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1.
Eur Rev Med Pharmacol Sci ; 25(24): 8019-8022, 2021 12.
Article in English | MEDLINE | ID: covidwho-1605687

ABSTRACT

Recently a new variant of SARS-CoV-2 was reported from South Africa. World Health Organization (WHO) named this mutant as a variant of concern - Omicron (B.1.1.529) on 26th November 2021. This variant exhibited more than thirty amino acid mutations in the spike protein. This mutation rate is exceeding the other variants by approximately 5-11 times in the receptor-binding motif of the spike protein. Omicron (B.1.1.529) variant might have enhanced transmissibility and immune evasion. This new variant can reinfect individuals previously infected with other SARS-CoV-2 variants. Scientists expressed their concern about the efficacy of already existing COVID-19 vaccines against Omicron (B.1.1.529) infections. Some of the crucial mutations that are detected in the receptor-binding domain of the Omicron variant have been shared by previously evolved SARS-CoV-2 variants. Based on the Omicron mutation profile in the receptor-binding domain and motif, it might have collectively enhanced or intermediary infectivity relative to its previous variants. Due to extensive mutations in the spike protein, the Omicron variant might evade the immunity in the vaccinated individuals.


Subject(s)
COVID-19/epidemiology , Reinfection/epidemiology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , COVID-19/immunology , COVID-19/transmission , COVID-19/virology , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Humans , Immune Evasion/genetics , Immunogenicity, Vaccine , Mutation , Reinfection/immunology , Reinfection/transmission , Reinfection/virology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Vaccine Potency
5.
Viruses ; 13(10)2021 10 17.
Article in English | MEDLINE | ID: covidwho-1470999

ABSTRACT

This study investigated the infectivity of severe acute respiratory syndrome (SARS-CoV-2) in individuals who re-tested positive for SARS-CoV-2 RNA after recovering from their primary illness. We investigated 295 individuals with re-positive SARS-CoV-2 polymerase chain reaction (PCR) test results and 836 of their close contacts. We attempted virus isolation in individuals with re-positive SARS-CoV-2 PCR test results using cell culture and confirmed the presence of neutralizing antibodies using serological tests. Viral culture was negative in all 108 individuals with re-positive SARS-CoV-2 PCR test results in whom viral culture was performed. Three new cases of SARS-CoV-2 infection were identified among household contacts using PCR. Two of the three new cases had had contact with the index patient during their primary illness, and all three had antibody evidence of past infection. Thus, there was no laboratory evidence of viral shedding and no epidemiological evidence of transmission among individuals with re-positive SARS-CoV-2 PCR test results.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , Reinfection/virology , SARS-CoV-2/immunology , Virus Shedding/physiology , Adolescent , Adult , Aged , COVID-19/diagnosis , COVID-19/transmission , COVID-19 Serological Testing , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Polymerase Chain Reaction , Reinfection/immunology , Republic of Korea , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index , Young Adult
8.
Int Immunopharmacol ; 100: 108108, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1401541

ABSTRACT

The possibility of human reinfection with SARS-CoV-2, the coronavirus responsible for COVID-19, has not previously been thoroughly investigated. Although it is generally believed that virus-specific antibodies protect against COVID-19 pathogenesis, their duration of function and temporal activity remain unknown. Contrary to media reports that people retain protective antibody responses for a few months, science does not exclude reinfection and disease relapse shortly after initiating all immune responses during the primary onset of COVID-19. Despite production of antiviral antibodies, activated CD4+/CD8+ lymphocytes, and long-lived memory B cells, susceptibility to reinfection in humans for extended periods cannot be precluded due to repeated exposures to coronavirus or potential reactivation of the virus due to incomplete virus clearance. However, the mechanism of reinfection remains unknown. The biological characteristics of SARS-CoV-2, such as emergence of multiple mutations in the virus RNA molecules, transmissibility, rates of infection, reactivation and reinfection, can all affect the trajectory of the virus spread. Innate and adaptive immune response variables, differences in underlying diseases, and comorbidities, particularly in high risk individuals, can influence the dynamics of the virus infection. In this article, immune parameters and viral mutations pertaining to reinfection and disease relapse are reviewed and scientific gaps are discussed.


