Efficacy and safety of Link Natural Sudarshana, an Ayurvedic herbal preparation in COVID-19 patients: A phase II multicenter double-blind randomized placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: In vitro and in vivo studies have shown anti-viral and immunomodulatory actions in components of many traditional medicines. Various constituents of traditional medicines have been found to be effective against coronavirus disease (COVID-19) in several clinical trials and in-silico studies. Sudarshana cúrna, a polyherbal Ayurvedic medicine, has been used over thousands of years for a variety of infectious fevers. AIMS OF THE STUDY: This study aimed to evaluate the efficacy and safety of Link Natural Sudarshana (LNS) tablets, in patients with COVID 19 disease. LNS is a polyherbal preparation comprising 49 medicinal plants included in the Sudarshana cúrna. MATERIALS AND METHODS: A randomized parallel-group double-blind placebo-controlled multi-center phase II clinical trial was conducted in patients with mild to moderate COVID-19 disease. They were randomly allocated to intervention and control groups. The intervention group received LNS tablets whereas the control group received placebo tablets for 10 days or until the patient was discharged from the hospital. All patients received standard symptomatic treatment. The primary outcome, a reduction in mean log viral load was assessed at day 5 of treatment. The secondary outcomes, clinical progression and safety, were assessed by, monitoring changes in symptoms daily on a Likert scale ranging from 1 to 4 and laboratory tests respectively. RESULTS: A total of 171 patients (treatment group 83, control group 88) completed the trial. There were no significant differences between the baseline status of the two groups except that body mass index was significantly higher in the placebo group. The mean log viral load reduction at day 5 was higher in the treatment group (2.20 ± 1.67) compared to the placebo group (1.93 ± 1.80), with a mean difference of -0.278. This difference was not statistically significant at the 5% significant level. Reduction of mean cumulative symptom score, which included 16 symptoms graded according to severity, was higher in the treatment group compared to the placebo group. This difference was not statistically significant. None of the study participants developed hypoxia. Among the 7 lymphopenia patients in the placebo group, 3 continued to have lymphopenia at day 10, whereas 9 lymphopenia patients in the treatment group, reverted to normal counts. C reactive proteins (CRP) showed a greater reduction in the treatment group. None reported adverse effects. No significant changes occurred in hematological and biochemical parameters that assessed safety. CONCLUSIONS: LNS is safe to use in COVID-19 patients and accelerated the decline in viral load, relieved symptoms, reduced CRP levels and reversed lymphopenia earlier, when compared to the placebo.

Reactogenicity and persistence of IgG antibodies against SARS-CoV-2 among recipients of ChAdOx1 nCoV-19 vaccine: A single center experience from Sri Lanka.

Objectives: Actual world data on vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are imperative for future immunization decisions. We studied the reactogenicity and IgG response in a cohort dually vaccinated with the ChAdOx1 nCoV-19 vaccine. Methods: This prospective study recruited 494 ChAdOx1 nCoV-19 vaccine recipients at the University Hospital KDU between January 30 and February 5, 2021, and followed up for 9 months. The two doses of the vaccine were administered 3-month apart, followed by a booster dose with the BNT162b2 (Pfizer-BioNTech) vaccine 6 months later. One-week post-vaccination surveillance ascertained the reactogenicity of the vaccine. Seroprevalence of IgG antibodies before each vaccination dose was determined using a commercially available quantitative ELISA kit (WANTAI SARS-CoV-2 IgG Quantitative ELISA Beijing China). Reactogenicity profiles after vaccination doses were compared. Association of pre-vaccination seropositivity and demographic variables with antibody levels was assessed. Results: Reactogenicity was reported by 78.5% (329/419) and 25.4% (104/410) participants after the first and second doses, respectively, with a significantly high mean total score of vaccine-related symptoms following the first dose (P = 0.015). Post-first dose seroconversion rate was 97.1%, and the immune response was more robust among pre-vaccination seropositive participants and females. Following the second dose, 100% seroconversion was observed. Subgroup analysis of 196 participants revealed persistent antibodies at nine months with a rise in the previously measured levels among 78.1% compared to 21.9% with declining titers. Antibody waning was significantly associated with pre-vaccination seropositivity (P = 0.015) and female gender (P = 0.022). Conclusions: High seroconversion rates and longevity of antibody response in the absence of serious concerns regarding reactogenicity suggest that the vaccine is immunogenic and safe. Significant antibody waning among females and pre-vaccination seropositive participants warrant further research.

