Repurposing Molnupiravir for COVID-19: The Mechanisms of Antiviral Activity

Molnupiravir is a β-d-N4-hydroxycytidine-5′-isopropyl ester (NHC) compound that exerts antiviral activity against various RNA viruses such as influenza, SARS, and Ebola viruses. Thus, the repurposing of Molnupiravir has gained significant attention for combatting infection with SARS-CoV-2, the etiological agent of COVID-19. Recently, Molnupiravir was granted authorization for the treatment of mild-to-moderate COVID-19 in adults. Findings from in vitro experiments, in vivo studies and clinical trials reveal that Molnupiravir is effective against SARS-CoV-2 by inducing viral RNA mutagenesis, thereby giving rise to mutated complementary RNA strands that generate non-functional viruses. To date, the data collectively suggest that Molnupiravir possesses promising antiviral activity as well as favorable prophylactic efficacy, attributed to its effective mutagenic property of disrupting viral replication. This review discusses the mechanisms of action of Molnupiravir and highlights its clinical utility by disabling SARS-CoV-2 replication, thereby ameliorating COVID-19 severity. Despite relatively few short-term adverse effects thus far, further detailed clinical studies and long-term pharmacovigilance are needed in view of its mutagenic effects.     

Care for Incarcerated Patients Hospitalized with COVID-19

The COVID-19 pandemic has reshaped health care delivery for all patients but has distinctly affected the most marginalized people in society. Incarcerated patients are both more likely to be infected and more likely to die from COVID-19. There is a paucity of guidance for the care of incarcerated patients hospitalized with COVID-19. This article will discuss how patient privacy, adequate communication, and advance care planning are rights that incarcerated patients may not experience during this pandemic. We highlight the role of compassionate release and note how COVID-19 may affect this prospect. A number of pragmatic recommendations are made to attenuate the discrepancy in hospital care experienced by those admitted from prisons and jails. Physicians must be familiar with the relevant hospital policies, be prepared to adapt their practices in order to overcome barriers to care, such as continuous shackling, and advocate to change these policies when they conflict with patient care. Stigma, isolation, and concerns over staff safety are shared experiences for COVID-19 and incarcerated patients, but incarcerated patients have been experiencing this treatment long before the current pandemic. It is crucial that the internist demand the equitable care that we seek for all our patients.     

Care of tuberculosis patients in the times of COVID-19

Globally during this time of Covid-19 pandemic health care services are overhelmed and it has negative impact on other diseases like Tuberculosis (TB). High TB burden countries like India despite being faced by several other problems in present times, is continuously trying to provide uninterrupted services to TB patients through the national programs. In this general perspective we have shared our opinion on problems faced by TB patients in the times of covid-19     

Health Care Implications of the COVID-19 Pandemic for the Cardiovascular Practitioner

There has been substantial excess morbidity and mortality during the COVID-19 pandemic, not all of which was directly attributable to SARS-CoV-2 infection, and many non-COVID-19 deaths were cardiovascular. The indirect effects of the pandemic have been profound, resulting in a substantial increase in the burden of cardiovascular disease and cardiovascular risk factors, both in individuals who survived SARS-CoV-2 infection and in people never infected. In this report, we review the direct effect of SARS-CoV-2 infection on cardiovascular and cardiometabolic disease burden in COVID-19 survivors as well as the indirect effects of the COVID-19 pandemic on the cardiovascular health of people who were never infected with SARS-CoV-2. We also examine the pandemic effects on health care systems and particularly the care deficits caused (or exacerbated) by health care delayed or foregone during the COVID-19 pandemic. We review the consequences of: (1) deferred/delayed acute care for urgent conditions; (2) the shift to virtual provision of outpatient care; (3) shortages of drugs and devices, and reduced access to: (4) diagnostic testing, (5) cardiac rehabilitation, and (6) homecare services. We discuss the broader implications of the COVID-19 pandemic for cardiovascular health and cardiovascular practitioners as we move forward into the next phase of the pandemic.     

