Effect of storage temperatures simulating transport conditions of nasopharyngeal swabs on the results of a chemiluminescence immunoassay (CLIA) to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen.

PURPOSE: Chemiluminescence Immunoassay (CLIA) is high throughput, rapid diagnostic test which has recently come up for the detection of SARS-CoV-2 antigen. The present study evaluated performance of CLIA antigen test in nasopharyngeal swab samples stored at different temperatures for 7 days to simulate the transport conditions and transit time across the country from remote peripheral laboratories to central facilities. MATERIALS AND METHODS: Limit of detection (LOD), sensitivity and specificity of VITROS® SARS-CoV-2 antigen assay was determined using Real-time reverse transcriptase PCR (rRT-PCR) confirmed SARS-CoV-2 positive and negative samples. To detect the effect of storage temperatures on VITROS ®SARS-CoV-2 antigen results, samples were stored at 4 â€‹°C, 25 â€‹°C & 37 â€‹°C for 7 days followed by detection of SARS-CoV-2 nucleocapsid antigen and compared with N-gene rRT-PCR. RESULTS: The VITROS® SARS-CoV-2 antigen test was found to have a sensitivity and specificity of 78.9% and 100% respectively with high sensitivity of 88.1% for samples with Ct â€‹< â€‹30. The LOD of VITROS assay was equivalent to 3800 copies of RNA per reactions as compared to 72 copies per reaction for rRT-PCR. We observed that more than 80% of samples with <30 Ct values could be detected by VITROS SARS-CoV-2 antigen assay at day 7 even when stored at 37 â€‹°C. For samples with Ct values between 26 and 30, on day 7 the positivity rate of N-antigen at 4 â€‹°C was 90.9% and 37 â€‹°C was 63.6%. CONCLUSIONS: CLIA testing can be carried out for the detection of SARS-CoV-2 N-protein in NP-swab samples transported in cold chain even with 7 days transit time, particularly for Ct â€‹< â€‹30 samples which represents cases with higher transmissibility. As drop in positivity for VITROS assay was lower as compared to rRT-PCR on day 7 in cold chain-maintained samples, the assay can be useful to screen samples received from remote peripheral areas before performing rRT-PCR.

Alternate Approach in Storing and Shipment of SARS-CoV-2 RNA Samples with the Use of FTA Cards.

Shipment of COVID-19 specimens within the country or overseas at long distances requires cold chain facility using dry ice and triple packing to prevent the risk of COVID-19 infection to the personnel involved in sample transport. The present study aimed to utilize FTA card technology as an alternate means of sample transport and storage across the country. Twenty-one SARS-CoV-2 lab confirmed samples with different Ct value (High, medium & low) were used to detect viral load in samples loaded on FTA card and further compared with VTM samples. The SARS-CoV-2 RNA was detected by rRT-PCR after storing for 14 days at 4 °C and 37 °C. The present study evaluated the utility of FTA cards for preserving the SARS CoV-2 RNA for 14-day period. A significant difference (P < 0.05) was observed in the cycle threshold (ΔCt 4-5) values obtained from FTA and VTM viral samples but it did not affect the positivity. The SARS-CoV-2 RNA could be recovered efficiently from FTA sample stored at 4 °C and 37 °C for 14 days. Thus, FTA cards could be an alternate option for transporting the samples at ambient temperature for a long time.

The 'myth of Hydroxychloroquine (HCQ) as post-exposure prophylaxis (PEP) for the prevention of COVID-19' is far from reality.

The efficacy of Hydroxychloroquine (HCQ) as post-exposure prophylaxis (PEP) for the prevention of COVID-19 was contentious. In this randomized control double-blind clinical trial, asymptomatic individuals with direct contact with laboratory-confirmed COVID-19 cases were randomized into PEP/HCQ (N = 574) and control/placebo (N = 594) group. The PEP/HCQ group received tablet HCQ 400 mg q 12 hourly on day one followed by 400 mg once weekly for 3 weeks, and the control/Placebo group received matching Placebo. The incidence of COVID-19 was similar (p = 0.761) in PEP [N = 24 out of 574, (4.2%)] and control [N = 27 out of 594, (4.5%)] groups. Total absolute risk reduction for the incidence of new-onset COVID-19 was -0.3% points with an overall relative risk of 0.91 (95% confidence interval, 0.52 to 1.60) and the number needed to treat (NNT) was 333 to prevent the incident of one case of COVID-19. The study found that, PEP with HCQ was not advantageous for the prevention of COVID-19 in asymptomatic individuals with high risk for SARS-CoV-2 infection. Though HCQ is a safer drug, the practice of irrational and indiscriminate use of HCQ for COVID-19 should be restrained with better pharmacovigilance.

