COVID 19: Prevention and treatment through the Indian perspective.

The most destructive period the world has experienced seems to be behind us. Not a single nation was spared by this disease, and many continue to struggle today. Even after recovering from COVID, patient may continue to experience some post-COVID effects, such as heart irregularities or a decline in lung vitality. In the past three years (2019-2022), the world has witnessed the power of a small entity, a single peculiar virus. Science initially appeared to be helpless in this regard, but due to the emergence of disease, pharmaceutics (the development of anti-covid drugs), immunology (the rapid antigen test), microbiology (the isolation of viruses from infected people), biotechnology (the development of recombinant vaccines), biochemistry (the blood profile, the D-dimer test), and biochemistry (blood profile, D-dimer test), biophysics (PCR, RT-PCR, CT Scan, MRI) had worked together to fight the disease. The results of these efforts are the development of new diagnostic techniques, possible treatment and finally the availability of vaccines against COVID-19. However, it is not proven that the treatment through the traditional medical system is directly active on SARS-CoV-2 but is instead indirectly acting on SARS-CoV-2 effects by improving symptoms derived from the viral disease. In India, the traditional system of medicine and tradition knowledge together worked in the pandemic and proved effective strategies in prevention and treatment of SARS-CoV-2. The use of effective masks, PPE kits, plasma therapy, yoga, lockdowns and social seclusion, use of modern antiviral drugs, monoclonal antibodies, herbal remedies, homoeopathy, hygienic practice, as well as the willpower of people, are all contributing to the fight against COVID. Which methods or practices will be effective against COVID nobody is aware since medical professionals who wear PPE kits do not live longer, and some people in India who remained unprotected and roamed freely were not susceptible to infection. The focus of this review is on the mode of transmission, diagnosis, preventive measures, vaccines currently under development, modern medicine developed against SARS-CoV-2, ayurvedic medicine used during pandemic, homoeopathic medicine used during pandemic, and specific yoga poses that can be used to lessen COVID-related symptoms.

Intracavernous injection of platelet-rich plasma reverses erectile dysfunction of chronic cavernous nerve degeneration through reduction of prostate hyperplasia evidence from an aging-induced erectile dysfunction rat model.

Age-induced erectile dysfunction (ED) is a convoluted medical condition, and restoring erectile function (EF) under geriatric conditions is highly complicated. Platelet-rich plasma (PRP) treatment is an inexpensive cell-based therapeutic strategy. We have aimed to restore EF in aged-ED rats with PRP as a therapeutic tool. Male rats were grouped into aged and young according to age. The young rats were considered as normal control (NC) and treated with saline. Aged were further divided into 2 groups and treated with intracavernous (IC) PRP and saline. Treatment was scheduled at the 9th and 10th week for NC and 41th and 42th week for aged-ED rats, with EF analysis scheduled on the 12th week for NC and 44th week for aged-ED rats, respectively. Erectile response, immunofluorescence staining, and electron microscopic analyses were performed. IC PRP treatment effectively reduced prostate hyperplasia (PH). EF response indicated a significant increase in crucial EF parameters in PRP-treated aged-ED rats. Histological evidence denoted a rigid and restored development of tunica adventitia of the dorsal artery, decreased vacuolation of the dorsal penile nerve, and structural expansion of the epineurium. Masson's trichrome and immunostaining results affirmed an elevated expression of α-smooth muscle actin (α-SMA) in the corpus cavernosum (CC). Ultrastructure findings revealed that PRP effectively rejuvenated degenerating nerves, preserved endothelium and adherent junctions of corporal smooth muscle, and restored the axonal scaffolds by upregulating neurofilament-H (NF-H) expression. Finally, PRP enhanced neural stability by enhancing the axonal remyelination processes in aged-ED rats. Hence, PRP treatment was proven to restore EF in aged-ED rats, which was considered a safe, novel, cost-effective, and hassle-free strategy for EF restoration in geriatric patients.

Recent developments on Junin virus, a causative agent for Argentine haemorrhagic fever.

