Nature and Dimensions of Systemic Hyperinflammation and its Attenuation by Convalescent Plasma in Severe COVID-19.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has led to significant morbidity and mortality. While most suffer from mild symptoms, some patients progress to severe disease with acute respiratory distress syndrome (ARDS) and associated systemic hyperinflammation. METHODS: First, to characterize key cytokines and their dynamics in this hyperinflammatory condition, we assessed abundance and correlative expression of a panel of 48 cytokines in patients progressing to ARDS as compared to patients with mild disease. Then, in an ongoing randomized controlled trial of convalescent plasma therapy (CPT), we analyzed rapid effects of CPT on the systemic cytokine dynamics as a correlate for the level of hypoxia experienced by the patients. RESULTS: We identified an anti-inflammatory role of CPT independent of its neutralizing antibody content. CONCLUSIONS: Neutralizing antibodies, as well as reductions in circulating interleukin-6 and interferon-γ-inducible protein 10, contributed to marked rapid reductions in hypoxia in response to CPT. CLINICAL TRIAL REGISTRY OF INDIA: CTRI/2020/05/025209. http://www.ctri.nic.in/.

A phase 2 single center open label randomised control trial for convalescent plasma therapy in patients with severe COVID-19.

A single center open label phase 2 randomised control trial (Clinical Trial Registry of India No. CTRI/2020/05/025209) was done to assess clinical and immunological benefits of passive immunization using convalescent plasma therapy. At the Infectious Diseases and Beleghata General Hospital in Kolkata, India, 80 patients hospitalized with severe COVID-19 disease and fulfilling the inclusion criteria (aged more than 18 years, with either mild ARDS having PaO2/FiO2 200-300 or moderate ARDS having PaO2/FiO2 100-200, not on mechanical ventilation) were recruited and randomized into either standard of care (SOC) arm (N = 40) or the convalescent plasma therapy (CPT) arm (N = 40). Primary outcomes were all-cause mortality by day 30 of enrolment and immunological correlates of response to therapy if any, for which plasma abundance of a large panel of cytokines was quantitated before and after intervention to assess the effect of CPT on the systemic hyper-inflammation encountered in these patients. The secondary outcomes were recovery from ARDS and time taken to negative viral RNA PCR as well as to report any adverse reaction to plasma therapy. Transfused convalescent plasma was characterized in terms of its neutralizing antibody content as well as proteome. The trial was completed and it was found that primary outcome of all-cause mortality was not significantly different among severe COVID-19 patients with ARDS randomized to two treatment arms (Mantel-Haenszel Hazard Ratio 0.6731, 95% confidence interval 0.3010-1.505, with a P value of 0.3424 on Mantel-Cox Log-rank test). No adverse effect was reported with CPT. In severe COVID-19 patients with mild or moderate ARDS no significant clinical benefit was registered in this clinical trial with convalescent plasma therapy in terms of prespecified outcomes.

Congenital Pulmonary Vein Stenosis and Pulmonary Artery Branch Stenosis: A Rare Combination.

Congenital pulmonary vein stenosis is a rare entity caused due to failed incorporation of common right and/or left pulmonary vein into the left atrium. Below is a case report of a combination of predominantly left-sided pulmonary vein stenosis with right pulmonary artery branch stenosis. The patient was an adolescent boy with mild symptoms. Clinical examination revealed features of pulmonary artery hypertension. Echocardiography and computed tomography scan were done to confirm the disease.

Musculoskeletal and rheumatological disorders in HIV infection: Experience in a tertiary referral center.

BACKGROUND: Musculoskeletal involvement in human immunodeficiency virus (HIV) infected patients are important disease manifestations, responsible for increased morbidity and also decreased quality of life. OBJECTIVES: To study the spectrum of different musculoskeletal involvement in HIV infected patients and its impact on quality of life. PATIENTS AND METHODS: Three hundred (n = 300) HIV-1 reactive patients were evaluated in respect to different musculoskeletal involvement including the quality of life from January 2010 to January 2011. RESULTS: Male to female ratio was 11:1 with a mean age of 35 (±6.4) years and mean duration of the disease was 3 (±1.54) years. Majority of cases were truck drivers, motel workers, and jewelry workers. Musculoskeletal disorders were observed in a total of 190 cases (63.33%). The spectrum of musculoskeletal involvement was: Body ache in 140 (46.7%), arthralgia in 80 (26.7%), mechanical low back pain in 25 (8.3%), osteoporosis in 20 (6.7%), painful articular syndrome in 10 (3.3%), hypertrophic osteoarthropathy in two (0.7%), pyomyositis in two (0.7%), osteomyelitis in one (0.3%), and avascular bone necrosis in one patient (0.3%). Rheumatologic disorders associated were: Reactive arthritis in seven (2.3%), fibromyalgia in four (1.3%), septic arthritis in three (1%), acute gout in three (1%), spondyloarthropathy in two (0.7%), rheumatoid arthritis in two (0.7%), dermatomyositis in one (0.3%), and systemic lupus erythematosus (SLE) in one patient (0.3%). But HIV associated arthritis and diffuse infiltrative lymphocytosis syndrome (DILS) were not detected. Most of the patients had decreased quality of life. CONCLUSIONS: Musculoskeletal involvement was common in HIV patients causing increased morbidity, so early detection and timely intervention is essential to improve quality of life.

Tetanus: still a public health problem in India - observations in an infectious diseases hospital in Kolkata.

BACKGROUND: Tetanus is a major health problem in many developing countries, including India, with significant morbidity and mortality due to lack of environmental hygiene and health education, incomplete vaccination, high case prevalence and inadequate intensive care facilities. OBJECTIVES: To observe the demography, clinical profile and outcomes of tetanus patients. MATERIALS AND METHODS: A total of 282 tetanus patients were screened and closely observed prospectively from January 2010 to December 2011. RESULTS: The mean age of the study patients was 31.15 years (± 14.26) and the majority were unvaccinated or incompletely vaccinated against tetanus. Patients were mainly farmers (140, 49.64%) and children (102, 36.17%). The sources of infection identified were mainly thorn/pin prick in 129 cases (45.7%), cut/lacerated injury in 83 cases (29.4%) and ear infection in 47 cases (16.7%), while definite injurywas not detected/remembered in 42 cases (14.8%). The average duration of hospital stay was 17.2 ± (4.7) days and autonomic nervous system dysfunction was the most common complication observed in this study. Death was the outcome in a total of 58 patients (20.6%) mostly due to aspiration pneumonia-induced sepsis, respiratory failure or cardiac complications. CONCLUSION: Environmental hygiene, basic health education, increased in immunization coverage, proper wound care - even following minor injuries - and more facilities for intensive care units, may reduce the overall incidence of tetanus and mortality following onset of the disease.