Characteristics and outcomes of parturients with COVID-19, admitted to a critical care unit: A single-center retrospective observational study.

Background: Data on outcomes of coronavirus disease 2019 (COVID-19) in pregnancy are scarce, although they represent a unique physiological state affecting both the mother and child. We present collated data from a tertiary care center in North India, encompassing the outcome, clinical characteristics, and management of these patients. Materials and Methods: Parturients ≥ 18 years old, with COVID-19 reverse transcriptase polymerase chain reaction positive for severe acute respiratory syndrome coronavirus 2, requiring intensive care unit (ICU) admission at a tertiary care hospital were included. Data were retrospectively collected from April 2020 to November 2021. Results: In all, 26 parturients were admitted to ICU with COVID-19. Five patients were admitted during the first wave, and all were asymptomatic. Twenty-one patients presented during the second wave (March 2021 onward), among which four were asymptomatic and 17 symptomatic (all with severe pneumonia). Three patients presented in the second trimester, all with critical disease, out of which one did not survive. Two patients had twin gestation, and others were singleton pregnancies. Seven patients (27%) were primigravida, and five patients (19.2%) had more than third pregnancy. Twenty critically ill women (77%) delivered during the hospital stay. Six patients died during the second wave, and four deaths (66.7%) were because of COVID-19 acute respiratory distress syndrome (ARDS). Conclusions: The number of admissions and mortality related to COVID-19 ARDS was higher in the second wave than in the first. We report the safe use of remdesivir and tocilizumab in our patients.

Theorizing on neo public assistance: How do race and class impact resource uptake and behavior following disaster?

The consequences of environmental disasters and other ecologic and communal crises are frequently worst in racially/ethnically minoritized and low-income populations relative to other groups. This disproportionality may create or deepen patterns of governmental distrust and stoke health promotion disengagement in these groups. To date, there has been limited contextualization of how historically disenfranchised populations utilize government-administered or facilitated resources following such disasters. Focusing on the water crisis in Flint, Michigan, we examine and theorize on the usage of neo public assistance, free risk reduction resources that are provided to disaster survivors as a liminal means of redressing ills created and/or insufficiently mitigated by the state. We surveyed 331 Flint residents, evaluating their usage of four neo public assistance resources following the FWC, finding low to moderate uptake: 131 residents (39.6%) indicated that they obtained blood lead level (BLL) screenings, 216 (65.3%) had their tap water tested for lead (Pb) and other contaminants, 137 (41.4%) had their home water infrastructure replaced, and 293 (88.5%) had acquired bottled water at community distribution sites. Unemployment, receiving public benefits, and lacking reliable transportation and stable housing were associated with lower uptake of some resources. Compared to White and "Other" race individuals, Black residents were generally more likely to acquire/utilize these resources, suggesting heightened concerns and health promotion proclivities even in the face of observed macro and individual-level challenges. Potential reasons and implications are discussed.

Do children with severe acute respiratory infection need cohorting & isolation before screening for COVID-19?

This retrospective analysis was done to ascertain the SARS-CoV-2-positivity rate in children (0-12 yr) with severe acute respiratory infection (SARI) and compare it to those without SARI to determine the need for running a dedicated SARI isolation facility for paediatric COVID-19 care. The case records of 8780 children (0-12 yr) admitted and/or tested for SARS-CoV-2 between June 2020 and May 2021 at a tertiary care centre in north India were analyzed. The overall SARS-CoV-2 reverse transcription (RT)-PCR positivity rate was 3.0 per cent (262/8780). There were 1155 (13.15%) children with SARI. Fifty of these 1155 (4.3%) children with SARI, as against 212 of the 7625 (2.8%) children without SARI, tested positive for COVID-19. The absolute difference in the positivity rate among SARI and non-SARI groups was only 1.54 per cent which translates to cohorting and isolating 65 children with SARI to pick up one extra SARS-CoV-2-positive child (compared to those without SARI). The positive predictive value of SARI as a screening test was 4.3 per cent. Our findings suggest that isolation of children with SARI as a transmission-prevention strategy for COVID-19 may not be required. This is particularly relevant in resource-limited settings.

