SARS-CoV-2 infection in patients with multiple myeloma: survey in 23 centers across Europe and USA

Introduction: Despite several studies, the impact of coronavirus disease 2019 on patients with multiple myeloma remains uncertain. Material(s) and Method(s): We performed a survey that covered the period of the first and second waves of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 23 centers inseven countries. Out of 352 patients with myeloma and SARS-CoV-2, 23% died. Results/Conclusions: Logistic regression showed a lower risk of death among patients treated with proteasome inhibitor and a higher risk of death for those who had a severe or a very severe course of disease.Copyright © 2023 Sciendo. All rights reserved.

Diminished Neutralization Capacity of SARS-CoV-2 Omicron BA.1 in Donor Plasma Collected from January to March 2021.

The 50% plaque reduction neutralization assay (PRNT50) has been previously used to assess the neutralization capacity of donor plasma against wild-type and variant of concern (VOC) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging data suggest that plasma with an anti-SARS-CoV-2 level of ≥2 × 104 binding antibody units/mL (BAU/mL) protects against SARS-CoV-2 Omicron BA.1 infection. Specimens were collected using a cross-sectional random sampling approach. For PRNT50 studies, 63 previously analyzed specimens by PRNT50 versus SARS-CoV-2 wild-type, Alpha, Beta, Gamma, and Delta were analyzed by PRNT50 versus Omicron BA.1. The 63 specimens plus 4,390 specimens (randomly sampled regardless of serological evidence of infection) were also tested using the Abbott SARS-CoV-2 IgG II Quant assay (anti-spike [S]; Abbott, Chicago, IL, USA; Abbott Quant assay). In the vaccinated group, the percentages of specimens with any measurable PRNT50 versus wild-type or VOC were wild type (21/25 [84%]), Alpha (19/25 [76%]), Beta (18/25 [72%]), Gamma (13/25 [52%]), Delta (19/25 [76%]), and Omicron BA.1 (9/25 [36%]). In the unvaccinated group, the percentages of specimens with any measurable PRNT50 versus wild type or VOC were wild-type SARS-CoV-2 (16/39 [41%]), Alpha (16/39 [41%]), Beta (10/39 [26%]), Gamma (9/39 [23%]), Delta (16/39 [41%]), and Omicron BA.1 (0/39) (Fisher's exact tests, vaccinated versus unvaccinated for each variant, P < 0.05). None of the 4,453 specimens tested by the Abbott Quant assay had a binding capacity of ≥2 × 104 BAU/mL. Vaccinated donors were more likely than unvaccinated donors to neutralize Omicron when assessed by a PRNT50 assay. IMPORTANCE SARS-CoV-2 Omicron emergence occurred in Canada during the period from November 2021 to January 2022. This study assessed the ability of donor plasma collected earlier (January to March 2021) to generate any neutralizing capacity against Omicron BA.1 SARS-CoV-2. Vaccinated individuals, regardless of infection status, were more likely to neutralize Omicron BA.1 than unvaccinated individuals. This study then used a semiquantitative binding antibody assay to screen a larger number of specimens (4,453) for individual specimens that might have high-titer neutralizing capacity against Omicron BA.1. None of the 4,453 specimens tested by the semiquantitative SARS-CoV-2 assay had a binding capacity suggestive of a high-titer neutralizing capacity against Omicron BA.1. These data do not imply that Canadians lacked immunity to Omicron BA.1 during the study period. Immunity to SARS-CoV-2 is complex, and there is still no wide consensus on correlation of protection to SARS-CoV-2.