Subject(s)
COVID-19/immunology , Mutation , Reinfection/immunology , SARS-CoV-2/genetics , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/virology , COVID-19 Vaccines/immunology , Cytokine Release Syndrome/etiology , Humans , Recurrence , Reinfection/virology , SARS-CoV-2/immunology
9.
Life Sci Alliance ; 4(4)2021 04.
Article in English | MEDLINE | ID: covidwho-1389962

ABSTRACT

A critical question in understanding the immunity to SARS-COV-2 is whether recovered patients are protected against re-challenge and transmission upon second exposure. We developed a Syrian hamster model in which intranasal inoculation of just 100 TCID50 virus caused viral pneumonia. Aged hamsters developed more severe disease and even succumbed to SARS-CoV-2 infection, representing the first lethal model using genetically unmodified laboratory animals. After initial viral clearance, the hamsters were re-challenged with 105 TCID50 SARS-CoV-2 and displayed more than 4 log reduction in median viral loads in both nasal washes and lungs in comparison to primary infections. Most importantly, re-challenged hamsters were unable to transmit virus to naïve hamsters, and this was accompanied by the presence of neutralizing antibodies. Altogether, these results show that SARS-CoV-2 infection induces protective immunity that not only prevents re-exposure but also limits transmission in hamsters. These findings may help guide public health policies and vaccine development and aid evaluation of effective vaccines against SARS-CoV-2.


Subject(s)
COVID-19/immunology , COVID-19/transmission , Immunity , Reinfection/immunology , Reinfection/transmission , SARS-CoV-2/immunology , Age Factors , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/virology , Chlorocebus aethiops , Cricetinae , Disease Models, Animal , Female , HEK293 Cells , Humans , Male , RNA, Viral/genetics , Reinfection/virology , SARS-CoV-2/genetics , Transfection , Vero Cells , Viral Load
12.
Microbiol Spectr ; 9(2): e0008721, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1381168

ABSTRACT

Uncertainty exists whether mild COVID-19 confers immunity to reinfection. Questions also remain regarding the persistence of antibodies against SARS-CoV-2 after mild infection. We prospectively followed at-risk individuals with and without SARS-CoV-2 for reinfection and monitored the spike and nucleocapsid antibodies. This prospective cohort study was conducted over two visits, 3 to 6 months apart, between May 2020 and February 2021. Adults with and without COVID-19, verified by FDA EUA-approved SARS-CoV-2 RT-PCR assays, were screened for spike and nucleocapsid antibody responses using FDA EUA-approved immunoassays and for pseudoviral neutralization activity. The subjects were monitored for symptoms, exposure to COVID-19, COVID-19 testing, seroconversion, reinfection, and vaccination. A total of 653 subjects enrolled; 129 (20%) had a history of COVID-19 verified by RT-PCR at enrollment. Most had mild disease, with only three requiring hospitalization. No initially seropositive subjects experienced a subsequent COVID-19 infection during the follow-up versus 15 infections among initially seronegative subjects (infection rates of 0.00 versus 2.05 per 10,000 days at risk [P = 0.0485]). In all, 90% of SARS-CoV-2-positive subjects produced spike and nucleocapsid responses, and all but one of these had persistent antibody levels at follow-up. Pseudoviral neutralization activity was widespread among participants, did not decrease over time, and correlated with clinical antibody assays. Reinfection with SARS-CoV-2 was not observed among individuals with mild clinical COVID-19, while infections continued in a group without known prior infection. Spike and nucleocapsid COVID-19 antibodies were associated with almost all infections and persisted at stable levels for the study duration. IMPORTANCE This article demonstrates that people who have mild COVID-19 illnesses and produce antibodies are protected from reinfection for up to 6 months afterward. The antibodies that people produce in this situation are stable for up to 6 months as well. Clinical antibody assays correlate well with evidence of antibody-related viral neutralization activity.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/prevention & control , Coronavirus Nucleocapsid Proteins/immunology , Reinfection/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Adult , COVID-19/immunology , COVID-19 Testing , Female , Humans , Immunoassay , Male , Phosphoproteins/immunology , Prospective Studies , Reinfection/immunology , SARS-CoV-2/immunology
13.
Sci Rep ; 11(1): 16543, 2021 08 16.
Article in English | MEDLINE | ID: covidwho-1360208