Essential oil nebulization in mild COVID-19(EONCO): Early phase exploratory clinical trial.

Background: Medications studied for therapeutic benefits in coronavirus disease 2019 (COVID-19) have produced inconclusive efficacy results except for steroids. Objective: A prospective randomized open-label, parallel-arm Phase I/II clinical trial was planned to compare essential oil (EO) blend versus placebo nebulization in mild COVID-19. Methods: A Phase I safety evaluation was carried out in a single ascending and multiple ascending dose study designs. We assessed Phase II therapeutic efficacy on COVID-19 and general respiratory symptoms on days 0, 3, 5, 7, 10, and 14 on the predesigned case record form. Viremia was evaluated on day 0, day 5, and day 10. Results: Dose-limiting toxicities were not reached with the doses, frequencies, and duration studied, thus confirming the formulation's preliminary safety. General respiratory symptoms (p < 0.001), anosmia (p < 0.05), and dysgeusia (p < 0.001) benefited significantly with the use of EO blend nebulization compared to placebo. Symptomatic COVID-19 participants with mild disease did not show treatment benefits in terms of symptomatic relief (p = 1.0) and viremia clearance (p = 0.74) compared to the placebo. EO blend was found to be associated with the reduced evolution of symptoms in previously asymptomatic reverse transcription polymerase chain reaction (RT-PCR)-positive study participants (p = 0.034). Conclusion: EO nebulization appears to be a safer add-on symptomatic relief approach for mild COVID-19. However, the direct antiviral action of the EO blend needs to be assessed with different concentrations of combinations of individual phytochemicals in the EO blend.

Clinico-Laboratory Profile, Intensive Care Needs and Short-Term Outcome of Multisystem Inflammatory Syndrome in Children (MIS-C): Experience during First and Second Waves from North India.

OBJECTIVES: To describe the clinico-laboratory profile, intensive care needs and outcome of multisystem inflammatory syndrome in children (MIS-C) during the first and second waves. METHODOLOGY: This retrospective study was conducted in the paediatric emergency and paediatric intensive care unit (PICU) of a tertiary care teaching hospital in North India involving 122 children with MIS-C admitted during the first wave (September 2020-January 2021, n = 40) and second wave (February 2021-September 2021, n = 82) of coronavirus disease 2019 (COVID-19). RESULTS: The median (interquartile range) age was 7 (4-10) years and 67% were boys. Common manifestations included fever (99%), abdominal symptoms (81%), rash (66%) and conjunctival injection (65%). Elevated C-reactive protein (97%), D-dimer (89%), procalcitonin (80%), IL-6 (78%), ferritin (56%), N-terminal pro B-type natriuretic peptide (84%) and positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibody (81%) were common laboratory abnormalities. Cardiovascular manifestations included myocardial dysfunction (55%), shock (48%) and coronary artery changes (10%). The treatment included intensive care support (57%), non-invasive (33%) and invasive (18%) ventilation, vasoactive drugs (47%), intravenous immunoglobulin (IVIG) (83%), steroids (85%) and aspirin (87%). The mortality was 5% (n = 6). During the second wave, a significantly higher proportion had positive SARS-CoV-2 antibody, contact with COVID-19 and oral mucosal changes; lower markers of inflammation; lower proportion had lymphopenia, elevated IL-6 and ferritin; lower rates of shock, myocardial dysfunction and coronary artery changes; lesser need of PICU admission, fluid boluses, vasoactive drugs and IVIG; and shorter hospital stay. CONCLUSION: MIS-C is a febrile multisystemic disease characterized by hyperinflammation, cardiovascular involvement, temporal relationship to SARS-CoV-2 and good outcome with immunomodulation and intensive care. During the second wave, the severity of illness, degree of inflammation, intensive care needs, and requirement of immunomodulation were less as compared to the first wave.

