A mathematical model for multiple COVID-19 waves applied to Kenya (preprint)

The COVID-19 pandemic, which began in December 2019, prompted governments to implement non-pharmaceutical interventions (NPIs) to curb its spread. Despite these efforts and the discovery of vaccines and treatments, the disease continued to circulate globally, evolving into multiple waves, largely driven by emerging COVID-19 variants. Mathematical models have been very useful in understanding the dynamics of the pandemic. Mainly, their focus has been limited to individual waves without easy adaptability to multiple waves. In this study, we propose a compartmental model that can accommodate multiple waves, built on three fundamental concepts. Firstly, we consider the collective impact of all factors affecting COVID-19 and express their influence on the transmission rate through piecewise exponential-cum-constant functions of time. Secondly, we introduce techniques to model the fore sections of observed waves, that change infection curves with negative gradients to those with positive gradients, hence, generating new waves. Lastly, we implement a jump mechanism in the susceptible fraction, enabling further adjustments to align the model with observed infection curve. By applying this model to the Kenyan context, we successfully replicate all COVID-19 waves from March 2020 to January 2023. The identified change points align closely with the emergence of dominant COVID-19 variants, affirming their pivotal role in driving the waves. Furthermore, this adaptable approach can be extended to investigate any new COVID-19 variant or any other periodic infectious diseases, including influenza. Keywords: Mathematical model, COVID-19 pandemic, non-pharmaceutical interventions, delay functions, multiple waves

Power relations and COVID-19 in New York City

With the Bronx as its metropolitan regional epicenter during the early American COVID-19 epidemic, New York City acted as the national epicenter. Because of a decades-long history of New York as epicenter of such contagious ills as AIDS, violent crime, and tuberculosis, identification of the neighborhood(s) which may act as municipal and metro regional epicenter of future epidemics assumes great importance. After the April 2020 COVID crest, how quickly a neighborhood declined in COVID markers indexed the vulnerability of that neighborhood to a second wave and to other contagious phenomena. With ZIP code areas of the four central boroughs having populations over 10,000 as the neighborhoods for analysis, the following measures allowed identification of vulnerability: (1) Decline in percent positive swab tests between specific post-crest dates. (2) Whether the area accumulated over 3000 cases per 100,000. (3) Percent increase in cumulative case rates between specific post-crest dates. (4) Increase in cases per square mile between specific post-crest dates. These markers reflect both vulnerability (socioeconomic and physical) and adequacy of authorities' response. Three sets of criteria qualified areas qualified as potential epicenters: Criteria set 1: Over 3000 cumulative cases per 100,000, above median percent positive swabs on the specific date, and above median percent increase in cumulative case rates between two specific dates. Criteria set 2: Over 3000 cumulative cases per 100,000, above median percent positive swabs on the specific date, and above median new cases/sq mi accrued between specific dates. Criteria set 3: Increase in new cases above 50 per sq mi between specific dates. Criteria set 1 was applied to July 28 data, as well as to August 17 data. Criteria sets 2 and 3 were applied only to August 17 data. Thus, four lists of qualified ZIP code areas arose: Criteria set 1 applied to two intervals and criteria sets 2 and 3 to one. Qualifying areas were mapped. Only Bronx areas appeared on all four lists. Mapping showed that Bronx areas formed large clusters for each of the four lists, the largest clusters for any borough. With the exception of ZIP code area 10035 in East Harlem, Manhattan areas appeared only on the map for criteria set 3. Several Upper Manhattan areas exceeded 100 new cases per sq mi amassed between July 28 and August 17. Several wealthy Manhattan areas also qualified, indicating vulnerability. The Queens cluster of "red alert" areas near LaGuardia Airport has a high proportion of foreign-born residents, a likely high number of airport employees and of essential workers. With its long history of authority-sponsored segregation and community-destroying modes of discrimination, the Bronx emerged as the likely future epicenter. Two strategic paths reduce the probability of epicenter development: (1) increase residential stability above the threshold for development of numerous large interacting social networks and (2) accelerate social network formation with deliberate organizing. The first step would outlaw all processes that destroy housing or push people out of their homes or decrease availability of low-cost housing. Areas without social organization are powerless against predatory forces whether they be capitalist entities such as landlords or government acting for capitalist entities. Further exploration of the epidemiological condition of the Upper Manhattan and wealthy areas with high new case densities would be wise. Manhattan had been the epicenter of AIDS, TB, violent crime, and low birthweight epidemics in the NYC metro region. Destabilized by massive emigration of wealthy white residents, gentrified Manhattan could be newly vulnerable. Residential destabilization is an enemy of public health and of community empowerment. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022. All rights reserved.

