The COVID-19 pandemic-led worldwide healthcare crisis necessitates prompt societal, ecological, and medical efforts to stop or reduce the rising number of fatalities. Numerous mRNA based vaccines and vaccines for viral vectors have been licensed for use in emergencies which showed 90% to 95% efficacy in preventing SARS-CoV-2 infection. However, safety issues, vaccine reluctance, and skepticism remain major concerns for making mass vaccination a successful approach to treat COVID-19. Hence, alternative therapeutics is needed for eradicating the global burden of COVID-19 from developed and low-resource countries. Repurposing current medications and drug candidates could be a more viable option for treating SARS-CoV-2 as these therapies have previously passed a number of significant checkpoints for drug development and patient care. Besides vaccines, this review focused on the potential usage of alternative therapeutic agents including antiviral, antiparasitic, and antibacterial drugs, protease inhibitors, neuraminidase inhibitors, and monoclonal antibodies that are currently undergoing preclinical and clinical investigations to assess their effectiveness and safety in the treatment of COVID-19. Among the repurposed drugs, remdesivir is considered as the most promising agent, while favipiravir, molnupiravir, paxlovid, and lopinavir/ritonavir exhibited improved therapeutic effects in terms of elimination of viruses. However, the outcomes of treatment with oseltamivir, umifenovir, disulfiram, teicoplanin, and ivermectin were not significant. It is noteworthy that combining multiple drugs as therapy showcases impressive effectiveness in managing individuals with COVID-19. Tocilizumab is presently employed for the treatment of patients who exhibit COVID-19-related pneumonia. Numerous antiviral drugs such as galidesivir, griffithsin, and thapsigargin are under clinical trials which could be promising for treating COVID-19 individuals with severe symptoms. Supportive treatment for patients of COVID-19 may involve the use of corticosteroids, convalescent plasma, stem cells, pooled antibodies, vitamins, and natural substances. This study provides an updated progress in SARS-CoV-2 medications and a crucial guide for inventing novel interventions against COVID-19.

Background: Sample size estimation is an essential step in the design of randomized controlled trials (RCTs) evaluating a treatment effect. Sample size is a critical variable in determining statistical significance and, thus, it significantly influences RCTs\' success or failure. During the COVID-19 pandemic, many RCTs tested the efficacy of COVID-19 convalescent plasma (CCP) in hospitalized patients but reported different efficacies, which could be attributed to, in addition to timing and dose, inadequate sample size estimates. Methods: To assess the sample size estimation in RCTs evaluating the effect of treatment with CCP in hospitalized COVID-19 patients, we searched the medical literature between January 2020 and March 2024 through PubMed and other electronic databases, extracting information on expected size effect, statistical power, significance level, and measured efficacy. Results: A total of 32 RCTs were identified. While power and significance level were highly consistent, heterogeneity in the expected size effect was relevant. Approximately one third of the RCTs did not reach the planned sample size for various reasons, with the most important one being slow patient recruitment during the pandemic\'s peaks. RCTs with a primary outcome in favor of CCP treatment had a significant lower median absolute difference in the expected size effect than unfavorable RCTs (20.0% versus 33.9%, P = 0.04). Conclusions: The analyses of sample sizes in RCTs of CCP treatment in hospitalized COVID-19 patients reveal that many underestimated the number of participants needed because of excessively high expectations on efficacy, and thus, these studies had low statistical power. This, in combination with a lower-than-planned recruitment of cases and controls, could have further negatively influenced the primary outcomes of the RCTs.

