Locally harvested Covid-19 convalescent plasma could probably help combat the geographically determined SARS-CoV-2 viral variants

The only effective way to provide individuals with herd immunity against the novel coronavirus [SARS-CoV-2] is to administer an effective vaccine that will help check the current pandemic status. In India, the central drugs standard control organization (CDSCO) has granted the emergency-use authorization [EUA] to three vaccines namely, Covishield (live vaccine, Oxford AstraZeneca, United Kingdom being manufactured by the Serum Institute of India), Covaxin (inactivated vaccine, Bharat Biotech, India) and Sputnik V (live vaccine, Gamaleya, Russia). However, there is a rising need for the efficacy of the vaccines to be proven against the “SARS-CoV-2 viral variants.” Also, human plasma is polyclonal in nature with an inherent propensity to identify multiple epitopes of either an antigen or pathogen. With this context in mind, the researchers hypothesize that using COVID-19 convalescent plasma [CCP] harvested from the locally recovered individuals [i.e. potential CCP donors] may be particularly beneficial in combating not only the founder SARS-CoV-2 virus but also the geographically determined SARS-CoV-2 variants among the regionally affected COVID-19 patients.     

Evaluation of serum soluble HLA-G levels post-recovery from COVID-19 and post-vaccination (Sinopharm and Pfizer-BioNTech)

Serum soluble HLA-G (sHLA-G) levels have been shown to be upregulated in COVID-19 patients. In this study, sHLA-G levels were examined in COVID-19 patients 14–21 days post-recovery (100 patients) and 80 uninfected controls. In addition, individuals vaccinated with Sinopharm or Pfizer-BioNTech (50 individuals each) were followed 21 days post-first dose and 21 days post-second dose. Serum sHLA-G levels were significantly higher in recovered patients than in controls. The first and second doses of Sinopharm and Pfizer-BioNTech were associated with significantly elevated levels of sHLA-G compared to controls or recovered patients, except for the first dose of Pfizer-BioNTech where sHLA-G levels did not show significant differences compared to recovered patients. In conclusion, recovery from COVID-19, as well as vaccination with two doses of Sinopharm or Pfizer-BioNTech, were associated with up-regulated levels of sHLA-G molecules, but the first dose of Sinopharm had the greatest effect in raising sHLA-G levels.     

Retest positive for SARS-CoV-2 RNA of “recovered” patients with COVID-19: Persistence,sampling issues,or re-infection?

“Retest Positive” for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) from “recovered” coronavirus disease-19 (COVID-19) has been reported and raised several important questions for this novel coronavirus and COVID-19 disease. In this commentary, we discussed several questions: (a) Can SARS-CoV-2 re-infect the individuals who recovered from COVID-19? This question is also associated with other questions: whether or not SARS-CoV-2 infection induces protective reaction or neutralized antibody? Will SARS-CoV-2 vaccines work? (b) Why could some recovered patients with COVID-19 be re-tested positive for SARS-CoV-2 RNA? (c) Are some recovered pwith atients COVID-19 with re-testing positive for SARS-CoV-2 RNA infectious? and (d) How should the COVID-19 patients with retest positive for SARS-CoV-2 be managed?     

Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections: a multicentre cohort study

ObjectivesHighly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections.MethodsWe conducted a multicentre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals.ResultsOut of 218 individuals with B.1.617.2 infection, 84 received an mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and four received a non-mRNA vaccine. Despite significantly older age in the vaccine breakthrough group, only 2.8% (2/71) developed severe COVID-19 requiring oxygen supplementation compared with 53.1% (69/130) in the unvaccinated group (p < 0.001). Odds of severe COVID-19 following vaccination were significantly lower (adjusted odds ratio 0.07 95% CI 0.015–0.335, p 0.001). PCR cycle threshold values were similar between vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients; however, these titres were significantly lower against B.1.617.2 than the wildtype vaccine strain.DiscussionThe mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of the COVID-19 pandemic.     