Donation after circulatory death liver transplants are higher and unevenly distributed in the United States after the implementation of the acuity circle allocation policy

Background: This study aimed to assess the impact of the recently (02/2020) implemented Acuity Circles (AC) liver allograft allocation policy on MELD at transplant and Donation after Circulatory Death (DCD) rates. Methods: Study period: 01/2016- 08/2021. Data retrieved from SRTR database. Inclusion criteria: All DCD liver transplants (LT). The cohort was dichotomized into a pre- and post-AC era. DCD rate (defined as DCD/ 50k population/year) was calculated for each State. The change (Δ) on the DCD rate (ΔDCD) and the MELD (ΔMELD) between the two periods was also calculated. Results: 1. Total LT increased in the post-AC era (26%/50k vs. 15%/50k, p=0.0567). 2. DCD LT increased in the post-AC era (15%/50k vs.10%/50k, p=0.0885). 3. MELD increased in the post-AC era in nearly all States (ΔMELD, fig.1, 2 & 3). 4. Uneven distribution of pre- & post-AC DCD activity, with a few States driving DCD LT in the US (fig.4 & 5). 5. Arizona and Louisiana had the highest pre-AC DCD rates (58%/50k & 31%/50k, respectively;fig.3). 6. The top post-AC DCD rate was reached in Arizona (78%/50k, fig.5). 7. Top post-AC ΔDCD was noted in Arkansas & Arizona (fig.6). 8. The highest ΔMELD was noted in low DCD/ negative ΔDCD areas (fig.7). 9. The lowest ΔMELD was noted in areas with the highest DCD rate (fig.7) 10. The State with the highest DCD rates pre-AC had the highest ΔDCD (fig.5). 11. 10/11 States with negative ΔDCD were located North of the 35o. Conclusions: AC implementation coincided with an increase in the overall LT & DCD LT activity. However, causation remains to be clarified, given the concurrent opioid crisis and SARS-CoV-2 pandemic. There was remarkable DCD rate variation. States with high DCD rates/ΔDCD demonstrated greater adaptability in the allocation change, maintaining low ΔMELD across eras. (Figure Presented).

Success in the Online Classroom: Lessons Learned

In the early 2000s, we embarked on research to study online education. At the time, online courses offered by traditional institutions was in its’ infancy. Through our research, we learned that increasing students’ intrinsic motivation could lead to more successful learning environments. Today’s online learning environments are afforded many more technological advances that were not available 20 years ago. In addition, the Covid19 Pandemic has forced the creation online learning environment. Therefore, we believe that revisiting the elements that lead to successful online learning is timely and necessary. Through this research, we affirm that technological advancements have led to more meaningful ways to enhance online learning environments. © 2022, North American Business Press. All rights reserved.

What Is to Be Done?

Disease infections rise to epidemic threshold in local communities from which they spread spatially. Spatial diffusion within metropolitan regions enables hierarchical diffusion among metropolitan regions. Thus, preventing pandemics requires containing infection rates within local communities. Culturally isolated communities and those targeted with discriminatory policies and practices remain most vulnerable to high rates of infection. Because of long-term abuse and neglect by governmental agencies and the economic powers behind government, these communities often disobey edicts from health departments. Local health departments must engage with all communities and community components to effect pandemic prevention and response. Chapter 7 lists tactics of engagement and of organizing an efficacious pandemic response planning board. Health departments must have emergency pandemic powers. Elected executives (mayors, county executives, governors) have proven the Achilles’ heel of pandemic response. Elected executives depend on big donors and befriend ascendant capitalists, favoring them with policies and governmental funds, aka corrupt cronyism.