Junin virus consists of ribonucleic acid as the genome and is responsible for a rapidly changing tendency of the virus. The virus is accountable for ailments in the human body and causes Argentine Haemorrhagic Fever (AHF). The infection is may be transmitted through contact between an infected animal/host and a person, and later between person to person. Prevention of outbreaks of AHF in humans can be a tough practice, as their occurrence is infrequent and unpredictable. In this review, recent information from the past 5 years available on the Junin virus including the risk of its emergence, infectious agents, its pathogenesis in humans, available diagnostic and therapeutic approaches, and disease management has been summarised. Altogether, this article would be highly significant in understanding the mechanistic basis behind virus interaction and other processes during the life cycle. Currently, no specific therapeutic options are available to treat the Junin virus infection. The information covered in this review could be important for finding possible treatment options for Junin virus infections.

Cold atmospheric plasma therapy as a novel treatment for Berlin Heart EXCOR pediatric cannula infections.

BACKGROUND: Cold atmospheric plasma (CAP) therapy has been recognized as effective treatment option for reducing bacterial load in chronic wounds, such as adult ventricular assist device (VAD) driveline exit-site infections. Currently, there have been no reports on the safety and efficacy of CAP therapy for pediatric cannula infections and inflammations in paracorporeal pulsatile VADs. METHODS: The mechanical strength of Berlin Heart EXCOR cannulas were tested both before and after CAP treatment (SteriPlas, Adtec Healthcare Limited, UK) to prove material safety. A ring tensile test of 20 untreated and 20 CAP-treated (5 min) EXCOR cannulas (Ø12mm), assessed the force at the breaking point of the cannulas (Fmax), at 25% (F25%) and 50% (F50%) of the maximum displacement. Additionally, the scanning electron microscope (SEM) micrographs for both groups examined any surface changes. Finally, the case of a 13-year-old male EXCOR patient with cannula infections, treated with CAP over 100 days, is presented. RESULTS: The in vitro measurements revealed no statistically significant differences in mechanical strength between the control and CAP group for F25% (8.18 ± 0.36 N, vs. 8.02 ± 0.43 N, p = 0.21), F50% (16.87 ± 1.07 N vs. 16.38 ± 1.32 N, p = 0.21), and FMAX (44.55 ± 3.24 N vs. 42.83 ± 4.32 N, p = 0.16). No surface structure alterations were identified in the SEM micrographs. The patient's cannula exit-sites showed a visible improvement in DESTINE wound staging, reduction in bacterial load and inflammatory parameters after CAP treatment without any side effects. CONCLUSION: Overall, CAP therapy proved to be a safe and effective for treating EXCOR cannula exit-site wound healing disorders in one pediatric patient, but further studies should investigate this therapy in more detail.

[The use of autologous platelet-rich plasma in the treatment of chronic pharyngitis]. / Primenenie obogashchennoi trombotsitami autoplazmy v terapii khronicheskogo faringita.

The results of a prospective open cohort study of the use of platelet-rich plasma (platelet-rich plasma - PRP) in patients with chronic pharyngitis during the exacerbation of the disease are presented. OBJECTIVE: To evaluate the clinical efficacy of autologous PRP in the treatment of chronic pharyngitis. MATERIAL AND METHODS: Autologous PRP was injected into the posterior pharyngeal wall as a course of endopharyngeal blockages as part of the complex therapy of chronic pharyngitis. Patients in the control group received standard therapy, without the use of autologous PRP. The effectiveness of the studied technique was evaluated by statistical analysis of the intensity of symptoms of the disease, determined by patients throughout the entire period of treatment in the patient's diary, as well as by analyzing data from mass spectrometry of microbial markers and bacteriological examination of the pharyngeal mucosa, collected at the beginning of the study and 14 days after completion of the course of therapy. CONCLUSION: The use of a course of endopharyngeal blockades with autologous platelet-rich plasma as part of the complex therapy of chronic pharyngitis, according to our estimates, provides a significant effect in the form of higher rates of reduction in the severity of symptoms of the disease, a significant reduction in the number of microorganisms deviating from the reference values (by 2 times or more), a decrease in the duration of the disease compared with the control group.