Providing End-of-Life Care for Patients Dying of COVID-19 and Their Families in Isolated Death During the Pandemic in Japan: The Providing End-of-life Care for COVID-19 Project

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Post-Acute Care Preparedness in a COVID-19 World

Coronavirus disease 2019 (COVID-19) has led to a surge of patients requiring post-acute care. In order to support federal, state and corporate planning, we offer a four-stage regionally oriented approach to achieving optimal systemwide resource allocation across a region's post-acute service settings and providers over time. In the first stage, the post-acute care system must, to the extent possible, help relieve acute hospitals of non-COVID-19 patients to create as much inpatient capacity as possible over the surge period. In the second stage after the initial surge as subsided, post-acute providers must protect vulnerable populations from COVID-19, prepare treat-in-place protocols for non-COVID-19 admissions, and create and formalize COVID-19 specific settings. In the third stage after a vaccine has been developed or an effective prophylactic option is available, post-acute care providers must assist with distribution and administration of vaccinations and prophylaxis, develop strategies to deliver non-COVID-19 related medical care, and begin to transition to the post-COVID-19 landscape. In the final stage, we must create health advisory bodies to review post-acute sector's response, identify opportunities to improve performance going forward, and develop a pandemic response plan for post-acute care providers. J Am Geriatr Soc 68:1150–1154, 2020.     

The Global Effect of the COVID-19 Pandemic on STEMI Care: A Systematic Review and Meta-analysis

BackgroundThe COVID-19 pandemic has affected patients with ST-segment elevation myocardial infarction (STEMI) requiring primary percutaneous coronary intervention (PCI) worldwide. In this review we examine the global effect of the COVID-19 pandemic on incidence of STEMI admissions, and relationship between the pandemic and door to balloon time (D2B), all-cause mortality, and other secondary STEMI outcomes.MethodsWe performed a systematic review and meta-analysis to primarily compare D2B time and in-hospital mortality of STEMI patients who underwent primary PCI during and before the pandemic. Subgroup analyses were performed to investigate the influence of geographical region and income status of a country on STEMI care. An online database search included studies that compared the aforementioned outcomes of STEMI patients during and before the pandemic.ResultsIn total, 32 articles were analyzed. Overall, 19,140 and 68,662 STEMI patients underwent primary PCI during and before the pandemic, respectively. Significant delay in D2B was observed during the pandemic (weighted mean difference, 8.10 minutes; 95% confidence interval [CI], 3.90-12.30 minutes; P = 0.0002; I² = 90%). In-hospital mortality was higher during the pandemic (odds ratio [OR], 1.27; 95% CI, 1.09-1.49; P = 0.002; I² = 36%), however this varied with factors such as geographical location and income status of a country. Subgroup analysis showed that low–middle-income countries observed a higher rate of mortality during the pandemic (OR, 1.52; 95% CI, 1.13-2.05; P = 0.006), with a similar but insignificant trend seen among the high income countries (OR, 1.17; 95% CI, 0.95-1.44; P = 0.13).ConclusionsThe COVID-19 pandemic is associated with worse STEMI performance metrics and clinical outcome, particularly in the Eastern low–middle-income status countries. Better strategies are needed to address these global trends in STEMI care during the pandemic.     

History of the Plague: An Ancient Pandemic for the Age of COVID-19

During the fourteenth century, the bubonic plague or Black Death killed more than one third of Europe or 25 million people. Those afflicted died quickly and horribly from an unseen menace, spiking high fevers with suppurative buboes (swellings). Its causative agent is Yersinia pestis, creating recurrent plague cycles from the Bronze Age into modern-day California and Mongolia. Plague remains endemic in Madagascar, Congo, and Peru. This history of medicine review highlights plague events across the centuries. Transmission is by fleas carried on rats, although new theories include via human body lice and infected grain. We discuss symptomatology and treatment options. Pneumonic plague can be weaponized for bioterrorism, highlighting the importance of understanding its clinical syndromes. Carriers of recessive familial Mediterranean fever (FMF) mutations have natural immunity against Y. pestis. During the Black Death, Jews were blamed for the bubonic plague, perhaps because Jews carried FMF mutations and died at lower plague rates than Christians. Blaming minorities for epidemics echoes across history into our current coronavirus pandemic and provides insightful lessons for managing and improving its outcomes.     