UNASSIGNED: The COVID-19 pandemic has revealed the importance of organizational resilience, the ability to effectively respond to a disruptive event before, during, and after it occurs. Team improvisation is an important component of organizational resilience as it describes characteristics of team skills and contextual qualities to create order from chaos. In Spring 2020, the Dutch national blood bank, began the convalescent plasma project (CCP). We aimed to study which elements of team improvisation in the CCP group were found and how lessons learned can contribute towards a non-crisis situation for blood establishments.
UNASSIGNED: Using Vera and Crossan\'s framework of improvisation, semi-structured interviews with eight members of the CCP group were conducted. This was simultaneous to performing a document analysis of 21 Intranet posts and seven internal reports. MAXDA 2020 was used to conduct deductive and inductive thematic analyses.
UNASSIGNED: The CCP group showed strong characteristics of expertise and memory, teamwork quality, experimental culture, and real-time information and communication that enabled them to improvise in all aspects of the donation process. Improvisation examples included comprehensive communication methods to identify and obtain new donors, asking additional intake questions and collecting additional aliquots to store while waiting for an internal antibody test to be developed, and regulatory respondents allowing a flexible change control procedure to meet the pace of the crisis. Training was evident to a lesser degree.
UNASSIGNED: While improvisation impacted set routines and procedures, the safety and quality of the product were not affected. Regarding organizational resilience, our results showed that the CCP group \"coped\" well using elements of team improvisation. Blood establishments may consider introducing improvisational training and innovation teams throughout the organization for future preparedness and improving organizational resilience.

UNASSIGNED: Convalescent plasma therapy (CPT) may reduce the risk of disease progression among patients with COVID-19. This study was undertaken to evaluate the efficacy and safety of CPT in preventing ICU admission among hospitalized COVID-19 patients.
UNASSIGNED: In this open-label randomized controlled trial, we randomly assigned hospitalized adult patients with COVID-19 in a 1:1 ratio to receive convalescent plasma as an adjunct to standard of care or standard of care alone. The primary endpoint was ICU admission within first 28 days of enrolment. Primary safety endpoints include rapid deterioration of respiratory or clinical status within four hours of convalescent plasma transfusion and cumulative incidence of serious adverse events during the study period including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), severe allergic reactions, and transfusion-related infections.
UNASSIGNED: A total of 22 patients were assigned to receive convalescent plasma as an adjunct to standard of care and 22 to receive standard of care alone. The median time from onset of COVID-19 symptoms to study enrolment was eight days (IQR, 4 to 10). Two patients (9.1%) in the CPT group and one patient (4.5%) in the control group were admitted to the ICU. The primary outcome measure, ICU admission, was not different between the two groups (q-value >0.9). No patient who received convalescent plasma had rapid deterioration of respiratory/clinical status within four hours of transfusion and none developed TRALI, TACO, anaphylaxis, severe allergic reactions, or transfusion-related infections. There was also no significant difference in the secondary outcomes of 28-day mortality (two patients in the CPT group and none in the control group, q-value >0.90), dialysis-free days, vasopressor-free days, and ICU-free days.
UNASSIGNED: Among hospitalized COVID-19 patients, no significant differences were observed in the need for ICU admission between patients given CPT as adjunct to standard of care and those who received standard of care alone. Interpretation is limited by early termination of the trial which may have been underpowered to detect a clinically important difference.