Highly Neutralizing COVID-19 Convalescent Plasmas Potently Block SARS-CoV-2 Replication and Pneumonia in Syrian Hamsters.

Despite various attempts to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with COVID-19 convalescent plasmas, neither appropriate approach nor clinical utility has been established. We examined the efficacy of administration of highly neutralizing COVID-19 convalescent plasma (hn-plasmas) and such plasma-derived IgG administration using the Syrian hamster COVID-19 model. Two hn-plasmas, which were in the best 1% of 340 neutralizing activity-determined convalescent plasmas, were intraperitoneally administered to SARS-CoV-2-infected hamsters, resulting in a significant reduction of viral titers in lungs by up to 32-fold compared to the viral titers in hamsters receiving control nonneutralizing plasma, while with two moderately neutralizing plasmas (mn-plasmas) administered, viral titer reduction was by up to 6-fold. IgG fractions purified from the two hn-plasmas also reduced viral titers in lungs more than those from the two mn-plasmas. The severity of lung lesions seen in hamsters receiving hn-plasmas was minimal to moderate as assessed using microcomputerized tomography, which histological examination confirmed. Western blotting revealed that all four COVID-19 convalescent plasmas variably contained antibodies against SARS-CoV-2 components, including the receptor-binding domain and S1 domain. The present data strongly suggest that administering potent neutralizing activity-confirmed COVID-19 convalescent plasmas would be efficacious in treating patients with COVID-19. IMPORTANCE Convalescent plasmas obtained from patients who recovered from a specific infection have been used as agents to treat other patients infected with the very pathogen. To treat using convalescent plasmas, despite that more than 10 randomized controlled clinical trials have been conducted and more than 100 studies are currently ongoing, the effects of convalescent plasma against COVID-19 remained uncertain. On the other hand, certain COVID-19 vaccines have been shown to reduce the clinical COVID-19 onset by 94 to 95%, for which the elicited SARS-CoV-2-neutralizing antibodies are apparently directly responsible. Here, we demonstrate that highly neutralizing effect-confirmed convalescent plasmas significantly reduce the viral titers in the lung of SARS-CoV-2-infected Syrian hamsters and block the development of virally induced lung lesions. The present data provide a proof of concept that the presence of highly neutralizing antibody in COVID-19 convalescent plasmas is directly responsible for the reduction of viral replication and support the use of highly neutralizing antibody-containing plasmas in COVID-19 therapy with convalescent plasmas.

Preserved SARS-CoV-2 neutralizing IgG activity of in-house manufactured COVID-19 convalescent plasma.

PURPOSE: In the current study, we aimed to evaluate the neutralizing IgG activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as the coagulation factors of convalescent plasmas which we manufactured in-house without a fast-freezing technique. METHODS: We collected plasmas from eligible participants who had confirmed certain titers of neutralizing antibodies. The plasmas were frozen and stored in the ordinary biofreezer without a fast-freezing function. The purified-IgG neutralizing activity of 20 samples from 19 participants and the coagulation factors of 49 samples from 40 participants were evaluated before and after freezing. RESULTS: Purified-IgG maintained its neutralizing activities, with the median 50 % inhibitory concentration (IC50) of 10.11 mg/ml (IQR 6.53-18.19) before freezing and 8.90 m g/ml (IQR 6.92-28.27) after thawing (p = 0.956). On the contrary, fibrinogen and factor Ⅷ decreased significantly after freezing and thawing in our environment. No significant temperature deviation was observed during the storage period. CONCLUSION: Neutralizing IgG activity, which largely contributes to the antiviral activity of convalescent plasma, did not change through our in-house manufacturing, without fastfreezing and storage conditions for more than 200 days. Ordinary freezers without the fast-freezing function are suitable enough to manufacture and store convalescent plasmas. Hospitals or facilities without specified resources could easily collect and store convalescent plasmas in case of upcoming emerging or re-emerging infectious diseases on-demand with appropriate neutralizing antibody levels measurements.

