Hospital Protection Correlates in Outpatient Covid-19 Convalescent Plasma Recipients

Background: High titer COVID-19 convalescent plasma (CCP) reduces hospitalizations among immunocompetent outpatients. This study evaluated recipient post-transfusion S receptor binding domain (S-RBD) IgG antibody levels and the association of progressing to hospitalization among unvaccinated outpatients with COVID-19 treated with CCP or control plasma. Method(s): This analysis focused on participants from a multicenter doubleblind, randomized, controlled trial comparing treatment of outpatients with COVID-19 convalescent plasma (CCP) or control plasma without SARS-CoV-2 antibodies. Participants with confirmed SARS-CoV-2 infection were transfused within 9-days of symptom onset between June 2020 and October 2021 (n=110 vaccinated control;n=105 vaccinated CCP;n=464 unvaccinated control;n=472 unvaccinated CCP;total n=574 control and n=577 CCP recipients). All subjects had specimens collected the day prior to transfusion (D-1), within 30 minutes after transfusion (D0), 14 (D14), 28 (D28), and 90 (D90) days post-transfusion. Ancestral SARS-CoV-2 S-RBD was measured by an in-house validated ELISA. All 54 COVID-19-related hospitalizations occurred within 2 weeks of transfusion. Result(s): Post-transfusion anti-S-RBD IgG levels on D0 were significantly greater for CCP (median=4 titer,log3) compared to control (median=2 titer,log3;p< 0.001) recipients. Neither sex nor age impacted antibody levels following CCP treatment at D14, D28, and D90. Vaccinated recipients had greater titers than unvaccinated recipients prior to transfusion with little change in titers post-transfusion. Unvaccinated recipients had low antibody titers on D-1 with CCP recipients exhibiting a significant increase in titer from D-1 to D0 compared to controls (mean fold change=1.89;p< 0.001). Among unvaccinated recipients, those who received CCP transfusion late ( >5 days after symptom onset) and had low D0 antibody levels (< 4.24 titer, log3) had the greatest proportion of hospitalizations (5.5%). In contrast, those who received CCP transfusion early (< 5 days after symptom onset) with high D0 antibody levels ( >4.24 titer, log3) had no hospitalizations. Unvaccinated CCP recipient anti-S-RBD IgG antibody levels on D0 correlated with donor anti-S-RBD IgG antibody levels (r=0.30, p< 0.001). Conclusion(s): Among unvaccinated outpatients with COVID-19, CCP recipient antibody dilutional titers after transfusion over 540 titer correlated with protection against hospitalization when transfusion occurred within 5 days of symptom onset. (Figure Presented).

Convalescent plasma for coronavirus disease 2019: A boon or bane

Coronavirus disease 2019 (COVID-19) pandemic emergence has re-evaluated the functionality of the notable convalescent plasma transfusion (CPT). It is a source of neutralising antibodies, which when transfused into severe acute respiratory syndrome coronavirus 2 infected patients are believed to employ an antiviral effect, suppressing the replication of virus before the patients regain their own effective humoral immune responses. The major accepted mode of action of the CPT therapy is viremia clearance, that happens mostly between 10 and 14 days after infection. Hence, CPT has been administered to the recipients typically after the emergence of early symptoms for anticipating maximize the efficacy of the therapy. CPT has been used in treating viral diseases including measles, mumps, poliomyelitis, and influenza in the pre-vaccine era. More recently, it has been used as a treatment approach for influenza, Ebola virus disease, and severe acute respiratory syndrome coronavirus epidemics, with varying success. The available evidence till date suggests that convalescent plasma which is collected from the COVID 19 survivors contains "receptor binding domain specific antibodies " possessing potent antiviral activity. Multicentred and well-designed clinical trial studies in establishing the efficacy of CPT among COVID-19 patients are being conducted globally. PubMed, EMBASE, and Medline databases were screened till November 01, 2020. This is an attempt to review studies of convalescent plasma on clinical outcomes in patients with COVID-19. From the outcomes of some of the completed studies, it is suggested that CPT therapy among COVID-19 patients seems to be safe and clinically efficacious to some extent.