Surface contamination by SARS-CoV2 RNA in dedicated COVID care area of a tertiary care hospital in North India.

Environmental surfaces are potential source of SARS-CoV2 transmission. The study assessed the efficacy of hospital disinfection policy and contamination of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) RNA in COVID management Hospital. Inanimate surfaces from both patient areas (n = 70) and non-patient areas (n = 39) were sampled through surface swabbing and subjected to Reverse transcriptase PCR. Out of the 70 samples collected from the COVID hospital, SARS-CoV2 RNA positivity of 17.5% (7/40) and 6.7% (2/30) was seen in high risk and moderate risk area respectively. Samples from Non COVID related patient area such as CD ward and administrative block were assessed and the SARS CoV-2 RNA positivity was 0% and 10% respectively. Among the total 8 environmental surface samples positive for SARS-CoV2 RNA detected from the area surrounding the SARS-CoV2 infected patients, maximum positivity of 31.8% (7/22) was found among the environmental samples collected around the patients with < 20 Ct value in nasopharyngeal swab samples followed by 3.3% positivity (1/30) around patients with Ct value ranging from 20 to 25 whereas no SARS-CoV2 RNA (0/5) was detected around the patient with > 25 Ct value. Nearly 50% (2/4) of the surface samples came positive from the resident PPE and mobile of the treating doctors which largely elaborates the need for stringent doffing measurement and hand hygiene policy post doffing. The study emphasizes the necessity of frequent and aggressive disinfection policy to prevent nosocomial infection in such high risk areas within close vicinity of the patients.

Validation of a noninvasive aMMP-8 point-of-care diagnostic methodology in COVID-19 patients with periodontal disease.

OBJECTIVES: The aim of this study was to validate an active matrix metalloproteinase (MMP-8) point-of-care diagnostic tool in COVID-19 patients with periodontal disease. SUBJECTS, MATERIALS, AND METHODS: Seventy-two COVID-19-positive and 30 COVID-19-negative subjects were enrolled in the study. Demographic data were recorded, periodontal examination carried out, and chairside tests run for evaluating the expression of active MMP-8 (aMMP-8) in the site with maximum periodontal breakdown via gingival crevicular fluid sampling as well as via a mouth rinse-based kit for general disease activity. In COVID-19-positive patients, the kits were run again once the patients turned COVID-19 negative. RESULTS: The overall (n = 102) sensitivity/specificity of the mouthrinse-based kits to detect periodontal disease was 79.41%/36.76% and that of site-specific kits was 64.71%/55.88% while adjusting for age, gender, and smoking status increased the sensitivity and specificity (82.35%/76.47% and 73.53%/88.24, respectively). Receiver operating characteristic (ROC) analysis for the adjusted model revealed very good area under the ROC curve 0.746-0.869 (p < .001) and 0.740-0.872 (p < .001) (the aMMP-8 mouth rinse and site-specific kits, respectively). No statistically significant difference was observed in the distribution of results of aMMP-8 mouth rinse test (p = .302) and aMMP-8 site-specific test (p = .189) once the subjects recovered from COVID-19. CONCLUSIONS: The findings of the present study support the aMMP-8 point-of-care testing (PoCT) kits as screening tools for periodontitis in COVID-19 patients. The overall screening accuracy can be further increased by utilizing adjunctively risk factors of periodontitis. The reported noninvasive, user-friendly, and objective PoCT diagnostic methodology may provide a way of stratifying risk groups, deciding upon referrals, and in the institution of diligent oral hygiene regimens.

Computational prediction of the molecular mechanism of statin group of drugs against SARS-CoV-2 pathogenesis.

