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1.
Clin J Am Soc Nephrol ; 16(11): 1755-1765, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526737

ABSTRACT

Despite evidence of multiorgan tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19), direct viral kidney invasion has been difficult to demonstrate. The question of whether SARS-CoV2 can directly infect the kidney is relevant to the understanding of pathogenesis of AKI and collapsing glomerulopathy in patients with COVID-19. Methodologies to document SARS-CoV-2 infection that have been used include immunohistochemistry, immunofluorescence, RT-PCR, in situ hybridization, and electron microscopy. In our review of studies to date, we found that SARS-CoV-2 in the kidneys of patients with COVID-19 was detected in 18 of 94 (19%) by immunohistochemistry, 71 of 144 (49%) by RT-PCR, and 11 of 84 (13%) by in situ hybridization. In a smaller number of patients with COVID-19 examined by immunofluorescence, SARS-CoV-2 was detected in 10 of 13 (77%). In total, in kidneys from 102 of 235 patients (43%), the presence of SARS-CoV-2 was suggested by at least one of the methods used. Despite these positive findings, caution is needed because many other studies have been negative for SARS-CoV-2 and it should be noted that when detected, it was only in kidneys obtained at autopsy. There is a clear need for studies from kidney biopsies, including those performed at early stages of the COVID-19-associated kidney disease. Development of tests to detect kidney viral infection in urine samples would be more practical as a noninvasive way to evaluate SARS-CoV-2 infection during the evolution of COVID-19-associated kidney disease.


Subject(s)
COVID-19/virology , Kidney Diseases/virology , Kidney/virology , SARS-CoV-2/pathogenicity , Animals , Biopsy , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , COVID-19 Testing , Host-Pathogen Interactions , Humans , Kidney Diseases/diagnosis , Kidney Diseases/mortality , Predictive Value of Tests , Prognosis , Risk Assessment , Risk Factors
2.
Plants (Basel) ; 10(2)2021 Feb 12.
Article in English | MEDLINE | ID: covidwho-1526860

ABSTRACT

The emergence of the COVID-19 pandemic has led to significant public health crisis all over the world. The rapid spreading nature and high mortality rate of COVID-19 places a huge pressure on scientists to develop effective diagnostics and therapeutics to control the pandemic. Some scientists working on plant biotechnology together with commercial enterprises for the emergency manufacturing of diagnostics and therapeutics have aimed to fulfill the rapid demand for SARS-CoV-2 protein antigen and antibody through a rapid, scalable technology known as transient/stable expression in plants. Plant biotechnology using transient/stable expression offers a rapid solution to address this crisis through the production of low-cost diagnostics, antiviral drugs, immunotherapy, and vaccines. Transient/stable expression technology for manufacturing plant-based biopharmaceuticals is already established at commercial scale. Here, current opinions regarding how plant biotechnology can help fight against COVID-19 through the production of low-cost diagnostics and therapeutics are discussed.

3.
J Clin Med ; 10(8)2021 Apr 19.
Article in English | MEDLINE | ID: covidwho-1526843

ABSTRACT

There is limited data on the effect of the novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) on pediatric rheumatology. We examined the prevalence of antibodies against SARS-CoV-2 in children with juvenile idiopathic arthritis (JIA) and a negative history of COVID-19 and the correlation of the presence of these antibodies with disease activity measured by juvenile arthritis disease activity score (JADAS). In total, 62 patients diagnosed with JIA, under treatment with various antirheumatic drugs, and 32 healthy children (control group) were included. Serum samples were analyzed for inflammatory markers and antibodies and their state evaluated with the juvenile arthritis disease activity score (JADAS). JIA patients do not have a higher seroprevalence of anti-SARS-CoV-2 antibodies than healthy subjects. We found anti-SARS-CoV-2 antibodies in JIA patients who did not have a history of COVID-19. The study showed no unequivocal correlation between the presence of SARS-CoV-2 antibodies and JIA activity; therefore, this relationship requires further observation. We also identified a possible link between patients' humoral immune response and disease-modifying antirheumatic treatment, which will be confirmed in follow-up studies.

4.
J Infect Dis ; 224(3): 415-419, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1526165

ABSTRACT

Mutagenic ribonucleosides can act as broad-based antiviral agents. They are metabolized to the active ribonucleoside triphosphate form and concentrate in genomes of RNA viruses during viral replication. ß-d-N4-hydroxycytidine (NHC, initial metabolite of molnupiravir) is >100-fold more active than ribavirin or favipiravir against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with antiviral activity correlated to the level of mutagenesis in virion RNA. However, NHC also displays host mutational activity in an animal cell culture assay, consistent with RNA and DNA precursors sharing a common intermediate of a ribonucleoside diphosphate. These results indicate highly active mutagenic ribonucleosides may hold risk for the host.