Multisystem Inflammatory Syndrome in an Adult after COVID-19 Vaccination: a Case Report and Literature Review

As the number of people vaccinated increases, people who complain of adverse reactions continue to occur. We experienced a case characterized by low blood pressure, persistent fever, edema due to increased systemic vascular permeability, and systemic inflammation confirmed by image and laboratory examinations after ChAdOx1 coronavirus disease 2019 (COVID-19) vaccination. The diagnostic criteria for multisystem inflammatory syndrome (MIS) in adults are known as fever of 3 days or more in adults, 2 or more mucocutaneous/gastrointestinal/neurologic symptoms, elevation of inflammatory markers, and clinical/imaging diagnosis of heart failure. A 67-year-old man who was medicated for hypertension and diabetes was admitted complaining of fever, maculopapular rash, diarrhea, headache, chills, and dizziness 6 days after the first vaccination of ChAdOx1 nCoV-19 in Korea. The COVID-19 test was negative but with low blood pressure, leukocytosis, skin rash, pulmonary edema, and increased inflammation markers. His lab findings and clinical course were consistent with those of MIS after COVID-19 vaccination. He was medicated with methylprednisolone 1 mg/kg and diuretics and recovered rapidly. He was discharged after 2 weeks and confirmed cure at outpatient clinic. We report an MIS case after COVID-19 vaccination in Korea.     

The blood supply management amid the COVID-19 outbreak

Due to the government's early intervention such as mass lockdown and curtailment strategies towards mass gatherings, amid the COVID-19 outbreak, the organization of the voluntary blood donation camps have been suspended. It's most significant impact on the blood community has been a dramatic decrease in the number of blood donors. Therefore, our blood stock has almost dried up and put our inventory in a state of jeopardy. Additionally, all the elective surgeries and non-urgent clinical interventions have also been deferred during this time. This has led to a drop in the blood collection, demand as well as the issue at our blood center. With this backdrop, we intended to assess the effect of this mass lockdown on our blood supply management, particularly in two phases [phase-I prior to the outbreak] and phase-II [during the outbreak]. Transitioning back to the normal conditions would most likely depend on the extent and the time duration of this pandemic and associated behavioural change, which is foreseen to remain in effect well beyond the original estimates.     

BNT162b2 vaccine breakthrough: clinical characteristics of 152 fully vaccinated hospitalized COVID-19 patients in Israel

ObjectivesThe mRNA coronavirus disease 2019 (COVID-19) vaccines have shown high effectiveness in the prevention of symptomatic COVID-19, hospitalization, severe disease and death. Nevertheless, a minority of vaccinated individuals might become infected and experience significant morbidity. Characteristics of vaccine breakthrough infections have not been studied. We sought to portray the population of Israeli patients, who were hospitalized with COVID-19 despite full vaccination.MethodsA retrospective multicentre cohort study of 17 hospitals included patients fully vaccinated with Pfizer/BioNTech's BNT162b2 vaccine who developed COVID-19 more than 7 days after the second vaccine dose and required hospitalization. The risk for poor outcome, defined as a composite of mechanical ventilation or death, was assessed.ResultsA total of 152 patients were included, accounting for half of hospitalized fully vaccinated patients in Israel. Poor outcome was noted in 38 patients and mortality rate reached 22% (34/152). Notably, the cohort was characterized by a high rate of co-morbidities predisposing to severe COVID-19, including hypertension (108; 71%), diabetes (73; 48%), congestive heart failure (41; 27%), chronic kidney and lung diseases (37; 24% each), dementia (29; 19%) and cancer (36; 24%), and only six (4%) had no co-morbidities. Sixty (40%) of the patients were immunocompromised. Higher viral load was associated with a significant risk for poor outcome. Risk also appeared higher in patients receiving anti-CD20 treatment and in patients with low titres of anti-Spike IgG, but these differences did not reach statistical significance.ConclusionsWe found that severe COVID-19 infection, associated with a high mortality rate, might develop in a minority of fully vaccinated individuals with multiple co-morbidities. Our patients had a higher rate of co-morbidities and immunosuppression compared with previously reported non-vaccinated hospitalized individuals with COVID-19. Further characterization of this vulnerable population may help to develop guidance to augment their protection, either by continued social distancing, or by additional active or passive vaccinations.     