Recently published clinical data from COVID-19 patients indicated that statin therapy is associated with a better clinical outcome and a significant reduction in the risk of mortality. In this study by computational analysis, we have aimed to predict the possible mechanism of the statin group of drugs by which they can inhibit SARS-CoV-2 pathogenesis. Blind docking of the critical structural and functional proteins of SARS-CoV-2 like RNA-dependent RNA polymerase, M-protease of 3-CL-Pro, Helicase, and the Spike proteins ( wild type and mutants from different VOCs) were performed using the Schrodinger docking tool. We observed that fluvastatin and pitavastatin showed fair, binding affinities to RNA polymerase and 3-CL-Pro, whereas fluvastatin showed the strongest binding affinity to the helicase. Fluvastatin also showed the highest affinity for the SpikeDelta and a fair docking score for other spike variants. Additionally, molecular dynamics simulation confirmed the formation of a stable drug-protein complex between Fluvastatin and target proteins. Thus our study shows that of all the statins, fluvastatin can bind to multiple target proteins of SARS-CoV-2, including the spike-mutant proteins. This property might contribute to the potent antiviral efficacy of this drug.

Association between city-wide lockdown and COVID-19 hospitalization rates in multigenerational households in New York City.

BACKGROUND: City-wide lockdowns and school closures have demonstrably impacted COVID-19 transmission. However, simulation studies have suggested an increased risk of COVID-19 related morbidity for older individuals inoculated by house-bound children. This study examines whether the March 2020 lockdown in New York City (NYC) was associated with higher COVID-19 hospitalization rates in neighborhoods with larger proportions of multigenerational households. METHODS: We obtained daily age-segmented COVID-19 hospitalization counts in each of 166 ZIP code tabulation areas (ZCTAs) in NYC. Using Bayesian Poisson regression models that account for spatiotemporal dependencies between ZCTAs, as well as socioeconomic risk factors, we conducted a difference-in-differences study amongst ZCTA-level hospitalization rates from February 23 to May 2, 2020. We compared ZCTAs in the lowest quartile of multigenerational housing to other quartiles before and after the lockdown. FINDINGS: Among individuals over 55 years, the lockdown was associated with higher COVID-19 hospitalization rates in ZCTAs with more multigenerational households. The greatest difference occurred three weeks after lockdown: Q2 vs. Q1: 54% increase (95% Bayesian credible intervals: 22-96%); Q3 vs. Q1: 48% (17-89%); Q4 vs. Q1: 66% (30-211%). After accounting for pandemic-related population shifts, a significant difference was observed only in Q4 ZCTAs: 37% (7-76%). INTERPRETATION: By increasing house-bound mixing across older and younger age groups, city-wide lockdown mandates imposed during the growth of COVID-19 cases may have inadvertently, but transiently, contributed to increased transmission in multigenerational households.

Evaluation of the Durability of the Immune Humoral Response to COVID-19 Vaccines in Patients With Cancer Undergoing Treatment or Who Received a Stem Cell Transplant.

Importance: The durability of the antibody response to COVID-19 vaccines in patients with cancer undergoing treatment or who received a stem cell transplant is unknown and may be associated with infection outcomes. Objective: To evaluate anti-SARS-CoV-2 spike protein receptor binding domain (anti-RBD) and neutralizing antibody (nAb) responses to COVID-19 vaccines longitudinally over 6 months in patients with cancer undergoing treatment or who received a stem cell transplant (SCT). Design, Setting, and Participants: In this prospective, observational, longitudinal cross-sectional study of 453 patients with cancer undergoing treatment or who received an SCT at the University of Kansas Cancer Center in Kansas City, blood samples were obtained before 433 patients received a messenger RNA (mRNA) vaccine (BNT162b2 or mRNA-1273), after the first dose of the mRNA vaccine, and 1 month, 3 months, and 6 months after the second dose. Blood samples were also obtained 2, 4, and 7 months after 17 patients received the JNJ-78436735 vaccine. For patients receiving a third dose of an mRNA vaccine, blood samples were obtained 30 days after the third dose. Interventions: Blood samples and BNT162b2, mRNA-1273, or JNJ-78436735 vaccines. Main Outcomes and Measures: Geometric mean titers (GMTs) of the anti-RBD; the ratio of GMTs for analysis of demographic, disease, and treatment variables; the percentage of neutralization of anti-RBD antibodies; and the correlation between anti-RBD and nAb responses to the COVID-19 vaccines. Results: This study enrolled 453 patients (mean [SD] age, 60.4 [13,1] years; 253 [56%] were female). Of 450 patients, 273 (61%) received the BNT162b2 vaccine (Pfizer), 160 (36%) received the mRNA-1273 vaccine (Moderna), and 17 (4%) received the JNJ-7846735 vaccine (Johnson & Johnson). The GMTs of the anti-RBD for all patients were 1.70 (95% CI, 1.04-2.85) before vaccination, 18.65 (95% CI, 10.19-34.11) after the first dose, 470.38 (95% CI, 322.07-686.99) at 1 month after the second dose, 425.80 (95% CI, 322.24-562.64) at 3 months after the second dose, 447.23 (95% CI, 258.53-773.66) at 6 months after the second dose, and 9224.85 (95% CI, 2423.92-35107.55) after the third dose. The rate of threshold neutralization (≥30%) was observed in 203 of 252 patients (80%) 1 month after the second dose and in 135 of 166 patients (81%) 3 months after the second dose. Anti-RBD and nAb were highly correlated (Spearman correlation coefficient, 0.93 [0.92-0.94]; P < .001). Three months after the second dose, anti-RBD titers were lower in male vs female patients (ratio of GMTs, 0.52 [95% CI, 0.34-0.81]), patients older than 65 years vs patients 50 years or younger (ratio of GMTs, 0.38 [95% CI, 0.25-0.57]), and patients with hematologic malignant tumors vs solid tumors (ratio of GMTs, 0.40 [95% CI, 0.20-0.81]). Conclusions and Relevance: In this cross-sectional study, after 2 doses of an mRNA vaccine, anti-RBD titers peaked at 1 month and remained stable over the next 6 months. Patients older than 65 years of age, male patients, and patients with a hematologic malignant tumor had low antibody titers. Compared with the primary vaccine course, a 20-fold increase in titers from a third dose suggests a brisk B-cell anamnestic response in patients with cancer.