The therapeutics, based on virus specific antibodies, for special prophylactic and current of COVID-19

The analyses of effectiveness of medical means of protection based on virus specific antibodies, intended for special prophylactic and current of COVID-19 is conducted. The plasma of patients, obtained from the blood takes the leading part among these prepares. It is concluded, that convalescents plasma, containing virus neutralizing antibodies, may be used for emergency prevention or in the early stages of the disease. A risk group, that primarily needs in such drugs for special prophylactics, is medical workers. The other prepares, based on virus specific antibodies, including purified prepares of monoclonal antibodies, that may have certain advantages to convalescent's plasma due to their safety and high activity, due to complexity of their production and presumably high cost are unlikely to be available in the near future for mass use in the practice of medicine. The use of convalescents plasma for the prevention and treatment of COVID-19.can be based on the experience of their application in specialized medical centers and summarizing data from randomized clinical trials.Copyright © 2021 Moscow State University of Psychology and Education. All right reserved.

Convalescent plasma therapy for managing infectious diseases: A narrative review

The coronavirus disease 2019 (COVID-19) pandemic in 2020 is one of the worst catastrophic events in human history. A number of therapeutic modalities have been utilized in order to fight the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although the majority of them failed to demonstrate a beneficial clinical effect. Among the anti-COVID-19 agents being investigated, the convalescent plasma collected from recovered donors has gained a growing interest. Convalescent plasma has been employed for over a hundred years to treat severe acute viral infections when a vaccine or a specific antiviral treatment was not yet available. In this narrative review, we summarize the literature data on the use of convalescent plasma during previous viral outbreaks and pandemics, including influenza viruses, coronaviruses other than SARS-CoV-2 and Ebola virus. A literature search, using the Medline and PubMed electronic database, was performed to retrieve publications on the use of convalescent plasma in previous viral epidemics. In conclusion, the available literature data suggest the safety profile of convalescent plasma and its potential benefit in treating emerging viral infectious diseases. In addition, these data retrieved from previous viral epidemics provide a solid rationale for the employment of plasma from convalescent donors also in COVID-19 patients.Copyright © 2021 AME Publishing Company. All rights reserved.

Cirrhosis and COVID-19: Diffuse venous thrombosis and its clinical implication

A 60-year-old woman with Hepatitis C infection, cirrhosis, recurrent hepatic hydrothorax, and hepatocellular carcinoma was hospitalized with Coronavirus disease-2019 (COVID-19). After her initial discharge, she was re-admitted three weeks later with decompensated liver disease. Imaging revealed extensive thrombosis in the portal vein, superior mesenteric vein, splenic vein and bilateral brachial veins. Given the acute onset and extent of the thrombosis, the patient received therapeutic anticoagulation despite elevated prothrombin time/ international normalized ratio, thrombocytopenia and low fibrinogen. Cirrhotic patients with COVID-19 maybe at high risk of thrombosis, which can present with significant hepatic decompensation.Copyright © 2022 The Author(s)

Dynamics of SARS-CoV-2 Antibody Responses up to 9 Months Post-Vaccination in Individuals with Previous SARS-CoV-2 Infection Receiving Inactivated Vaccines.

Humoral immunity confers protection against COVID-19. The longevity of antibody responses after receiving an inactivated vaccine in individuals with previous SARS-CoV-2 infection is unclear. Plasma samples were collected from 58 individuals with previous SARS-CoV-2 infection and 25 healthy donors (HDs) who had been vaccinated with an inactivated vaccine. The neutralizing antibodies (NAbs) and S1 domain-specific antibodies against the SARS-CoV-2 wild-type and Omicron strains and nucleoside protein (NP)-specific antibodies were measured using a chemiluminescent immunoassay. Statistical analysis was performed using clinical variables and antibodies at different timepoints after SARS-CoV-2 vaccination. NAbs targeting the wild-type or Omicron strain were detected in individuals with previous SARS-CoV-2 infection at 12 months after infection (wild-type: 81%, geometric mean (GM): 20.3 AU/mL; Omicron: 44%, GM: 9.4 AU/mL), and vaccination provided further enhancement of these antibody levels (wild-type: 98%, GM: 53.3 AU/mL; Omicron: 75%, GM: 27.8 AU/mL, at 3 months after vaccination), which were significantly higher than those in HDs receiving a third dose of inactivated vaccine (wild-type: 85%, GM: 33.6 AU/mL; Omicron: 45%, GM: 11.5 AU/mL). The level of NAbs in individuals with previous infection plateaued 6 months after vaccination, but the NAb levels in HDs declined continuously. NAb levels in individuals with previous infection at 3 months post-vaccination were strongly correlated with those at 6 months post-vaccination, and weakly correlated with those before vaccination. NAb levels declined substantially in most individuals, and the rate of antibody decay was negatively correlated with the neutrophil-to-lymphocyte ratio in the blood at discharge. These results suggest that the inactivated vaccine induced robust and durable NAb responses in individuals with previous infection up to 9 months after vaccination.

