Effectiveness of Convalescent Plasma Therapy in COVID-19 Patients with Hematological Malignancies: A Systematic Review.

Background: Immunocompromised patients, including those with hematological malignancies, are at a high risk of developing severe coronavirus disease 2019 (COVID-19) complications. Currently, there is a limited number of systematic reviews into the efficacy of convalescent plasma therapy (CPT) use in the treatment of COVID-19 patients with hematological malignancies. Therefore, the aim of this review was to systematically appraise the current evidence for the clinical benefits of this therapy in COVID-19 patients with hematological malignancies. Methods: A comprehensive search was conducted up to April 2022, using four databases: PubMed, Web of Science, Science Direct, and Scopus. Two reviewers independently assessed the quality of the included studies. Data collection analysis was performed using Microsoft Excel 365 and GraphPad Prism software. Results: 18 studies met the inclusion criteria; these records included 258 COVID-19 patients who had hematological malignancies and were treated with CPT. The main findings from the reviewed data suggest that CPT may be associated with improved clinical outcomes, including (a) higher survival rate, (b) improved SARS-CoV-2 clearance and presence of detectable anti-SARS-CoV-2 antibodies post CP transfusion, and (c) improved hospital discharge time and recovery after 1 month of CPT. Furthermore, treatment with convalescent plasma was not associated with the development of adverse events. Conclusions: CPT appears to be an effective supportive therapeutic option for hematological malignancy patients infected with COVID-19. To our knowledge, this is one of the first systematic reviews of the clinical benefits of CPT in COVID-19 patients with hematological malignancies.

Challenges in Laboratory Diagnosis of the Novel Coronavirus SARS-CoV-2.

The recent outbreak of the Coronavirus disease 2019 (COVID-19) has quickly spread worldwide since its discovery in Wuhan city, China in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, clinical treatment, and development of vaccines, is urgently needed to win the battle against COVID-19. The past three unprecedented outbreaks of emerging human coronavirus infections at the beginning of the 21st century have highlighted the importance of readily available, accurate, and rapid diagnostic technologies to contain emerging and re-emerging pandemics. Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) based assays performed on respiratory specimens remain the gold standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging with high sensitivity and specificity as well. Even though excellent techniques are available for the diagnosis of symptomatic patients with COVID-19 in well-equipped laboratories; critical gaps still remain in screening asymptomatic people who are in the incubation phase of the virus, as well as in the accurate determination of live viral shedding during convalescence to inform decisions for ending isolation. This review article aims to discuss the currently available laboratory methods and surveillance technologies available for the detection of COVID-19, their performance characteristics and highlight the gaps in current diagnostic capacity, and finally, propose potential solutions. We also summarize the specifications of the majority of the available commercial kits (PCR, EIA, and POC) for laboratory diagnosis of COVID-19.

COVID-19 Vaccine Platforms: Challenges and Safety Contemplations.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic as of March 2020, creating a global crisis and claiming millions of lives. To halt the pandemic and alleviate its impact on society, economy, and public health, the development of vaccines and antiviral agents against SARS-CoV-2 was a dire need. To date, various platforms have been utilized for SARS-CoV-2 vaccine development, and over 200 vaccine candidates have been produced, many of which have obtained the United States Food and Drug Administration (FDA) approval for emergency use. Despite this successful development and licensure, concerns regarding the safety and efficacy of these vaccines have arisen, given the unprecedented speed of vaccine development and the newly emerging SARS-CoV-2 strains and variants. In this review, we summarize the different platforms used for Coronavirus Disease 2019 (COVID-19) vaccine development, discuss their strengths and limitations, and highlight the major safety concerns and potential risks associated with each vaccine type.

COVID-19 Vaccination: The Mainspring of Challenges and the Seed of Remonstrance.