An unusual presentation of anaphylaxis with severe hypertension: a case report.

BACKGROUND: Low blood pressure and associated postural symptoms are well-recognized manifestations of anaphylaxis. Nonetheless, anaphylaxis can present with high blood pressure and is rarely reported in the literature. We report an unusual presentation of anaphylaxis with severe supine hypertension and orthostatic intolerance. CASE PRESENTATION: A 43-year-old Asian female presented to the emergency department with generalized itching, hives, and postural dizziness after taking a slow-release diclofenac sodium 100 mg tablet. On admission, the patient was tachycardic with a supine blood pressure of 200/100 mmHg. She had urticaria and bilateral rhonchi. A clinical diagnosis of anaphylaxis was made. She was treated with intravenous hydrocortisone and chlorpheniramine, but intramuscular adrenaline was withheld owing to her high blood pressure. She was kept in the supine position, and her vital parameters were closely monitored. Although the respiratory and cutaneous symptoms improved with treatment, her blood pressure remained elevated. Forty minutes later, the postural dizziness recurred as she sat up on the bed and her blood pressure plummeted from 198/100 mmHg to 80/60 mmHg. She was put back in the supine position immediately, and the blood pressure was restored with three doses of intramuscular adrenaline and a fluid bolus. Her postural symptoms completely resolved after adrenaline, but her blood pressure remained elevated. Two weeks after the initial presentation, a diagnosis of essential hypertension was made, which probably had been undetected. In anaphylaxis, where the cardiovascular system is involved, a blood pressure reduction from baseline is expected in patients with preexisting hypertension. Despite cardiovascular involvement, our patients' blood pressure on presentation to the emergency department was much higher than her pretreatment ambulatory blood pressure, thus making this presentation unusual. CONCLUSIONS: Diagnosis and treatment of anaphylaxis can be delayed in patients presenting with high blood pressure. Postural symptoms should alert the clinician to cardiovascular involvement despite elevated supine blood pressure. Early treatment with adrenaline should be considered in these patients with extreme caution.

Severity of SARS-CoV-2 infection among vaccinated individuals: A hospital-based study.

Introduction: Post-vaccination infections impart the need for real-world data on protection conferred by the vaccines against SARS-CoV-2. We aimed to evaluate the severity of post-vaccination COVID-19 and the predictors of severe disease. Methods: This cross-sectional study analysed data from 307 patients admitted to the University Hospital KDU with confirmed COVID- 19 from March 1st to November 1st, 2021, after receiving at least a single dose of a vaccine against SARS-CoV-2. Vaccination status and the disease severity were classified using standard definitions. A binary logistic regression model was fitted to investigate severe/critical disease predictors. Results: Of the surveyed patients, 122(39.7%) were fully vaccinated, 127(41.4%) were partially vaccinated and 58 (18.9%) had developed the disease within 14 days of the first vaccine dose. Most were Sinopharm vaccine recipients (52.4 %). Non- severe disease was observed among 249(81.1%) patients and 47(15.3%) had severe disease, while 11(3.6%) needed ICU care (critical illness). Severe/critical disease was reported among 32(25.2%) partially vaccinated and 13(22.4%) patients who developed the disease within 14 days of the first vaccine dose. Of the patients deemed to have vaccine breakthrough infections (122 fully vaccinated patients), 13(10.6%) suffered severe/critical disease. Patients with comorbidity experienced more severe/critical illness (adjusted odds ratio [AOR]= 3.684, P=0.003) than those without pre-existing medical conditions. Disease progression to severe or critical illness was significantly higher among Sinopharm recipients than Covisheild recipients (AOR:2.064, P=0.048). Conclusions: Comorbidity was the most important predictor of severe COVID-19 irrespective of the vaccination status. Observed higher incidence of severe disease among Sinopharm recipients warrants more extensive population studies.

Late presentation of a cauda equina lesion with a vulval abscess: a case report.