Phase II Study of Acalabrutinib and High-Frequency Low-Dose Subcutaneous Rituximab in Patients with Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Background: Continuous Bruton's tyrosine kinase (BTK) inhibition represents an effective and easily administered oral therapy for patients with CLL;however, it is not curative, can have serious side effects, and is expensive. Novel combinations may provide deep remissions allowing fixed duration therapy. The second generation BTK inhibitor acalabrutinib (ACALA) has demonstrated an improved safety profile compared to ibrutinib. Importantly, unlike ibrutinib, ACALA does not inhibit anti-CD20 monoclonal antibody dependent cellular phagocytosis (VanDerMeid et al, Cancer Immuno Res 2018). Using standard doses, rituximab (RTX) rapidly exhausts the finite innate immune system cytotoxic capacity (Pinney, et al Blood 2020) and also causes loss of cell membrane CD20 from CLL cells by trogocytosis. Previous studies have shown that high frequency low dose (HFLD) IV RTX (20mg/m 2 three times per week) was effective and limited loss of CD20 (Zent, et al Am J Hematol, 2014). Subcutaneous (SQ) RTX is FDA approved in CLL, has similar efficacy and pharmacokinetics, and can be self-administered. This phase II study tested the efficacy and tolerability of the combination of ACALA and HFLD RTX as initial treatment for patients with treatment-naïve CLL. Methods: Eligible patients were treated with 50mg RTX on day 1 and 3 of each week for six 28-day cycles. The first dose was administered IV over 2 hours. If tolerated, subsequent doses were SQ and could be self-administered at home by trained patients. ACALA 100mg BID therapy was initiated on cycle 1 day 8 for a minimum of 12 cycles. Treatment response was assessed during cycles 12 and 24. Patients achieving an iwCLL complete response (CR) with undetectable minimal residual disease (uMRD) by 6-color flow cytometry (£ 1:10 -4)at either time point could stop therapy. The primary objective was to determine the rate of iwCLL CR with a secondary endpoint of rate of uMRD. Results: 37 patients have been treated with a median follow-up of 14 months. Baseline demographics were male/female (22/15) and median age 67 years (range 40-78). High-risk genetic features included TP53 mutation (21.6%), del17p (13.5%), del 11q (16.2%), unmutated IGHV (62.2%), NOTCH1 mutation (21.6%) and SF3B1 mutation (10.8%). Grade 3/4 AEs occurring in ≥5% of patients were infections (13.5%), neutropenia (8.1%) and anemia (8.1%). No patients discontinued therapy due to AEs and there were no deaths on treatment. The most common (≥20%) AEs (all grades and all causality) were infusion-related reactions (62.1%), infections (56.8%) (upper respiratory infections in 29.7% of patients, urinary tract infections in 18.9%, COVID-19 pneumonia in 8.1%), fatigue (51.3%), anemia (51.3%), headache (43.2%), rash or other skin changes (32.4%), thrombocytopenia (29.7%), bruising (27.0%), and diarrhea (21.6%). Injection site reactions (8.1%) from SQ RTX were grade 1. Three patients contracted COVID-19 while on study during times of high community transmission prior to the availability of vaccines. Two required hospitalization, one contracted the virus following cycle 1 requiring a delay in RTX, and all patients remained on ACALA while COVID-19 positive. 27 patients have completed 12 cycles and been evaluated for response. All patients responded with 1 MRD+ CR, 20 partial responses (PR), and 6 PR with sustained lymphocytosis. 10 of these patients have completed 24 cycles and had a sustained PR. One patient with del17p and TP53 mutation had progressive disease after 25 cycles of therapy. All other patients remain on treatment per protocol. Conclusion: HFLD RTX and ACALA is a tolerable, effective and convenient therapy that could be the basis for regimens incorporating other novel agents. It is notable that three patients have contracted COVID-19 during the trial;however, none required intubation, and all remained on ACALA during their infection. This at-home combination markedly decreased patient infection risk during the COVID-19 pandemic. This regimen has the potential to enable RTX to be administered at facilities with limited medica IV infusion capacity which could be very useful in rural and economically disadvantaged areas. While all patients have responded to therapy, no patients to date have achieved an uMRD CR, suggesting that additional agents are required to allow for time-limited treatment. Disclosures: Baran: AstraZeneca/Acerta: Research Funding. Friedberg: Novartis: Other: DSMC;Acerta: Other: DSMC;Bayer: Other: DSMC. Reagan: Kite, a Gilead Company: Consultancy;Genentech: Research Funding;Seagen: Research Funding;Curis: Consultancy. Casulo: Verastem: Research Funding;Genentech: Research Funding;BMS: Research Funding;Gilead: Research Funding. Zent: TG Therapeutics: Research Funding;Acerta/AstraZeneca: Research Funding. Barr: Morphosys: Consultancy;Janssen: Consultancy;Bristol Meyers Squibb: Consultancy;AstraZeneca: Consultancy;Genentech: Consultancy;TG Therapeutics: Consultancy;Beigene: Consultancy;Seattle Genetics: Consultancy;Abbvie/Pharmacyclics: Consultancy;Gilead: Consultancy.