As of March 2020, the time when the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a pandemic, our existence has been threatened and the lives of millions have been claimed. With this ongoing global issue, vaccines are considered of paramount importance in curtailing the outbreak and probably a prime gamble to bring us back to 'ordinary life'. To date, more than 200 vaccine candidates have been produced, many of which were approved by the Food and Drug Administration (FDA) for emergency use, with the research and discovery phase of their production process passed over. Capering such a chief practice in COVID-19 vaccine development, and manufacturing vaccines at an unprecedented speed brought many challenges into play and raised COVID-19 vaccine remonstrance. In this review, we highlight relevant challenges to global COVID-19 vaccine development, dissemination, and deployment, particularly at the level of large-scale production and distribution. We also delineate public perception on COVID-19 vaccination and outline the main facets affecting people's willingness to get vaccinated.

Effect of multiple freeze-thaw cycles on the detection of anti-SARS-CoV-2 IgG antibodies.

Several studies have investigated the effect of repeated freeze-thaw (F/T) cycles on RNA detection for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, no data are available regarding the effect of repeated F/T cycles on SARS-CoV-2 antibody detection in serum. We investigated the effect of multiple F/T cycles on anti-SARS-CoV-2 IgG detection using an ELISA test targeting the nucleocapsid antibodies. Ten positive and 1 negative SARS-CoV-2 IgG sera from 11 participants, in replicates of 5, were subjected to a total of 16 F/T cycles and stored at 4 °C until tested by ELISA. Statistical analysis was performed to test for F/T cycle effect. None of the 10 positive sera became negative after 16 F/T cycles. There was no significant difference in the OD average reading between the first and last F/T cycles, except for one serum with a minimal decline in the OD. The random effect linear regression of log (OD) on the number of cycles showed no significant trend, with a slope consistent with zero (B=-0.0001; 95 % CI -0.0008; 0.0006; P-value=0.781). These results suggest that multiple F/T cycles had no effect on the ability of the ELISA assay to detect SARS-CoV-2 IgG antibodies.

Can commercial automated immunoassays be utilized to predict neutralizing antibodies after SARS-CoV-2 infection? A comparative study between three different assays.

Background: High-throughput assays that can infer neutralizing activity against SARS-CoV-2 are of great importance for assessing the immunity induced by natural infection and COVID-19 vaccines. We aimed to evaluate the performance and degree of correlation of three fully automated anti-SARS-CoV-2 immunoassays with neutralization activity using a surrogate virus-neutralizing test (sVNT) from GenScript, targeting the receptor-binding domain. Methods: 110 sera collected from PCR-confirmed asymptomatic COVID-19 individuals were tested for neutralizing antibodies (nAbs) using the sVNT. Positive samples were tested on three automated immunoassays targeting different viral antigens: Mindray CL-900i®, Abbott Architect, and Ortho VITROS®. The diagnostic sensitivity, specificity, agreement, and correlation with the sVNT were assessed. Receiver operating characteristic (ROC) curve analysis was performed to determine optimal thresholds for predicting the presence of neutralizing activity by each assay. Results: All three assays showed 100% specificities. The highest sensitivity was 99.0%, demonstrated by VITROS®, followed by 94.3%, for CL-900i®, and 81.0%, for Architect. Both VITROS® and CL-900i® had the strongest correlation with the sVNT (ρ = 0.718 and ρ = 0.712, respectively), while Architect showed a moderate correlation (ρ = 0.618). ROC curve analysis indicated that the manufacturer's recommended cutoff values are adequate for predicting the presence of nAbs and providing a strong correlation with the sVNT. Conclusion: VITROS® and CL-900i® serological assays, which detect antibodies against SARS-CoV-2 spike protein, could serve as reliable assays to predict neutralization activity after infection or vaccination.

Epidemiology of SARS-CoV2 in Qatar's primary care population aged 10 years and above.