BACKGROUND: Cauda equina syndrome is a rare clinical condition that requires prompt diagnosis and timely surgical decompression with postoperative rehabilitation to prevent devastating complications. CASE PRESENTATION: A 55-year-old Sinhalese woman presented with a vulval abscess, with a history of involuntary leakage of urine for the last 7 years. Her sexual activity has been compromised due to coital incontinence, and she had also been treated for recurrent urinary tract infections during the last 7 years. On examination, a distended bladder was found. Neurological examination revealed a saddle sensory loss of S2-S4 dermatomes. There was no sensory loss over the lower limbs. Bladder sensation was absent, but there was some degree of anal sphincter tone. Motor functions and reflexes were normal in the limbs. Magnetic resonance imaging revealed L5-S1 spondylolisthesis. Ultrasound imaging confirmed the finding of a distended bladder, in addition to bilateral hydroureters with hydronephrosis. An incision and drainage with concomitant intravenous antibiotics were started for the vulval abscess. An indwelling catheter was placed to decompress the bladder and to reduce vulval excoriations due to urine. Bilateral ureteric stenting was performed later for persistent hydronephrosis and hydroureter despite an empty bladder. CONCLUSION: This is a tragic case that illustrates the devastating long-term sequelae that ensues if cauda equina syndrome is left undiagnosed. It reiterates the importance of prompt referral and surgical decompression.

Medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome.

BACKGROUND: Medullary nephrocalcinosis and distal renal tubular acidosis are closely associated and each can lead to the other. These clinical entities are rare in patients with nephrotic syndrome and polycythaemia is an unusual finding in such patients. We describe the presence of medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome due to minimal change disease. Proposed mechanisms of polycythaemia in patients with nephrotic syndrome and distal renal tubular acidosis include, increased erythropoietin production and secretion of interleukin 8 which in turn stimulate erythropoiesis. CASE PRESENTATION: A 22 year old Sri Lankan Sinhala male with nephrotic syndrome due to minimal change disease was investigated for incidentally detected polycythaemia. Investigations revealed the presence of renal tubular acidosis type I and medullary nephrocalcinosis. Despite extensive investigation, a definite cause for polycythaemia was not found in this patient. Treatment with potassium and bicarbonate supplementation with potassium citrate led to correction of acidosis thereby avoiding the progression of nephrocalcinosis and harmful effects of chronic acidosis. CONCLUSION: The constellation of clinical and biochemical findings in this patient is unique but the pathogenesis of erythrocytosis is not clearly explained. The proposed mechanisms for erythrocytosis in other patients with proteinuria include increased erythropoietin secretion due to renal hypoxia and increased secretion of interleukin 8 from the kidney. This case illustrates that there may exist hitherto unknown connections between tubular and glomerular dysfunction in patients with nephrotic syndrome.

Cytomegalovirus associated transverse myelitis in an immunocompetent host with DNA detection in cerebrospinal fluid; a case report.

BACKGROUND: Cytomegalovirus associated transverse myelitis among immunocompetent adults has been rarely reported. We report a patient presenting with clinical myelitis followed by previously unreported finding of cytomegalovirus deoxyribonucleic acid in cerebrospinal fluid. CASE REPORT: A forty year old immunocompetent male presented with acute onset progressive bilateral lower limb weakness. His spinal magnetic resonance imaging findings, cerebrospinal fluid analysis and clinical picture were compatible with transverse myelitis. Polymerase chain reaction of the cerebrospinal fluid for cytomegalovirus was positive while other infectious agents were not detected by serology or polymerase chain reaction. He was treated with intravenous ganciclovir with partial clinical response. CONCLUSION: Viral genome detection in the cerebrospinal fluid was performed but negative in five out of ten reported cases of cytomegalovirus associated transverse myelitis in the immunocompetent host. In previous cases the inability to isolate the virus in cerebrospinal fluid was considered favouring an immunological mechanism leading to pathogenesis rather than direct viral toxicity but this case is against that theory. This case highlights the fact that Cytomegalovirus should be considered as an aetiological agent in patients with transverse myelitis and that the virus may cause serious infections in immunocompetent host. Therefore this report is of importance to neurologists and physicians in general.

Cold autoimmune haemolytic anaemia secondary to Epstein Barr virus infection presenting with peripheral gangrene; case report.

A sixty year old male presented with dark urine, symptomatic anaemia and peripheral gangrene following cold exposure. Investigations revealed that he had haemolysis and serological evidence of recent Epstein Barr virus infection. Although acrocyanosis is commonly associated with cold agglutinin disease, gangrene is a rare complication. Management of secondary cold agglutinin disease is mainly supportive.