A network meta-analysis of arthroscopic rotator cuff repair.

OBJECTIVE: Rotator cuff tear is a common shoulder injury that often leads to serious limitations in daily life. Herein, a network Meta-analysis using frequency theory was performed to evaluate the clinical outcomes of five rotator cuff repair techniques, including single-row repair, double-row repair, suture bridge repair, platelet-rich plasma therapy, and bone marrow stimulation, thus guiding clinical decision-making on rotator cuff repair. METHODS: PubMed, EMbase, The Cochrane Library, and Web of Science were searched for randomized controlled trials and cohort studies comparing rotator cuff repair techniques published from inception to May 2022. Combined analysis and quality assessment were performed using software STATA15.1 and Review Manager5.3. RESULTS: A total of 51 articles were finally included, including 27 randomized controlled trials and 24 cohort studies. Results from the network Meta-analysis showed that: (1) In terms of the American Shoulder and Elbow Surgeons score, platelet-rich plasma therapy, double-row repair, bone marrow stimulation, and single-row repair were significantly better than suture bridge repair. (2) In terms of Constant score, bone marrow stimulation was significantly better than double-row repair, single-row repair, and suture bridge repair. (3) In terms of visual analog scale score, platelet-rich plasma therapy was significantly better than double-row repair and suture bridge repair. (4) In terms of the Shoulder Rating Scale of the University of California at Los Angeles score, platelet-rich plasma therapy and double-row repair were relatively better but not significantly different from the other treatments. (5) In terms of the risk of re-tear, the re-tear rate of platelet-rich plasma therapy and double-row repair was significantly lower than that of single-row repair and suture bridge repair. CONCLUSION: Based on the results of network Meta-analysis and surface under the cumulative ranking, platelet-rich plasma therapy, bone marrow stimulation, and double-row repair have good overall rehabilitation effects. It is recommended to choose appropriate repair techniques as per the actual clinical situation.

Efficacy of extracorporeal plasma therapy for adult native kidney patients with Primary FSGS: a Systematic review.

PURPOSE: This study aimed to assess efficacy of extracorporeal plasma therapy (EPT), including plasmapheresis (PE), immunoadsorption (IA), low-density lipoprotein apheresis (LDL-A), and lymphocytapheresis (LCAP) for adult native kidney patients with primary focal segmental glomerulosclerosis (FSGS). METHODS: A literature search was conducted using MEDLINE, EMBASE and Cochrane Databases through August 2022. Studies that reported outcomes of EPT in adult native kidneys with primary FSGS were enrolled. RESULTS: 18 studies with 104 therapy-resistant or refractory primary native FSGS patients were identified. Overall EPT response rate was 56%, with long-term benefit of 46%. Of the 101 non-hemodialysis (HD) patients, 54% achieved remission, with 30% complete remission (CR) and 23% partial remission (PR). Of 31 patients with PE, response rate was 65%; CR and PR rates were 27% and 37% in 30 non-HD patients. Of 61 patients with LDL-A, the response rate was 54%; CR and PR rates were 41% and 3% in 29 non-HD patients. Of 10 patients with IA, response rate was 40%. Of 2 patients with LCAP, 1 achieved CR, and one developed renal failure. All 3 HD patients showed increase in urine output and gradual decrease in urine protein excretion following PE (n = 1) or LDL-A (n = 2). 2 of 3 HD patients ultimately discontinued dialysis. CONCLUSION: EPT with immunosuppressive therapy showed benefit in some patients with refractory primary FSGS, and PE appeared to have a higher response rate.

Specific T-cell responses for guiding treatment with convalescent plasma in severe COVID-19 and humoral immunodeficiency: a case report.