Subject(s)
Antiviral Agents/pharmacology , Cytidine/analogs & derivatives , Mutagens/pharmacology , SARS-CoV-2/drug effects , Animals , Antiviral Agents/adverse effects , CHO Cells/drug effects , Cells, Cultured , Cricetulus , Cytidine/adverse effects , Cytidine/pharmacology , Dose-Response Relationship, Drug , Mutagenesis/drug effects , Mutagens/adverse effects , SARS-CoV-2/genetics , Virus Replication/drug effects
5.
Clin Transl Immunology ; 10(4): e1271, 2021.
Article in English | MEDLINE | ID: covidwho-1525427

ABSTRACT

Objectives: Emerging evidence of dysregulation of the myeloid cell compartment urges investigations on neutrophil characteristics in coronavirus disease 2019 (COVID-19). We isolated neutrophils from the blood of COVID-19 patients receiving general ward care and from patients hospitalised at intensive care units (ICUs) to explore the kinetics of circulating neutrophils and factors important for neutrophil migration and activation. Methods: Multicolour flow cytometry was exploited for the analysis of neutrophil differentiation and activation markers. Multiplex and ELISA technologies were used for the quantification of protease, protease inhibitor, chemokine and cytokine concentrations in plasma. Neutrophil polarisation responses were evaluated microscopically. Gelatinolytic and metalloproteinase activity in plasma was determined using a fluorogenic substrate. Co-culturing healthy donor neutrophils with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) allowed us to investigate viral replication in neutrophils. Results: Upon ICU admission, patients displayed high plasma concentrations of granulocyte-colony-stimulating factor (G-CSF) and the chemokine CXCL8, accompanied by emergency myelopoiesis as illustrated by high levels of circulating CD10-, immature neutrophils with reduced CXCR2 and C5aR expression. Neutrophil elastase and non-metalloproteinase-derived gelatinolytic activity were increased in plasma from ICU patients. Significantly higher levels of circulating tissue inhibitor of metalloproteinase 1 (TIMP-1) in patients at ICU admission yielded decreased total MMP proteolytic activity in blood. COVID-19 neutrophils were hyper-responsive to CXCL8 and CXCL12 in shape change assays. Finally, SARS-CoV-2 failed to replicate inside human neutrophils. Conclusion: Our study provides detailed insights into the kinetics of neutrophil phenotype and function in severe COVID-19 patients, and supports the concept of an increased neutrophil activation state in the circulation.

6.
Clin Infect Dis ; 73(10): 1768-1775, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1522134

ABSTRACT

BACKGROUND: We performed a population-based study to describe the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on pregnancy outcomes. METHODS: This prospective, population-based study included pregnant women who consecutively presented at first/second trimester visits or at delivery at 3 hospitals in Barcelona, Spain. SARS-CoV-2 antibodies (immunoglobulin [Ig] G and IgM/IgA) were measured in all participants, and nasopharyngeal real-time polymerase chain reaction (RT-PCR) was performed at delivery. The primary outcome was a composite of pregnancy complications in SARS-CoV-2-positive vs negative women that included miscarriage, preeclampsia, preterm delivery, perinatal death, small-for-gestational-age newborn, or neonatal admission. Secondary outcomes were components of the primary outcome plus abnormal fetal growth, malformation, or intrapartum fetal distress. Outcomes were also compared between positive symptomatic and positive asymptomatic SARS-CoV-2 women. RESULTS: Of 2225 pregnant women, 317 (14.2%) were positive for SARS-CoV-2 antibodies (n = 314, 99.1%) and/or RT-PCR (n = 36, 11.4%). Among positive women, 217 (68.5%) were asymptomatic, 93 (29.3%) had mild coronavirus disease 2019 (COVID-19), and 7 (2.2%) had pneumonia, of whom 3 required intensive care unit admission. In women with and without SARS-CoV-2 infection, the primary outcome occurred in 43 (13.6%) and 268 (14%), respectively (risk difference, -0.4%; 95% confidence interval, -4.1% to 4.1). Compared with noninfected women, those with symptomatic COVID-19 had increased rates of preterm delivery (7.2% vs 16.9%, P = .003) and intrapartum fetal distress (9.1% vs 19.2%, P = .004), while asymptomatic women had rates that were similar to those of noninfected cases. Among 143 fetuses from infected mothers, none had anti-SARS-CoV-2 IgM/IgA in cord blood. CONCLUSIONS: The overall rate of pregnancy complications in women with SARS-CoV-2 infection was similar to that of noninfected women. However, symptomatic COVID-19 was associated with modest increases in preterm delivery and intrapartum fetal distress.

