The Humoral Response to the BNT162b2 Vaccine in Hemodialysis Patients

ImportanceHemodialysis patients have an exceptionally high mortality from COVID-19 and this patient population often has a poor response to vaccinations. Randomized controlled trials for COVID-19 vaccines included few patients with kidney disease, therefore vaccine immunogenicity is uncertain in this population. ObjectiveEvaluate the SARS-CoV-2 antibody response in chronic hemodialysis patients following one versus two doses of BNT162b2 COVID-19 vaccination compared to health care worker controls and convalescent serum. DesignProspective observational cohort study. SettingSingle centre study in Toronto, Ontario, Canada. Participants142 in-centre hemodialysis patients and 35 health care worker controls. ExposureBNT162b2 (Pfizer-BioNTech) COVID-19 vaccine. Main Outcomes and MeasuresSARS-CoV-2 IgG antibodies to the spike protein (anti-spike), receptor binding domain (anti-RBD), and nucleocapsid protein (anti-NP) were measured in 66 hemodialysis patients receiving one vaccine dose following a public health policy change, 76 patients receiving two vaccine doses, and 35 health care workers receiving two vaccine doses. ResultsDetectable anti-NP suggestive of natural SARS-CoV-2 infection was detected in 15/142 (11%) of patients at baseline while only three patients had prior RT-PCR confirmed COVID-19. Two additional patients contracted COVID-19 after receiving two doses of vaccine. In patients receiving a single BNT162b2 dose, seroconversion occurred in 53/66 (80%) for anti-spike and 35/66 (55%) for anti-RBD by 28 days post dose, but only 15/66 (23%) and 4/66 (6%), respectively attained a robust response as defined by reaching the median level of anti-spike and anti-RBD in convalescent serum from COVID-19 survivors. In patients receiving two doses of BNT162b2 vaccine, seroconversion occurred in 69/72 (96%) for anti-spike and 63/72 (88%) for anti-RBD by 2 weeks following the second dose while 52/72 (72%) and 43/76 (41%) reached the median convalescent serum level of anti-spike and anti-RBD, respectively. In contrast, 35/35 (100%) of health care workers exceeded the median level of anti-spike and anti-RBD found in convalescent serum 2-4 weeks after the second dose. Conclusions and RelevanceThis study confirms poor immunogenicity 28 days following a single dose of BNT162b2 vaccine in the hemodialysis population, supporting adherence to recommended vaccination schedules, and avoiding delay of the second dose in these at-risk individuals. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the serologic response to the BNT162b2 COVID-19 vaccine in hemodialysis patients? FindingsIn this prospective observational study, humoral response was compared in 66 hemodialysis patients sampled 28 days after receipt of one dose of vaccine to 76 patients who received two doses of vaccine sampled 14 days after the second dose. Among those receiving one dose, 6% had anti-RBD response above the median level of convalescent serum versus 41% who received two doses. MeaningGiven that hemodialysis patients exhibit a poor humoral response to a single dose of BNT162b2 vaccine, the second dose should not be delayed.

The Diagnostic Accuracy of Subjective Dyspnea in Detecting Hypoxemia Among Outpatients with COVID-19

ObjectivesThe majority of patients with mild-to-moderate COVID-19 can be managed using virtual care. Dyspnea is challenging to assess remotely, and the accuracy of subjective dyspnea measures in capturing hypoxemia have not been formally evaluated for COVID-19. We explored the accuracy of subjective dyspnea in diagnosing hypoxemia in COVID-19 patients. MethodsThis is a retrospective cohort study of consecutive outpatients with COVID-19 who met criteria for home oxygen saturation monitoring at a university-affiliated acute care hospital in Toronto, Canada from April 3, 2020 to June 8, 2020. Hypoxemia was defined by oxygen saturation <95%. Dyspnea measures were treated as diagnostic tests, and we determined their sensitivity (SN), specificity (SP), negative/positive predictive value (NPV/PPV), and positive/negative likelihood ratios (+LR/-LR) for detecting hypoxemia. ResultsDuring the study period 64/298 (21.5%) of patients met criteria for home oxygen saturation monitoring, and of these 14/64 (21.9%) were diagnosed with hypoxemia. The presence/absence of dyspnea had limited accuracy for diagnosing hypoxemia, with SN 57% (95% CI 30-81%), SP 78% (63%-88%), NPV 86% (72%-94%), PPV 42% (21%-66%), +LR 2.55 (1.3-5.1), -LR 0.55 (0.3-1.0). An mMRC dyspnea score >1 (SP 97%, 95%CI 82%-100%), Roth Maximal Count <12 (SP 100%, 95%CI 75-100%), and Roth Counting time < 8 seconds (SP 93%, 95%CI 66%-100%) had high SP that could be used to rule in hypoxemia, but displayed low SN ([≤]50%). ConclusionsSubjective dyspnea measures have inadequate accuracy for ruling out hypoxemia in high-risk patients with COVID-19. Safe home management of patients with COVID-19 should incorporate home oxygenation saturation monitoring.