Physical function and mental health trajectories in COVID-19 patients following invasive mechanical ventilation: a prospective observational study (preprint)

This prospective observational cohort study was performed to investigate the physical function and mental health trajectories of novel coronavirus disease 2019 (COVID-19) patients requiring invasive mechanical ventilation (IMV) after discharge from the intensive care unit (ICU). The study population consisted of 64 patients (median age, 60 years; 85.9% male; median IMV duration, 9 days). At ICU discharge, 28.1% of the patients had Medical Research Council (MRC) sum score <48 points, and prolonged IMV was significantly associated with lower MRC sum score and handgrip strength. Symptoms were similar between groups at ICU discharge, and the symptoms most commonly reported as moderate-to-severe were impaired well-being (52%), anxiety (43%), tiredness (41%), and depression (35%). Although muscle strength and mobility status were significantly improved after ICU discharge, Edmonton Symptom Assessment System score did not improve significantly in the prolonged IMV group. EuroQol five-dimension five-level summary index was significantly lower in the prolonged than short IMV group at 6 months after ICU discharge. We found substantial negative physical function and mental health consequences in the majority of surviving COVID-19 patients requiring IMV, with prolonged period of IMV showing greater negative effects not only immediately but also at 6 months after discharge from the ICU.

Increase in ventilatory ratio indicates progressive alveolar damage and suggests poor prognosis in severe COVID-19: A single-center retrospective observational study. (preprint)

Background: The symptoms of severe COVID-19 are complex and wide-ranging even in intensive care unit (ICU) patients, who may successfully discontinue respiratory support in a short period or conversely require prolonged respiratory support. Damage in the lungs of COVID-19 patients is characterized pathologically as diffuse alveolar damage, the degree of which correlates with the severity of the disease. We hypothesized that the ventilatory ratio (VR), a surrogate parameter for the dead space fraction, might stratify the severity of COVID-19 and predict the successful discontinuation of respiratory support. Methods: Forty COVID-19 patients in our ICU were enrolled in this study. Respiratory variables were collected from 2 hours (day 0) after the initiation of respiratory support. We monitored the longitudinal values of VR and other respiratory parameters for 28 days. Patients successfully discontinued from respiratory support by day 28 of ICU stay were defined as the successfully discontinued group, while those who died or failed to discontinue were defined as the failed to discontinue group. VR and other respiratory parameters were compared between these groups. Results: Except for advanced age, prolonged ventilation period, and higher mortality in the failed to discontinue group, there were no significant differences between the groups in terms of any other background or respiratory parameter at 2 hours (day 0) after initiation of respiratory support. Longitudinal VR monitoring revealed significantly higher VR values in the failed to discontinue group than the successfully discontinued group on day 4 of respiratory support. Upon predicting the failure to discontinue respiratory support, the area under the receiver operating characteristic curve of VR values on day 4 of respiratory support was 0.748. A threshold of 1.56 achieved the highest predictive performance with a sensitivity of 0.667 and a specificity of 0.762. This threshold enabled the prediction of the successfully discontinued outcome at 0.810 of the negative predictive value. Conclusions: Elevated VR values on day 4 of respiratory support were predictive of successful discontinuation of respiratory support in patients with severe COVID-19. Longitudinal VR values after initiation of respiratory support can be used as a practical index to stratify severe COVID-19.

High resolution linear epitope mapping of the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 mRNA vaccine recipients. (preprint)

The prompt rollout of the coronavirus disease (COVID-19) messenger RNA (mRNA) vaccine is facilitating population immunity, which shall become more dominant than natural infection-induced immunity. At the beginning of the vaccine era, understanding the epitope profiles of vaccine-elicited antibodies will be the first step in assessing functionality of vaccine-induced immunity. In this study, the high-resolution linear epitope profiles of Pfizer-BioNTech COVID-19 mRNA vaccine recipients and COVID-19 patients were delineated by using microarrays mapped with overlapping peptides of the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. The vaccine-induced antibodies targeting RBD had broader distribution across the RBD than that induced by the natural infection. Thus, relatively lower neutralizability was observed when a half-maximal neutralization titer measured in vitro by live virus neutralization assays was normalized to a total anti-RBD IgG titer. However, mutation panel assays targeting the SARS-CoV-2 variants of concern have shown that the vaccine-induced epitope variety, rich in breadth, may grant resistance against future viral evolutionary escapes, serving as an advantage of vaccine-induced immunity. ImportanceEstablishing vaccine-based population immunity has been the key factor in attaining herd protection. Thanks to expedited worldwide research efforts, the potency of messenger RNA vaccines against the coronavirus disease 2019 (COVID-19) is now incontestable. The next debate is regarding the coverage of SARS-CoV-2 variants. At the beginning of this vaccine era, it is of importance to describe the similarities and differences between the immune responses of COVID-19 vaccine recipients and naturally infected individuals. In this study, we demonstrated that the antibody profiles of vaccine recipients are richer in variety, targeting a key protein of the invading virus, than those of naturally infected individuals. Yet vaccine-elicited antibodies included more non-neutralizing antibodies than infection-elicited, their breadth in antibody variations suggested possible resilience against future SARS-CoV-2 variants. The antibody profile achieved by vaccinations in naive individuals pose important insight into the first step towards vaccine-based population immunity.