Parsing Meaning from the 152 ZIP Code Data

The Bronx held top position for 2nd wave ZC mean and median % positive (%pos). A month after crest, the mean and median %pos of Bronx ZCs exceeded 10%. For the three other boroughs, associations between ZC SE factors and %pos tightened over time, even into post-crest weeks. The Bronx associations began tighter than the other three boroughs but disappeared during the crest. Infections swamped the Bronx and allowed no SE haven. With the Bronx crest exception, SE factors clearly associated with patterns of %pos over the boroughs. The high R-squares of the SE multivariate associations with %pos reveal failure of public health efforts. Testing intensity in the boroughs reflected race and class. Manhattan was tested most;the Bronx, least. The frequent negative association of % Black with % pos in the multivariate regressions hinted that testing within the Black neighborhoods was biased toward better-educated, wealthier residents. Public health resources were allotted in a deeply discriminatory manner. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Discussion of County Data from the Second Wave of COVID-19

Epicenters outside the State initiated the second NYS wave;rural counties became early state epicenters;the ebb was as rapid as the rise to the crest. The major factor associating with percent positive county patterns was percent Trump vote 2020. The rapid decline occurred after the events of January 6, 2021 at the US Capitol. After Jan 9, the association between Trump vote and percent positive pattern disappeared. The socioeconomic profile of Trump-voting counties echoed their national profile: white, low percent with college or higher degree, and middling household income. This population in pain longs for a nonexistent past when white men earned high wages and advanced through hard work;white women stayed home;everyone had a place and stayed in that place. They long for a stable hierarchical system and will follow the leader promising it. They will sacrifice health and safety if their leader tells them that they will gain freedom by doing so. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

The Second Wave Storm-Surges Across New York City

The Bronx operated as one unit during the first wave. At the second wave peak, ZC percent positive tests had no SE associations in the Bronx, different from the other three boroughs. The Bronx had the highest % positive ZC mean, median, and maximum of the boroughs during the 2nd wave crest. Very high % positives persisted in the Bronx post-crest, while plummeting in other boroughs. Certain SE factors associated frequently with % positive in multivariate regressions: college or higher degrees per 100 adults, % Latinx, % Black, % foreign-born, and rent stress. Persistent negative strong associations with % Black hint of nonrepresentational ZC testing. Black case and fatality rates greatly exceeded those of whites in NYC DOH (Department of Health) data. Data on percent positive tests across the ZCs likely understated true infection rates in poor ZCs of color. The infection situation in the Bronx and in Black Brooklyn and Queens neighborhoods was worse than the official data. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