7.
Transbound Emerg Dis ; 2020 Dec 09.
Article in English | MEDLINE | ID: covidwho-1526424

ABSTRACT

The recently emerged novel coronavirus, SARS-CoV-2, is phylogenetically related to bat coronaviruses (CoVs), specifically SARS-related CoVs from the Eurasian bat family Rhinolophidae. As this human pandemic virus has spread across the world, the potential impacts of SARS-CoV-2 on native North American bat populations are unknown, as is the ability of North American bats to serve as reservoirs or intermediate hosts able to transmit the virus to humans or to other animal species. To help determine the impacts of the pandemic virus on North American bat populations, we experimentally challenged big brown bats (Eptesicus fuscus) with SARS-CoV-2 under BSL-3 conditions. We inoculated the bats both oropharyngeally and nasally, and over the ensuing three weeks, we measured infectivity, pathology, virus concentrations in tissues, oral and rectal virus excretion, virus transmission, and clinical signs of disease. We found no evidence of SARS-CoV-2 infection in any examined bat, including no viral excretion, no transmission, no detectable virus in tissues, and no signs of disease or pathology. Based on our findings, it appears that big brown bats are resistant to infection with the SARS-CoV-2. The potential susceptibility of other North American bat species to SARS-CoV-2 remains to be investigated.

8.
Vox Sang ; 116(10): 1076-1083, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1515248

ABSTRACT

BACKGROUND AND OBJECTIVES: Convalescent plasma (CP) has been embraced as a safe therapeutic option for coronavirus disease 2019 (COVID-19), while other treatments are developed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not transmissible by transfusion, but bloodborne pathogens remain a risk in regions with high endemic prevalence of disease. Pathogen reduction can mitigate this risk; thus, the objective of this study was to evaluate the effect of riboflavin and ultraviolet light (R + UV) pathogen reduction technology on the functional properties of COVID-19 CP (CCP). MATERIALS AND METHODS: COVID-19 convalescent plasma units (n = 6) from recovered COVID-19 research donors were treated with R + UV. Pre- and post-treatment samples were tested for coagulation factor and immunoglobulin retention. Antibody binding to spike protein receptor-binding domain (RBD), S1 and S2 epitopes of SARS-CoV-2 was assessed by ELISA. Neutralizing antibody (nAb) function was assessed by pseudovirus reporter viral particle neutralization (RVPN) assay and plaque reduction neutralization test (PRNT). RESULTS: Mean retention of coagulation factors was ≥70%, while retention of immunoglobulins was 100%. Starting nAb titres were low, but PRNT50 titres did not differ between pre- and post-treatment samples. No statistically significant differences were detected in levels of IgG (P ≥ 0·3665) and IgM (P ≥ 0·1208) antibodies to RBD, S1 and S2 proteins before and after treatment. CONCLUSION: R + UV PRT effects on coagulation factors were similar to previous reports, but no significant effects were observed on immunoglobulin concentration and antibody function. SARS-CoV-2 nAb function in CCP is conserved following R + UV PRT treatment.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive , Riboflavin , SARS-CoV-2 , Technology , Ultraviolet Rays
9.
Lancet Infect Dis ; 21(5): 637-646, 2021 05.
Article in English | MEDLINE | ID: covidwho-1510469