Research progress on clinical application of convalescent plasma from COVID-19 patients.

COVID-19 is an acute respiratory infectious disease caused by 2019-nCoV, which has become a major global public health event and a serious threat to human health. So far, specific antiviral drugs, safe and effective vaccines for 2019-nCoV are still under development, so there is an urgent need to find alternative strategies for the treatment of COVID-19. Convalescent plasma(CP) contains high titer neutralizing antibodies from patients recovering from infectious diseases, which has been used in the treatment of major infectious diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and achieved satisfactory clinical results. Therefore, CP from COVID-19 patient is a meaningful choice for the treatment of severe or life-threatening COVID-19 patients, but its potential risks need to be studied. This review focuses on the clinical mechanism, collection points, clinical application and potential benefits and risks of clinical treatment of CP from COVID-19 patients, which will provide reference for the clinical application of CP from COVID-19 patients.Copyright © 2021 Chinese Medical Association

Major Drugs Used in COVID-19 Treatment: Molecular Mechanisms, Vali-dation and Current Progress in Trials

Background: Currently, the present world is facing a new deadly challenge from a pandemic disease called COVID-19, which is caused by a coronavirus named SARS-CoV-2. To date, no drug or vaccine can treat COVID-19 completely, but some drugs have been used primarily, and they are in different stages of clinical trials. This review article discussed and compared those drugs which are running ahead in COVID-19 treatments. Method(s): We have explored PUBMED, SCOPUS, WEB OF SCIENCE, as well as press releases of WHO, NIH and FDA for articles related to COVID-19 and reviewed them. Result(s): Drugs like favipiravir, remdesivir, lopinavir/ritonavir, hydroxychloroquine, azithromycin, ivermectin, corticosteroids and interferons have been found effective to some extent, and partially approved by FDA and WHO to treat COVID-19 at different levels. However, some of these drugs have been disapproved later, although clinical trials are going on. In parallel, plasma therapy has been found fruitful to some extent too, and a number of vaccine trials are going on. Conclusion(s): This review article discussed the epidemiologic and mechanistic characteristics of SARS-CoV-2, and how drugs could act on this virus with the comparative discussion on progress and drawbacks of major drugs used till date, which might be beneficial for choosing therapies against COVID-19 in different countries.Copyright © 2022 Bentham Science Publishers.

Anti-SARS-CoV-2 antibody responses in convalescent plasma donors with varying clinical manifestation severity of COVID-19

