IntroductionA single center open label phase II randomised control trial was done to assess the pathogen and host-intrinsic factors influencing clinical and immunological benefits of passive immunization using convalescent plasma therapy (CPT), in addition to standard of care (SOC) therapy in severe COVID-19 patients, as compared to patients only on SOC therapy.MethodsConvalescent plasma was collected from patients recovered from COVID-19 following a screening protocol which also included measuring plasma anti SARS-CoV2 spike IgG content. Retrospectively, neutralizing antibody content was measured and proteome was characterized by LC-MS/MS for all convalescent plasma units that were transfused to patients. Severe COVID-19 patients with evidence for acute respiratory distress syndrome (ARDS) with PaO2/FiO2 ratio 100-300 (moderate ARDS) were recruited and randomised into two parallel arms of SOC and CPT, N=40 in each arm. Peripheral blood samples were collected on the day of enrolment (T1) followed by day3/4 (T2) and day 7 (T3). RT-PCR and sequencing was done for SARS-CoV2 RNA isolated from nasopharyngeal swabs collected at T1. A panel of cytokines and neutralizing antibody content were measured in plasma at all three timepoints. Patients were followed up for 30 days post-admission to assess the primary outcomes of all cause mortality and immunological correlates for clinical benefits.ResultsWhile across all age-groups no statistically significant clinical benefit was registered for patients in the CPT arm, significant immediate mitigation of hypoxia, reduction in hospital stay as well as survival benefit was recorded in severe COVID-19 patients with ARDS aged less than 67 years receiving convalescent plasma therapy. In addition to its neutralizing antibody content a prominent effect of convalescent plasma on attenuation of systemic cytokine levels possibly contributed to its benefits.ConclusionPrecise targeting of severe COVID-19 patients is necessary for reaping the clinical benefits of convalescent plasma therapy.Clinical trial registrationClinical Trial Registry of India No. CTRI/2020/05/025209

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.

No abstract

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.

Novel coronavirus SARS-CoV2, causing coronavirus disease 2019 or COVID-19, led to significant morbidity and mortality. While most suffer from mild symptoms, some patients progress to a severe disease with acute respiratory distress syndrome (ARDS) and an associated systemic hyper-inflammation. First to characterize key cytokines and their dynamics in this hyper-inflammatory condition, we assessed abundance and correlative expression of a panel of forty eight cytokines in patients progressing to ARDS, as compared to patients with mild disease. Then in an ongoing randomized control 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. We identified an anti-inflammatory role of CPT independent of its neutralizing antibody content. Neutralizing antibodies as well as reductions in circulating interleukin-6 and interferon gamma induced protein 10, contributed to marked rapid reductions in hypoxia in response to CPT.