Heterologous immunity induced by 1st generation COVID-19 vaccines and its role in developing a pan-coronavirus vaccine.

Severe acute respiratory syndrome virus-2 (SARS-CoV-2), the causative infectious agent of the COVID-19 pandemic, has led to multiple (4-6) waves of infections worldwide during the past two years. The development of vaccines against SARS-CoV-2 has led to successful mass immunizations worldwide, mitigating the worldwide mortality due the pandemic to a great extent. Yet the evolution of new variants highlights a need to develop a universal vaccine which can prevent infections from all virulent SARS-CoV-2. Most of the current first generation COVID-19 vaccines are based on the Spike protein from the original Wuhan-hu-1 virus strain. It is encouraging that they still protect from serious illnesses, hospitalizations and mortality against a number of mutated viral strains, to varying degrees. Understanding the mechanisms by which these vaccines provide heterologous protection against multiple highly mutated variants can reveal strategies to develop a universal vaccine. In addition, many unexposed individuals have been found to harbor T cells that are cross-reactive against SARS-CoV-2 antigens, with a possible protective role. In this review, we will discuss various aspects of natural or vaccine-induced heterologous (cross-reactive) adaptive immunity against SARS-CoV-2 and other coronaviruses, and their role in achieving the concept of a pan-coronavirus vaccine.

Case Report: Severe SARS-CoV-2 Infection Treated with Remdesivir in a Patient with ESRD.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has led to a global pandemic since its emergence from Wuhan, China, in December of 2019. As research continues to evolve, there is a paucity of reports describing the management and treatment of COVID-19 in patients with acute kidney failure and End-Stage Renal Disease (ESRD). These patients have increased susceptibility to developing severe clinical symptoms from SARS-CoV-2 infection due to their underlying comorbidities. Remdesivir has emerged as a promising antiviral drug against SARS-CoV-2. However, data regarding the clinical benefits of remdesivir in patients with severe renal impairment is unavailable as they have been excluded from clinical trials due to the risk of sulfobutylether-ß-cyclodextrin (SBECD) accumulation in patients with eGFR<30 ml/min per 1.73m2. CASE PRESENTATION: We present the first case of a 47-year-old male with end-stage renal disease who was successfully treated with remdesivir during hospitalization for acute respiratory distress syndrome and respiratory failure arising from COVID-19. The worsening clinical progress of the patient despite intensive care and treatment with intravenous azithromycin therapy led to the decision to utilize remdesivir after a risk-benefit analysis, despite his eGFR being <15 ml/min per 1.73m2. Although the patient developed reversible hepatotoxicity, marked improvement of symptoms was observed after the five-day course of remdesivir was completed. CONCLUSION: Our findings describe the first instance of compassionate use of remdesivir for the treatment of COVID-19 in the setting of end-stage renal disease, acute respiratory distress syndrome, and hypoxemic respiratory failure.

Complex contraception provision during the COVID-19 pandemic, how did sexual health services fare?

BACKGROUND: This study evaluated whether sexual health services (SHS) across the UK could meet the Faculty of Sexual and Reproductive Health (FSRH) standard for access by being able to offer an appointment for a long-acting reversible contraception (LARC) fitting within 2 weeks of initial contact. METHODS: SHSs offering LARCs were identified using the British Association for Sexual Health and HIV (BASHH) clinic database. During October 2020, all clinics open for more than 1 day a week were contacted by telephone. The researcher posed as a 20-year-old woman in a regular heterosexual relationship who was using condoms and requesting a contraceptive implant. Data collected included the time to wait to appointment and whether clinics offered bridging methods of contraception during any delay in appointment. It was also noted whether a local COVID-19 restriction was in place at the time of the call. The information collected was coded, and data was analysed using chi-square tests in SPSSv27. RESULTS: Of the 218 contactable clinics, 51.4% (n = 112) of clinics offered the patient an appointment within two weeks, and 66.1% (n = 144) of clinics could offer appointments within four weeks. 7.3% (n = 16) of clinics offered the patient adjunct bridging oral contraception until the time of appointment. Comparing the devolved nations, 11/17 (64.7%) clinics in Scotland, 8/13 (61.5%) clinics in Wales, 0/4 (0.0%) clinics in Northern Ireland and 93/182 (51.1%) clinics in England offered an appointment within two weeks with significant regional variation across England (p = .005). No statistically significant difference was demonstrated in access between clinics with or without high-level COVID-19 restrictions (p = .056). CONCLUSION: The 2-week standard was met in just over half of the occasions, with significant variation across regions across the UK. The development of a national target for access may improve access to LARCs.

COVID-19 in Immunocompromised Cancer Patients: A Case Series and Review of the Literature.

The global pandemic of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented newfound challenges to the oncology community regarding management of disease progression in immunocompromised and cancer patients. Further, the large influx of COVID-19 patients has overwhelmed healthcare facilities, limited access to intensive care unit beds and ventilators, and canceled elective surgeries causing disruptions to the cancer care continuum and re-organization of oncological care. While it is known that the potential threat of infection is greatest in elderly patients (>60 years of age) and patients with underlying comorbidities, there is still insufficient data to determine the risk of COVID-19 in cancer patients. Given the immunosuppressive status in cancer patients arising from chemotherapy and other comorbidities, management of COVID-19 in this patient population carries a unique set of challenges. We report three cases of COVID-19 in immunocompromised cancer patients and discuss the challenges in preventing, diagnosing, and treating this vulnerable group.