Therapeutic Options for the Treatment of 2019-Novel Coronavirus in India: A Review

Purpose: As of, from 30th Jan to 31st May, 2020, more than 182,143 confirmed cases were reported in India along with 86,984 recovered cases and 5164 deceased cases of COVID-19. More than 53 countries are also affected with this pandemic virus. However, the lack of specific drugs to prevent/treat this pandemic disease is a major problem in this current scenario. In this re-gard, this systemic review was conducted to identify the therapeutic approaches and researches, which are ongoing in India against COVID-19. Method(s): We had screened Google Scholar database with the keywords nCoV, corona virus in In-dia, effect of SARS-CoV-2 in India, 2019-nCoV, treatment pattern in India for nCoV and therapy used to treat nCoV in India. In the final review, we had included a total of 49 articles. Result(s): As a result we had found that the Indian Council of Medical Research and NIH have giv-en a standard guideline of Hydroxychloroquine and other antiviral drugs for nCoV, and also there are various researches going on related to nCoV treatment like, chemicals from natural products, herbs and spices commonly used in India, combination therapy of lopinavir and ritonavir, ultra-vio-let radiation therapy, molecular dynamic (MD) simulations of molecules for vaccine preparation, Convalescent plasma transfusion (CPT) therapy and many more. Conclusion(s): New drugs and therapy are in the premature stage for this hazardous pandemic. We need more time to gain the detailed knowledge of the life cycle of the nCoV, which can speed up the drug/vaccine development process against nCoV.Copyright © 2022 Bentham Science Publishers.

Covid-19: All facts, no myth

On December 31, 2019, the China Health Authority alerted WHO about 27 cases of pneumonia of unknown etiology in Wuhan City. It was subsequently named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and the disease as Coronavirus Disease 2019 (COVID-19). The disease has now become pandemic. Current review was done to summarize information on COVID-19 published in various scientific works. Electronic databases containing medical articles viz., MEDLINE/PubMed, Google Scholar etc were searched using the Medical Subject Headings 'COVID-19', '2019-nCoV', 'coronavirus' and 'SARS-CoV-2' during antecedent one year. All study designs were incorporated to harvest clinical, laboratory, imaging, and hospital course data. The intermediate host of the virus is still unknown. Respiratory droplets produced by the patient is main source of transmission. SARS-CoV-2 invades the airway epithelium by binding to angiotensin-converting enzyme-2 (ACE2) receptor with Coronavirus spike (S) protein. Most common symptoms are fever (98%), dry cough (77%), and dyspnea (63.5%). Later, complications like acute respiratory distress syndrome, septic shock etc may occur. Advanced age and co-morbidities like Diabetes have higher mortality otherwise Case Fatality Rate is 2-3%. RT-PCR is the diagnosis of choice. Since no universally accepted registered drug or FDA approved vaccine has come by now, prevention is the key. Hands should be regularly cleaned with soap or alcohol based sanitizer and in public, Nose and Mouth should be covered with face-mask and social distance of one meter should be maintained. While Vaccines are expected by early 2021, we should not forget to take comprehensive measures to prevent future outbreaks of zoonotic origin. Copyright © 2020, Kathmandu University. All rights reserved.

Patient supply with convalescent plasma at a university hospital during the first two pandemic waves

Background: The blood bank of the Department Transfusion Medicine in a University Hospital supplied between April 6th, 2020, and June 9st, 2021, convalescent plasma (CP) to 133 patients and 38 patients in other Bavarian hospitals. We evaluated the data regarding the therapy of our own patients. Method(s): We used the matrix initiated by COVIM - one of 13 joint projects within the network of university medicine and is funded by the Federal Ministry of Education and Research - to examine our own data regarding therapy with CP. We collected following data: patient identification number, age, sex, blood group, date of hospitalization, date of transfusions batch-number (Konservennummer) of applied CP, volume of CP units and total volume, titer of neutralizing antibodies against SAR-CoV-2 in each unit, the total volume of CP, documented comorbidities, date and transfer to ICU, duration of stay in hospital. We also regarded and analyzed the neutralizing antibody titers and the mortality during the hospitalization. Result(s): The median age of the patients was 60.9 years (23 to 89). Men were overrepresented at 69.2%. The blood group distribution was: 40.6% (0), 44.4% (A), 8.3 (B) and 6.7% (AB). A total of 347 CPs (volume: 196 ml) were used, a mean of 2.6 units (481.7 ml) per patient. Figure 1 shows the distribution of the neutralizing antibody titers. The need for CP was variable and well correlated with the course of the first two pandemic waves. 38 of 133 patients (28.6%) died. The first CP transfusion was performed on average on day 6 after hospital admission in the deceased and on day 4 after admission in the non-deceased patients. The mortality was slightly lower (23.4%) in the group of 64 patients treated within 48 hours after admission in the hospital. Conclusion(s): In the first two waves of the corona pandemics, there were still no reliable study results regarding the dosage of CP. Our results correlate with international experience (Piechotta et al, 2021;Rijnders BJA et al, 2022) and the recommendations of "S3-Leitlinie: Empfehlungen zur stationaren Therapie von Patienten mit COVID-19 (28.02.2022)". In summary: the CP were applied mostly too late and at too low a dose. This may also be related to the low antibody titer in the available CP. (Figure Presented).