BACKGROUND: There is an urgent need to elucidate the epidemiology of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and characterize its potential impact. Investing in characterising the SARS-CoV2 will help plan and improve the response to the pandemic. Furthermore, it will help identify the most efficient ways of managing the pandemic, avoiding public health policies and interventions that may be unduly restrictive of normal activity or unnecessarily costly. This paper describes the design and reports findings of a population based epidemiological study undertaken to characterise SARS-CoV2 in Qatar using limited resources in a timely manner. METHODS: Asymptomatic individuals ≥10 years registered with Qatar's publicly funded primary health provider were eligible. A stratified random sampling technique was utilized to identify the study sample. Participants were invited to an appointment where they completed a questionnaire and provided samples for polymerase chain reaction and Immunoglobulin M and G immunoassay tests. Data collected were analyzed to calculate point and period prevalence by sociodemographic, lifestyle and clinical characteristics. RESULTS: Of 18,918 individuals invited for the study, 2084 participated (response rate 10.8%). The overall point prevalence and period prevalence were estimated to be 1.6% (95% CI 1.1-2.2) and 14.6% (95% CI 13.1-16.2) respectively. Period prevalence of SARS-CoV2 infection was not considerably different across age groups (9.7-19.8%). It was higher in males compared to females (16.2 and 12.7% respectively). A significant variation was observed by nationality (7.1 to 22.2%) and municipalities (6.9-35.3%). CONCLUSIONS: The study provides an example of a methodologically robust approach that can be undertaken in a timely manner with limited resources. It reports much-needed epidemiological data about the spread of SARS-CoV2. Given the low prevalence rates, majority of the population in Qatar remains susceptible. Enhanced surveillance must continue to be in place, particularly due to the large number of asymptomatic cases observed. Robust contact tracing and social distancing measures are key to prevent future outbreaks.

Analytic comparison between three high-throughput commercial SARS-CoV-2 antibody assays reveals minor discrepancies in a high-incidence population.

Performance of three automated commercial serological IgG-based assays was investigated for assessing SARS-CoV-2 "ever" (past or current) infection in a population-based sample in a high exposure setting. PCR and serological testing was performed on 394 individuals. SARS-CoV-2-IgG seroprevalence was 42.9% (95% CI 38.1-47.8%), 40.6% (95% CI 35.9-45.5%), and 42.4% (95% CI 37.6-47.3%) using the CL-900i, VidasIII, and Elecsys assays, respectively. Between the three assays, overall, positive, and negative percent agreements ranged between 93.2-95.7%, 89.3-92.8%, and 93.8-97.8%, respectively; Cohen's kappa statistic ranged from 0.86 to 0.91; and 35 specimens (8.9%) showed discordant results. Among all individuals, 12.5% (95% CI 9.6-16.1%) had current infection, as assessed by PCR. Of these, only 34.7% (95% CI 22.9-48.7%) were seropositive by at least one assay. A total of 216 individuals (54.8%; 95% CI 49.9-59.7%) had evidence of ever infection using antibody testing and/or PCR during or prior to this study. Of these, only 78.2%, 74.1%, and 77.3% were seropositive in the CL-900i, VidasIII, and Elecsys assays, respectively. All three assays had comparable performance and excellent agreement, but missed at least 20% of individuals with past or current infection. Commercial antibody assays can substantially underestimate ever infection, more so when infection rates are high.

Evaluation of Antibody Response in Symptomatic and Asymptomatic COVID-19 Patients and Diagnostic Assessment of New IgM/IgG ELISA Kits.

This study aims to study the immune response and evaluate the performances of four new IgM and five IgG enzyme-linked immunosorbent assay (ELISA) kits for detecting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies against different antigens in symptomatic and asymptomatic coronavirus disease 2019 (COVID-19) patients. A total of 291 samples collected from symptomatic and asymptomatic RT-PCR-confirmed patients were used to evaluate the ELISA kits' performance (EDI, AnshLabs, DiaPro, NovaLisa, and Lionex). The sensitivity was measured at three different time-intervals post symptoms onset or positive SARS-CoV-2 RT-PCR test (≤14, 14-30, >30 days). The specificity was investigated using 119 pre-pandemic serum samples. The sensitivity of all IgM kits gradually decreased with time, ranging from 48.7% (EDI)-66.4% (Lionex) at ≤14 days, 29.1% (NovaLisa)-61.8% (Lionex) at 14-30 days, and 6.0% (AnshLabs)-47.9% (Lionex) at >30 days. The sensitivity of IgG kits increased with time, peaking in the latest interval (>30 days) at 96.6% (Lionex). Specificity of IgM ranged from 88.2% (Lionex)-99.2% (EDI), while IgG ranged from 75.6% (DiaPro)-98.3% (Lionex). Among all RT-PCR-positive patients, 23 samples (7.9%) were seronegative by all IgG kits, of which only seven samples (30.4%) had detectable IgM antibodies. IgM assays have variable and low sensitivity, thus considered a poor marker for COVID-19 diagnosis. IgG assays can miss at least 8% of RT-PCR-positive cases.