ABSTRACT

BACKGROUND: To mitigate the effects of COVID-19, a vaccine is urgently needed. BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) or alum (Algel). METHODS: We did a double-blind, multicentre, randomised, controlled phase 1 trial to assess the safety and immunogenicity of BBV152 at 11 hospitals across India. Healthy adults aged 18-55 years who were deemed healthy by the investigator were eligible. Individuals with positive SARS-CoV-2 nucleic acid and/or serology tests were excluded. Participants were randomly assigned to receive either one of three vaccine formulations (3 µg with Algel-IMDG, 6 µg with Algel-IMDG, or 6 µg with Algel) or an Algel only control vaccine group. Block randomisation was done with a web response platform. Participants and investigators were masked to treatment group allocation. Two intramuscular doses of vaccines were administered on day 0 (the day of randomisation) and day 14. Primary outcomes were solicited local and systemic reactogenicity events at 2 h and 7 days after vaccination and throughout the full study duration, including serious adverse events. Secondary outcome was seroconversion (at least four-fold increase from baseline) based on wild-type virus neutralisation. Cell-mediated responses were evaluated by intracellular staining and ELISpot. The trial is registered at ClinicalTrials.gov (NCT04471519). FINDINGS: Between July 13 and 30, 2020, 827 participants were screened, of whom 375 were enrolled. Among the enrolled participants, 100 each were randomly assigned to the three vaccine groups, and 75 were randomly assigned to the control group (Algel only). After both doses, solicited local and systemic adverse reactions were reported by 17 (17%; 95% CI 10·5-26·1) participants in the 3 µg with Algel-IMDG group, 21 (21%; 13·8-30·5) in the 6 µg with Algel-IMDG group, 14 (14%; 8·1-22·7) in the 6 µg with Algel group, and ten (10%; 6·9-23·6) in the Algel-only group. The most common solicited adverse events were injection site pain (17 [5%] of 375 participants), headache (13 [3%]), fatigue (11 [3%]), fever (nine [2%]), and nausea or vomiting (seven [2%]). All solicited adverse events were mild (43 [69%] of 62) or moderate (19 [31%]) and were more frequent after the first dose. One serious adverse event of viral pneumonitis was reported in the 6 µg with Algel group, unrelated to the vaccine. Seroconversion rates (%) were 87·9, 91·9, and 82·8 in the 3 µg with Algel-IMDG, 6 µg with Algel-IMDG, and 6 µg with Algel groups, respectively. CD4+ and CD8+ T-cell responses were detected in a subset of 16 participants from both Algel-IMDG groups. INTERPRETATION: BBV152 led to tolerable safety outcomes and enhanced immune responses. Both Algel-IMDG formulations were selected for phase 2 immunogenicity trials. Further efficacy trials are warranted. FUNDING: Bharat Biotech International.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/adverse effects , Double-Blind Method , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged , Toll-Like Receptor 7/agonists , Toll-Like Receptor 8/agonists , Vaccination , Vaccines, Inactivated/immunology , Young Adult
10.
J Virol ; 95(13): e0019221, 2021 06 10.
Article in English | MEDLINE | ID: covidwho-1486499

ABSTRACT

Understanding factors that affect the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is central to combatting coronavirus disease 2019 (COVID-19). The virus surface spike protein of SARS-CoV-2 mediates viral entry into cells by binding to the ACE2 receptor on epithelial cells and promoting fusion. We found that Epstein-Barr virus (EBV) induces ACE2 expression when it enters the lytic replicative cycle in epithelial cells. By using vesicular stomatitis virus (VSV) particles pseudotyped with the SARS-CoV-2 spike protein, we showed that lytic EBV replication enhances ACE2-dependent SARS-CoV-2 pseudovirus entry. We found that the ACE2 promoter contains response elements for Zta, an EBV transcriptional activator that is essential for EBV entry into the lytic cycle of replication. Zta preferentially acts on methylated promoters, allowing it to reactivate epigenetically silenced EBV promoters from latency. By using promoter assays, we showed that Zta directly activates methylated ACE2 promoters. Infection of normal oral keratinocytes with EBV leads to lytic replication in some of the infected cells, induces ACE2 expression, and enhances SARS-CoV-2 pseudovirus entry. These data suggest that subclinical EBV replication and lytic gene expression in epithelial cells, which is ubiquitous in the human population, may enhance the efficiency and extent of SARS-CoV-2 infection of epithelial cells by transcriptionally activating ACE2 and increasing its cell surface expression. IMPORTANCE SARS-CoV-2, the coronavirus responsible for COVID-19, has caused a pandemic leading to millions of infections and deaths worldwide. Identifying the factors governing susceptibility to SARS-CoV-2 is important in order to develop strategies to prevent SARS-CoV-2 infection. We show that Epstein-Barr virus, which infects and persists in >90% of adult humans, increases susceptibility of epithelial cells to infection by SARS-CoV-2. EBV, when it reactivates from latency or infects epithelial cells, increases expression of ACE2, the cellular receptor for SARS-CoV-2, enhancing infection by SARS-CoV-2. Inhibiting EBV replication with antivirals may therefore decrease susceptibility to SARS-CoV-2 infection.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , Epithelial Cells/virology , Herpesvirus 4, Human/physiology , SARS-CoV-2/physiology , Virus Internalization , Virus Replication , Angiotensin-Converting Enzyme 2/metabolism , Cell Line , DNA Methylation , Epithelial Cells/metabolism , Gene Expression Regulation , Humans , Promoter Regions, Genetic , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Trans-Activators/metabolism , Virus Activation
11.
J Clin Microbiol ; 59(7): e0051421, 2021 06 18.
Article in English | MEDLINE | ID: covidwho-1486483