BACKGROUND: The immune response to SARS-CoV-2 virus, the cause of COVID-19, is complex. Antibody mediated responses are important for viral clearance but may also drive hyperinflammation in severe COVID-19. We present a case of an individual with a genetic inability to produce antibodies and severe COVID-19, receiving no other specific anti-viral treatment than convalescent COVID-19 plasma, illustrating that hyperinflammation can occur in the absence of a humoral anti-viral response. In addition, the case illustrates that the assessment of SARS-CoV-2 T cell responses can facilitate clinical decision making in patients with COVID-19 and weak or absent humoral immune responses. CASE PRESENTATION: A male with X-linked agammaglobulinemia on regular immunoglobulin replacement therapy, hospitalized for 35 days due to severe COVID-19. Systemic inflammatory parameters were highly elevated. After treatment with convalescent COVID-19 plasma he became afebrile and the fatigue diminished. He was discharged on day 42 and nasopharyngeal SARS-CoV-2 PCR eventually was negative on day 49. Evidence of SARS-CoV-2 specific T cells prior to administration of plasma therapy suggested that antibodies were crucial for viral clearance. Regular assessment showed robust and persistent SARS-CoV-2 specific T-cell responses after recovery suggested that prophylactic administration of convalescent COVID-19 plasma was unnecessary. CONCLUSION: Assessment of SARS-CoV-2T-cell responses can facilitate the clinical management of COVID-19 patients with humoral immunodeficiencies.

Current views on the potentials of convalescent plasma therapy (CPT) as Coronavirus disease 2019 (COVID-19) treatment: A systematic review and meta-analysis based on recent studies and previous respiratory pandemics.

Convalescent plasma therapy (CPT) has been investigated as a treatment for COVID-19. This review evaluates CPT in COVID-19 and other viral respiratory diseases, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and influenza. PubMed and Google scholar databases were used to collect eligible publications until 8 December 2020. Meta-analysis used Mantel-Haenszel risk ratio (RR) with 95% confidence interval (CI) and pooled analysis for individual patient data with inverse variance weighted average. The study is registered at PROSPERO with the number of CRD4200270579. Forty-four studies with 36,716 participants were included in the pooled analysis and 20 studies in the meta-analysis. Meta-analysis showed reduction of mortality (RR 0.57, 95% CI [0.43, 0.76], z = 3.86 [p < 0.001], I2  = 44% [p = 0.03]) and higher number of discharged patients (RR 2.53, 95% CI [1.72, 3.72], z = 4.70 [p < 0.001], I2  = 3% [p = 0.39]) in patients receiving CPT compared to standard care alone. A possible mechanism of action is prompt reduction in viral titre. Serious transfusion-related adverse events were reported to be less than 1% of cases, suggesting the overall safety of CPT; nevertheless, the number of patients participating in the studies was still limited. It is also important to notice that in all the studies, the majority of patients were also given other medications, such as antivirals, antibiotics and corticosteroid; furthermore, randomized controlled studies involving more patients and in combination with other treatment modalities are urgently needed.

Effect of convalescent plasma therapy on mortality in moderate-to-severely Ill COVID-19 patients.

INTRODUCTION: The role of plasma therapy in the management of the COVID-19, pandemic has been speculated. However, in view of the varied response regarding its effectiveness from various multicenter studies, there is a need to conduct more single center population-specific studies. We, thus, aimed to assess the role of convalescent plasma therapy in COVID-19 patient management in a single -center. METHODS: This retrospective study was conducted using records of all COVID-19 patients who received plasma therapy over a period of 6 months in a dedicated COVID-19 hospital in Delhi. Information pertaining to transfusion, disease severity, associated comorbidities, the treatment given and patient outcome were recorded. Data was analyzed using SPSSv23. RESULTS: Of the141 patients who received plasma therapy, 62% were discharged after treatment. Mortality was found to be significantly higher in patients > 60 years of age (p < 0.001), those with severe COVID-19 infection (p < 0.05) and pre-existing renal disease (p < 0.05). The admission-transfusion interval was significantly correlated to mortality and was a sensitive parameter for predicting outcome at cut off value of < 5 days (p < 0.001). There was no significant association of mortality with patient blood group, plasma antibody levels or donor hemoglobin levels. CONCLUSIONS: We report improvement and recovery in a large number of patients who received convalescent plasma within the first 5 days of hospitalization with moderate to severe disease. Further research to compare dosage and administration protocols to delineate role of CCP in survival of COVID-19 patients is needed before it is prematurely shelved.

