摘要
Background: SARS-CoV-2 produces variable immune responses leading to different levels of immune protection. The relationship between neutralizing antibody level (NAb) and protective immunity has been well characterized after infection and vaccination. While comparatively specific T cell responses tend to be more variable, the impacts of these responses have broad implications on long-term immunity and their role in protective immunity has not been as clearly defined. Using data from our prospective cohort study and studies of clinical protective immunity/efficacy (from vaccines), we predicted protective immunity over time in relation to SARS-CoV-2-specific T cell dynamics. Methods: With linear mixed-effects models from our published immune data from people recovering from COVID-19, we simulated the Spike (S)-specific interferon-γ (IFNγ)+ CD4+, S-specific IFNγ+ CD8+, and nucleocapsid (N)-specific IFNγ+ CD8+ T cells over time (n=500 individuals). We then predicted NAbs from linear regression models developed from the same cohort. Finally, protective immunity from NAb titers was simulated from a published model. We similarly simulated 25, 50, and 75% lower T cell responses than those observed post-COVID-19 to understand how immune response variation may impact protective immunity. Results: Virus-specific T cell responses resulted in similar protective immunity across T cell subsets, but with differences in variability over time. Protective immunity for IFNγ+ S CD8 T cells spanned from 86-95%, while for IFNγ+ S CD4 T cells and IFNγ+ N CD4 T cells it ranged from 81-96% and 84-95% respectively. Further, based on simulated dampened T cell responses, protective immunity overall did not drop below 81% less than nine months after infection even with a 75% reduction in specific T cell immunity. Conclusion: NAbs are often the singular focus to predict protective immunity and the role of virus-specific T cell immunity has often been discussed as a secondary immune response. Our analysis demonstrates that for SARS-CoV-2, certain T cells responses can reliably predict protective immunity and may be intrinsically linked. Simulating dampened T cell response to mimic a more virulent strain or inadequate immune response, demonstrated that dampened T cell response may not be responsible for inadequate protective immunity in these scenarios. In the absence of prospective clinical data, similar models may be utilized to explore the impact of potential therapeutics on immune responses and resulting protective immunity.
摘要
Rationale: Obese patients represent a vulnerable population at risk of developing severe COVID-19 infections. Patients with COVID-19 pneumonia are at increased risk for developing acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS). Prone positioning has long been studied as a measure to improve hypoxemia in ARDS. We hypothesize that the critically ill obese patient may represent a unique subset of the population when considering their innate respiratory mechanic variations and distinctive physiology who may benefit most from prone positioning as an adjunctive measure to improve oxygenation in COVID-19 pneumonia. Methods: We conducted a retrospective, dual-hospital, single institution cohort analysis of confirmed diagnosed COVID-19 infection patients admitted to our 1227-bed tertiary care center. The data pool was subdivided into obese and non-obese adult patients, defined by body mass index ≥ 30 kg/m2. Proning was defined by at least 4 hours a day spent fully pronated. The primary outcome was in-hospital mortality. Secondary outcomes included the requirement of mechanical ventilation (MV) and ICU length of stay (LOS). Results: Between February and August 2020, 55% (144/259) of the total study population patients admitted to our ICU for AHRF secondary to COVID-19 pneumonia were obese. Of these obese patients, 25% (36/144) were proned and 75% (108/144) were not proned. In-hospital mortality was 11.11% in the proned/obese patients compared to 30.55% in the non-proned/obese patients (p=0.0207). In comparison, 26% (30/115) of the non-obese patients were proned and 74% (85/115) were not proned. In-hospital mortality was 36.66% in the proned/nonobese patients compared to 34.11% in the non-proned/non-obese patients (p=0.8010). A total of 43.05% (62/144) of obese versus 43.47% (50/115) of the non-obese patients required mechanical ventilation (MV) at some point in their ICU stay. In the obese population, 41.66% of proned/obese patients compared to 43.51% of the non-proned/obese patients required MV (p=0.8459). While in the non-obese population 46.66% of proned/non-obese patients compared to 42.35% of the non-proned/non-obese patients required MV (p=0.6819). The average ICU LOS was 8.17 days in non-proned compared to 6.77 days in proned obese patients. Conclusion: In regards to obese patients, there was a clinically significant improvement in mortality between patients that were proned versus non-proned patients. There was no clinically significant difference in the effect of proning on non-obese patients in terms of mortality. There was also no clinically significant difference in the effects of proning in obese and non-obese patients in regards to the requirement of mechanical ventilation.