Background/Aim. Plasma containing a high titer of anti-SARS-CoV-2 antibodies, donated from individuals who re-covered from COVID-19, has the potential to be used as initial therapy for patients who have been infected (passive immunization). It is a challenge to find suitable donors. The aim of the study was to successively monitor antibody titer in donations and to investigate the correlation between an-tibody titer and the severity of the clinical manifestations. Methods. The retrospective study was conducted from May 1 to October 31, 2020, at the Blood Transfusion Insti-tute of Vojvodina. Donors had to meet certain criteria for inclusion in the study: proven SARS-CoV-2 infection, de-tected SARS-CoV-2 antibodies in the serum/plasma, ful-fillment of general criteria for performing plasmapheresis, and adequate laboratory findings. Results. During the study, 651 apheresis plasma units were collected and divided into two equal doses. Plasma was donated by 311 COVID-19 convalescents, including 208 (66.9%) men and 103 (33.1%) women. There were 15 (4.8%) plasma donors with asymptomatic infection, 235 (75. 6%) with a mild form of illness, 45 (14.5%) with a moderate form of illness, 16 (5.1%) with a severe form of illness, and none with a critical form of illness. Anti-SARS-CoV-2 IgG antibodies were pre-sent in the plasma of donors for more than 6 months after the disease. Plasma donors with a more severe clinical mani-festation of COVID-19 had stable antibody levels for a longer period. However, the Pearson correlation of clinical severity and antibody titer did not confirm a statistically sig-nificant correlation between the variables. Conclusion. An-ti-SARS-CoV-2 antibodies were present in the sample of re-covered patients, plasma donors, for more than 6 months after the disease. Even though no statistically significant correlation was found between the anti-SARS-CoV-2 anti-body titer and the clinical severity of COVID-19, in patients with a more severe clinical manifestations of the disease, stable antibody levels were maintained for a longer period.Copyright © 2022 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Outcome of COVID-19 in children: results of a 12-month follow-up.

At present, there are isolated data on the clinical outcomes of COVID-19 in children, especially those who have experienced asymptomatic and mild forms of infection. Purpose(s): to analyze the nature and frequency of post-COVID symptoms in children during 12 months. after recovery. Materials and methods. The influence of demographic indicators, premorbid background, severity of infection and therapy in the acute period of the disease on the nature and frequency of symptoms in 1079 children who underwent laboratory-confirmed COVID-19 was studied. The results are presented with proportions (%) and calculation of 95% confidence interval according to Klopper-Pearson. Differences between groups were assessed using Pearson's chi-square test. Differences in the groups were considered statistically significant at p < 0,05. Results. Health disorders in the post-COVID period were observed in 8,5% of children, more often in schoolchildren aged 7-17 years (68.4%). Concomitant conditions were found in 38,0%. In most cases, the consequences were noted after a mild form of COVID-19 (77.2%), however, 13,0% of patients experienced an asymptomatic form of infection. Among convalescents, changes in the emotional sphere (2,1%), headache (1,8%), symptoms of asthenia (1,6%), cardiovascular (1,5%), dyspeptic (1,3%) were more often observed, cognitive (1,3%) disorders, neurotic disorders (1,0%), less often respiratory (0.8%), endocrine (0,4%) and visual (0,4%) systems, musculoskeletal system were involved (0.2%). Girls were significantly more likely to have vegetative disorders, while boys were significantly more likely to suffer from cognitive functions. Various antiviral therapy options (interferon-alpha, an oral antiviral drug, or a combination thereof) in the acute period of COVID-19 did not affect the possibility of post-COVID disorders, but there was a tendency to increase the frequency in children who did not receive etiotropic treatment (control group). In 14.1% of cases, post-COVID symptoms appeared late - after 5-10 months. after recovery. The course of rehabilitation therapy, including drug treatment and non-drug methods, made it possible to quickly restore the state of health of the observed children. Conclusion. In most cases, the violations were of a functional nature, due to a disorder of autonomic regulation. Rehabilitation and dispensary observation programs will allow timely restoration of the quality of life of children who have had COVID-19, including in a mild and asymptomatic form.Copyright © 2022 Authors. All rights reserved.

Coronavirus Disease 2019 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-Analysis of Individual Participant Data From 5 Randomized Trials.