A possible dose-response equation: Viral load after plasma infusion in COVID-19 patients and anti-SARS-CoV-2 antibody titers in convalescent plasma.

BACKGROUND: Clinical trials of convalescent plasma therapy for coronavirus disease 2019 (COVID-19) are extensive, but the relationship between antibody titers, infused volume of plasma and virus clearance in patients remains unknown. This study proposed a possible estimating equation for clinical use of high antibody titer convalescent plasma. METHODS: A total of 38 patients were recruited in the Guanggu District Maternal and Child Health Hospital of Hubei Province from March 1 to 30, 2020. COVID-19 convalescent plasma was collected and high-titer (≥1:640) anti-S-RBD units used. The SARS-CoV-2 nucleic acid viral load was measured 24 h before and 72 h after convalescent plasma infusion. RESULTS: Convalescent plasma therapy was associated with reduced viral load in patients with moderate and severe severity. The viral negative rate at 72 h was 65.8%. The disappearance of viral nucleic acid in study patients was positively correlated with infuscate antibody titer and volume (r = 0.3375, p = 0.04). A possible estimation equation was as follows: Log10 (Reduction in viral load) = 0.18 + 0.001 × (Log2 S-RBD antibody titer × Plasma infusion volume) (r = 0.424, p = 0.009). In a single case, the viral nucleic acid persisted 14 days after the fourth plasma infusion. CONCLUSIONS: This study proposes a potential dose-response equation that adds a convenient way to estimate the dose of convalescent plasma product. It is beneficial to facilitate the rational allocation of plasma with high antibody titers and provide an individualised use strategy for convalescent plasma therapy.

Hyperbaric oxygen for the treatment of severe subcutaneous and mediastinal emphysema after Renuvion/J-Plasma therapy®.

Subcutaneous and mediastinal emphysema are known complications of liposuction and body sculpting procedures. Treatment options are limited, and recovery is often prolonged. We discuss a case of severe subcutaneous and mediastinal emphysema after a skin-tightening procedure involving helium gas. The patient received one treatment of hyperbaric oxygen and was followed until symptom resolution. We review the known literature on hyperbaric oxygen therapy as a treatment for subcutaneous emphysema.

SARS-CoV-2 IgG Antibody and its Clinical Correlates in Convalescent Plasma Donors: An Indian Experience.

SARS-CoV-2, a novel coronavirus, emerged a year ago in Wuhan, China causing a new pandemic. Convalescent plasma therapy has been applied previously to many infectious diseases and has shown a successful result. This study was planned to assess the Anti-SARS-CoV-2 IgG antibody levels in convalescent COVID-19 patients. In this study, serum samples from 210 persons infected by SARS-CoV-2, treated and discharged from the hospital were collected. Anti-SARS-CoV-2 IgG antibody levels were detected using a chemiluminescence assay. A directory of convalescent plasma donors was created. Anti-SARS-CoV-2 IgG antibody levels vary substantially in the study population with a mean of 51.2 AU/ml. On comparing the serum anti-SARS-CoV-2 IgG antibody levels, a significant difference was observed between the subjects who had cough and those who did not (p = 0.0004). Similar significant findings were found with total protein and globulin levels on comparing the individuals with different antibody status (positive, negative and equivocal). The middle-aged and old age people had high Ab titres compared to younger individuals and the duration of the hospital stay was found to be positively correlated with the anti-SARS-CoV-2 IgG antibody. Cough, age and duration of the hospital stay was found to play a significant role in the development of Anti-SARS-CoV-2 IgG levels. Further, the data suggests that blood groups have a lesser impact on the severity of disease and the development of antibodies. Patients who present with the cough are more likely to develop antibodies.

Sustained Responses of Neutralizing Antibodies Against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Recovered Patients and Their Therapeutic Applicability.