Diagnostic Efficiency of Three Fully Automated Serology Assays and Their Correlation with a Novel Surrogate Virus Neutralization Test in Symptomatic and Asymptomatic SARS-COV-2 Individuals.

To support the deployment of serology assays for population screening during the COVID-19 pandemic, we compared the performance of three fully automated SARS-CoV-2 IgG assays: Mindray CL-900i® (target: spike [S] and nucleocapsid [N]), BioMérieux VIDAS®3 (target: receptor-binding domain [RBD]) and Diasorin LIAISON®XL (target: S1 and S2 subunits). A total of 111 SARS-CoV-2 RT-PCR- positive samples collected at ≥ 21 days post symptom onset, and 127 pre-pandemic control samples were included. Diagnostic performance was assessed in correlation to RT-PCR and a surrogate virus-neutralizing test (sVNT). Moreover, cross-reactivity with other viral antibodies was investigated. Compared to RT-PCR, LIAISON®XL showed the highest overall specificity (100%), followed by VIDAS®3 (98.4%) and CL-900i® (95.3%). The highest sensitivity was demonstrated by CL-900i® (90.1%), followed by VIDAS®3 (88.3%) and LIAISON®XL (85.6%). The sensitivity of all assays was higher in symptomatic patients (91.1-98.2%) compared to asymptomatic patients (78.4-80.4%). In correlation to sVNT, all assays showed excellent sensitivities (92.2-96.1%). In addition, VIDAS®3 demonstrated the best correlation (r = 0.75) with the sVNT. The present study provides insights on the performance of three fully automated assays, which could help diagnostic laboratories in the choice of a particular assay according to the intended use.

Performance evaluation of five ELISA kits for detecting anti-SARS-COV-2 IgG antibodies.

OBJECTIVES: To evaluate and compare the performances of five commercial ELISA assays (EDI, AnshLabs, Dia.Pro, NovaTec, and Lionex) for detecting anti-SARS-CoV-2 IgG. METHODS: Seventy negative control samples (collected before the COVID-19 pandemic) and samples from 101 RT-PCR-confirmed SARS-CoV-2 patients (collected at different time points from symptom onset: ≤7, 8-14 and >14 days) were used to compare the sensitivity, specificity, agreement, and positive and negative predictive values of each assay with RT-PCR. A concordance assessment between the five assays was also conducted. Cross-reactivity with other HCoV, non-HCoV respiratory viruses, non-respiratory viruses, and nuclear antigens was investigated. RESULTS: Lionex showed the highest specificity (98.6%; 95% CI 92.3-99.8), followed by EDI and Dia.Pro (97.1%; 95% CI 90.2-99.2), NovaTec (85.7%; 95% CI 75.7-92.1), then AnshLabs (75.7%; 95% CI 64.5-84.2). All ELISA kits cross-reacted with one anti-MERS IgG-positive sample, except Lionex. The sensitivity was low during the early stages of the disease but improved over time. After 14 days from symptom onset, Lionex and NovaTec showed the highest sensitivity at 87.9% (95% CI 72.7-95.2) and 86.4% (95% CI 78.5-91.7), respectively. The agreement with RT-PCR results based on Cohen's kappa was as follows: Lionex (0.89) > NovaTec (0.70) > Dia.Pro (0.69) > AnshLabs (0.63) > EDI (0.55). CONCLUSION: The Lionex and NovaLisa IgG ELISA kits, demonstrated the best overall performance.