BACKGROUND: Outpatient monoclonal antibodies are no longer effective and antiviral treatments for coronavirus disease 2019 (COVID-19) disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma (CCP) is promising, clinical trials among outpatients have shown mixed results. METHODS: We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching Medline, Embase, medRxiv, World Health Organization COVID-19 Research Database, Cochrane Library, and Web of Science from January 2020 to September 2022. RESULTS: Five included studies from 4 countries enrolled and transfused 2620 adult patients. Comorbidities were present in 1795 (69%). The virus neutralizing antibody dilutional titer levels ranged from 8 to 14 580 in diverse assays. One hundred sixty of 1315 (12.2%) control patients were hospitalized, versus 111 of 1305 (8.5%) CCP-treated patients, yielding a 3.7% (95% confidence interval [CI], 1.3%-6.0%; P = .001) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titer with a 7.6% absolute risk reduction (95% CI, 4.0%-11.1%; P = .0001) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment >5 days after symptom onset or in those receiving CCP with antibody titers below the median titer. CONCLUSIONS: Among outpatients with COVID-19, treatment with CCP reduced the rate of all-cause hospitalization and may be most effective when given within 5 days of symptom onset and when antibody titer is higher.

Effectiveness of COVID-19 Convalescent Plasma (CCP) During the Pandemic Era: A Literature Review.

Worldwide pandemic with coronavirus disease-2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As November 2, 2022, World Health Organization (WHO) received 628,035,553 reported incidents on COVID-19, with 6,572,800 mortalities and, with a total 12,850,970,971 vaccine doses have been delivered as of October 31, 2022. The infection can cause mild or self-limiting symptoms of pulmonary and severe infections or death may be caused by SARS-CoV-2 infection. Simultaneously, antivirals, corticosteroids, immunological treatments, antibiotics, and anticoagulants have been proposed as potential medicines to cure COVID-19 affected patients. Among these initial treatments, COVID-19 convalescent plasma (CCP), which was retrieved from COVID-19 recovered patients to be used as passive immune therapy, in which antibodies from cured patients were given to infected patients to prevent illness. Such treatment has yielded the best results in earlier with preventative or early stages of illness. Convalescent plasma (CP) is the first treatment available when infectious disease initially appears, although few randomized controlled trials (RCTs) were conducted to evaluate its effectiveness. The historical record suggests with potential benefit for other respiratory infections, as coronaviruses like Severe Acute Respiratory Syndrome-CoV-I (SARS-CoV-I) and Middle Eastern Respiratory Syndrome (MERS), though the analysis of such research is constrained by some non-randomized experiments (NREs). Rigorous studies on CP are made more demanding by the following with the immediacy of the epidemics, CP use may restrict the ability to utilize it for clinical testing, non-homogenous nature of product, highly decentralized manufacturing process; constraints with capacity to measure biologic function, ultimate availability of substitute therapies, as antivirals, purified immune globulins, or monoclonal antibodies. Though, it is still not clear how effectively CCP works among hospitalized COVID-19 patients. The current review tries to focus on its efficiency and usage in clinical scenarios and identifying existing benefits of implementation during pandemic or how it may assist with future pandemic preventions.

Demographics of first-time donors returning for donation during the pandemic: COVID-19 convalescent plasma versus standard blood product donors.

BACKGROUND: Previous studies have demonstrated low first-time donor return rates (DRR) following catastrophic events. Little is known, however, about the influence of demographic factors on the DRR of first-time donors during the COVID-19 pandemic, including the unique motivation of COVID-19 convalescent plasma (CCP) donors as compared to non-CCP donors. STUDY DESIGN AND METHODS: Thirteen blood collection organizations submitted deidentified data from first-time CCP and non-CCP donors returning for regular (non-CCP) donations during the pandemic. DRR was calculated as frequencies. Demographic factors associated with returning donors: race/ethnicity, gender, and generation (Gen Z: 19-24, Millennial: 25-40, Gen X: 41-56, and Boomer: ≥57 years old), within the CCP and non-CCP first-time cohorts were compared using chi-square test at p < .05 statistical significance. RESULTS: From March 2020 through December 2021, there were a total of 44,274 first-time CCP and 980,201 first-time non-CCP donors. DRR were 14.6% (range 11.9%-43.3%) and 46.6% (range 10.0%-76.9%) for CCP and non-CCP cohorts, respectively. Age over 40 years (Gen X and Boomers), female gender, and White race were each associated with higher return in both donor cohorts (p < .001). For the non-CCP return donor cohort, the Millennial and Boomers were comparable. CONCLUSION: The findings demonstrate differences in returning donor trends between the two donor cohorts. The motivation of a first-time CCP donor may be different than that of a non-CCP donor. Further study to improve first-time donor engagement would be worthwhile to expand the donor base with a focus on blood donor diversity emphasizing engagement of underrepresented minorities and younger donors.