ABSTRACT

Accurate SARS-CoV-2 serological assays are critical for COVID-19 serosurveillance. However, previous studies have indicated possible cross-reactivity of these assays, including in areas where malaria is endemic. We tested 213 well-characterized prepandemic samples from Nigeria using two SARS-CoV-2 serological assays, Abbott Architect IgG and Euroimmun NCP IgG assay, both targeting SARS-CoV-2 nucleocapsid protein. To assess antibody binding strength, an avidity assay was performed on these samples and on plasma from SARS-CoV-2 PCR-positive persons. Thirteen (6.1%) of 212 samples run on the Abbott assay and 38 (17.8%) of 213 run on the Euroimmun assay were positive. Anti-Plasmodium IgG levels were significantly higher among false positives for both Abbott and Euroimmun; no association was found with active Plasmodium falciparum infection. An avidity assay using various concentrations of urea wash in the Euroimmun assay reduced loosely bound IgG: of 37 positive/borderline prepandemic samples, 46%, 86%, 89%, and 97% became negative using 2 M, 4 M, 5 M, and 8 M urea washes, respectively. The wash slightly reduced avidity of antibodies from SARS-CoV-2 patients within 28 days of PCR confirmation; thereafter, avidity increased for all urea concentrations except 8 M. This validation found moderate to substantial cross-reactivity on two SARS-CoV-2 serological assays using samples from a setting where malaria is endemic. A simple urea wash appeared to alleviate issues of cross-reactivity.


Subject(s)
COVID-19 , Malaria , Antibodies, Viral , Humans , Malaria/diagnosis , Nigeria , SARS-CoV-2 , Sensitivity and Specificity
12.
Antimicrob Agents Chemother ; 65(7): e0009721, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1486469

ABSTRACT

Efforts to mitigate the coronavirus disease 2019 (COVID-19) pandemic include the screening of existing antiviral molecules that could be repurposed to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Although SARS-CoV-2 replicates and propagates efficiently in African green monkey kidney (Vero) cells, antivirals such as nucleos(t)ide analogs (NUCs) often show decreased activity in these cells due to inefficient metabolization. SARS-CoV-2 exhibits low viability in human cells in culture. Here, serial passages of a SARS-CoV-2 isolate (original-SARS2) in the human hepatoma cell clone Huh7.5 led to the selection of a variant (adapted-SARS2) with significantly improved infectivity in human liver (Huh7 and Huh7.5) and lung cancer (unmodified Calu-1 and A549) cells. The adapted virus exhibited mutations in the spike protein, including a 9-amino-acid deletion and 3 amino acid changes (E484D, P812R, and Q954H). E484D also emerged in Vero E6-cultured viruses that became viable in A549 cells. Original and adapted viruses were susceptible to scavenger receptor class B type 1 (SR-B1) receptor blocking, and adapted-SARS2 exhibited significantly less dependence on ACE2. Both variants were similarly neutralized by COVID-19 convalescent-phase plasma, but adapted-SARS2 exhibited increased susceptibility to exogenous type I interferon. Remdesivir inhibited original- and adapted-SARS2 similarly, demonstrating the utility of the system for the screening of NUCs. Among the tested NUCs, only remdesivir, molnupiravir, and, to a limited extent, galidesivir showed antiviral effects across human cell lines, whereas sofosbuvir, ribavirin, and favipiravir had no apparent activity. Analogously to the emergence of spike mutations in vivo, the spike protein is under intense adaptive selection pressure in cell culture. Our results indicate that the emergence of spike mutations will most likely not affect the activity of remdesivir.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/pharmacology , Chlorocebus aethiops , Humans , Pandemics , Spike Glycoprotein, Coronavirus , Virus Replication
13.
Viral Immunol ; 34(6): 416-420, 2021.
Article in English | MEDLINE | ID: covidwho-1475758

