The relationship between SARS-CoV-2 neutralising antibody titres and avidity in plasma collected from convalescent non-vaccinated and vaccinated blood donors.

Convalescent plasma (CP) treatment of COVID-19 has shown significant therapeutic effect when administered early (e.g. Argentinian trial showing reduced hospitalisation) but has in general been ineffective (e.g. REMAP-CAP trial without improvement during hospitalisation). To investigate whether the differences in CP used could explain the different outcomes, we compared neutralising antibodies, anti-spike IgG and avidity of CP used in the REMAP-CAP and Argentinian trials and in convalescent vaccinees. We found no difference between the trial plasmas emphasising initial patient serostatus as treatment efficacy predictor. By contrast, vaccinee convalescent plasma showed significantly higher titres and avidity, being preferable for future CP-treatment.

Mounting evidence for immunizing previously infected subjects with a single dose of SARS-CoV-2 vaccine.

Efforts to best protect the world from SARS-CoV-2 as variants emerge and despite limited vaccine supply are ongoing. One strategy that may maximize vaccine coverage and expedite immunization campaigns involves providing single mRNA vaccine doses to individuals with previous COVID-19. In this issue of the JCI, two independent studies, one by Levi and Azzolini et al. and another by Mazzoni and Di Lauria et al., explored vaccine responses in individuals previously infected with the virus. Levi and Azzolini and colleagues used multilinear regression models to correlate exposure and symptoms with antibody response to the vaccine. Mazzoni and Di Lauria and colleagues characterized B cell and T cell kinetics in whole blood after one and two doses of vaccine in health care workers with and without previous infection. Both studies indicated that one vaccine dose may sufficiently protect individuals who have recovered from COVID-19. Implementing a single-dose mRNA vaccine protocol in previously symptomatic individuals may facilitate and expedite immunization campaigns.

Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults.

BACKGROUND: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. RESULTS: A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. CONCLUSIONS: Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.).

Identifying pathophysiological bases of disease in COVID-19.

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus that can affect lung physiology encompassing a wide spectrum of severities, ranging from asymptomatic and mild symptoms to severe and fatal cases; the latter including massive neutrophil infiltration, stroke and multiple organ failure. Despite many recents findings, a clear mechanistic description underlying symptomatology is lacking. In this article, we thoroughly review the available data involving risk factors, age, gender, comorbidities, symptoms of disease, cellular and molecular mechanisms and the details behind host/pathogen interaction that hints at the existence of different pathophysiological mechanisms of disease. There is clear evidence that, by targeting the angiotensin-converting enzyme II (ACE2) -its natural receptor-, SARS-CoV-2 would mainly affect the renin-angiotensin-aldosterone system (RAAS), whose imbalance triggers diverse symptomatology-associated pathological processes. Downstream actors of the RAAS cascade are identified, and their interaction with risk factors and comorbidities are presented, rationalizing why a specific subgroup of individuals that present already lower ACE2 levels is particularly more susceptible to severe forms of disease. Finally, the notion of endotype discovery in the context of COVID-19 is introduced. We hypothesize that COVID-19, and its associated spectrum of severities, is an umbrella term covering different pathophysiological mechanisms (endotypes). This approach should dramatically accelerate our understanding and treatment of disease(s), enabling further discovery of pathophysiological mechanisms and leading to the identification of specific groups of patients that may benefit from personalized treatments.