Risk factors for transfer from Respiratory Intermediate Care Unit to Intensive Care Unit in COVID-19

BackgroundPatients hospitalized for COVID-19-related pneumonia often need several degrees of ventilatory support, which are performed between Respiratory Intermediate Care Units (RICUs) and Intensive Care Units (ICUs), and which depend on the severity of acute respiratory distress syndrome. There is no firm consensus on transfer predictors from the RICU to the ICU.MethodsIn this retrospective observational single center study, we evaluated 96 COVID-19 patients referred to the RICU for acute respiratory failure (ARF) according to their transferal to the ICU or their stay at the RICU. We compared demographic data, baseline laboratory profile, and final clinical outcomes to identify early risk factors for transfer.ResultsThe best predictors for transfer to the ICU were elevated C-reactive protein and lymphopenia. The mortality rate was lower in the RICU than in the ICU, where transferred patients who died were mostly younger men and with less comorbidities than those in the RICU.ConclusionsFew inflammatory markers can predict the need for transfer from the RICU to the ICU. Due to the ongoing COVID-19 pandemic, we urge better clinical stratification by early and meaningful profiles in patients admitted to the RICU who are at risk of transferal to the ICU.     

COVID-19 in the Long-Term Care Setting: The CMS Perspective

Safeguarding the health and promoting the well-being and quality of life of the most vulnerable and fragile citizens is a top priority for the Centers for Medicare & Medicaid Services (CMS). In response to the Coronavirus Disease 2019 (COVID-19) pandemic, numerous regulatory policies and 1,135 waivers of federal requirements have been implemented by CMS to give long-term care providers and professionals flexibility to meet the demands of resident and patient care needs during this public health emergency. Goals for these policies and waivers are increasing capacity, enhancing workforce and capability, improving oversight and transparency, preventing COVID-19 transmission, and reducing provider burden. J Am Geriatr Soc 68:1366-1369, 2020.     

Missing Care: the Initial Impact of the COVID-19 Pandemic on CKD Care Delivery

BackgroundChronic kidney disease (CKD) is a common condition with adverse health outcomes addressable by early disease management. The impact of the COVID-19 pandemic on care utilization for the CKD population is unknown.ObjectiveTo examine pandemic CKD care and identify factors associated with a high care deficit.DesignRetrospective observational studyParticipants248,898 insured individuals (95% Medicare Advantage, 5% commercial) with stage G3–G4 CKD in 2018Main MeasuresPredicted (based on the pre-pandemic period of January 1, 2019–February 28, 2020) to observed per-member monthly face-to-face and telehealth encounters, laboratory testing, and proportion of days covered (PDC) for medications, evaluated during the early (March 1, 2020–June 30, 2020), pre-vaccine (July 1, 2020–December 31, 2020), and late (January 2021–August 2021) periods and overall.Key ResultsIn-person encounters fell by 24.1% during the pandemic overall; this was mitigated by a 14.2% increase in telehealth encounters, resulting in a cumulative observed utilization deficit of 10% relative to predicted. These reductions were greatest in the early pandemic period, with a 19.8% cumulative deficit. PDC progressively decreased during the pandemic (range 9–20% overall reduction), with the greatest reductions in hypertension and diabetes medicines. CKD laboratory monitoring was also reduced (range 11.8–43.3%). Individuals of younger age (OR 1.63, 95% CI 1.16, 2.28), with commercial insurance (1.43, 95% CI 1.25, 1.63), residing in the Southern US (OR 1.17, 95% CI 1.14, 1.21), and with stage G4 CKD (OR 1.21, 95% CI 1.17, 1.26) had greater odds of a higher care deficit overall.ConclusionsThe early COVID-19 pandemic resulted in a marked decline of healthcare services for individuals with CKD, with an incomplete recovery during the later pandemic. Increased telehealth use partially compensated for this deficit. The downstream impact of CKD care reduction on health outcomes requires further study, as does evaluation of effective care delivery models for this population.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-022-07805-w.KEY WORDS: chronic kidney disease, COVID-19, epidemiology