Respiratory viral infections other than SARS CoV-2 among the North Indian patients presenting with acute respiratory illness during the first COVID-19 wave.

Acute respiratory infections due to viral or bacterial etiology can cause 60 deaths per one lakh population. Viral etiology is more common as compared to bacterial, but lack of definite diagnosis leads to increased usage of empirical antibiotics. During the first wave of the COVID-19 pandemic, there was a need to identify co-infections especially in severe acute respiratory illness (SARI) patients to identify it as one of the cofactors for increased severity of illness and to identify the causative agents in COVID-19 negative individuals. The SARS CoV-2 real time PCR was carried out using ICMR approved kits and the other respiratory viruses were detected using the multiplex commercially available real time  kit. A total of 186 patients presenting with either SARI (89.8%) or influenza like illness (10.2%) were included in the study. Out of these, 43 (23.1%) were positive for SARS CoV-2 RNA and 2 (4.6%) patients with SARI showed concomitant infection with either human rhinovirus or human respiratory syncytial virus . Out of 143 patients negative for SARS CoV-2, 35 (24.5%) were positive for one or more microbial infections and 28 (19.6%) infected with other respiratory viral infection most common being human rhinovirus. The results suggest that viral coinfections are significantly higher among COVID-19 negative individuals (24.5% vs 4.6%) presenting with respiratory illness as compared to COVID-19 positive individuals possibly due to viral interference and competitive advantage of SARS-CoV-2 in modulating the host immunity. Further detailed research is required for the understanding of mechanisms of viral co-infection.

Association between neighborhood overcrowdedness, multigenerational households, and COVID-19 in New York City

IMPACT: Patients living in overcrowded zip codes were at increased risk of contracting severe COVID-19 after controlling for confounding disease and socioeconomic factors OBJECTIVES/GOALS: This study sought to examine whether residences in over-crowded zip codes with higher reported over-crowding represented an independent risk factor for severe COVID-19 infection, defined by presentation to an emergency department. METHODS/STUDY POPULATION: In this zip code tabulated area (ZCTA)-level analysis, we used NYC Department of Health disease surveillance data in March 2020 merged with data from the CDC and ACS to model suspected COVID-19 case rates by zip code over-crowdedness (households with greater than 1 occupant per room, in quartiles). We defined suspected COVID-19 cases as emergency department reported cases of pneumonia and influenza-like illness. Our final model employed a multivariate Poisson regression models with controls for known COVID-19 clinical (prevalence of obesity, coronary artery disease, and smoking) and related socioeconomic risk factors (percentage below federal poverty line, median income by zip-code, percentage White, and proportion of multigenerational households) after accounting for multicollinearity. RESULTS/ANTICIPATED RESULTS: Our analysis examined 39,923 suspected COVID-19 cases across 173 ZCTAs in NYC between March 1 and March 30 2020. We found that, after adjusted analysis, for every quartile increase in defined over-crowdedness, case rates increased by 32.8% (95% CI: 22.7%% to 34.0%, P < 0.001). DISCUSSION/SIGNIFICANCE OF FINDINGS: Over-crowdedness by zip code may be an independent risk factor for severe COVID-19. Social distancing measures such as school closures that increase house-bound populations may inadvertently worsen the risk of COVID-19 contraction in this setting.