Sera from donors of COVID-19 convalescent plasma do not induce procoagulant phenotype in platelets

Background: COVID-19 convalescent plasma (CCP) has been suggested to be beneficial to prevent disease progression in COVID-19. However, concerns have been expressed whether plasma components in CCP can shift the already imbalanced coagulation system to a more hypercoagulable state. Aim(s): To investigate the effect of CCP on platelet phenotype and activation. Method(s): We investigated platelets from CCP donors who had a history of mild COVID-19 infection. Donors who did not have COVID-19 were used as controls (non-CCP donors). We analyzed phosphatidylserine (PS) externalization, CD62p expression, and GPVI shedding in healthy platelets after incubation with sera from CCP and non-CCP donors using flow cytometry. The study protocol was approved by the ethics committee of the University Hospital of Tubingen. (Figure Presented) Results: Forty-seven CCP donors [22 Male, 25 Female;and mean age (+/-SD) 41.4 +/- 13.7 years] with a history of mild COVID-19 infection were included. Median duration after acute COVID-19 infection was 97 days (range, 34-401). Compared to sera from non-CCP donors, sera from CCP donors did not induce higher PS externalization (Fold increase [FI] of PS positive platelets: 1.16% +/- 0.66 vs. 1.51% +/- 0.74, respectively, p = 0.11) or increased the rate of CD62p/PS double positive procoagulant phenotype (FI in CD62p/PS positive platelets: 1.86 +/- 0.87 vs. 1.37 +/- 0.63, respectively, p = 0.10) in platelets from healthy persons. Of note, CD62p expression in healthy platelets after incubation with sera from CCP plasma donors was significantly lower compared to sera from non-CCP donors (FI in CD62p: 2.09 +/- 1.36 vs. 1.16 +/- 0.45, p< 0.01). Sera-mediated GPVI shedding was similar between non-CCP and CCP donors (1.07 +/- 0.16 vs. 1.27 +/- 0.91, p = 0.52). Conclusion(s): Our findings support data from clinical studies, which indicate that transfusion of CCP to treat or prevent severe COVID-19 is not associated with increased risk of exacerbation of the coagulopathy in COVID-19.

Clinical Efficacy of Early Administration of Convalescent Plasma among COVID-19 Cases in Egypt

BACKGROUND: The rapid worldwide spread of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) or COVID-19 pandemic from its epicenter;Wuhan was first reported in December 2019. Egypt reported its first COVID-19 case on February 14, 2020. Thereafter, Egypt scaled-up preventive measures, with a partial lockdown starting on March 25. Several therapeutic agents along with convalescent plasma transfusion (CPT) are under investigation and data from CPTs have been receiving a lot of attention, after Emergency approvals from the Food and Drug Administration suggesting that it may provide a clinical effect in the treatment of SARS-COV-2. IMPORTANCE: Early and effective treatment of COVID-19 is vital for control of SARS-CoV-2 infection. METHODS: Designs: An interventional, single-arm, and non-randomized clinical trial conducted in Egypt from April 15 to July 21, 2020. Settings: This was a multi-center study conducted in three hospitals in Egypt. Participants: A total of 94 COVID-19 laboratory-confirmed patients using quantitative real-time polymerase chain reaction were enrolled in the study. Intervention: All patients were administered with two plasma units (each unit is 200 cc). The volume of donated plasma was 800 cc. Main Outcome and measures: Primary measure was the degree of clinical improvement among the COVID-19 patients who received CPT within 7 days. RESULTS: A total of 94 patients were enrolled who received CPT either within 7 days or after 7 days of hospitalization. 82 were severely ill and 12 were critically ill. The average age remained 58 years (±standard deviation 15.1 years). Male were 69% and 49% patients got cured while 51% died with case fatality rate 51%. Seventy-five percent deaths were above 45 years of age. The symptoms were dyspnea (55%), fever (52%), cough (46%), and loss of taste and smell (21%), and cyanosis (15%). The most common co-morbidities among the <40 years remained diabetes mellitus (21%) and asthma (14%). Among 40–60 years hypertension (56%), diabetes mellitus (39%) and among >60 years age group hypertension (57%), and chronic heart disease (24%) were reported. CPT within 7 days remained significant as compared with the CPT after 7 days with the number of days to cure (p=0.007) and ICU stay (p = 0.008) among severely ill cured cases. CONCLUSIONS: Among patients with COVID-19 and severe or critical illness, the use of CPT along with routine standard therapy resulted in a statistically significant improvement when administered within seven days of hospital admission. However, plasma transfusion, irrespective of days to transfusion may not help treat critically ill patients. The overall mean time to cure in severely ill patients was 15 days if CPT provided within 7 days with 65% cure rate. TRIAL REGISTRATION: Clinical Intervention identifier: MOHP_COVID-19_Ver1.1 registered April 2020.

