Clinical performance of rapid antigen tests in comparison to RT-PCR for SARS-COV-2 diagnosis in Omicron variant: A systematic review and meta-analysis

The Omicron variant of concern has a high level of mutations in different genes that has raised awareness about the performance of immunological products such as vaccines and antigen detection kits. In this systematic review and meta-analysis, we investigated whether Omicron had a significant influence on rapid antigen test (RAT) performance in comparison to PCR. We registered this systematic review and meta-analysis in PROSPERO with the registration number CRD42022355510. We searched PubMed, Scopus, Embase, and Web of Science databases systematically to 1 August 2022. After article screening, we assessed the quality of the included studies based on the JBI checklist. Following data extraction, we performed a meta-analysis using R software. We included 18 qualified articles presenting sufficient data about RATs performance in comparison to RT-PCR in Omicron infections. The pooled specificity and sensitivity of RATs were 1.000 (0.997–1.000) and 0.671 (0.595–0.721), respectively. The FDA-approved kits showed a better performance than WHO-approved ones with a sensitivity of 0.728 (0.620–0.815). The use of RATs with nasal swabs showed a higher sensitivity compared with nasopharyngeal swabs. The sensitivity for samples with a CT-value >25 was 0.108 (0.048–0.227). Rapid antigen tests show impaired performance for COVID-19 diagnosis when the Omicron variant is circulating, particularly in samples with low viral loads.     

A retrospective analysis of COVID-19 diagnosis results obtained by rapid antigen tests and RT-PCR: Implications for disease management

There is a need for understanding and establishment of the most appropriate testing algorithm for COVID-19 diagnosis in asymptomatic high-risk groups. Here, we present a retrospective analysis of RT-PCR results obtained from 412 cases tested negative for coronavirus disease 2019 (COVID-19) by rapid antigen testing method. Among 178 (43.2%) asymptomatic individuals, 44.9% of the high risk contacts, 12.2% of police custody individuals, 22.22% of the pregnant women and 33.33% of individuals hospitalised for preoperative or other medical conditions showed RT-PCR positivity. Our results suggest a need for focussed and intensive (multi-modality) testing in groups at high risk for SARS-CoV-2 infection.     

N-antigenemia detection by a rapid lateral flow test predicts 90-day mortality in COVID-19: A prospective cohort study

ObjectivesTo evaluate if the detection of N antigen of SARS-CoV-2 in plasma by a rapid lateral flow test predicts 90-day mortality in COVID-19 patients hospitalized at the wards.MethodsThe presence of N-antigenemia was evaluated in the first 36 hours after hospitalization in 600 unvaccinated COVID-19 patients, by using the Panbio COVID-19 Ag Rapid Test Device from Abbott (Abbott Laboratories Inc., Chicago, IL, USA). The impact of N-antigenemia on 90-day mortality was assessed by multivariable Cox regression analysis.ResultsPrevalence of N-antigenemia at hospitalization was higher in nonsurvivors (69% (82/118) vs. 52% (250/482); p < 0.001). The patients with N-antigenemia showed more frequently RNAemia (45.7% (148/324) vs. 19.8% (51/257); p < 0.001), absence of anti-SARS-CoV-2 N antibodies (80.7% (264/327) vs. 26.6% (69/259); p < 0.001) and absence of S1 antibodies (73.4% (240/327) vs. 23.6% (61/259); p < 0.001). The patients with antigenemia showed more frequently acute respiratory distress syndrome (30.1% (100/332) vs. 18.7% (50/268); p = 0.001) and nosocomial infections (13.6% (45/331) vs. 7.9% (21/267); p = 0.026). N-antigenemia was a risk factor for increased 90-day mortality in the multivariable analysis (HR, 1.99 (95% CI,1.09–3.61), whereas the presence of anti-SARS-CoV-2 N-antibodies represented a protective factor (HR, 0.47 (95% CI, 0.26–0.85).DiscussionThe presence of N-antigenemia or the absence of anti-SARS-CoV-2 N-antibodies after hospitalization is associated to increased 90-day mortality in unvaccinated COVID-19 patients. Detection of N-antigenemia by using lateral flow tests is a quick, widely available tool that could contribute to early identify those COVID-19 patients at risk of deterioration.     