A novel scoring system for selecting the target patients of COVID-19 convalescent plasma therapy: A hypothesis

The primary cause of mortality in patients of coronavirus disease 2019 (COVID-19) is the cytokine storm and not directly due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Therefore, it is being stressed by transfusion medicine specialists to use COVID-19 convalescent plasma (CCP) therapy early in the course of the disease, preferably within 72 h of diagnosis. The authors herein, propose a scoring system for the rapid assessment of the patients who have tested positive for SARS-CoV-2. Therefore, a systematic approach may be followed where the patients are categorised into two groups, namely, the low-risk group [LRG; score < 5] and the high-risk group [HRG; score ≥ 5] based on this scoring system. Those classified as an HRG should be administered CCP therapy within 72 h of a confirmed diagnosis of COVID-19 to neutralise the SARS-CoV-2 virus and prevent the occurrence of the cytokine storm. This in turn could help reduce the overall mortality in the recipients.     

The autonomic aspects of the post-COVID19 syndrome

The SARS-CoV-2 outbreak, responsible for the widespread COVID-19, led to one of the most rogue pandemics in modern time, yet the major effects of the pandemic may still be ahead of us. SARS-CoV-2 had been found to possess autoimmune properties. Close to 20 distinct autoantibodies which target GPCR of the nervous system and renin-angiotensin system-related molecules were found significantly associated with the clinical severity of COVID-19. The new on-set of more than 10 various autoimmune disorders were documented as well. Additionally, clinical presentations of persisted symptoms were triggered in numerous recently recovered COVID-19 patients, which led to the formulation of the novel term “post-COVID19 syndrome”. Manifestations related to post-COVID-19 syndrome exist among approximately 50–80% of symptomatic COVID-19 patients who recovered, and among patients reported more than 50 different long-term effects of the SARS-CoV-2 infection. Many of the common symptoms of the post-COVID19 syndrome are not explained by the virus-related injury alone. Similarly to chronic fatigue syndrome and fibromyalgia, autoimmune-mediated autonomic nervous system dysfunction may play a significant part in the pathogenesis of such symptoms, including chronic fatigue, cognitive impairment, mood related disorders, and numerous more. Importantly, therapeutic options such as immunomodulatory and immunosuppressive therapy may favor some post-COVID19 patients, while plasmapheresis and IVIG could be considered in severe cases. Nevertheless, as physical exercise has been found to stabilize the autonomic nervous system, exercise therapy might be a safer and more effective remedy for the post-COVID19 syndrome.     

The effectiveness of quarantine of Wuhan city against the Corona Virus Disease 2019 (COVID-19): A well-mixed SEIR model analysis

A novel coronavirus pneumonia, first identified in Wuhan City and referred to as COVID-19 by the World Health Organization, has been quickly spreading to other cities and countries. To control the epidemic, the Chinese government mandated a quarantine of the Wuhan city on January 23, 2020. To explore the effectiveness of the quarantine of the Wuhan city against this epidemic, transmission dynamics of COVID-19 have been estimated. A well-mixed “susceptible exposed infectious recovered” (SEIR) compartmental model was employed to describe the dynamics of the COVID-19 epidemic based on epidemiological characteristics of individuals, clinical progression of COVID-19, and quarantine intervention measures of the authority. Considering infected individuals as contagious during the latency period, the well-mixed SEIR model fitting results based on the assumed contact rate of latent individuals are within 6–18, which represented the possible impact of quarantine and isolation interventions on disease infections, whereas other parameter were suppose as unchanged under the current intervention. The present study shows that, by reducing the contact rate of latent individuals, interventions such as quarantine and isolation can effectively reduce the potential peak number of COVID-19 infections and delay the time of peak infection.     