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has infected millions of individuals in the world. However, the long-term effect of SARS-CoV-2 on the organs of recovered patients remains unclear. This study is to evaluate the impact of SARS-CoV-2 on the spleen and T lymphocytes. Seventy-six patients recovered from COVID-19, including 66 cases of moderate pneumonia and 10 cases of severe pneumonia were enrolled in the observation group. The control group consisted of 55 age-matched healthy subjects. The thickness and length of spleen were measured by using B-ultrasound and the levels of T lymphocytes were detected by flow cytometry. Results showed that the mean length of spleen in the observation group was 89.57 ± 11.49 mm, which was significantly reduced compared with that in the control group (103.82 ± 11.29 mm, p < 0.001). The mean thicknesses of spleen between observation group and control group were 29.97 ± 4.04 mm and 32.45 ± 4.49 mm, respectively, and the difference was significant (p < 0.001). However, no significant difference was observed in the size of spleen between common pneumonia and severe pneumonia (p > 0.05). In addition, the decreased count of T lymphocyte was observed in part of recovered patients. The counts of T suppressor lymphocytes in patients with severe pneumonia were significantly decreased compared with those with moderate pneumonia (p = 0.005). Therefore, these data indicate that SARS-CoV-2 infection affects the size of spleen and T lymphocytes.


Subject(s)
COVID-19/immunology , SARS-CoV-2 , Spleen/pathology , T-Lymphocytes/immunology , Adult , Aged , Female , Humans , Lymphocyte Count , Male , Middle Aged , Young Adult
14.
Clin Infect Dis ; 73(7): e1762-e1765, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1455264

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered virus for which remdesivir is the only antiviral available. We report the occurrence of a mutation in RdRP (D484Y) following treatment with remdesivir in a 76-year-old female with post-rituximab B-cell immunodeficiency and persistent SARS-CoV-2 viremia. A cure was achieved after supplementation with convalescent plasma.


Subject(s)
COVID-19 , RNA-Dependent RNA Polymerase , Adenosine Monophosphate/analogs & derivatives , Aged , Alanine/analogs & derivatives , B-Lymphocytes , COVID-19/drug therapy , COVID-19/therapy , Female , Humans , Immunization, Passive , Mutation , SARS-CoV-2
15.
Clin Infect Dis ; 73(7): e2444-e2449, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1455256

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) and dengue fever are difficult to distinguish given shared clinical and laboratory features. Failing to consider COVID-19 due to false-positive dengue serology can have serious implications. We aimed to assess this possible cross-reactivity. METHODS: We analyzed clinical data and serum samples from 55 individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To assess dengue serology status, we used dengue-specific antibodies by means of lateral-flow rapid test, as well as enzyme-linked immunosorbent assay (ELISA). Additionally, we tested SARS-CoV-2 serology status in patients with dengue and performed in-silico protein structural analysis to identify epitope similarities. RESULTS: Using the dengue lateral-flow rapid test we detected 12 positive cases out of the 55 (21.8%) COVID-19 patients versus zero positive cases in a control group of 70 healthy individuals (P = 2.5E-5). This includes 9 cases of positive immunoglobulin M (IgM), 2 cases of positive immunoglobulin G (IgG), and 1 case of positive IgM as well as IgG antibodies. ELISA testing for dengue was positive in 2 additional subjects using envelope protein directed antibodies. Out of 95 samples obtained from patients diagnosed with dengue before September 2019, SARS-CoV-2 serology targeting the S protein was positive/equivocal in 21 (22%) (16 IgA, 5 IgG) versus 4 positives/equivocal in 102 controls (4%) (P = 1.6E-4). Subsequent in-silico analysis revealed possible similarities between SARS-CoV-2 epitopes in the HR2 domain of the spike protein and the dengue envelope protein. CONCLUSIONS: Our findings support possible cross-reactivity between dengue virus and SARS-CoV-2, which can lead to false-positive dengue serology among COVID-19 patients and vice versa. This can have serious consequences for both patient care and public health.


Subject(s)
COVID-19 , Dengue Virus , Antibodies, Viral , Cross Reactions , Humans , SARS-CoV-2
16.
Clin Infect Dis ; 73(7): e1870-e1877, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1455249