Possible transmission of COVID-19 epidemic by a dog as a passive mechanical carrier of SARS-CoV-2, Chongqing,China, 2022

An outbreak of coronavirus disease 2019 (COVID-19) was reported in Yongchuan district of Chongqing, China in March 2022, while the source was unknown. We aimed to investigate the origin and transmission route of the virus in the outbreak. We conducted field investigations for all cases and collected their epidemiological and clinical data. We performed gene sequencing and phylogenetic analysis for the cases, and draw the epidemic curve and the case relationship chart to analyze interactions and possible transmission mode of the outbreak. A total of 11 cases of COVID-19, including 5 patients and 6 asymptomatic cases were laboratory-confirmed in the outbreak. The branch of the virus was Omicron BA.2 which was introduced into Yongchuan district by a traveler in early March. Patient F and asymptomatic case G had never contact with other positive-infected individuals, but close contact with their pet dog that sniffed the discarded cigarette butts and stepped on the sputum of patient B. Laboratory test results showed that the dog hair and kennel were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the 10 isolates were highly homologous to an epidemic strain in a province of China. The investigation suggested that the contaminated dog by SARS-CoV-2 can act as a passive mechanical carrier of the virus and might transmit the virus to humans through close contact. Our findings suggest that during the COVID-19 pandemic, increasing hygiene measures and hand washing after close contact with pets is essential to minimize the risk of community spread of the virus.     

Self-testing for the detection of SARS-CoV-2 infection with rapid antigen tests for people with suspected COVID-19 in the community

ObjectivesTo evaluate the performance of nasal mid-turbinate self-testing using rapid antigen detection tests (RDT) for persons with suspected coronavirus disease 2019 (COVID-19) in the community. Self-testing for COVID-19 infection with lateral flow assay severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RDT, provides rapid results and could enable frequent and extensive testing in the community, thereby improving the control of SARS-CoV-2.MethodsParticipants visiting a municipal SARS-CoV-2 testing centre, received self-testing kits containing either the BD Veritor System (BD-RDT) or Roche SARS-CoV-2 antigen detection test (Roche-RDT). Oro-nasopharyngeal swabs were collected from the participants for quantitative RT-PCR (qRT-PCR) testing. As a proxy for contagiousness, viral culture was performed on a selection of qRT-PCR positive samples to determine the Ct-value at which the chance of a positive culture dropped below 0.5 (Ct-value cut-off). Sensitivity and specificity of self-testing were compared to qRT-PCR with a Ct-value below the Ct value cut-off. Determinants independently associated with a false-negative self-test result were determined.ResultsA total of 3201 participants were included (BD-RDT n = 1595; Roche-RDT n = 1606). Sensitivity and specificity of self-testing compared with the qRT-PCR results with a Ct-value below the Ct-value cut-off were 78.4% (95% CI 73.2%–83.5%) and 99.4% (95% CI 99.1%–99.7%), respectively. A higher age was independently associated with a false-negative self-testing result with an odds ratio of 1.024 (95% CI 1.003–1.044).ConclusionsSelf-testing using currently available RDT has a high specificity and relatively high sensitivity to identify individuals with a high probability of contagiousness.     

COVID-19 (SARS-CoV-2 infection) in lymphoma patients: A review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection now has a global resonance and represents a major threat for several patient populations. Observations from initial case series suggested that cancer patients in general might have an unfavorable outcome following coronavirus disease 2019 (COVID-19), due to their underlying conditions and cytotoxic treatments. More recently, data regarding the incidence and clinical evolution of COVID-19 in lymphomas have been reported with the aim to identify those more frequently associated with severe complications and death. Patients with lymphoma appear particularly vulnerable to SARS-CoV-2 infection, only partly because of the detrimental effects of the anti-neoplastic regimens (chemotherapy, pathway inhibitors, monoclonal antibodies) on the immune system. Here, we systematically reviewed the current literature on COVID-19 in adult patients with lymphoma, with particular emphasis on disease course and prognostic factors. We also highlighted the potential differences in COVID-19 clinical picture according to lymphoma subtype, delivered treatment for the hematological disease and its relationship on how these patients have been managed thus far.     

