODS: Adults with virologically-documented SARS-CoV-2 infection in a convalescent plasma donor screening program were tested for serum IgG to SARS-CoV-2 spike protein S1 domain, nucleoprotein (NP), and for nAb. RESULTS: Amongst 250 consecutive persons studied a median of 67 days since symptom onset, 243/250 (97%) were seropositive on one or more assays. Sixty percent of donors had nAb titers ≥1:80. Correlates of higher nAb titer included older age (adjusted OR [AOR] 1.03/year of age, 95% CI 1.00-1.06), male sex (AOR 2.08, 95% CI 1.13-3.82), fever during acute illness (AOR 2.73, 95% CI 1.25-5.97), and disease severity represented by hospitalization (AOR 6.59, 95% CI 1.32-32.96). Receiver operating characteristic (ROC) analyses of anti-S1 and anti-NP antibody results yielded cutoffs that corresponded well with nAb titers, with the anti-S1 assay being slightly more predictive. NAb titers declined in 37 of 41 paired specimens collected a median of 98 days (range, 77-120) apart (P<0.001). Seven individuals (2.8%) were persistently seronegative and lacked T cell responses. CONCLUSIONS: Nab titers correlated with COVID-19 severity, age, and sex. Standard commercially available SARS-CoV-2 IgG results can serve as useful surrogates for nAb testing. Functional nAb levels were found to decline and a small proportion of COVID-19 survivors lack adaptive immune responses.

5.
Emerg Infect Dis ; 26(12)2020 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-33089772

RESUMEN

In March 2020, mild signs and symptoms of coronavirus disease developed in a healthy 33-year-old man in Hong Kong. His first infection did not produce virus neutralizing antibodies. In August, he had asymptomatic reinfection, suggesting that persons without a robust neutralizing antibody response might be at risk for reinfection.

6.
Am J Case Rep ; 21: e927812, 2020 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-33009361

RESUMEN

BACKGROUND This is a case report of an immunocompromised patient with a history of non-Hodgkin lymphoma and persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who was seronegative and successfully treated with convalescent plasma. CASE REPORT A 63-year-old woman with a past medical history of non-Hodgkin lymphoma in remission while on maintenance therapy with the anti-CD20 monoclonal antibody, obinutuzumab, tested positive for SARS-CoV-2 via nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR) testing over 12 weeks and persistently tested seronegative for immunoglobulin G (IgG) antibodies using SARS-CoV-2 IgG chemiluminescent microparticle immunoassay technology. During this time, the patient experienced waxing and waning of symptoms, which included fever, myalgia, and non-productive cough, but never acquired severe respiratory distress. She was admitted to our hospital on illness day 88, and her symptoms resolved after the administration of convalescent plasma. CONCLUSIONS As the understanding of the pathogenesis of SARS-CoV-2 continues to evolve, we can currently only speculate about the occurrence of chronic infection vs. reinfection. The protective role of antibodies and their longevity against SARS-CoV-2 remain unclear. Since humoral immunity has an integral role in SARS-CoV-2 infection, various phase 3 vaccine trials are underway. In the context of this pandemic, the present case demonstrates the challenges in our understanding of testing and treating immunocompromised patients.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Huésped Inmunocomprometido , Linfoma no Hodgkin/inmunología , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Antineoplásicos Inmunológicos/administración & dosificación , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/terapia , Femenino , Estudios de Seguimiento , Humanos , Inmunización Pasiva/métodos , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/tratamiento farmacológico , Persona de Mediana Edad , Pandemias , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Pruebas Serológicas/métodos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
7.
Lancet Infect Dis ; 2020 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-33058797