ABSTRACT

BACKGROUND: We evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface and air contamination during the coronavirus disease 2019 (COVID-19) pandemic in London. METHODS: Prospective, cross-sectional, observational study in a multisite London hospital. Air and surface samples were collected from 7 clinical areas occupied by patients with COVID-19 and a public area of the hospital. Three or four 1.0-m3 air samples were collected in each area using an active air sampler. Surface samples were collected by swabbing items in the immediate vicinity of each air sample. SARS-CoV-2 was detected using reverse-transcription quantitative polymerase chain reaction (PCR) and viral culture; the limit of detection for culturing SARS-CoV-2 from surfaces was determined. RESULTS: Viral RNA was detected on 114 of 218 (52.3%) surfaces and in 14 of 31 (38.7%) air samples, but no virus was cultured. Viral RNA was more likely to be found in areas immediately occupied by COVID-19 patients than in other areas (67 of 105 [63.8%] vs 29 of 64 [45.3%]; odds ratio, 0.5; 95% confidence interval, 0.2-0.9; P = .025, χ2 test). The high PCR cycle threshold value for all samples (>30) indicated that the virus would not be culturable. CONCLUSIONS: Our findings of extensive viral RNA contamination of surfaces and air across a range of acute healthcare settings in the absence of cultured virus underlines the potential risk from environmental contamination in managing COVID-19 and the need for effective use of personal protective equipment, physical distancing, and hand/surface hygiene.


Subject(s)
COVID-19 , SARS-CoV-2 , Cross-Sectional Studies , Delivery of Health Care , Humans , London/epidemiology , Pandemics , Prospective Studies
17.
Transplantation ; 105(10): 2165-2169, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1447690

ABSTRACT

BACKGROUND: Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in kidney transplant recipients (KTRs) remain rare. We sought to shed further light on this issue by conducting a single-center study in a kidney transplant center located in one of the France's highest risk zone (Grand Est) for coronavirus disease 2019 (Covid-19) during the initial disease outbreak. METHODS: To this aim, we used a survey approach coupled with systematic investigation of SARS-CoV-2 serology in a cohort of 1390 KTRs. RESULTS: SARS-CoV-2 serologies were available for 780 survey respondents, among whom 48 had anti-SARS-CoV-2 antibodies (total seroprevalence: 6.2%). Thirty-five of the 48 seropositive KTRs had previously received a diagnosis of Covid-19, whereas the remaining 13 patients were not known to be infected (8 asymptomatic cases). Specifically, 18.7% of seropositive KTRs and 1.1% of the entire cohort were asymptomatic. Household exposure was found to markedly increase the risk of SARS-CoV-2 transmission. CONCLUSIONS: Our findings demonstrate that the overall SARS-CoV-2 seroprevalence in KTRs living in one of the France's highest risk zone for Covid-19 during the first French lockdown was as low as 6.3%. Rapid and strict implementation of protective measures could have significantly mitigated virus spread even in an area of high virus circulation.


Subject(s)
Antibodies, Viral/blood , COVID-19/epidemiology , Kidney Transplantation , SARS-CoV-2/immunology , France/epidemiology , Humans , Seroepidemiologic Studies
18.
Ghana Med J ; 54(4 Suppl): 77-85, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1436198

ABSTRACT

Background: A novel coronavirus, SARS-CoV-2 is currently causing a worldwide pandemic. The first cases of SARS-CoV-2 infection were recorded in Ghana on March 12, 2020. Since then, the country has been combatting countrywide community spread. This report describes how the Virology Department, Noguchi Memorial Institute for Medical Research (NMIMR) is supporting the Ghana Health Service (GHS) to diagnose infections with this virus in Ghana. Methods: The National Influenza Centre (NIC) in the Virology Department of the NMIMR, adopted real-time Polymerase Chain Reaction (rRT-PCR) assays for the diagnosis of the SARS-CoV-2 in January 2020. Samples from suspected cases and contact tracing across Ghana were received and processed for SARS-CoV-2. Samples were 'pooled' to enable simultaneous batch testing of samples without reduced sensitivity. Outcomes: From February 3 to August 21, the NMIMR processed 283 946 (10%) samples. Highest number of cases were reported in June when the GHS embarked on targeted contact tracing which led to an increase in number of samples processed daily, peaking at over 7,000 samples daily. There were several issues to overcome including rapid consumption of reagents and consumables. Testing however continued successfully due to revised procedures, additional equipment and improved pipeline of laboratory supplies. Test results are now provided within 24 to 48 hours of sample submission enabling more effective response and containment. Conclusion: Following the identification of the first cases of SARS-CoV-2infection by the NMIMR, the Institute has trained other centres and supported the ramping up of molecular testing capacity in Ghana. This provides a blueprint to enable Ghana to mitigate further epidemics and pandemics. Funding: The laboratory work was supported with materials from the Ghana Health Service Ministry of Health, the US Naval Medical Research Unit #3, the World Health Organization, the Jack Ma Foundation and the University of Ghana Noguchi Memorial Institute for Medical Research. Other research projects hosted by the Noguchi Memorial Institute for Medical Research contributed reagents and laboratory consumables. The funders had no role in the preparation of this manuscript.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , Infection Control/methods , Population Surveillance , SARS-CoV-2/isolation & purification , COVID-19/epidemiology , Contact Tracing/methods , Contact Tracing/statistics & numerical data , Ghana/epidemiology , Humans , National Health Programs , SARS-CoV-2/genetics
19.
Glycobiology ; 31(9): 1080-1092, 2021 09 20.
Article in English | MEDLINE | ID: covidwho-1434394