High-titer post-vaccine COVID-19 convalescent plasma for immunocompromised patients during the first omicron surge.

BACKGROUND: Transplant and hematologic malignancy patients have high Coronavirus disease 2019 (COVID-19) mortality and impaired vaccination responses. Omicron variant evades several monoclonal antibodies previously used in immunocompromised patients. Polyclonal COVID-19 convalescent plasma (CCP) may provide broader neutralizing capacity against new variants at high titers. Vaccination increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titer in convalescent donors. METHODS: We conducted a retrospective chart review of hospitalized immunocompromised patients with COVID-19 who received high-titer CCP during the first omicron surge, collected from vaccinated donors within 6 months of pre-omicron COVID-19. Data on safety and outcomes were extracted. RESULTS: A total of 44 immunocompromised patients were included, 59.1% with solid organ transplant, 22.7% with hematopoietic cell transplant, 11.4% with hematologic malignancy, and 6.8% with autoimmune disease. Overall, 95% of CCP units transfused were from recently recovered and vaccinated donors and had SARS-CoV-2 antibody results 8- to 37-fold higher than the Food and Drug Administration's cutoff for high-titer CCP. There were two mild transfusion reactions. A total of 30-day mortality was 4.5%. There were no differences in 100-day mortality by underlying diagnosis, levels of immunosuppression, and timing of CCP administration. Patients with higher immunosuppression had significantly higher mean World Health Organization clinical progression scores at 30-day post-CCP compared to those with lower immunosuppression. CONCLUSIONS: CCP is a safe, globally available treatment for immunocompromised patients with COVID-19. Mortality was lower in our cohort than that of COVID-19 patients with similar immunocompromising conditions. Post-vaccine CCP with very high titers should be prioritized for study in immunocompromised patients. Post-vaccine CCP has the potential to keep pace with new variants by overcoming mutations at sufficiently high titer.

Simple prediction of COVID-19 convalescent plasma units with high levels of neutralization antibodies.

BACKGROUND: Hyperimmune convalescent COVID-19 plasma (CCP) containing anti-SARS-CoV-2 neutralizing antibodies (NAbs) was proposed as a therapeutic option for patients early in the new coronavirus disease pandemic. The efficacy of this therapy depends on the quantity of neutralizing antibodies (NAbs) in the CCP units, with titers ≥ 1:160 being recommended. The standard neutralizing tests (NTs) used for determining appropriate CCP donors are technically demanding and expensive and take several days. We explored whether they could be replaced by high-throughput serology tests and a set of available clinical data. METHODS: Our study included 1302 CCP donors after PCR-confirmed COVID-19 infection. To predict donors with high NAb titers, we built four (4) multiple logistic regression models evaluating the relationships of demographic data, COVID-19 symptoms, results of various serological testing, the period between disease and donation, and COVID-19 vaccination status. RESULTS: The analysis of the four models showed that the chemiluminescent microparticle assay (CMIA) for the quantitative determination of IgG Abs to the RBD of the S1 subunit of the SARS-CoV-2 spike protein was enough to predict the CCP units with a high NAb titer. CCP donors with respective results > 850 BAU/ml SARS-CoV-2 IgG had a high probability of attaining sufficient NAb titers. Including additional variables such as donor demographics, clinical symptoms, or time of donation into a particular predictive model did not significantly increase its sensitivity and specificity. CONCLUSION: A simple quantitative serological determination of anti-SARS-CoV-2 antibodies alone is satisfactory for recruiting CCP donors with high titer NAbs.