Impact of Chronic Obstructive Pulmonary Disease and Emphysema on Outcomes of Hospitalized Patients with Coronavirus Disease 2019 Pneumonia.

BACKGROUND: Comorbid disease is a risk factor for severe coronavirus disease 2019 (COVID-19) infection. However, initial rates of chronic obstructive pulmonary disease (COPD) in case series were low and severity of COVID-19 in COPD patients was variable. METHODS: We performed a retrospective study of patients admitted with COVID-19 and evaluated outcomes in those with and without COPD and/or emphysema. Patients were identified as having COPD if they had a diagnosis in the medical record and a history of airflow-obstruction on spirometry, or a history of tobacco use and prescribed long-acting bronchodilator(s). Computed tomography scans were evaluated by radiologists. Propensity matching was performed for age, body mass index (BMI), and serologic data correlated with severity of COVID-19 disease (D-dimer, C-reactive protein, ferritin, fibrinogen, absolute lymphocyte count, lymphocyte percentage, and lactate dehydrogenase). RESULTS: Of 577 patients admitted with COVID-19, 103 had a diagnosis of COPD and/or emphysema. The COPD/emphysema cohort was older (67 versus 58, p<0.0001) than the other cohort and had a lower BMI. Among unmatched cohorts those with COPD/emphysema had higher rates of intensive care unit (ICU) admission (35% versus 24.9%, p=0.036) and maximal respiratory support requirements, with more frequent invasive mechanical ventilation (21.4% versus 11.8%), but no significant difference in mortality. After propensity-matching there was no difference in ICU admission, maximal respiratory support requirements, or mortality. Univariate and multivariate regression analyses yielded similar results. DISCUSSION: Our propensity-matched retrospective cohort study suggests that patients hospitalized with COVID-19 who have COPD and/or emphysema may not have worse outcomes than those without these comorbid conditions.

Human Immunodeficiency Virus and Severe Acute Respiratory Syndrome Coronavirus 2 Coinfection: A Systematic Review of the Literature and Challenges.

The concurrence of infection with human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), presents an intriguing problem with many uncertainties underlying their pathogenesis. Despite over 96.2 million cases of COVID-19 worldwide as of January 22, 2021, reports of patients coinfected with HIV and SARS-CoV-2 are scarce. It remains unknown whether HIV patients are at a greater risk of infection from SARS-CoV-2, despite their immunocompromised status. We present a systematic review of the literature reporting cases of HIV and SARS-CoV-2 coinfection, and examine trends of clinical outcomes among coinfected patients. We systematically compiled 63 reports of HIV-1 and SARS-CoV-2 coinfection, published as of January 22, 2021. These studies were retrieved through targeted search terms applied to PubMed/Medline and manual search. Despite scattered evidence, reports indicate a favorable prognosis for HIV patients with strict adherence to combined antiretroviral therapy (cART). However, the presence of comorbidities was associated with a poorer prognosis in HIV/SARS-CoV-2 patients, despite cART and viral suppression. Studies were limited by geographic coverage, small sample size, lack of patient details, and short follow-up durations. Although some anti-HIV drugs have shown promising in vitro activity against SARS-CoV-2, there is no conclusive evidence of the clinical efficacy of any anti-HIV drug in the treatment of COVID-19. Further research is needed to explain the under-representation of severe COVID-19 cases among the HIV patient population and to explore the possible protective mechanisms of cART in this vulnerable population.

Postdischarge venous thromboembolism following hospital admission with COVID-19.

The association of severe coronavirus disease 2019 (COVID-19) with an increased risk of venous thromboembolism (VTE) has resulted in specific guidelines for its prevention and management. The VTE risk appears highest in those with critical care admission. The need for postdischarge thromboprophylaxis remains controversial, which is reflected in conflicting expert guideline recommendations. Our local protocol provides thromboprophylaxis to COVID-19 patients during admission only. We report postdischarge VTE data from an ongoing quality improvement program incorporating root-cause analysis of hospital-associated VTE (HA-VTE). Following 1877 hospital discharges associated with COVID-19, 9 episodes of HA-VTE were diagnosed within 42 days, giving a postdischarge rate of 4.8 per 1000 discharges. Over 2019, following 18 159 discharges associated with a medical admission; there were 56 episodes of HA-VTE within 42 days (3.1 per 1000 discharges). The odds ratio for postdischarge HA-VTE associated with COVID-19 compared with 2019 was 1.6 (95% confidence interval, 0.77-3.1). COVID-19 hospitalization does not appear to increase the risk of postdischarge HA-VTE compared with hospitalization with other acute medical illness. Given that the risk-benefit ratio of postdischarge thromboprophylaxis remains uncertain, randomized controlled trials to evaluate the role of continuing thromboprophylaxis in COVID-19 patients following hospital discharge are required.

COVID-19 cardiovascular epidemiology, cellular pathogenesis, clinical manifestations and management.

Coronavirus Disease 2019 (COVID-19) is a rapidly progressing global pandemic that may present with a variety of cardiac manifestations including, but not limited to, myocardial injury, myocardial infarction, arrhythmias, heart failure, cardiomyopathy, shock, thromboembolism, and cardiac arrest. These cardiovascular effects are worse in patients who have pre-existing cardiac conditions such as coronary artery disease, hypertension, diabetes mellitus, and coagulation abnormalities. Other predisposing risk factors include advanced age, immunocompromised state, and underlying systemic inflammatory conditions. Here we review the cellular pathophysiology, clinical manifestations and treatment modalities of the cardiac manifestations seen in patients with COVID-19.