BACKGROUND: There is a need to understand the relationship between COVID-19 Convalescent Plasma (CCP) anti-SARS-CoV-2 IgG levels and clinical outcomes to optimize CCP use. This study aims to evaluate the relationship between recipient baseline clinical status, clinical outcomes, and CCP antibody levels.
METHODS: The study analyzed data from the COMPILE study, a meta-analysis of pooled individual patient data from 8 randomized clinical trials (RCTs) assessing the efficacy of CCP vs. control, in adults hospitalized for COVID-19 who were not receiving mechanical ventilation at randomization. SARS-CoV-2 IgG levels, referred to as \'dose\' of CCP treatment, were retrospectively measured in donor sera or the administered CCP, semi-quantitatively using the VITROS Anti-SARS-CoV-2 IgG chemiluminescent immunoassay (Ortho-Clinical Diagnostics) with a signal-to-cutoff ratio (S/Co). The association between CCP dose and outcomes was investigated, treating dose as either continuous or categorized (higher vs. lower vs. control), stratified by recipient oxygen supplementation status at presentation.
RESULTS: A total of 1714 participants were included in the study, 1138 control- and 576 CCP-treated patients for whom donor CCP anti-SARS-CoV2 antibody levels were available from the COMPILE study. For participants not receiving oxygen supplementation at baseline, higher-dose CCP (/control) was associated with a reduced risk of ventilation or death at day 14 (OR = 0.19, 95% CrI: [0.02, 1.70], posterior probability Pr(OR < 1) = 0.93) and day 28 mortality (OR = 0.27 [0.02, 2.53], Pr(OR < 1) = 0.87), compared to lower-dose CCP (/control) (ventilation or death at day 14 OR = 0.79 [0.07, 6.87], Pr(OR < 1) = 0.58; and day 28 mortality OR = 1.11 [0.10, 10.49], Pr(OR < 1) = 0.46), exhibiting a consistently positive CCP dose effect on clinical outcomes. For participants receiving oxygen at baseline, the dose-outcome relationship was less clear, although a potential benefit for day 28 mortality was observed with higher-dose CCP (/control) (OR = 0.66 [0.36, 1.13], Pr(OR < 1) = 0.93) compared to lower-dose CCP (/control) (OR = 1.14 [0.73, 1.78], Pr(OR < 1) = 0.28).
CONCLUSIONS: Higher-dose CCP is associated with its effectiveness in patients not initially receiving oxygen supplementation, however, further research is needed to understand the interplay between CCP anti-SARS-CoV-2 IgG levels and clinical outcome in COVID-19 patients initially receiving oxygen supplementation.

Understanding the antibody response to SARS-CoV-2, the virus responsible for COVID-19, is crucial to comprehending disease progression and the significance of vaccine and therapeutic development. The emergence of highly contagious variants poses a significant challenge to humoral immunity, underscoring the necessity of grasping the intricacies of specific antibodies. This review emphasizes the pivotal role of antibodies in shaping immune responses and their implications for diagnosing, preventing, and treating SARS-CoV-2 infection. It delves into the kinetics and characteristics of the antibody response to SARS-CoV-2 and explores current antibody-based diagnostics, discussing their strengths, clinical utility, and limitations. Furthermore, we underscore the therapeutic potential of SARS-CoV-2-specific antibodies, discussing various antibody-based therapies such as monoclonal antibodies, polyclonal antibodies, anti-cytokines, convalescent plasma, and hyperimmunoglobulin-based therapies. Moreover, we offer insights into antibody responses to SARS-CoV-2 vaccines, emphasizing the significance of neutralizing antibodies in order to confer immunity to SARS-CoV-2, along with emerging variants of concern (VOCs) and circulating Omicron subvariants. We also highlight challenges in the field, such as the risks of antibody-dependent enhancement (ADE) for SARS-CoV-2 antibodies, and shed light on the challenges associated with the original antigenic sin (OAS) effect and long COVID. Overall, this review intends to provide valuable insights, which are crucial to advancing sensitive diagnostic tools, identifying efficient antibody-based therapeutics, and developing effective vaccines to combat the evolving threat of SARS-CoV-2 variants on a global scale.

SUMMARYSince the emergence of COVID-19 in 2020, an unprecedented range of therapeutic options has been studied and deployed. Healthcare providers have multiple treatment approaches to choose from, but efficacy of those approaches often remains controversial or compromised by viral evolution. Uncertainties still persist regarding the best therapies for high-risk patients, and the drug pipeline is suffering fatigue and shortage of funding. In this article, we review the antiviral activity, mechanism of action, pharmacokinetics, and safety of COVID-19 antiviral therapies. Additionally, we summarize the evidence from randomized controlled trials on efficacy and safety of the various COVID-19 antivirals and discuss unmet needs which should be addressed.