Multi-institutional experience with COVID-19 convalescent plasma in children.

BACKGROUND AND OBJECTIVES: Convalescent COVID-19 plasma (CCP) was developed and used worldwide as a treatment option by supplying passive immunity. Adult studies suggest administering high-titer CCP early in the disease course of patients who are expected to be antibody-negative; however, pediatric experience is limited. We created a multi-institutional registry to characterize pediatric patients (<18 years) who received CCP and to assess the safety of this intervention. METHODS: A REDCap survey was distributed. The registry collected de-identified data including demographic information (age, gender, and underlying conditions), COVID-19 disease features and concurrent treatments, CCP transfusion and safety events, and therapy response. RESULTS: Ninety-five children received CCP: 90 inpatients and 5 outpatients, with a median age of 10.2 years (range 0-17.9). They were predominantly Latino/Hispanic and White. The most frequent underlying medical conditions were chronic respiratory disease, immunosuppression, obesity, and genetic syndromes. CCP was primarily given as a treatment (95%) rather than prophylaxis (5%). Median total plasma dose administered and transfusion rates were 5.0 ml/kg and 2.6 ml/kg/h, respectively. The transfusions were well-tolerated, with 3 in 115 transfusions reporting mild reactions. No serious adverse events were reported. Severity scores decreased significantly 7 days after CCP transfusion or at discharge. Eighty-five patients (94.4%) survived to hospital discharge. All five outpatients survived to 60 days. CONCLUSIONS: CCP was found to be safe and well-tolerated in children. CCP was frequently given concurrently with other COVID-19-directed treatments with improvement in clinical severity scores ≥7 days after CCP, but efficacy could not be evaluated in this study.

Omicron variants escape the persistent SARS-CoV-2-specific antibody response in 2-year COVID-19 convalescents regardless of vaccination.

With the ongoing COVID-19 pandemic and the emergence of various SARS-CoV-2 variants, a comprehensive evaluation of long-term efficacy of antibody response in convalescent individuals is urgently needed. Several longitudinal studies had reported the antibody dynamics after SARS-CoV-2 acute infection, but the follow-up was mostly limited to 1 year or 18 months at the maximum. In this study, we investigated the durability, potency, and susceptibility to immune evasion of SARS-CoV-2-specific antibody in COVID-19 convalescents for 2 years after discharge. These results showed the persistent antibody-dependent immunity could protect against the WT and Delta variant to some extent. However, the Omicron variants (BA.1, BA.2, and BA.4/5) largely escaped this preexisting immunity in recovered individuals. Furthermore, we revealed that inactivated vaccines (BBIBP-CorV, CoronaVac, or KCONVAC) could improve the plasma neutralization and help to maintain the broadly neutralizing antibodies at a certain level. Notably, with the time-dependent decline of antibody, 1-dose or 2-dose vaccination strategy seemed not to be enough to provide immune protection against the emerging variants. Overall, these results facilitated our understanding of SARS-CoV-2-induced antibody memory, contributing to the development of immunization strategy against SARS-CoV-2 variants for such a large number of COVID-19 survivors.

Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents.

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

COVID-19 convalescent plasma therapy through the lens of the third year of the pandemic.

Serum obtained from recovered persons (convalescent serum) was the inaugural form of antimicrobial therapy for infectious diseases. Its efficacy required the administration of a sufficient amount of microbe-specific serum to mediate a biological effect early in the course of disease. Although serum therapy was discontinued when antibiotics were introduced early in the 20th century, the principles that governed its efficacy were prescient as they apply to the use of COVID-19 convalescent plasma (CCP) to treat COVID-19. Lessons learned from studies of CCP therapy for COVID-19 dating to the onset of the pandemic provide further proof of the principles of serum therapy. Analysis of these studies shows that like serum therapy, the efficacy of CCP in patients with COVID-19 depends on the administration of a high titer of SARSCoV-2 antibodies early in the course of disease.