Efficacy and Safety of COVID-19 Treatment Using Convalescent Plasma Transfusion: Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This study investigated the efficacy and safety of convalescent plasma (CP) transfusion against the coronavirus disease 2019 (COVID-19) via a systematic review and meta-analysis of randomized controlled trials (RCTs). A total of 5467 articles obtained from electronic databases were assessed; however, only 34 RCTs were eligible after manually screening and eliminating unnecessary studies. The beneficial effect was addressed by assessing the risk ratio (RR) and standardized mean differences (SMDs) of the meta-analysis. It was demonstrated that CP therapy is not effective in improving clinical outcomes, including reducing mortality with an RR of 0.88 [0.76; 1.03] (I2 = 68% and p = 0.10) and length of hospitalization with SMD of -0.47 [-0.95; 0.00] (I2 = 99% and p = 0.05). Subgroup analysis provided strong evidence that CP transfusion does not significantly reduce all-cause mortality compared to standard of care (SOC) with an RR of 1.01 [0.99; 1.03] (I2 = 70% and p = 0.33). In addition, CP was found to be safe for and well-tolerated by COVID-19 patients as was the SOC in healthcare settings. Overall, the results suggest that CP should not be applied outside of randomized trials because of less benefit in improving clinical outcomes for COVID-19 treatment.

The Successful Recovery of a Critically Ill COVID-19 Patient, Following the Combination of Therapeutic Plasma Exchange and Convalescent Plasma Transfusion: A Case Report.

With an intricate symptom pattern involving a dysregulated host response to infection, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause severe inflammation and cytokine storms, acute respiratory distress syndrome, coagulopathy, multi-organ failure, and finally death. The uniqueness of this case report lies in the nature of the therapeutic intervention performed. While numerous studies are available on both the use of therapeutic plasma exchange in coronavirus disease 2019 (COVID-19) patients and convalescent plasma transfusion as separate treatment methods, there is very little information regarding the combination of these procedures. We present the case of a 52-year-old male, unvaccinated for COVID-19, who tested positive on reverse transcriptase polymerase chain reaction for SARS-CoV-2 for the first time and presented in the emergency room with fever, chills, severe cough, tachypnea, tachycardia, and dyspnea that started two days before presentation. Upon rapid assessment, the patient showed signs of acute respiratory failure, so it was decided to transfer the patient to the intensive care unit, COVID-19 ward, after preliminary radiological examination. For the next 24 days, the patient was stationed in the intensive care unit, where he was closely monitored and treated. Invasive mechanical ventilation was required following the initial worsening of his respiratory status. We performed therapeutic plasma exchange on the first day of his stay in the intensive care unit, and immediately after the procedure, the patient was transfused with 500 mL of convalescent plasma from healthy donors. The patient's condition improved over the next few days, which led to the cessation of mechanical ventilation and, after treating the superinfection, the patient was discharged home, making a full recovery. The early initiation of therapeutic plasma exchange followed by transfusion of convalescent plasma in severe and critical forms of COVID-19 may reduce the risk of the progression of the disease and ultimately reduce the risk of negative outcomes in a selected group of patients.

A case of category five COVID-19 patient transfused with convalescent plasma

Background: COVID-19 is an emerging infectious disease, caused by a novel coronavirus, named SARS-CoV-2. It emerged in Wuhan city, Hubei province, China in December 2019. Convalescent plasma (CP) has been used in a number of emerging infections for which there are no proven antivirals, including SARS, MERS, and Ebola virus disease (EVD). It may also be a potentially effective treatment strategy for COVID-19 disease before COVID-19 vaccinations was introduced. In this case report, we described a case of a 59 years old lady with no known medical illness or no known drug allergies and she was diagnosed with Covid-19 with Class 4A (requiring nasal prong) on 8/10/2020, her oxygen saturation was 96% under nasal prong. During her initial admission, she was given favipravir and interferon as alternative treatment for Covid-19. Unfortunately, at 3rd day of illness, her oxygen level deteriorated to 94% under nasal prong (72% from arterial blood gas) thus, she was transferred to intensive care unit for non-invasive ventilation support. The next day, she was intubated as her condition worsen. On 5th day of illness, she was transfused with convalescent plasma and subsequently extubated as she improved clinically. Aims: To evaluate the effectiveness of convalescent plasma in treating a case of category 5 Covid-19 patient at Hospital Tuanku Ja'afar. Methods: The data regarding the patient's clinical information was retrospectively collected from the patient case notes and the laboratory information system. Results: Other than clinically improved, we noted the CT value from tracheal aspirate PCR prior to the transfusion was 24.60 while the CT value 48 h post transfusion showed 31.62. This showed that the patient had clinical improvement post convalescent plasma transfusion. Summary/Conclusions: Convalescent plasma should be considered in treatment of Covid-19.