Characteristics of patients with coronavirus disease (COVID-19) confirmed using an IgM-IgG antibody test

Coronavirus disease (COVID-19), caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly developed into a pandemic since it was first reported in December 2019. Nucleic acid testing is the standard method for the diagnosis of viral infections. However, this method reportedly has a low positivity rate. To increase the sensitivity of COVID-19 diagnoses, we developed an IgM-IgG combined assay and tested it in patients with suspected SARS-CoV-2 infection. In total, 56 patients were enrolled in this study and SARS-CoV-2 was detected by using both IgM-IgG antibody and nucleic acid tests. Clinical and laboratory data were collected and analyzed. Our findings suggest that patients who develop severe illness might experience longer virus exposure times and develop a more severe inflammatory response. The IgM-IgG test is an accurate and sensitive diagnostic method. A combination of nucleic acid and IgM-IgG testing is a more sensitive and accurate approach for diagnosis and early treatment of COVID-19.     

The Risk Factors and Outcomes for Radiological Abnormalities in Early Convalescence of COVID-19 Patients Caused by the SARS-CoV-2 Omicron Variant: A Retrospective,Multicenter Follow-up Study

BackgroundThe emergence of the severe acute respiratory syndrome coronavirus 2 omicron variant has been triggering the new wave of coronavirus disease 2019 (COVID-19) globally. However, the risk factors and outcomes for radiological abnormalities in the early convalescent stage (1 month after diagnosis) of omicron infected patients are still unknown.MethodsPatients were retrospectively enrolled if they were admitted to the hospital due to COVID-19. The chest computed tomography (CT) images and clinical data obtained at baseline (at the time of the first CT image that showed abnormalities after diagnosis) and 1 month after diagnosis were longitudinally analyzed. Uni-/multi-variable logistic regression tests were performed to explore independent risk factors for radiological abnormalities at baseline and residual pulmonary abnormalities after 1 month.ResultsWe assessed 316 COVID-19 patients, including 47% with radiological abnormalities at baseline and 23% with residual pulmonary abnormalities at 1-month follow-up. In a multivariate regression analysis, age ≥ 50 years, body mass index ≥ 23.87, days after vaccination ≥ 81 days, lymphocyte count ≤ 1.21 × 10^-9/L, interleukin-6 (IL-6) ≥ 10.05 pg/mL and IgG ≤ 14.140 S/CO were independent risk factors for CT abnormalities at baseline. The age ≥ 47 years, presence of interlobular septal thickening and IL-6 ≥ 5.85 pg/mL were the independent risk factors for residual pulmonary abnormalities at 1-month follow-up. For residual abnormalities group, the patients with less consolidations and more parenchymal bands at baseline could progress on CT score after 1 month. There were no significant changes in the number of involved lung lobes and total CT score during the early convalescent stage.ConclusionThe higher IL-6 level was a common independent risk factor for CT abnormalities at baseline and residual pulmonary abnormalities at 1-month follow-up. There were no obvious radiographic changes during the early convalescent stage in patients with residual pulmonary abnormalities.     

Long-term coexistence of SARS-CoV-2 with antibody response in COVID-19 patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) has spread worldwide. Whether antibodies are important for the adaptive immune responses against SARS-CoV-2 infection needs to be determined. Here, 26 cases of COVID-19 in Jinan, China, were examined and shown to be mild or with common clinical symptoms, and no case of severe symptoms was found among these patients. Strikingly, a subset of these patients had SARS-CoV-2 and virus-specific IgG coexist for an unexpectedly long time, with two cases for up to 50 days. One COVID-19 patient who did not produce any SARS-CoV-2–bound IgG successfully cleared SARS-CoV-2 after 46 days of illness, revealing that without antibody-mediated adaptive immunity, innate immunity alone may still be powerful enough to eliminate SARS-CoV-2. This report may provide a basis for further analysis of both innate and adaptive immunity in SARS-CoV-2 clearance, especially in nonsevere cases.     

Booster BNT162b2 COVID-19 Vaccination Increases Neutralizing Antibody Titers Against the SARS-CoV-2 Omicron Variant in Both Young and Elderly Adults

Concerns about the effectiveness of current vaccines against the rapidly spreading severe acute respiratory syndrome-coronavirus-2 omicron (B.1.1.529) variant are increasing. This study aimed to assess neutralizing antibody activity against the wild-type (BetaCoV/Korea/KCDC03/2020), delta, and omicron variants after full primary and booster vaccinations with BNT162b2. A plaque reduction neutralization test was employed to determine 50% neutralizing dilution (ND₅₀) titers in serum samples. ND₅₀ titers against the omicron variant (median [interquartile range], 5.3 [< 5.0–12.7]) after full primary vaccination were lower than those against the wild-type (144.8 [44.7–294.0]) and delta (24.3 [14.3–81.1]) variants. Furthermore, 19/30 participants (63.3%) displayed lower ND₅₀ titers than the detection threshold (< 10.0) against omicron after full primary vaccination. However, the booster vaccine significantly increased ND₅₀ titers against BetaCoV/Korea/KCDC03/2020, delta, and omicron, although titers against omicron remained lower than those against the other variants (P < 0.001). Our study suggests that booster vaccination with BNT162b2 significantly increases humoral immunity against the omicron variant.     