RESUMEN

BACKGROUND: The degree of protective immunity conferred by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently unknown. As such, the possibility of reinfection with SARS-CoV-2 is not well understood. We describe an investigation of two instances of SARS-CoV-2 infection in the same individual. METHODS: A 25-year-old man who was a resident of Washoe County in the US state of Nevada presented to health authorities on two occasions with symptoms of viral infection, once at a community testing event in April, 2020, and a second time to primary care then hospital at the end of May and beginning of June, 2020. Nasopharyngeal swabs were obtained from the patient at each presentation and twice during follow-up. Nucleic acid amplification testing was done to confirm SARS-CoV-2 infection. We did next-generation sequencing of SARS-CoV-2 extracted from nasopharyngeal swabs. Sequence data were assessed by two different bioinformatic methodologies. A short tandem repeat marker was used for fragment analysis to confirm that samples from both infections came from the same individual. FINDINGS: The patient had two positive tests for SARS-CoV-2, the first on April 18, 2020, and the second on June 5, 2020, separated by two negative tests done during follow-up in May, 2020. Genomic analysis of SARS-CoV-2 showed genetically significant differences between each variant associated with each instance of infection. The second infection was symptomatically more severe than the first. INTERPRETATION: Genetic discordance of the two SARS-CoV-2 specimens was greater than could be accounted for by short-term in vivo evolution. These findings suggest that the patient was infected by SARS-CoV-2 on two separate occasions by a genetically distinct virus. Thus, previous exposure to SARS-CoV-2 might not guarantee total immunity in all cases. All individuals, whether previously diagnosed with COVID-19 or not, should take identical precautions to avoid infection with SARS-CoV-2. The implications of reinfections could be relevant for vaccine development and application. FUNDING: Nevada IDEA Network of Biomedical Research, and the National Institute of General Medical Sciences (National Institutes of Health).

8.
Eur J Clin Invest ; : e13423, 2020 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-33026101

RESUMEN

As of October 2020, there are >1 million documented deaths with COVID-19. Excess deaths can be caused by both COVID-19 and the measures taken. COVID-19 shows extremely strong risk stratification across age, socioeconomic factors, and clinical factors. Calculation of years-of-life-lost from COVID-19 is methodologically challenging and can yield misleading over-estimates. Many early deaths may have been due to suboptimal management, malfunctional health systems, hydroxychloroquine, sending COVID-19 patients to nursing homes, and nosocomial infections; such deaths are partially avoidable moving forward. About 10% of the global population may be infected by October 2020. Global infection fatality rate is 0.15-0.20% (0.03-0.04% in those <70 years), with large variability across locations with different age-structure, institutionalization rates, socioeconomic inequalities, population-level clinical risk profile, public health measures, and health care. There is debate on whether at least 60% of the global population must be infected for herd immunity, or, conversely, mixing heterogeneity and pre-existing cross-immunity may allow substantially lower thresholds. Simulations are presented with a total of 1.58-8.76 million COVID-19 deaths over 5-years (1/2020-12/2024) globally (0.5-2.9% of total global deaths). The most favorable figures in that range would be feasible if high risk groups can be preferentially protected with lower infection rates than the remaining population. Death toll may also be further affected by potential availability of effective vaccines and treatments, optimal management and measures taken, COVID-19 interplay with influenza and other health problems, reinfection potential, and any chronic COVID-19 consequences. Targeted, precise management of the pandemic and avoiding past mistakes would help minimize mortality.