Safety and efficacy of COVID-19 convalescent plasma in a French monitored therapeutic use in omicron vs other SARSCoV- 2 variants-infected patients

Background: Several studies have evaluated COVID-19 convalescent plasma (CCP)'s safety and effectiveness in the prevention of severe COVID-19's worsening. Some of these studies have shown a trend for its efficacy in immunosuppressed patients and that CCP was safe. These studies were performed before the emergence of Omicron variant of SARS-CoV-2, which appeared in December 2021 in France. Aims: All CCP transfusions in France have been performed in a monitored use protocol allowed by the national agency of drug and blood components safety (ANSM). After giving their consent to be transfused, patients were followed to assess this compassionate therapy. All CCPs were qualified with a high titre of antibody, either by seroneutralization (SN) or an ELISA based surrogate for SN. We describe results of this follow-up with a focus on omicron infection. Methods: Consultative multidisciplinary meeting validated the indication for CCP and the order of a medical prescription of CCP. All CCP demands were sent to the EFS medical department to be pseudonymized. Initial and follow-up data of cases were recorded as requested for an assessment. Variables were analysed in relation with the last available follow-up. Results: From May 2020 to the end of February 2022, 1539 patients had received CCP, of whom 455 had an available follow-up more than 24 h after the last CCP transfusion. Most of them (99.8%) have got a comorbidity: 62.6% have a malignant hemopathy and 19.3% an auto-immune pathology. Among the At the time of CCP request, majority of patients (76.9%) were hospitalized without mechanical ventilation (MV), 18.2% were intubated and a few were not hospitalized for COVID-19 (1.3%) but for another reason. At the last available follow-up, 26.2% were dead but the majority (40.9%) have left the hospital, 23.7% were hospitalized without MV and 9.2% were intubated. Variables associated with a decreased percentage of death were: • The young age (p < 0.0001;N = 455) and the female gender (p = 0.0177;N = 455). • The better state at the time of CCP request (p < 0.0001;N = 439). • The longer delay between the beginning of symptoms and the transfusion (p = 0.0023;N = 445). • A trend was observed for immunosuppression, but it did not reach statistical significance (p = 0.0548;N = 346). There were no difference between Infection due to Omicron variant compared to other variants (p = 0.1560;N = 443). However, follow-up was available in only 33 patients infected with omicron (32.7% of transfused patients infected with omicron) while it was available in 410 patients infected with others SARS-CoV-2 variants (94.4%). Among all transfused patients, 75 adverse events (AE) were reported in 1539 patients (4.8%). Imputability was excluded for 11. Allergy was the most frequent (N = 26;34.6% of AE) always scored as not severe, TACO have occurred in 8 patients, with possible or likely imputability, and TRALI have occurred in 3 patients with possible imputability in 2 cases and non evaluable in one case. Summary/Conclusions: CCP transfusion was more effective when the patient were in better state at the time of CCP request and in immunocompromised than in immunocompetent patients, but this was not statistically significant. Due to the low number of patients infected with omicron with an available follow-up at this day, no conclusion can be drawn on survival of these patients versus patients infected with previous variants.

Clinical outcome of severe COVID-19 patients transfused with convalescent plasma in Malaysia