Predictors of life-threatening complications in relatively lower-risk patients hospitalized with COVID-19.

Older individuals with chronic health conditions are at highest risk of adverse clinical outcomes from COVID-19, but there is widespread belief that risk to younger, relatively lower-risk individuals is negligible. We assessed the rate and predictors of life-threatening complications among relatively lower-risk adults hospitalized with COVID-19. Of 3766 adults hospitalized with COVID-19 to three hospitals in New York City from March to May 2020, 963 were relatively lower-risk based on absence of preexisting health conditions. Multivariable logistic regression models examined in-hospital development of life-threatening complications (major medical events, intubation, or death). Covariates included age, sex, race/ethnicity, hypertension, weight, insurance type, and area-level sociodemographic factors (poverty, crowdedness, and limited English proficiency). In individuals ≥55 years old (n = 522), 33.3% experienced a life-threatening complication, 17.4% were intubated, and 22.6% died. Among those <55 years (n = 441), 15.0% experienced a life-threatening complication, 11.1% were intubated, and 5.9% died. In multivariable analyses among those ≥55 years, age (OR 1.03 [95%CI 1.01-1.06]), male sex (OR 1.72 [95%CI 1.14-2.64]), being publicly insured (versus commercial insurance: Medicare, OR 2.02 [95%CI 1.22-3.38], Medicaid, OR 1.87 [95%CI 1.10-3.20]) and living in areas with relatively high limited English proficiency (highest versus lowest quartile: OR 3.50 [95%CI 1.74-7.13]) predicted life-threatening complications. In those <55 years, no sociodemographic factors significantly predicted life-threatening complications. A substantial proportion of relatively lower-risk patients hospitalized with COVID-19 experienced life-threatening complications and more than 1 in 20 died. Public messaging needs to effectively convey that relatively lower-risk individuals are still at risk of serious complications.

Cancer Therapy and Immunogenicity of COVID Vaccine – CANINE Study (preprint)