The Second COVID Wave Washes Over New York State

By Oct 30, 2020 nine NYS counties had over 3% positive tests. By Nov 9, 29 counties exceeded 3% positive. By Nov 29, 45 counties out of 62 did. The contagion showed classic spatial diffusion from epicenters with great rapidity. Data on percent of positive COVID tests for 16 days out of 57 between Oct 30 and the Dec 25 crest showed no SE association with percent positive. The 31 rural counties often had significantly higher means and medians than the 31 urban. The sole factor frequently associating with percent positive was 2020 percent Trump vote. The Trump vote signaled risk behaviors that led to epicenters in rural counties spreading COVID to the rest of the state. After early January 2021, the means and medians declined as rapidly as they had built up to the crest, an indication that behaviors changed massively toward interventions, especially in the rural, Trump-voting counties. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

The Sixty-Two Counties of New York State

Well over half the population of New York State (NYS) lives in New York City (NYC) and three abutting counties (Westchester, Nassau, Suffolk). Socio-economic (SE) measures such as median household income, percent adults with college or higher degrees, and percent of population with various “race”/ethnic labels (white, Black, Latinx) differ significantly between the 31 rural and 31 urban counties. NYS has a functional SE system. For example: counties with high median income have high percent of adults with college degrees, lower percent white population, higher poverty rate, higher population, and higher population density. The COVID-19 pandemic led to much higher unemployment rates in 2020 in all counties than in 2019, with the NYC counties more than doubling their rates. The SE profile of counties that voted for Trump (Donald Trump) in the 2020 election was consistent with the national pattern: low educational attainment, high percent white population, high percent vote in rural counties. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Gastrointestinal symptoms in patients with inflammatory bowel disease after SARS-CoV-2 mRNA vaccination

Introduction: In the SARS-CoV2 mRNA vaccine trials, post-vaccination gastrointestinal (GI) symptoms were reported in 10-20% of participants. These symptoms could be perceived as inflammatory bowel disease (IBD) flare which could lead to patient anxiety, and unnecessary tests or treatment. We aimed to assess GI symptoms after SARS-CoV2 mRNA vaccination in patients with IBD relative to non-IBD healthcare workers (HCW). Methods: We assessed GI symptoms in adults with IBD and HCW at baseline and after each dose of a SARS-CoV-2 mRNA vaccine. We analyzed patient-reported IBD-specific disease activity (PRO2) after each dose (stool frequency (SF) and rectal bleeding for ulcerative colitis (UC), SF and abdominal pain for Crohn's disease (CD)). We also compared the frequency, severity, and duration of postvaccination GI symptoms in IBD patients compared to HCW. Severity was defined by impact on daily activities (mild, did not interfere;moderate, some interference;severe, prevented routine activity;extreme, required hospitalization). Severe and extreme were combined and designated as severe+. Duration was classified as<2 days, 2-7 days, or>7 days. Results: Post-vaccination GI symptoms were assessed after dose 1 (D1) (1391 IBD, 933 HCW) and dose 2 (D2) (1271 IBD, 884 HCW) (Table). About 60% of IBD and>99% of HCW received the BNT162b vaccine (Pfizer);the remainder received mRNA-1273 (Moderna). New GI symptoms after D1 were more frequent among IBD than HCW (6.0% vs 2.9%, p=0.001) but not after D2 (12.1% vs 12.7%, p=NS). Relative to HCW, IBD patients reported more diarrhea (3.8% vs. 1% (p<0.001) after D1 and 7.5% vs 4.2% (p=0.003) after D2) and abdominal pain (2.2% vs. 0.4% (p=0.001) after D1 and 6.2% vs 3% (p=0.002) after D2). Severe1 symptoms were noted in 1.5% IBD and 0.3% HCW (p=NS) after D1 and in 3.3% IBD and 0.1% HCW (p<0.001) after D2 (Figure 1). Longer GI symptom duration was more common in IBD than HCW after D1 (2.1% vs 0.5%, p=0.002) and D2 (5.4% vs. 2.1%, p<0.001). Among 423 CD and 300 UC patients with PRO2 data, 71%, 68%, and 65% of CD and 86%, 86%, and 83% of UC were in clinical remission at baseline, after D1, and after D2, respectively. Conclusion: The frequency of GI symptoms in IBD was greater than HCW after D1, but similar after D2. More severe and longer duration of GI symptoms were noted in a small number of IBD patients. Reassuringly, the mRNA vaccines do not seem to increase the risk of a disease flare in the vast majority of IBD patients.