9.
Sci Total Environ ; : 142746, 2020 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-33092831

RESUMEN

The contagious SARS-CoV-2 virus, responsible for COVID-19 disease, has infected over 27 million people across the globe within a few months. While literature on SARS-CoV-2 indicates that its transmission may occur predominantly via aerosolization of virus-laden droplets, the possibility of alternate routes of transmission and/or reinfection via the environment requires considerable scientific attention. This review aims to collate information on possible transmission routes of this virus, to ascertain its fate in the environment. Concomitant with the presence of SARS-CoV-2 viral RNA in faeces and saliva of infected patients, studies also indicated its occurrence in raw wastewater, primary sludge and river water. Therefore sewerage system could be a possible route of virus outbreak, a possible tool to assess viral community spread and future surveillance technique. Hence, this review looked into detection, occurrence and fate of SARS-CoV-2 during primary, secondary, and tertiary wastewater and water treatment processes based on published literature on SARS-CoV and other enveloped viruses. The review also highlights the need for focused research on occurrence and fate of SARS-CoV-2 in various environmental matrices. Utilization of this information in environmental transmission models developed for other enveloped and enteric viruses can facilitate risk assessment studies. Preliminary research efforts with SARS-CoV-2 and established scientific reports on other coronaviruses indicate that the threat of virus transmission from the aquatic environment may be currently non-existent. However, the presence of viral RNA in wastewater provides an early warning that highlights the need for effective sewage treatment to prevent a future outbreak of SARS-CoV-2.

10.
Nat Med ; 2020 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-33093682
11.
J Hematol Oncol ; 13(1): 131, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-33008453

RESUMEN

SARS-CoV-2 has infected millions of people worldwide, but little is known at this time about second infections or reactivation. Here, we report a case of a 55-year-old female undergoing treatment for CD20+ B cell acute lymphoblastic leukemia who experienced a viral reactivation after receiving rituximab, cytarabine, and dasatinib. She was initially hospitalized with COVID-19 in April and developed a high antibody titer with two negative nasal polymerase chain reaction (PCR) swabs for SARS-CoV-2 on discharge. After recovery, she resumed treatment in June for her leukemia, which included rituximab, cytarabine, and dasatinib. She promptly lost her COVID-19 antibodies, and her nasal PCR turned positive in June. She developed a severe COVID-19 pneumonia with lymphopenia, high inflammatory markers, and characteristic bilateral ground-glass opacities on chest CT, requiring high-flow nasal cannula and transfer to the intensive care unit. She received steroids, anticoagulation, and convalescent plasma, and within 48 h she was off oxygen. She was discharged home in stable condition several days later. Given the short time frame from leukemia treatment to PCR positivity and the low case rate in mid-June in New York City, reinfection appears to have been unlikely and SARS-CoV-2 reactivation is a possible explanation. This case illustrates the risks of treating recently recovered COVID-19 patients with immunosuppressive therapy, particularly lymphocyte- and antibody-depleting therapy, and raises new questions about the potential of SARS-CoV-2 reactivation.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/inmunología , Citarabina/uso terapéutico , Inmunosupresores/uso terapéutico , Neumonía Viral/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Rituximab/uso terapéutico , Enfermedad Aguda , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Anticoagulantes/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/virología , Citarabina/efectos adversos , Femenino , Humanos , Inmunización Pasiva , Inmunosupresores/efectos adversos , Persona de Mediana Edad , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , Reacción en Cadena de la Polimerasa , Recurrencia , Rituximab/efectos adversos , Esteroides/uso terapéutico , Resultado del Tratamiento
12.
Artículo en Inglés | MEDLINE | ID: mdl-33052872

RESUMEN

BACKGROUND: The novel coronavirus SARS-CoV-2, which causes the COVID-19 disease, has resulted in a global pandemic. Since its emergence in December 2019, the virus has infected millions of people, caused the deaths of hundreds of thousands and resulted in incalculable social and economic damage. Understanding the infectivity and transmission dynamics of the virus is essential for understanding how best to reduce mortality whilst ensuring minimal social restrictions to the lives of the general population. Anecdotal evidence is available, but detailed studies have not yet revealed whether infection with the virus results in immunity. OBJECTIVE: The objective of the study was to use mathematical modelling to investigate the reinfection frequency of COVID-19. METHODS: We have used the SIR (Susceptible, Infected, Recovered) framework and random processing based on empirical SARS-CoV-2 infection and fatality data from different regions to calculate the number of reinfections that would be expected to occur if no immunity to the disease occurred. RESULTS: Our model predicts that cases of reinfection should have been observed by now if primary SARS-CoV-2 infection did not protect from subsequent exposure in the short term, however, no such cases have been documented. CONCLUSIONS: This work concludes that infection with the SARS-CoV-2 virus provides short-term immunity to reinfection and therefore provides a useful insight for serological testing strategies, lockdown easing and vaccine design.