OBJECTIVE: To analyze the seroprevalence of SARS-CoV-2 IgG antibodies and neutralizing antibodies in blood donors during the second wave of the pandemic and to explore the utility of COVID-19 seropositive plasma as convalescent plasma.
METHODS: In this study, 696 blood donors were tested for anti-SARS-CoV-2 IgG antibodies using a chemiluminescence assay. By blinding, 271 samples were chosen randomly for testing of neutralizing antibodies by enzyme-linked immunosorbent assay (ELISA) in duplicate among the 696 blood donors tested for anti-SARS-CoV-2 IgG antibodies, irrespective of the positivity or negativity of the result of the anti-SARS-CoV-2 IgG antibodies by chemiluminescence assay. IgG antibody levels were analyzed in signal-to-cutoff (S/Co), while neutralizing antibody levels were analyzed in percentage inhibition.
RESULTS: The seroprevalence of IgG antibodies based on the S/Co for the positive results ≥ 1.00 was 82.75%, while the seroprevalence of neutralizing antibodies based on the percentage inhibition for the positive results ≥ 30% was 89.59%. Frontline workers (FLWs) and Covishield-vaccinated individuals showed higher levels of the anti-SARS-CoV-2 IgG antibodies regarding higher S/Co. In comparison, levels of neutralization antibodies regarding percentage inhibition were higher only in FLWs. Covishield-vaccinated donors elicited a statistically higher seroprevalence of anti-SARS-CoV-2 IgG antibodies compared to the Covaxin-vaccinated, while the seroprevalence of neutralizing antibodies was not statistically different among this group. There was a positive correlation (0.762) between anti-SARS-CoV-2 IgG antibodies and neutralizing antibodies, and almost all donors\' of S/Co ≥ 9.5 had neutralizing antibodies.
CONCLUSIONS: This study showed higher seroprevalence in the blood donor population compared to published seroprevalence in India\'s second wave of the pandemic. In the current study, 328 donors (47.12%) of the 696 screened donors were neither vaccinated nor had previous SARS-CoV-2 infection, but many had antibodies. The seroprevalence of neutralizing antibodies (96.42%) was higher than the seroprevalence of the anti-SARS-CoV-2 IgG antibodies (85.71%) in the donors who had previous infection of COVID-19. On the other hand, vaccinated donors showed similar immune responses for neutralizing antibodies and the anti-SARS-CoV-2 IgG antibodies. Higher IgG immune reactivity in S/Co showed a good correlation with neutralizing antibodies and can be used to screen whole blood donors for convalescent plasma donations.

Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS), and SARS-CoV-2 infection (causing coronavirus disease 2019 [COVID-19]) are serious diseases. To date, no effective post-exposure prophylaxis, prevention, or therapeutic agents are recommended as effective for these diseases. Convalescent plasma (CP), donated by individuals with established humoral immunity to the virus after recovering from coronavirus infection, has been successfully applied to treat several infectious diseases, including SARS, MERS, and COVID-19. Nonetheless, there are obstacles and challenges to using CP that should be taken into account. In this review, we summarize the evidence derived from clinical attempts to treat COVID-19 with CP, which represents a promising therapy for severe coronavirus infection. Furthermore, we outline the remaining challenges and general issues that should be considered when using CP treatment for therapeutic or prophylactic purposes.

Since the first case of COVID-19 was detected in Wuhan, China in December 2019, COVID-19 has become a pandemic causing a global economic and public health emergency. There is no known treatment or vaccine available for COVID-19 during the initial period of the outbreak. Immunotherapy and plasma therapy has been used with satisfactory efficacy over the past two decades in many viral infections like SARS (Systemic Acute Respiratory Syndrome), MERS (Middle East Respiratory Syndrome) and H1N1. Limited data from China show clinical benefit, radiological resolution, reduction in viral loads and improved survival. We aim to create a mathematical model for COVID-19 transmission and then apply various control parameters to see their effects on recovery from COVID-19 disease. We have formulated a system of non-linear ordinary differential equations, calculated basic reproduction R0 and applied five different controls (self-isolation, quarantine, herd immunity, immunotherapy, plasma therapy) to test the effectiveness of plasma therapy. Control optimality was checked by Lagrangian functions. Numerical simulations and bifurcation analysis were carried out. The study concludes that the COVID-19 outbreak can be controlled up to a significant level in three weeks after applying all the control strategies together. These strategies lead to reduction in hospitalization and a rise in recovery from infection. Immunotherapy is highly effective initially in hospitalized infected individuals however better results were seen in the long term with plasma therapy.