ABSTRACT

Since COVID-19 risk of reinfection is of great concern, the safety and efficacy of the mRNA-based vaccines in previously infected populations should be assessed. We studied 78 individuals previously infected with SARS-CoV-19, who received a single dose of BNT162b2 mRNA COVID-19 vaccine, and 1:2 ratio matched infection-naïve cohort who received two injections. The evaluation procedure included symptom monitoring, and serological tests. Among the post-infected population, the median IgG-S response after the first vaccine dose was 3.35 AU, compared to 2.38 AU after the second vaccine injection in the infection naive group. A strong correlation was demonstrated between IgG-S level before vaccination, and the corresponding responses after a single vaccine dose (r = 0.8, p < 0.001) in the post infected population. Short-term severe symptoms that required medical attention were found in 6.8% among the post-infected individuals, while none were found in the infection naïve population. Our data suggest that a single vaccine dose is sufficient to induce an intense immune response in post-infected population regardless of seropositivity. Although some short-term safety issues were observed compared to the infection naïve population, a single dose regimen can be considered safe in post-infected populations.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Reinfection/prevention & control , SARS-CoV-2/immunology , Vaccination/adverse effects , Adult , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/diagnosis , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , Female , Humans , Immunity, Humoral , Immunogenicity, Vaccine , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Reinfection/immunology , Reinfection/virology , Retrospective Studies , SARS-CoV-2/isolation & purification , Vaccination/methods
14.
Front Immunol ; 12: 690653, 2021.
Article in English | MEDLINE | ID: covidwho-1359187

ABSTRACT

Although vaccine resources are being distributed worldwide, insufficient vaccine production remains a major obstacle to herd immunity. In such an environment, the cases of re-positive occurred frequently, and there is a big controversy regarding the cause of re-positive episodes and the infectivity of re-positive cases. In this case-control study, we tracked 39 patients diagnosed with COVID-19 from the Jiaodong Peninsula area of China, of which 7 patients tested re-positive. We compared the sex distribution, age, comorbidities, and clinical laboratory results between normal patients and re-positive patients, and analysed the correlation between the significantly different indicators and the re-positive. Re-positive patients displayed a lower level of serum creatinine (63.38 ± 4.94 U/L vs. 86.82 ± 16.98 U/L; P =0.014) and lower albumin (34.70 ± 5.46 g/L vs. 41.24 ± 5.44 g/L, P =0.039) at the time of initial diagnosis. In addition, two positive phases and the middle negative phase in re-positive patients with significantly different eosinophil counts (0.005 ± 0.005 × 109/L; 0.103 ± 0.033 × 109/L; 0.007 ± 0.115 × 109/L; Normal range: 0.02-0.52 × 109/L). The level of eosinophils in peripheral blood can be used as a marker to predict re-positive in patients who once had COVID-19.


Subject(s)
COVID-19/pathology , Creatinine/blood , Eosinophils/cytology , Reinfection/blood , Serum Albumin/analysis , Biomarkers/blood , Case-Control Studies , China , Eosinophils/immunology , Female , Humans , Leukocyte Count , Male , Middle Aged , Reinfection/immunology , Reinfection/virology , SARS-CoV-2/immunology , Severity of Illness Index
16.
J Am Soc Nephrol ; 32(8): 1880-1886, 2021 08.
Article in English | MEDLINE | ID: covidwho-1337589

ABSTRACT

BACKGROUND: Although reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rare among individuals with few coronavirus disease 2019 (COVID-19) risk factors, the ability of naturally acquired immunity to prevent reinfection among patients with ESKD is not known. METHODS: This prospective study was conducted among adults with ESKD treated with in-center hemodialysis (ICHD) in the United States. Exposure was ascribed on the basis of the presence or absence of IgG against SARS-CoV-2 at baseline, and separately, a history of documented COVID-19 before study entry. Outcomes were assessed after an infection-free period, and were any SARS-CoV-2 infection (i.e., detected by protocolized PCR tests or during routine clinical surveillance), and clinically manifest COVID-19 (consisting of only the latter). RESULTS: Of 2337 consented participants who met study inclusion criteria, 9.5% were anti-SARS-CoV-2 IgG positive at baseline; 3.6% had a history of COVID-19. Over 6679 patient-months of follow-up, 263 participants had evidence of any SARS-CoV-2 infection, including 141 who had clinically manifest COVID-19. Presence of anti-SARS-CoV-2 IgG (versus its absence) at baseline was associated with lower risk of any SARS-CoV-2 infection (incidence rate ratio, 0.55; 95% confidence interval, 0.32 to 0.95) and clinically manifest COVID-19 0.21 (95% confidence interval, 0.07 to 0.67). CONCLUSION: Among patients with ESKD, naturally acquired anti-SARS-CoV-2 IgG positivity is associated with a 45% lower risk of subsequent SARS-CoV-2 infection, and a 79% lower risk of clinically manifest COVID-19. Because natural immunity is incomplete, patients with ESKD should be prioritized for SARS-CoV-2 vaccination, independent of their COVID-19 disease history.