摘要
RATIONALE: Severity of some infections has been correlated to ABO blood type. We sought to determine if ABO blood type correlated with outcome or other measures of disease severity in critically ill patients with COVID-19 requiring ICU level of care. METHODS: We conducted a retrospective, dual-hospital, single-institution cohort analysis of adult patients (>18 yo) with confirmed diagnosed SARS-CoV-19 infection admitted to our medical intensive care unit between 3/11/2020 and 8/19/2020. The primary outcome of our study was in-hospital mortality when comparing various blood types;A-, A+, B-, B+, O-, O+, AB+, AB-. Secondary outcomes were ICU length of stay, need for mechanical ventilation (MV), and oxygenation requirement at discharge. RESULTS: Of the total 270 patients 48 were excluded for absence of blood type data and 11 were excluded due to Covid-19 being incidental to another major medical condition. Blood type distribution and outcome among the 211 patients with COVID-19 admitted to our ICU are given in the table: Statistical analysis using chi square for categories with a substantial number of cases (A+, B+, O+) analyzed for death, MV, or discharge need for O2 revealed no significant differences (p=0.11). Similarly, the ICU length of stay (LOS) was not significantly different among groups. CONCLUSION: Unlike some recent literature has suggested, in our population, blood type did not correlate with death or markers of disease severity in patients with COVID-19 that required ICU level of care.
摘要
RATIONALE: Pneumothorax (PTX) incidence, risk factors and impact on outcomes in patients with COVID-19 are unknown. We hypothesized that PTX is associated with a higher rate of mortality and is more likely to occur in patients with severe COVID-19 requiring mechanical ventilation (MV) at higher maximal PEEP and with higher levels of markers of inflammation. METHODS: We conducted a retrospective, cohort study of all adult patients (>18 years) with confirmed diagnosed SARS-CoV-19 infection admitted to our medical intensive care units (ICU) between 3/11/2020 and 8/19/2020 at our 2 hospital healthcare system. Exclusion criteria were non-Covid illness resulting in ICU level of care and ICU stay less than 24 hours. Presence or absence of PTX was determined by retrospective review of chest imaging reports. The primary outcome was mortality at discharge. Secondary outcome measures assessed at the p=0.05 level included age, ethnicity, BMI, maximum PEEP on MV and laboratory inflammatory markers (CRP, D-dimer, LDH, Ferritin). RESULTS: 270 patients with COVID-19 were admitted to the ICU. 11 patients were excluded leaving 259 for analysis. PTX was identified in 16 (6.2%). In the entire group, 9 of 16 (56.2%) patients with PTX died in the hospital compared to 68 of 243 (28%) without PTX (p=0.017). There were no significant differences in age, BMI, highest PEEP, or mortality in the subgroup treated with MV. The rate of PTX was significantly lower in the Black population and higher in the Hispanic population (p=0.01). There were no significant differences in the levels of the inflammatory markers for those patients who developed PTX compared to those who did not (CRP p=0.71;D-dimer p=0.11;Ferritin p=0.36;LDH p=0.41). CONCLUSION: PTX occurred in about 6% of COVID-19 patients requiring ICU level of care with most on mechanical ventilation and was significantly associated with a higher rate of mortality for the entire population, but not in the subgroup of patients requiring mechanical ventilation. PTX frequency was significantly lower in the Black population and higher in the Hispanic population. PTX was not associated with higher PEEP values. The absence of an association with PEEP suggests that barotrauma may not be the etiology of pneumothorax in COVID-19. Age, BMI, and the levels of inflammatory markers were not significantly different in these groups.
摘要
Rationale: SARS-CoV-19 (COVID-19) and its associated lung physiology, most notably its role in acute respiratory distress syndrome (ARDS), is an evolving medical illness. Clinical management is still being studied, however, it is well documented that pronated patients with non-COVID ARDS can improve oxygenation and V/Q mismatch, as well as increase lung volume and recruitment of collapsed alveoli. We hypothesized that proning patients with COVID-19 pneumonia will have similar pathophysiologic advantages and lead to less need for mechanical ventilation, lower mortality, and shorter hospitalization time. Methods: We conducted a large retrospective, single-institution cohort analysis of adult patients with diagnosed SARS-CoV-19 pneumonia who were admitted to our medical intensive care unit (ICU) between 3/11/2020 and 8/19/2020. We categorized patients into proning (at least 4 hours daily) versus non-proning cohorts. The primary outcome of our study was progression to mechanical ventilation while secondary outcomes compared in-hospital mortality rates, ICU and hospital length of stay (HLOS). We used the quick-COVID Severity Index (qCSI) to assign baseline severity scores to all patients. Results: A total of 270 patients with severe COVID-19 pneumonia were admitted to the ICU. Nine patients were excluded due to unrelated illness confounders, leaving a total of 261 patients (including 9 patients who were intubated before their first proning session). Of the patients who proned for 4 or more hours daily, 38.99% (23/59) required mechanical ventilation after proning compared with 41.97% (81/193) who were not proned (pvalue = .68). Secondary outcomes for those proned vs not proned include;in-hospital mortality of 22.06% (15/68) vs 33.12% (62/193) a p-value of .12, median HLOS 14 days vs 13 days, ICU LOS 6 days vs 4 days. The qCSI score for the proned group was 6.77 vs 6.68 for those not proned. Conclusions: Based on our analysis, there was not a statistically significant reduction in the progression to MV in patients with severe SARS-CoV-19 pneumonia who proned compared to those who did not prone. However, there was a positive correlation associated with proning and reduction in the in-hospital mortality rate of these patients, a difference of 11%. Additionally, there was no significant difference in ICU LOS or HLOS.