Background: Information regarding antibody response to COVID-19 vaccines in cancer patients undergoing therapy is needed for vaccine recommendations and timing of additional doses. This longitudinal study evaluates anti-RBD and neutralizing antibody (NAb) response to COVID-19 vaccines in patients on treatment and post stem cell transplant (SCT).Methods: For mRNA vaccines, anti-RBD and NAb were assessed before vaccination (T0), prior to 2nd dose (T1), 1 month after the 2nd dose (T2), and 3 months after the 2nd dose (T3). For J&J, T1 was 1 month, T2, 2 months and T3, 4 months after vaccine. Primary objective was GMTs of anti-RDB and NAb (%) at above timepoints. Other objectives were a) proportion of patients with anti-RBD ≥100 U/mL, b) correlation between anti-RBD and NAb, c) antibody responses of the 2 mRNA vaccines, and d) anti-RBD in breakthrough COVID-19 cases.Findings: Between 3/2/2021 and 7/30/2021, 438 cancer patients were enrolled. 108 (25%) were post-SCT and 330 (75%) on treatment: 176 (40%) on chemotherapy (C), 21 (5%) on chemoimmunotherapy (C+I), 72 (19%) on immunotherapy (I), and 58 (13%) on targeted oral agents (TOA). 60 % received Pfizer, 36 % Moderna, and 4% J&J. 11·82% of patients had anti-RBD ≥100 U/mL at T0, 25·15% at T1, 75·44 % at T2, and 81·38% at T3. At T3, 84·91% of patients on C, 81·89% on C+I, 86·67% on I, 78·18% post-SCT, and 77·50% on TOA had anti-RBD ≥ 100 U/mL. GMTs were 1·59 at T0, 12·91 at T1, 480·8 at T2 and 439·1 at T3. Neutralization (≥30%) was observed in 14·71%, 38·89%, 80·56% and 81·33% of patients at T0, T1, T2, and T3. There was no difference between the mRNA vaccines. Five patients had breakthrough infection. Four with anti-RBD available had pre-infection anti-RBD <100 U/mL. Interpretation: Four months after SARS-CoV-2 vaccination, ~ 80% of patients on cancer therapy or post-SCT have anti-RBD ≥100 U/mL and ≥30% NAb. Anti-RBD ≥100 U/mL predicts virus neutralization with accuracy. In regions with limited vaccine availability/hesitancy, antibody testing can identify 20% of the patients with relatively low titres for booster prioritization..Funding Information: This work was supported in part by the University of Kansas Cancer Centre and the Investigator Initiated Steering Committee, a grant from the NIGMS (P20 GM130423), and The University of Kansas Cancer Centre Support Grant from the NCI (P30 CA168524). A.K.G. is the Chancellors Distinguished Chair in Biomedical Sciences Endowed. Declaration of Interests: AKG and ZYP are co-founders of Sinochips Diagnostics; PS serves as advisory board member and consultant to Merck, Novartis, Exact Sciences, Seattle Genetics, Immunomedics, Myriad Genetics, AstraZeneca, Puma Biotechnology; JZ served as a scientific advisor/consultant for AstraZeneca, Biodesix, Novocure, Bayer, Daiichi Sankyo, Mirati, Novartis, Cardinal Health, Bristol Myers Squibb, Nexus Health and Sanofi and is on the speakers’ bureau for AstraZeneca and MJH Life Sciences and has received research funding from AstraZeneca, Biodesix, Novartis, Genentech/Roche, Mirati, AbbVie and Hengrui Therapeutics; GCD serves on an advisory board for Novartis; JPM serves as advisory board member and consultant to Novartis, Kite Pharmaceuticals, BMS and Allovir; RAR received institutional support from Bayer, NuCana, Incyte, AstraZeneca, Eureka therapeutics, Merck, Pfizer, and owns stock in Seattle Genetics, Actinium Pharmaceuticals Inc.; MH received consulting fees from Janssen, Pharmacyclics, Novartis Inc., Kite Pharmaceuticals and TG therapeutics. The remaining authors declare no competing interests.Ethics Approval Statement: This study was approved by the Institutional Review Board of the University of Kansas Medical Centre.

The clinical association between Periodontitis and COVID-19.

OBJECTIVES: The study aimed to clinically assess the association between periodontitis and COVID-19-related outcomes. MATERIAL AND METHODS: Data pertaining to patient demographics, medical history, blood parameters, periodontal clinical examination and aMMP-8 point-of-care diagnostics (both site-level and patient-level) was recorded for eighty-two COVID-19-positive patients. COVID-19-related outcomes such as COVID-19 pneumonia, death/survival, types of hospital admission and need of assisted ventilation were also assessed. RESULTS: Males were predominantly afflicted with COVID-19, with advanced age exhibiting a greater association with the presence of periodontitis. Higher severity of periodontitis led to 7.45 odds of requiring assisted ventilation, 36.52 odds of hospital admission, 14.58 odds of being deceased and 4.42 odds of COVID-19-related pneumonia. The aMMP-8 mouthrinse kit was slightly more sensitive but less specific than aMMP-8 site-specific tests. CONCLUSIONS: Based on the findings of the present study, periodontitis seems to be related to poorer COVID-19-related outcomes. However, within the constraints of this work, a direct causality may not be established. Periodontitis, by means of skewing the systemic condition for a number of comorbidities, may eventually influence COVID-19 outcomes in an indirect manner. CLINICAL RELEVANCE: The study is the first to clinically, and by means of a validated point-of-care diagnostic methodology, assess the association between periodontal health and COVID-19-related outcomes. Assessment of the periodontal status of individuals can aid in the identification of risk groups during the pandemic along with reinforcing the need to maintain oral hygiene and seeking periodontal care.