Subject(s)
Antibodies, Viral/blood , COVID-19/complications , COVID-19/immunology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/immunology , Renal Dialysis , SARS-CoV-2/immunology , Aged , COVID-19/epidemiology , COVID-19 Vaccines/pharmacology , Cohort Studies , Female , Humans , Immunity, Innate , Immunoglobulin G/blood , Incidence , Kidney Failure, Chronic/therapy , Male , Middle Aged , Pandemics , Prospective Studies , Reinfection/complications , Reinfection/epidemiology , Reinfection/immunology , Risk Factors , United States/epidemiology
17.
Nat Commun ; 12(1): 3991, 2021 06 28.
Article in English | MEDLINE | ID: covidwho-1286457

ABSTRACT

As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees' neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants.


Subject(s)
Broadly Neutralizing Antibodies/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibodies, Viral/immunology , Broadly Neutralizing Antibodies/immunology , COVID-19/blood , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , Cross Protection/immunology , Female , Finland/epidemiology , Humans , Immunization, Secondary/methods , Immunization, Secondary/statistics & numerical data , Male , Mass Vaccination/methods , Mass Vaccination/statistics & numerical data , Middle Aged , Neutralization Tests/statistics & numerical data , Reinfection/immunology , Reinfection/prevention & control , Reinfection/virology , SARS-CoV-2/genetics , Young Adult
19.
J Virol ; 95(13): e0223220, 2021 06 10.
Article in English | MEDLINE | ID: covidwho-1263906

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has initiated a global pandemic, and several vaccines have now received emergency use authorization. Using the reference strain SARS-CoV-2 USA-WA1/2020, we evaluated modes of transmission and the ability of prior infection or vaccine-induced immunity to protect against infection in ferrets. Ferrets were semipermissive to infection with the USA-WA1/2020 isolate. When transmission was assessed via the detection of viral RNA (vRNA) at multiple time points, direct contact transmission was efficient to 3/3 and 3/4 contact animals in 2 respective studies, while respiratory droplet transmission was poor to only 1/4 contact animals. To determine if previously infected ferrets were protected against reinfection, ferrets were rechallenged 28 or 56 days postinfection. Following viral challenge, no infectious virus was recovered in nasal wash samples. In addition, levels of vRNA in the nasal wash were several orders of magnitude lower than during primary infection, and vRNA was rapidly cleared. To determine if intramuscular vaccination protected ferrets, ferrets were vaccinated using a prime-boost strategy with the S protein receptor-binding domain formulated with an oil-in-water adjuvant. Upon viral challenge, none of the mock or vaccinated animals were protected against infection, and there were no significant differences in vRNA or infectious virus titers in the nasal wash. Combined, these studies demonstrate direct contact is the predominant mode of transmission of the USA-WA1/2020 isolate in ferrets and that immunity to SARS-CoV-2 is maintained for at least 56 days. Our studies also indicate protection of the upper respiratory tract against SARS-CoV-2 will require vaccine strategies that mimic natural infection or induce site-specific immunity. IMPORTANCE The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) USA-WA1/2020 strain is a CDC reference strain used by multiple research laboratories. Here, we show that the predominant mode of transmission of this isolate in ferrets is by direct contact. We further demonstrate ferrets are protected against reinfection for at least 56 days even when levels of neutralizing antibodies are low or undetectable. Last, we show that when ferrets were vaccinated by the intramuscular route to induce antibodies against SARS-CoV-2, ferrets remain susceptible to infection of the upper respiratory tract. Collectively, these studies suggest that protection of the upper respiratory tract will require vaccine approaches that mimic natural infection.


Subject(s)
COVID-19/transmission , Disease Models, Animal , Reinfection/prevention & control , SARS-CoV-2/physiology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Ferrets , Injections, Intramuscular , Nose/virology , Reinfection/immunology , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/administration & dosage , Viral Load
20.
J Infect Dis ; 224(5): 788-792, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1262141

ABSTRACT

A 77-year-old man (case R) with previous diagnosis of a mild COVID-19 episode was hospitalized 35 days later. On day 23 postadmission, he developed a second COVID-19 episode, now severe, and finally died. Initially, case R's COVID-19 recurrence was interpreted as a reinfection due to the exposure to a SARS-CoV-2 RT-PCR-positive roommate. However, whole-genome sequencing indicated that case R's recurrence corresponded to a reactivation of the strain involved in his first episode. Case R's reactivation had major consequences, leading to a more severe episode, and causing subsequent transmission to another 2 hospitalized patients, 1 of them with fatal outcome.


Subject(s)
COVID-19/diagnosis , Reinfection/diagnosis , Reinfection/virology , Aged , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/virology , Humans , Male , Recurrence , Reinfection/immunology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Whole Genome Sequencing/methods
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