Bioethical perspective of convalescent plasma therapy for COVID-19: A systematic review

Convalescent plasma therapy (CP) has long been used to prevent and treat various infectious diseases before COVID-19 such as SARS, MERS, and H1N1. Because the viral and clinical characteristics of COVID-19 share the similarities between SARS and MERS, CP treatment could be a promising treatment option to save COVID-19. With only low quality medical evidence, but massive media support and a very significant public demand for the use of convalescent plasma for COVID-19, we are now faced with an ethical dilemma. Therefore, this paper uses a structured analysis that focuses on the preferred reporting items for a systematic review of ethical issues regarding the use of Convalescent Plasma Therapy for COVID-19. The use of convalescent plasma must meet the ethical principles of autonomy; such as voluntary, informed consent, and confidentiality. Consideration of the risk-benefit ratio for potential donor recipients also needs to be considered in order to meet the beneficence and non-maleficence principles. The principle of justice also needs to be applied both to donors, donor recipients and health workers, such as determining the priority of donor recipients, due to the increasing demand for convalescent plasma amid the limited circumstances of patients who have recovered from Covid-19 who voluntarily donate.     

The impact of COVID-19 vaccinations on stillbirth rates among pregnant women in the Metro-Detroit area

Infection by COVID-19 increases maternal morbidity and mortality prompting both the American College of Obstetrics and Gynecology and the Society of Maternal Fetal Medicine to strongly recommend vaccination during pregnancy. Limited data exist assessing the risk of intrauterine fetal death (IUFD) associated with COVID vaccination during pregnancy.This was a retrospective chart review at a large multisite hospital system in Metro Detroit which reviewed data from 13,368 pregnancies. We compared IUFD rates between vaccinated and unvaccinated patients. The rate of stillbirths among unvaccinated women (0.75%) was not statistically different from those who were vaccinated (0.60%). Individuals with government insurance were less likely to be vaccinated and more likely to have IUFD in comparison to patients with private insurance. The rate of stillbirths among Black women was significantly higher than among White women at a rate of 1.1% compared to 0.53% (p=0.008) with no difference in stillbirth rates among vaccinated vs unvaccinated racial distribution. Lastly, it is worth noting that the overall vaccination rate at our healthcare system in pregnancy was very poor (0.26%).In conclusion, this is a large population of highly diverse patients which indicates that COVID-19 vaccination does not lead to IUFD. We plan to use this data to help drive an educational vaccination campaign to try to increase our COVID-19 vaccination rate in our pregnant patients. Systemic racism and social determinants of health have played a large factor in COVID-19 outcomes, and our data highlights that this is the case for IUFD in Black women. Improvements must be made to identify barriers for these women to allow for better pregnancy outcomes. We acknowledge that individuals with government insurance may also have other barriers to healthcare or face healthcare inequity which leaves room for improvement on getting these individuals vaccinated and getting the resources they need to have better pregnancy outcomes.     

Breakthrough COVID-19 Infection During the Delta Variant Dominant Period: Individualized Care Based on Vaccination Status Is Needed

BackgroundThe clinical features of coronavirus disease 2019 (COVID-19) patients in the COVID-19 vaccination era need to be clarified because breakthrough infection after vaccination is not uncommon.MethodsWe retrospectively analyzed hospitalized COVID-19 patients during a delta variant-dominant period 6 months after the national COVID-19 vaccination rollout. The clinical characteristics and risk factors for severe progression were assessed and subclassified according to vaccination status.ResultsA total of 438 COVID-19 patients were included; the numbers of patients in the unvaccinated, partially vaccinated and fully vaccinated groups were 188 (42.9%), 117 (26.7%) and 133 (30.4%), respectively. The vaccinated group was older, less symptomatic and had a higher Charlson comorbidity index at presentation. The proportions of patients who experienced severe progression in the unvaccinated and fully vaccinated groups were 20.3% (31/153) and 10.8% (13/120), respectively. Older age, diabetes mellitus, solid cancer, elevated levels of lactate dehydrogenase and chest X-ray abnormalities were associated with severe progression, and the vaccination at least once was the only protective factor for severe progression. Chest X-ray abnormalities at presentation were the only predictor for severe progression among fully vaccinated patients.ConclusionIn the hospitalized setting, vaccinated and unvaccinated COVID-19 patients showed different clinical features and risk of oxygen demand despite a relatively high proportion of patients in the two groups. Vaccination needs to be assessed as an initial checkpoint, and chest X-ray may be helpful for predicting severe progression in vaccinated patients.     