Background: The Coronavirus Disease 2019 (COVID-19) pandemic was first detected in Wuhan, China. It is caused by a novel coronavirus known as Severe Acute Respiratory Distress Syndrome Coronavirus-2 (SARS-Cov-2). The pandemic presents a challenge to the healthcare system worldwide due to widespread infection and limited definitive therapeutic options available. The previous research suggested that convalescent plasma (CP) may be effective against infection. Aims: To investigate the effect of CP transfusion in the clinical outcome of severe COVID-19 patients. Methods: A cross-sectional study was conducted among severe COVID-19 adult patients admitted to six public hospitals across Malaysia from 1st August 2020 to 28th February 2021. A total of 53 patients received CP transfusion along with the standard care (intervention group) and another 53 patients received standard care only (control group) were recruited. An age, gender and comorbidity between the two groups were manually matched approximately at a 1:1 ratio. Each patient (intervention group) received at least a unit (approximately 250 ml) ABO-compatible CP over 1 or 2 h infusion. Another unit of CP was transfused after 24 h in 18 patients (34.0%) after being assessed by a treating physician. The convalescent plasma was collected from an individual who was recovered from COVID-19 infection, negative for COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) and fulfilled the eligibility criteria for blood donation according to the national guideline. The anti-COVID-19 antibody was tested before the donation. However, the anti-COVID-19 neutralizing antibody (nAb) titre was not determined. The median interval between CP transfusion and severe COVID-19 staging was 2 days. The data were analysed using International Business Machines Corporation (IBM) Statistical Package for the Social Science (SPSS) Statistics Version 26 IBM, New York, USA. Results: The demographics of selected patients were male (60.4%), Malay race (83.0%), and has one or more comorbidity (74.5%). The commonest comorbidities were hypertension (47.2%), followed by diabetes mellitus (44.3%), dyslipidaemia (16.0%), and cardiovascular disease (16.0%). The commonest symptoms upon admission were cough (63.2%), followed by fever (60.4%), and shortness of breath (17.0%). The patients in the intervention group received a shorter duration of oxygen supplementation (median: 12 vs. 14 days, p = 0.030) and a shorter duration of mechanical ventilation (median: 6 vs. 10 days, p = 0.048). The difference in the mechanical ventilation rate, length of intensive care unit (ICU) stay, length of hospital stay, and mortality rate across both groups was not statistically significant (p = 0.492, 0.793, 0.614 and 0.374). The prevalence of adverse transfusion reactions was 5.7%. Summary/Conclusions: CP transfusion is safe and seems to be effective in the treatment of severe COVID-19 patients. However, a randomized-controlled trial with a larger sample size is necessary at the national level to ascertain the benefits of CP transfusion among severe COVID-19 patients.

ACUTE KIDNEY INJURY AMONG COVID-19 POSITIVE PATIENTS IS ASSOCIATED WITH HIGHER MORTALITY: SINGLE CENTER EXPERIENCE

BACKGROUND AND AIMS: Despite the lungs are the major targets of COVID-19, other organs such as the kidneys are also affected. Renal complications of COVID-19 are not yet well studied. We aimed to study the prevalence of acute kidney injury (AKI) among positive COVID-19 cases that were managed in the intensive care unit (ICU) in a single isolation hospital during the pandemic, and to explore its impact on patient outcome. METHOD: This retrospective study included 616 patients with COVID-19 who were managed in the ICU in a single isolation hospital in Kuwait during the pandemic, from February to December 2020. AKI was defined according to the serum creatinine criteria in the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Of the 616 patients, 40.2% developed AKI (group 1, n = 248) and were compared with the patients without AKI (group 2, n = 368). RESULTS: Most of cases in the two groups were males (73% versus 70.7%), aged (60.8 ± 14 versus 51.7 ± 16 years), respectively. The two groups were comparable regarding chronic kidney disease (2% versus 0.8%) and chronic pulmonary disease. Other factors were significantly predominating among group 1 as diabetes mellitus (63.7 versus 40.5%), hypertension (74.2% versus 40.5%) and ischemic heart disease (26.2% versus 12.5%) (P < .05). Fever, cough, shortness of breath and dehydration were significantly more frequent presentations among patients of group 1, and had radiological findings that were synchronized with COVID-19 (89.5% versus 50.8%) (P < .05). Moreover, sepsis, volume depletion, shock, arrhythmias and ARDS predominated among the AKI group (P < .05). The number of cases who were managed by therapeutic anticoagulation was significantly higher in AKI patients (89.9% versus 51.9%);also, cases who received supportive vasopressors and convalescent plasma transfusion as well as steroid were significantly higher in the same group (P < .05). Other therapeutic modalities such as antivirals, tocilizumab and hydroxychloroquine were comparable in both groups. We found that acute respiratory failure requiring mechanical ventilation was significant among the AKI group (66.8% versus 29.4%), and the overall mortality rate was significantly higher in the same group (62.5% versus 32.8%). CONCLUSION: The prevalence of AKI in patients with COVID-19 was 40.2%, and it was associated with poor prognosis among ICU COVID-19 positive cases.

ADRS due to COVID-19 in midterm pregnancy: successful management with plasma transfusion and corticosteroids.

BACKGROUND: Management of acute respiratory distress syndrome (ARDS) in pregnant women infected with new severe acute respiratory syndrome Corona virus 2 (SARS-CoV2) is a challenging clinical task. CASE: A 30- year-old woman (gravid 3, parity 2) presented at her 21 and 2/7 weeks gestation (pre pregnancy BMI: 36.1 kg/m2), with ARDS caused by SARS-CoV2 infection. She received lopinavir/ritonavir and azithromycin as well as early methyl prednisolone therapy. Given the persistent hypoxemia despite oxygen therapy via non rebreather face mask (FiO2:80%), convalescent plasma transfusion was administered that led to a mild clinical improvement as well as decrease in inflammatory markers. Growth of her fetus assessed by obstetric sonography was normal during hospital stay. CONCLUSION: Judicious corticosteroid therapy along with convalescent plasma transfusion to suppress viremia and cytokine storm can lead to favorable outcome in the pregnant women with ARDS caused by SARS-CoV2 infection without superimposed bacterial infection.