COVID-19: Experiences of lockdown and support needs in children and young adults with kidney conditions

Background During the initial COVID-19 pandemic, young United Kingdom (UK) kidney patients underwent lockdown and those with increased vulnerabilities socially isolated or 'shielded' at home. The experiences, information needs, decision- making and support needs of children and young adult (CYA) patients or their parents during this period is not well known. Objectives To understand the concerns and decision-making in CYA during the first lockdown, and perform subgroup analysis on shielded vs non-shielded patients Methods UK wide online survey co-produced with patients was conducted in May 2020 among CYA aged 12-30, or parents of children aged <18 years with any degree of chronic kidney disease. Participants answered qualitative open text alongside quantitative closed questions. Thematic content analysis using a three-stage coding process was conducted. Results 118 CYA (median age 21) and 197 parents of children (median age 10) responded. Predominant concerns from CYA were heightened vigilance about viral (68%) and kidney symptoms (77%) and detrimental impact on education or work opportunities (70%). Parents feared the virus more than CYA (71% vs 40%), that their child would catch the virus from them (64%) and adverse impact on other children at home (65%). CYA thematic analysis revealed: strong belief of becoming seriously ill if they contract COVID-19, lost educational opportunities, socialisation, and career development, and frustration at public for not following social distancing rules. Positive outcomes included improved family relationships and community cohesion. Only a minority (14-21% CYA and 20 - 31% parents, merged questions) desired more support. Subgroup analysis identified greater negative psychological impact in the shielded group. Conclusions This is the first study specifically surveying CYA with kidney conditions and their parents' experience of the COVID-19 pandemic during lockdown. We found substantial concern and need for accurate tailored advice for CYA based on individualised risks to improve shared decision making.

Flap coverage for necrotising soft tissue infections: A systematic review.

BACKGROUND: Necrotising soft tissue infections (NSTI) are destructive and often life-threatening infections of the skin and soft tissue, necessitating prompt recognition and aggressive medical and surgical treatment. After debridement, the aim of surgical closure and reconstruction is to minimize disability and optimize appearance. Although skin grafting may fulfil this role, techniques higher on the reconstructive ladder, including local, regional and free flaps, are sometimes undertaken. This systematic review sought to determine the circumstances when this is true, which flaps were most commonly employed, and for which anatomical areas. METHODS: A systematic review of the literature was conducted utilising electronic databases (Medline, Embase, Cochrane Library). Full text studies of flaps used for the management of NSTI's (including Necrotising Fasciitis and Fournier Gangrene) were included. The web-based program 'Covidence' facilitated storage of references and data management. Data obtained in the search included reference details (journal, date and title), the study design, the purpose of the study, the study findings, number of patients with NSTI included, the anatomical areas of NSTI involved, the types of flaps used, and the complication rate. RESULTS: After screening 4555 references, 501 full text manuscripts were assessed for eligibility after duplicates and irrelevant studies were excluded. 230 full text manuscripts discussed the use of 888 flap closures in the context of NSTI in 733 patients; the majority of these were case series published in the last 20 years in a large variety of journals. Reconstruction of the perineum following Fournier's gangrene accounted for the majority of the reported flaps (58.6%). Free flaps were used infrequently (8%), whereas loco-regional muscle flaps (18%) and loco-regional fasciocutaneous flaps (71%) were employed more often. The reported rate of partial or complete flap loss was 3.3%. CONCLUSION: Complex skin and soft tissue defects from NSTIs, not amenable to skin grafting, can be more effectively and durably covered using a spectrum of flaps. This systematic review highlights the important contribution that the plastic surgeon makes as an integral member of multidisciplinary teams managing these patients.