BACKGROUND: Zoonotic coronaviruses have emerged as a global threat by causing fatal respiratory infections. Given the lack of specific antiviral therapies, application of human convalescent plasma retaining neutralizing activity could be a viable therapeutic option that can bridges this gap. METHODS: We traced antibody responses and memory B cells in peripheral blood collected from 70 recovered Middle East respiratory syndrome coronavirus (MERS-CoV) patients for 3 years after the 2015 outbreak in South Korea. We also used a mouse infection model to examine whether the neutralizing activity of collected sera could provide therapeutic benefit in vivo upon lethal MERS-CoV challenge. RESULTS: Anti-spike-specific IgG responses, including neutralizing activity and antibody-secreting memory B cells, persisted for up to 3 years, especially in MERS patients who suffered from severe pneumonia. Mean antibody titers gradually decreased annually by less than 2-fold. Levels of antibody responses were significantly correlated with fever duration, viral shedding periods, and maximum viral loads observed during infection periods. In a transgenic mice model challenged with lethal doses of MERS-CoV, a significant reduction in viral loads and enhanced survival was observed when therapeutically treated with human plasma retaining a high neutralizing titer (> 1/5000). However, this failed to reduce pulmonary pathogenesis, as revealed by pathological changes in lungs and initial weight loss. CONCLUSIONS: High titers of neutralizing activity are required for suppressive effect on the viral replication but may not be sufficient to reduce inflammatory lesions upon fatal infection. Therefore, immune sera with high neutralizing activity must be carefully selected for plasma therapy of zoonotic coronavirus infection.

Effectiveness of convalescent plasma in Indian patients with COVID-19.

BACKGROUND: Convalescent plasma (CP) is being used as a treatment option in hospitalized patients with COVID-19. Till date, there is conflicting evidence on efficacy of CP in reducing COVID-19 related mortality. OBJECTIVE: To evaluate the effect of CP on 28-day mortality reduction in patients with COVID-19. METHODS: We did a multi-centre, retrospective case control observational study from 1st May 2020 to 31st August 2020. A total of 1079 adult patients with moderate and severe COVID-19 requiring oxygen, were reviewed. Of these, 694 patients were admitted to ICU. Out of these, 333 were given CP along with best supportive care and remaining 361 received best supportive care only. RESULTS: In the overall group of 1079 patients, mortality in plasma vs no plasma group was statistically not significant (22.4% vs 18.5%; p = 0.125; OR = 1.27, 95% CI: 0.94--1.72). However, in patients with COVID-19 admitted to ICU, mortality was significantly lower in plasma group (25.5% vs 33.2%; p = 0.026; OR = 0.69, 95%CI: 0.50-0.96). This benefit of reduced mortality was most seen in age group 60 to 74 years (26.7% vs 43.0%; p = 0.004; OR = 0.48, 95% CI: 0.29-0.80), driven mostly by females of this age group (23.1% vs 53.5%; p = 0.013; OR = 0.26, 95% CI: 0.09-0.78). Significant difference in mortality was observed in patients with one comorbidity (22.3% vs 36.5%; p = 0.004; OR = 0.50, 95% CI: 0.31-0.80). Moreover, patients on ventilator had significantly lower mortality in the plasma arm (37.2% vs 49.3%; p = 0.009; OR = 0.61, 95% CI: 0.42-0.89); particularly so for patients on invasive mechanical ventilation (63.9% vs 82.9%; p = 0.014; OR = 0.37, 95% CI: 0.16-0.83). CONCLUSION: The use of CP was associated with reduced mortality in COVID-19 elderly patients admitted in ICU, above 60 years of age, particularly females, those with comorbidities and especially those who required some form of ventilation.

Convalescent plasma is a clutch at straws in COVID-19 management! A systematic review and meta-analysis.