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), started in 2019 in China and quickly spread into a global pandemic. Nucleocapsid protein (N protein) is highly conserved and is the most abundant protein in coronaviruses and is thus a potential target for both vaccine and point-of-care diagnostics. N Protein has been suggested in the literature as having posttranslational modifications (PTMs), and accurately defining these PTMs is critical for its potential use in medicine. Reports of phosphorylation of N protein have failed to provide detailed site-specific information. We have performed comprehensive glycomics, glycoproteomics and proteomics experiments on two different N protein preparations. Both were expressed in HEK293 cells; one was in-house expressed and purified without a signal peptide (SP) sequence, and the other was commercially produced with a SP channeling it through the secretory pathway. Our results show completely different PTMs on the two N protein preparations. The commercial product contained extensive N- and O-linked glycosylation as well as O-phosphorylation on site Thr393. Conversely, the native N Protein model had O-phosphorylation at Ser176 and no glycosylation, highlighting the importance of knowing the provenance of any commercial protein to be used for scientific or clinical studies. Recent studies have indicated that N protein can serve as an important diagnostic marker for COVID-19 and as a major immunogen by priming protective immune responses. Thus, detailed structural characterization of N protein may provide useful insights for understanding the roles of PTMs on viral pathogenesis, vaccine design and development of point-of-care diagnostics.


Subject(s)
Coronavirus Nucleocapsid Proteins/metabolism , Protein Processing, Post-Translational/physiology , SARS-CoV-2/metabolism , Amino Acid Motifs , Amino Acid Sequence , Binding Sites , Coronavirus Nucleocapsid Proteins/chemistry , Glycosylation , HEK293 Cells , Humans , Phosphorylation , SARS-CoV-2/chemistry
20.
J Med Virol ; 93(10): 5864-5872, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1432419

ABSTRACT

The aim was to investigate the association of the delivery mode and vertical transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) through the samples of vaginal secretions, placenta, cord blood, or amniotic fluid as well as the neonatal outcomes. This cross-sectional study presents an analysis of prospectively gathered data collected at a single tertiary hospital. Sixty-three pregnant women with confirmed coronavirus disease 2019 (COVID-19) participated in the study. Vertical transmission of SARS-CoV-2 was analyzed with reverse transcriptase-polymerase chain reaction (RT-PCR) tests and blood tests for immunoglobulin G (IgG)-immunoglobulin M (IgM) antibodies. All patients were in the mild or moderate category for COVID-19. Only one placental sample and two of the vaginal secretion samples were positive for SARS-CoV-2. Except for one, all positive samples were obtained from patients who gave birth by cesarean. All cord blood and amniotic fluid samples were negative for SARS-CoV-2. Two newborns were screened positive for COVID-19 IgG-IgM within 24 h after delivery, but the RT-PCR tests were negative. A positive RT-PCR result was detected in a neof a mother whose placenta, cord blood, amniotic fluid, and vaginal secretions samples were negative. He died due to pulmonary hemorrhage on the 11th day of life. In conclusion, we demonstrated that SARS-CoV-2 can be detectable in the placenta or vaginal secretions of pregnant women. Detection of the virus in the placenta or vaginal secretions may not be associated with neonatal infection. Vaginal delivery may not increase the incidence of neonatal infection, and cesarean may not prevent vertical transmission. The decision regarding the mode of delivery should be based on obstetric indications and COVID-19 severity.


Subject(s)
COVID-19/transmission , SARS-CoV-2/isolation & purification , Adolescent , Adult , COVID-19/diagnosis , COVID-19/epidemiology , Cesarean Section , Cross-Sectional Studies , Female , Humans , Infant, Newborn , Infant, Newborn, Diseases/diagnosis , Infant, Newborn, Diseases/epidemiology , Infant, Newborn, Diseases/virology , Infectious Disease Transmission, Vertical/statistics & numerical data , Male , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/virology , Pregnancy Outcome , Prospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Tertiary Care Centers , Vagina/virology , Young Adult
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