Pulmonary mucormycosis in the aftermath of critical COVID-19 in an immunocompromised patient: Mind the diagnostic gap

Mucormycosis has recently been recognized as a severe complication of COVID-19 with high fatality rates. We report a fatal case of COVID-19 associated mucormycosis (CAM) in a non-diabetic immunocompromised patient, who was first misdiagnosed and treated for COVID-19 associated aspergillosis (CAPA). The risk factors and initial clinical presentation of CAPA and CAM are similar, but CAM has a more aggressive course and CAPA and CAM are treated differently. Dedicated diagnostic workup is essential to ensure early treatment of CAM with surgical debridement and targeted antifungal therapy.     

The Importance of Early Recognition,Timely Management,and the Role of Healthcare Providers in Multisystem Inflammatory Syndrome in Children

In April 2020, a pediatric report of an unusual inflammatory illness associated with coronavirus disease 2019 (COVID-19) led to similar cases in Europe and North America, which was referred to as multisystem inflammatory syndrome in children (MIS-C). Herein, we describe the case of a 12-year-old boy who had a history of polymerase chain reaction-confirmed COVID-19 and developed MIS-C approximately three weeks after an initial diagnosis of COVID-19. High fever with abdominal pain mimicking appendicitis was the initial manifestation of MIS-C, which could have been easily missed if the patient''s history of COVID-19 was ignored. Intravenous immunoglobulin was administered twice, 24 hours apart, five days after the onset of MIS-C, and the patient fully recovered without any obvious sequelae. Early recognition by disease awareness and prompt management are the keys to saving the lives of children affected by MIS-C.     

COVID-19 in dialysis units: A comprehensive review

The coronavirus disease 2019 (COVID-19) pandemic has been challenging for healthcare professionals worldwide. One of the populations affected by the pandemic are patients on renal replacement therapy, as kidney disease is an independent risk factor for severe COVID-19 and maintenance dialysis (a life-sustaining therapy) cannot be interrupted in the vast majority of cases. Over the past months, several authors and medical societies have published recommendations and guidelines on the management of this population. This article is a comprehensive review regarding the measures to prevent, contain and deal with a COVID-19 pandemic in the dialysis setting. We recapitulate the epidemiology and pathophysiology of COVID-19 in kidney dysfunction and present the main recommendations concerning the screening of healthcare personnel, dialysis patients and visitors as well as measures to improve the safety of the dialysis facilities’ environments. In addition to preventive measures, this article briefly describes actions directed towards management of an outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within a dialysis facility, the management of complications in dialysis patients with COVID-19 and overall data regarding the management of children with kidney disease.     

The impact of COVID-19 on transfusion-dependent thalassemia patients of Karachi,Pakistan: A single-center experience

ObjectivesWith the advent of COVID-19 in Pakistan, the already fragmented blood transfusion services (BTS) received a severe blow, putting the lives of transfusion-dependent thalassemia children on stake. This study aimed to assess the impact of the COVID-19 on blood transfusion therapy (BTT) of thalassemia patients and suggest ways to ensure safe and reliable blood supplies amid such health crises.Material and methodsA retrospective, cross-sectional study was conducted from October 2019 (before COVID-19) to July 2020 (during COVID-19) based on the data provided by a thalassemia center, named Help International Welfare Trust, Karachi, Pakistan. SPSS version 24.0 was used for the data analysis. Data were described in the form of means and percentages.ResultsThere was a significant reduction in the consumption of PRBCs bags after the emergence of COVID-19 (P = 0.002). Moreover, the number of thalassemia patients receiving BTT was dropped by 10.56% during the pandemic. There was a strong negative correlation observed between the rising cases of COVID-19 in Pakistan and the number of patients missing their therapy sessions (r = ?0.914, P = 0.030). A considerable decline in the reserves of all Rhesus-negative blood groups amid the COVID-19 outbreak was also observed.ConclusionThe COVID-19 pandemic adversely affected the already suboptimal care catered to thalassemia patients in Karachi, Pakistan. The fear of the virus contraction coupled with the lockdown and restricted mobility has disrupted the entire transfusion chain from donor to the recipient. Collaborated efforts by the government and healthcare authorities are essential to ensure sufficient blood for thalassemia patients amid the pandemic.     