In the absence of definitive therapy for coronavirus disease (COVID-19), convalescent plasma therapy (CPT) may be a critical therapeutic option. This review was conducted to evaluate the impact of CPT in COVID-19 patients based on the publications reported to date. A robust screening of electronic databases was conducted up to 10th July 2020. Randomized controlled trials (RCTs), cohort studies, and case series with a control group evaluating the effectiveness and safety of CPT in patients with COVID-19 are included for the meta-analyses. Our search retrieved seven studies, including two RCTs and five cohort studies, with a total of 5444 patients. In patients with COVID-19, the use of CPT reduces mortality (odd's ratio [OR] 0.44; 95% CI, 0.25-0.77), increases viral clearance (OR, 11.29; 95% CI, 4.9-25.9) and improves clinically (OR, 2.06; 95% CI, 0.8 to 4.9). However, the evidence is of low quality (mortality reduction, and viral clearance), and very low quality (clinical improvement). CPT may be beneficial for reducing mortality, viral shedding and improving clinical conditions in COVID-19 patients. However, further randomized control trials (RCT) are required to substantiate the safety margin, initiation, optimal dosage, titre and duration of CPT.

Antibodies at work in the time of severe acute respiratory syndrome coronavirus 2.

In view of devastating effects of COVID-19 on human life, there is an urgent need for the licened vaccines or therapeutics for the SARS-CoV-2 infection. Age-old passive immunization with protective antibodies to neutralize the virus is one of the strategies for emergency prophylaxis and therapy for coronavirus disease 2019 (COVID-19). In this review, the authors discuss up-to-date advances in immune-based therapy for COVID-19. The use of convalescent plasma therapy as the first line of defense to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been established, with encouraging results. Monoclonal antibodies (mAbs) that bind to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein or block the interaction between SARS-CoV-2 RBD and the human angiotensin-converting enzyme 2 receptor have been found to be very promising as a countermeasure for tackling the SARS-CoV-2 infection, and clinical trials are underway. Considering the counterproductive antibody-dependent enhancement of the virus, mAbs therapy that is safe and efficacious, even in people with underlying conditions, will be a significant breakthrough. In addition, emerging immunotherapeutic interventions using nanobodies and cellular immunotherapy are promising avenues for tackling the COVID-19 pandemic. The authors also discuss the implication of mAbs as mediators of cytokine storm syndrome to modify the immune response of COVID-19 patients, thus reducing the fatality rate of COVID-19 infection.

Surrogate test performance for SARS-CoV-2 neutralizing antibodies (nAbs) for convalescent plasma (CCP): How useful could they be?

BACKGROUND: COVID-19 high-titer CCP selection is a concern, because neutralizing antibody (nAb) testing requires sophisticated labs and methods. Surrogate tests are an alternative for measuring nAb levels in plasma bags, including those that are pathogen-reduced. STUDY DESIGN/METHODS: We studied a panel consisting of 191 samples from convalescent donors tested by nAb (CPE-VNT), obtained from 180 CCP donations (collection: March 20-January 21) and 11 negative controls, with a total of 80 and 111 serum and plasma samples (71 amotosalen/UV treated), with nAb titers ranging from negative to 10,240. Samples were blindly tested for several surrogates: one anti-RBD, two anti-spike, and four anti-nucleocapsid tests, either isolated or combined to improve their positive predictive values as predictors of the presence of high-titer nAbs, defined as those with titers ≥160. RESULTS: Except for combined and anti-IgA/M tests, all isolated surrogate tests showed excellent performance for nAb detection: sensitivity (98.3%-100%), specificity (85.7%-100%), PPV (98.9%-100%), NPV (81.3%-100%), and AUC (0.93-0.96), with a variable decrease in sensitivity and considerably lower specificity when using FDA authorization and concomitant nAb titers ≥160. All surrogates had AUCs that were statistically different from CPE-VNT if nAb≥160, including when using combined, orthogonal approaches. CONCLUSIONS: Surrogate tests (isolated or in combination) have an indirect good performance in detecting the presence of nAb, with lower sensitivity and specificity when high nAb titer samples are used, possibly accepting a considerable number of donors whose nAb titers are actually low, which should be evaluated by each laboratory responsible for CCP collection.