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IntroductionA major concern amidst the ongoing coronavirus pandemic has been the longer term persistence of morbidities in individuals recovering from COVID-19 disease, called long COVID. We aimed at documenting the prevalence and key associations of post-COVID symptoms (PCS) in India in telephonic survey among recovered patients in a single hospital in eastern India as well as a parallel web-survey covering a wider population of the country. MethodsSelf-reported PCS, ranging up to one year since the original COVID-19 diagnosis, were documented in a telephonic survey of subjects (analyzed N=986), treated for acute COVID-19 in Infectious Diseases and Beleghata General Hospital, Kolkata, between April 1, 2020 and April 13, 2021. In parallel, we ran a web-based survey (analyzed N=580), to evaluate concordance. ResultsShortness of breath, fatigue and insomnia were identified to be the most commonly reported PCS in both the surveys, with higher prevalence in females. In the telephonic survey, a 3.65% post-discharge mortality was registered within a median of 39 days since COVID diagnosis. Intensive care during acute disease and hypertension were more often associated with PCS, while fatigue was more often reported by the 20-40 years age-group. The web-survey revealed a gradual decline in PCS with time since COVID-19 diagnosis and type 2 diabetes to be associated with higher prevalence of these symptoms. ConclusionsWe assessed the predominant PCS among Indian COVID-19 patients and identified key demographic and clinical associations in our surveys, which warrants deeper epidemiological and mechanistic studies for guiding management of long-COVID in the country.
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Disease caused by SARS-CoV-2 coronavirus (COVID-19) has resulted in significant morbidity and mortality world-wide. A systemic hyper-inflammation characterizes the severe COVID-19 disease often associated with acute respiratory distress syndrome (ARDS). Blood biomarkers capable of risk stratification are of great importance in effective triage and critical care of severe COVID-19 patients. In the present study we report higher plasma abundance of soluble urokinase-type plasminogen activator receptor (sUPAR), expressed by an abnormally expanded circulating myeloid cell population, in severe COVID-19 patients with ARDS. Plasma sUPAR level was found to be linked to a characteristic proteomic signature of plasma, linked to coagulation disorders and complement activation. Receiver operator characteristics curve analysis identified a cut-off value of sUPAR at 1996.809 pg/ml that could predict survival in our cohort (Odds ratio: 2.9286, 95% confidence interval 1.0427-8.2257). Lower sUPAR level than this threshold concentration was associated with a differential expression of the immune transcriptome as well as favourable clinical outcomes, both in terms of survival benefit (Hazard ratio: 0.3615, 95% confidence interval 0.1433-0.912) and faster disease remission in our patient cohort. Thus we identified sUPAR as a key pathogenic circulating molecule linking systemic hyperinflammation to the hypercoagulable state and stratifying clinical outcomes in severe COVID-19 patients with ARDS.
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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
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In a randomized control trial on convalescent plasma therapy (CPT) in severe COVID-19, we characterized the nature, in terms of abundance of forty eight cytokines, and dimensions, in terms of their interrelationships, of the hyper-immune activation-associated cytokine storm in patients suffering from acute respiratory distress syndrome. We found reduced plasma level of the chemokine MCP3 to be a key correlate for clinical improvement, irrespective of therapeutic regimen. We also identified an anti-inflammatory role of CPT independent of its neutralizing antibody content, and a linear regression analysis revealed that neutralizing antibodies as well as the anti-inflammatory effect of CPT both contribute to marked immediate reductions in hypoxia, as compared to patients on standard therapy.