13.
Epidemiol Infect ; 148: e249, 2020 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-33028445

RESUMEN

A compartmental model is proposed to predict the coronavirus 2019 (Covid-19) spread. It considers: detected and undetected infected populations, social sequestration, release from sequestration, plus reinfection. This model, consisting of seven coupled equations, has eight coefficients which are evaluated by fitting data for eight US states that make up 43% of the US population. The evolution of Covid-19 is fairly similar among the states: variations in contact and undetected recovery rates remain below 5%; however, variations are larger in recovery rate, death rate, reinfection rate, sequestration adherence and release rate from sequestration. Projections based on the current situation indicate that Covid-19 will become endemic. If lockdowns had been kept in place, the number of deaths would most likely have been significantly lower in states that opened up. Additionally, we predict that decreasing contact rate by 10%, or increasing testing by approximately 15%, or doubling lockdown compliance (from the current ~15% to ~30%) will eradicate infections in Texas within a year. Extending our fits for all of the US states, we predict about 11 million total infections (including undetected), and 8 million cumulative confirmed cases by 1 November 2020.

14.
Nat Microbiol ; 2020 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-33106674

RESUMEN

Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10-15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection.

15.
Lancet Infect Dis ; 2020 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-33058796
18.
Eur J Case Rep Intern Med ; 7(10): 001922, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33083371

RESUMEN

Introduction: The coronavirus disease COVID-19 is considered a pandemic disease that has developed rapidly all over the world. As of today, it is unclear whether immunosuppression confers an increased risk for pulmonary complications, or conversely, whether it can be a protective factor with respect to a cytokine storm. Case description: We report the case of a 55-year-old male patient with granulomatosis with polyangiitis treated with rituximab who was infected with COVID-19 pneumonia. To the best of our knowledge, only 1 case has been reported in the literature with similar characteristics. The patient had a non-classic evolution of clinical symptoms with persistent fever and viral shedding, in addition to a negative serology. Conclusion: This case emphasizes the management and immunity response to COVID-19 pneumonia in such patients. Data are still needed regarding patients who have prolonged B-cell depletion, which may put the patient at a higher risk for reinfection. LEARNING POINTS: Demonstration of the immunity response to COVID-19 pneumonia in an immunosuppressed patient.To highlight the management and evolution of such rare cases during this pandemic.

19.
ACS Nano ; 2020 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-33034449

RESUMEN

Humanity is experiencing a catastrophic pandemic. SARS-CoV-2 has spread globally to cause significant morbidity and mortality, and there still remain unknowns about the biology and pathology of the virus. Even with testing, tracing, and social distancing, many countries are struggling to contain SARS-CoV-2. COVID-19 will only be suppressible when herd immunity develops, either because of an effective vaccine or if the population has been infected and is resistant to reinfection. There is virtually no chance of a return to pre-COVID-19 societal behavior until there is an effective vaccine. Concerted efforts by physicians, academic laboratories, and companies around the world have improved detection and treatment and made promising early steps, developing many vaccine candidates at a pace that has been unmatched for prior diseases. As of August 11, 2020, 28 of these companies have advanced into clinical trials with Moderna, CanSino, the University of Oxford, BioNTech, Sinovac, Sinopharm, Anhui Zhifei Longcom, Inovio, Novavax, Vaxine, Zydus Cadila, Institute of Medical Biology, and the Gamaleya Research Institute having moved beyond their initial safety and immunogenicity studies. This review analyzes these frontrunners in the vaccine development space and delves into their posted results while highlighting the role of the nanotechnologies applied by all the vaccine developers.

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