The efficacy of Paxlovid against COVID-19 is the result of the tight molecular docking between Mpro and antiviral drugs (nirmatrelvir and ritonavir)

PurposeCurrently, a number of medications for coronavirus disease 2019 (COVID-19) treatment are tested in clinical trials; however, credible clinical studies are becoming increasingly difficult to come by. Paxlovid is a ritonavir-boosted nirmatrelvir drug that the U.S. Food and Drug Administration (FDA) authorized for the treatment of COVID-19.This study aimed to demonstrate the interaction of nirmatrelvir and ritonavir on the active site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M^pro).Materials and methodsTo locate the optimal docking between M^pro and antiviral drugs, and to conduct dynamic simulations between atoms in the fusion areas, various bioinformatics and mathematical equations were applied.ResultsAccording to the docking data, nirmatrelvir has a stronger interaction with M^pro than ritonavir, which has more multiple bonds. Molecular docking of antiviral drugs such as Paxlovid has a significant impact on the treatment of COVID-19 virus.ConclusionsAccording to this study, Paxlovid may work on new strains, including Omicron, because the M^pro mutation P132H in the Omicron variant has no direct effect on the protein.     

Importation and Transmission of SARS-CoV-2 B.1.1.529 (Omicron) Variant of Concern in Korea,November 2021

In November 2021, 14 international travel-related severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant of concern (VOC) patients were detected in South Korea. Epidemiologic investigation revealed community transmission of the omicron VOC. A total of 80 SARS-CoV-2 omicron VOC-positive patients were identified until December 10, 2021 and 66 of them reported no relation to the international travel. There may be more transmissions with this VOC in Korea than reported.     

Gold nanoparticle conjugate-based lateral flow immunoassay (LFIA) for rapid detection of RBD antigen of SARS-CoV-2 in clinical samples using a smartphone-based application

The coronavirus disease 2019 (COVID-19) pandemic has emphasized the need for development of a rapid diagnostic device for the effective treatment and its mitigation. Lateral flow immunoassay (LFIA) belongs to a class of diagnostic devices, which has the benefit of providing quick results, easy to handle, low cost, and on-site applicable. So far, several LFIA has been developed for the detection of infectious severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), however, only a few of them are antigen (Ag)-based. Here, we describe an antibody (Ab)-labeled gold nanoparticles (AuNPs)-based LFIA (AuNPs-LFIA) for the detection of Receptor-Binding Domain (RBD) of SARS-CoV-2. For this, RBD Ab of SARS-CoV-2 was conjugated with the AuNPs, which served as a detecting probe. The fabricated LFIA strip was optimized for different parameters such as membrane pore size, blocking conditions, Ab coating concentration, and conjugate incubation. The optimized LFIA strips were validated in spiked buffer samples and the optimal limit of detection was found to be 1 ng/ml, which was confirmed by a smartphone-based application. Moreover, the developed AuNPs-LFIA strips effectively detected RBD Ag in 100 clinical samples with 94.3% sensitivity and 90.9% specificity in clinical samples when compared with the gold standard (RT-PCR). The fabricated LFIAs are reported to have storage stability of up to 21 days at 4°C and room temperature (RT). Hence, the developed LFIA can be used as a portable, cost-effective diagnostic device for rapid detection of SARS-CoV-2.     