Convalescent Plasma in Hospitalized Pediatric and Obstetric patients with COVID-19

Background. Published data on COVID-19 convalescent plasma (CCP) use in children and obstetric patients is limited. We describe a single-center experience of hospitalized patients who received CCP for acute COVID-19. Methods. We performed a retrospective review of children 0-18-years-old and pregnant patients hospitalized with laboratory-confirmed acute COVID-19 who received CCP from March 1st, 2020 to March 1st, 2021. Clinical and laboratory data were collected to assess the safety of CCP administration. Antibodies to SARS-CoV-2 were measured before and at various timepoints post CCP transfusion. Correlation between SARS-CoV-2 immunoglobulin administered versus the SARS-CoV-2 anti-Spike immunoglobulin response in patient serum was assessed. Results. Twenty-two children and 10 obstetric patients were eligible. 12 pediatric and 8 obstetric patients had moderate disease and 10 pediatric and 2 obstetric patients had severe disease. 5 pediatric patients died. 18/37 (48.6%) CCP units that were measured met FDA criteria for a high IgG titer. There were no complications with transfusion based on CDC, NHSN Biovigilance Component: Hemovigilance Module Surveillance Protocol. Two pediatric patients had fevers a few hours after CCP with low suspicion for a transfusion reaction. Median SARS-CoV-2 anti-spike antibody levels of pediatric patients post-transfusion for 0-7 days was 80.6AU/mL (range: 2-1070), 8-21 days was 180AU/mL (range: 12-661) and >21 days was 210AU/mL (range: 4.1-1220). For obstetric patients, post-transfusion antibody levels were only obtained 0-7 days post-transfusion with median 45AU/mL (range: 9.5-100). High-titer CCP showed a positive correlation with rise in patient immunoglobulin levels only in the obstetric patients but not in pediatric patients. Conclusion. CCP was administered safely to our moderately to severely ill pediatric and obstetric patients. Among pediatric patients, the median serum antibody level increased over time after transfusion and suggested that CCP did not interfere with the endogenous antibody production. Antibody dose of high-titer CCP correlated with post-transfusion response in only obstetric patients. Randomized trials in pediatric and obstetric patients are needed to further understand how to dose CCP and evaluate efficacy.

The Use of Convalescent Plasma (CP) Transfusion Therapy in Moderate to Severe COVID-19 Patients: A Single Center Experience in Indonesia

Coronavirus disease 2019 (COVID-19) was declared as a world pandemic since early 2020. There was no specific antiviral agent that appeared to be active against the virus, and antiviral agent such as remdesivir, favipiravir were in limited supply. We evaluated the use of convalescent plasma (CP) administered as adjuctive treatment to standard of care in moderate to severe COVID-19 patients. We conducted a series of 9 moderate to severe patients of COVID-19 older than 18 years received CP transfusion from 9 recovered donors at a single institution (Sulianti Saroso Infectious Disease Hospital, Jakarta, Indonesia) from January 2021 to June 2021. Out of 9 patients (age range 30-81 years, 6 males and 3 female), and all patients received at least 1 or 2 unit of 200 mL of CP from 9 recovered donors. There were 4 patients (age range 30-71 years, 4 male) that were not treated with antiviral therapy. Of the 9 patients, 2 severe cases were died, while all of moderate cases survived and they were discharged from the hospital (length of stay: 8-22 days). Our experience showed that CP transfusion in moderate COVID-19 patients might provide clinical benefit and it was well-tolerated. However, further development clinical trials with better designs and greater power is needed to evaluate the efficacy and safety of this treatment.

Efficacy and safety of convalescent plasma transfusion administered as adjunctive treatment to standard treatment in moderate, severe, and/or critically ill patients with covid-19 in dr. M. djamil general hospital

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2. High mortality rate due to COVID-19 has become a serious health problem globally. At present, there is no definitive therapy for COVID-19. AIM: The objective of this study is to evaluate convalescent plasma therapy (CPT) in COVID-19 patients. METHODS: The study was conducted in prospective experimental design with sample population of COVID-19 inpatient in Dr. M. Djamil General Hospital, Padang, isolation ward. This study was involving 20 patients consisted of 10 patients of experimental group who received standard therapy and CPT and 10 patients of control group who received standard therapy only;10 males and 10 females. Differences in laboratory results in both groups were analyzed by T-test or Mann–Whitney U-test. RESULTS: Twenty subjects included in this study with average of age 56.50 (9.606) years. The mean of C-reactive protein (CRP) serum of the experimental group on day 1 (CRP +1) after CPT was 17.50 (25.343) while the control group was 77.50 (75.177) with p = 0.028 (p < 0.05). However, there were no differences in sequential organ failure assessment, hemoglobin, leukocyte, platelet, partial pressure of oxygen, D-dimer, procalcitonin, interleukin-6, lactate dehydrogenase, ferritin, aspartate aminotransferase, alanine aminotransferase, urea, creatinine, glomerular filtration rate, bilirubin, cycle threshold values, and chest X-ray finding between both groups. CONCLUSION: There was a significant difference in CRP +1 between the experimental group and control group, while no significant differences found in other parameters between both groups. As CRP is an inflammatory indicator, CPT showed benefit in reducing inflammation in COVID-19 patient.