Prevalence of COVID-19 in Iran: results of the first survey of the Iranian COVID-19 Serological Surveillance programme

ObjectivesThis study aims to estimate the prevalence of coronavirus disease 2019 (COVID-19) in the general population of Iran.MethodsThe target population was all Iranian people aged 6 years and older in the country. A stratified random sampling design was used to select 28 314 people from among the individuals registered in the electronic health record systems used in primary health care in Iran. Venous blood was taken from each participant and tested for the IgG antibody against COVID-19. The prevalence of COVID-19 was estimated at provincial and national levels after adjusting for the measurement error of the laboratory test, non-response bias and sampling design.ResultsOf the 28 314 Iranians selected, 11 256 (39.75%) participated in the study. Of these, 5406 (48.0%) were male and 6851 (60.9%) lived in urban areas. The mean (standard deviation) participant age was 35.89 (18.61) years. The adjusted prevalence of COVID-19 until 20 August 2020 was estimated as 14.2% (95% uncertainty interval 13.3%–15.2%), which was equal to 11 958 346 (95% CI 11 211 011–12 746 776) individuals. The adjusted prevalences of infection were 14.6%, 13.8%, 16.6%, 11.7% and 19.4% among men, women, urban population, rural population and individuals aged 60 years or more, respectively. Ardabil, Golestan and Khuzestan provinces had the highest prevalence and Alborz, Hormozgan and Kerman provinces had the lowest.ConclusionsBased on the study results, a large proportion of the Iranian population had not yet been infected by COVID-19. The observance of hygienic principles and social restrictions should therefore continue until the majority of the population has been vaccinated.     

Post-donation information and haemovigilance reporting for COVID-19 in Greece: Information supporting the absence of SARS-CoV-2 possible transmission through blood components

BackgroundAlthough the SARS-CoV-2 virus is transmitted mainly through the respiratory tract, possible transmission by transfusion from asymptomatic carriers should be explored. As yet there are no reports of transfusion transmission of COVID-19. Haemovigilance findings within a three-month surveillance period during the new coronavirus pandemic are presented.Materials and methodsDue to great demand and shortage, blood sessions in outpatient facilities were organized during the high prevalence period of COVID-19, alongside a national plan to monitor the evolving public health situation by random molecular screening of high-risk groups of the population. Haemovigilance protocols were implemented as well as surveillance for any COVID-19 case reported post-transfusion. A 14-day quarantine and follow-up molecular and antibody testing of any COVID-19 positive case was obligatory.ResultsPost-donation, post-transfusion information and molecular testing of swab samples collected from three asymptomatic donors at risk for COVID-19, revealed the case of an immunosupressed patient who had been transfused with whole blood derived platelets from a donor subsequently diagnosed with COVID-19. The recipient exhibited no symptoms of the disease. Molecular and antibody testing results were negative.ConclusionHaemovigilance provided information supporting the absence of transfusion transmission of COVID-19, thus strengthening the hypothesis that, even if it cannot yet be definitively ruled out, COVID-19 is not transmitted through blood transfusion. As of early June 2020, a perfect test does not exist, therefore haemovigilance along with the implementation of strict proactive measures is crucial to identify eluding asymptomatic individuals and ensure blood safety during the pandemic.