A whole blood test to measure SARS-CoV-2-specific response in COVID-19 patients

ObjectivesTo examine whether specific T-cell-responses to SARS-CoV-2 peptides can be detected in COVID-19 using a whole-blood experimental setting, which may be further explored as a potential diagnostic tool.MethodsWe evaluated interferon (IFN)-γ levels after stimulating whole-blood with spike and remainder-antigens peptides megapools (MP) derived from SARS-CoV-2 sequences; interleukin (IL)-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, eotaxin, basic fibroblast growth factor (FGF), granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-γ, Interferon gamma-induced protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1β, Platelet-derived growth factor (PDGF), RANTES (regulated on activation, normal T cell expressed and secreted), tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF) were also evaluated.ResultsIFN-γ-response to spike and remainder-antigens MPs was significantly increased in 35 COVID-19 patients compared with 29 ‘no COVID-19’ individuals (medians spike-MP: 0.26 vs 0, p = 0.0002; medians remainder-antigens-MP: 0.07 vs 0.02; p = 0.02).This response was detected independently of patients' clinical parameters. IFN-γ-response to SARS-CoV-2-unrelated antigens cytomegalovirus (CMV) and Staphylococcal Enterotoxin B (SEB) was similar in COVID-19 compared with ‘no COVID-19’ individuals (median CMV: 3.46 vs 5.28, p = 0.16; median SEB: 12.68 vs 15.05; p = 0.1). In response to spike-MPs in COVID-19- compared with ‘no COVID-19’ -individuals, we found significant higher median of IL-2 (50.08 vs 0, p = 0.0018), IFN-γ (90.16 vs 0, p = 0.01), IL-4 (0.52 vs 0, p = 0.03), IL-13 (0.84 vs 0, p = 0.007) and MCP-1 (4602 vs 359.2, p = 0.05).ConclusionsImmune response to SARS-CoV-2 peptides in a whole-blood assay is associated with COVID-19 and it is characterized by both Th1 and Th2 profile. This experimental approach may be useful for developing new T-cell based diagnostic tests for disease and vaccine settings.     

Impact of dexamethasone on SARS-CoV-2 concentration kinetics and antibody response in hospitalized COVID-19 patients: results from a prospective observational study

ObjectivesDexamethasone has become the standard of care for severe coronavirus disease 2019 (COVID-19), but its virological impact is poorly understood. The objectives of this work were to characterize the kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) concentration in the upper respiratory tract (URT) and the antibody response in patients with (D⁺) and without (D^–) dexamethasone treatment.MethodsData and biosamples from hospitalized patients with severe COVID-19, enrolled between 4th March and 11th December 2020 in a prospective observational study, were analysed. SARS-CoV-2 virus concentration in serial URT samples was measured using RT-PCR. SARS-CoV-2-specific immunoglobulins A and G (IgA and IgG) were measured in serum samples using S1-ELISA.ResultsWe compared 101 immunocompetent patients who received dexamethasone (according to the inclusion criteria and dosage determined in the RECOVERY trial) to 93 immunocompetent patients with comparable disease severity from the first months of the pandemic, who had not been treated with dexamethasone or other glucocorticoids. We found no inter-group differences in virus concentration kinetics, duration of presence of viral loads >10⁶ viral copies/mL (D⁺ median 17 days (IQR 13–24), D^– 19 days (IQR 13–29)), or time from symptom onset until seroconversion (IgA: D⁺ median 11.5 days (IQR 11–12), D^– 14 days (IQR 11.5–15.75); IgG: D⁺ 13 days (IQR 12–14.5), D^– 12 days (IQR 11–15)).ConclusionDexamethasone does not appear to lead to a change in virus clearance or a delay in antibody response in immunocompetent patients hospitalized with severe COVID-19.     

The emergence of a novel coronavirus (SARS-CoV-2) disease and their neuroinvasive propensity may affect in COVID-19 patients

An outbreak of a novel coronavirus (SARS-CoV-2) infection has recently emerged and rapidly spreading in humans causing a significant threat to international health and the economy. Rapid assessment and warning are crucial for an outbreak analysis in response to serious public health. SARS-CoV-2 shares highly homological sequences with SARS-CoVs causing highly lethal pneumonia with respiratory distress and clinical symptoms similar to those reported for SARS-CoV and MERS-CoV infections. Notably, some COVID-19 patients also expressed neurologic signs like nausea, headache, and vomiting. Several studies have reported that coronaviruses are not only causing respiratory illness but also invade the central nervous system through a synapse-connected route. SARS-CoV infections are reported in both patients and experimental animals' brains. Interestingly, some COVID-19 patients have shown the presence of SARS-CoV-2 virus in their cerebrospinal fluid. Considering the similarities between SARS-CoV and SARS-CoV-2 in various aspects, it remains to clarify whether the potent invasion of SARS-CoV-2 may affect in COVID-19 patients. All these indicate that more detailed criteria are needed for the treatment and the prevention of SARS-CoV-2 infected patients. In the absence of potential interventions for COVID-19, there is an urgent need for an alternative strategy to control the spread of this disease.