Oxygenation and Inflammatory Markers after Early Covid-19 Convalescent Plasma: A Comparison of Survivors and Non-Survivors

Background Acute respiratory distress syndrome (ARDS) is a major complication in patients with severe coronavirus disease in 2019 (COVID-19). COVID-19 convalescent plasma (CCP) has been proposed as a specific therapy for patients with COVID-19. Our goal is to assess changes in oxygenation and inflammatory markers in patients after receiving CCP. Methods This is a retrospective, health system-based, a case-control study comparing hospitalized patients with COVID-19 who received CCP and were discharged (survivors) to patients who died after receiving CCP (non-survivors). We analyzed the severity of ARDS, oxygenation, and inflammatory markers of 295 patients, comparing 202 survivors to 93 non-survivors with COVID-19 who received CCP. Demographic information and laboratory data were collected on the day of the admission (initial), the day of the plasma infusion (D1), and post-infusion days 3, 7, 15, and 30 (when available). Results Survivors were younger (52.48 y versus 64.02 y;p<0.001) with no pre-existing conditions (25.2% versus 13.9%;p=0.03) compared to non-survivors. Severe ARDS (PaO2/FiO2 <100) was predictive of increased mortality after CCP in non-survivors (p<0.001). Survivors with mild (20%) or moderate (46%) ARDS on D1 had a 54% resolution of ARDS on D7 after CCP (p<0.001). After 72 hours of transfusion, supplemental oxygen requirements decreased by 63% of the survivors, compared to 33% of non-survivors (p<0.001). Inflammatory markers, including white blood cells, absolute neutrophils, platelets, C-reactive protein (CRP), lactate dehydrogenase (LDH), and creatinine, improved within three days in survivors after CCP (p<0.05). Baseline findings associated with a poor prognosis on D1 include a lower platelet count (219.02 versus 281.64, p<0.001), higher blood urea nitrogen (BUN) (35.41 versus 21.48, p<0.001), higher creatinine (2.24 versus 1.26, p<0.001), higher D-dimer (5.88 versus 2.46, p<0.001) and elevated lactate dehydrogenase (LDH) (698.3 versus 464.51, p<0.001) when comparing non-survivors to survivors, respectively. After 72 hours post-transfusion, the following changes were remarkable: normalization of creatinine with a mean of 1.07 in survivors versus 1.92 in non-survivors (p<0.001), a significant decrease in CRP improving from 129.27 to 84.25 in survivors versus 139.11 to 130.0 in non-survivors (p<0.001), and lower lactate dehydrogenase (LDH) in survivors (459.47) versus non-survivors (674.56, p<0.001). Conclusion In this retrospective, health system-based, case-control study, we found that the improvement in oxygenation, resolution of ARDS, and reduced inflammatory markers are seen in survivor patients after early COVID-19 convalescent plasma transfusion. These parameters can be used to assess response to COVID-19 convalescent plasma after 72 hours of the transfusion and could help physicians in the decision-making when administering CCP, especially if resources are scarce. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

SIR mathematical model of convalescent plasma transfusion applied to the COVID-19 pandemic data in Indonesia to control the spread of the disease

In this paper we develop a mathematical model of disease transmission dynamics. Although some vaccines for some infectious diseases are available, there are some cases where handling new emerging infectious diseases, such as COVID-19 pandemic, is still a difficult problem to handle. Preventive actions, such as wearing masks, distance guarding, frequent hand washing, and others are still the most important interventions in handling the transmission of this disease. Recently, several countries have allowed the use of convalescent plasma transfusion (CPT) in the management of moderate and severe COVID-19 patients. Several early studies of this use have yielded prospective results with reduced mortality rates. A recent work also shows that using a simple discrete mathematical model of CPT could reduce the outbreak of disease transmission, in the sense of reducing the peak number of active cases and the length of the outbreak itself. In this paper, we use a continuous SIR model applied to COVID-19 pandemic data in Indonesia to address an important question whether convalescent plasma transfusion may reduce the transmission of the disease. © Content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence.