Post Acute Coronavirus (COVID-19) Syndrome

Coronavirus disease 2019 (COVID-19), the viral illness caused by the novel coronavirus SARS-CoV-2 has resulted in significant morbidity and mortality across the world since the first cases were identified in Wuhan China, in December 2019. Although the majority of the patients who contract COVID-19 are asymptomatic or have mild to moderate disease, approximately 5% to 8% of infected patients develop hypoxia, bilateral lung infiltrates, decreased lung compliance requiring non-invasive ventilation(NIV) or mechanical ventilatory support.[1] The management of COVID-19 infection is mainly supportive. Although many therapeutics such as antiviral drugs (remdesevir), monoclonal antibodies (e.g., bamlanivimab/etesevimab, casirivimab/imdevimab), anti-inflammatory drugs (e.g., dexamethasone), immunomodulatory agents (e.g., baricitinib, tocilizumab) is available under emergency use authorization(EUA) for the management of COVID-19, the utility of these treatments varies based on the timing and severity of illness and/or certain risk factors.[2] The previous epidemics of SARS-CoV and MERS-CoV left individuals who recovered from these viral illnesses with persistent symptoms of severe fatigue, decreased quality of life (QOL), persistent shortness of breath, and behavioral health problems that resulted in a significant burden on local healthcare systems where the epidemics occurred. Similarly, a constellation of various clinical symptoms termed post-acute COVID-19 syndrome has been described in a minor proportion of patients who recovered from SARS-CoV-2 induced COVID-19 despite biochemical evidence that the replication of SARS CoV 2 ceases to exist after four weeks after the initial infection (based on the sampling of viral isolates from the respiratory tract and not the nasopharyngeal/oropharyngeal specimen). Post-acute COVID-19 is a syndrome characterized by the persistence of clinical symptoms beyond four weeks from the onset of acute symptoms. The Center for Disease Control (CDC) has formulated "post-Covid conditions" to describe health issues that persist more than four weeks after being infected with COVID-19. These include: Long Covid (which consists of a wide range of symptoms that can last weeks to months) or persistent post-Covid syndrome (PPCS). Multiorgan effects of COVID-19. Effects of COVID-19 treatment/hospitalization. The typical clinical symptoms in "long covid" are tiredness, dyspnea, fatigue, brain fogginess, autonomic dysfunction, headache, persistent loss of smell or taste, cough, depression, low-grade fevers, palpitations, dizziness, muscle pain, and joint pains. Multiorgan effects of COVID-19 include clinical manifestations pertaining to the cardiovascular, pulmonary, renal, and neuropsychiatric organ systems, although the duration of these multiorgan system effects is unclear. Long-term "effects of COVID-19 treatment or hospitalization" are similar to other severe infections. They include post-intensive care syndrome(PICS), resulting in extreme weakness and posttraumatic stress disorder. Many of the patients with these complications from COVID-19 are getting better with time. Post COVID-19 care clinics are being opened at multiple medical centers across the USA to address these specific needs. Based on the chronicity of symptoms post COVID-19 infection, Nalbandian et al. classified post-acute COVID-19 as follows-: Subacute or persistent symptomatic COVID-19 symptoms (up to 12 weeks from the initial acute episode). Chronic or post-Covid syndrome, symptoms present beyond 12 weeks. However, it should not be attributable to an alternative diagnosis.[3]. This review article describes the prevalence, system-based manifestations, relevant clinical investigations, treatment, and importance of an interprofessional team approach in the management of patients with post-acute COVID-19 syndrome.

Monoclonal Antibody Therapy For High-Risk Coronavirus (COVID 19) Patients With Mild To Moderate Disease Presentations

Since being declared a global pandemic by the World Health Organization WHO), Coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating effect on the global health and economy. The virus primarily affects the respiratory system and is spread from person to person via respiratory particles from coughing and sneezing. The majority of transmission occurs from close contact with presymptomatic, asymptomatic, or symptomatic carriers. The early course of the pandemic was characterized by the rapid spread of the virus that created an urgency to mitigate this new viral illness with experimental therapies and drug repurposing. Since then, due to an intense global research effort, significant progress has been made that has resulted in the development of novel therapeutics and vaccines at an unprecedented speed, leading to favorable patient outcomes. Currently, a variety of therapeutic options that include antiviral medications, monoclonal antibodies, and immunomodulatory agents are available in the management of COVID-19. However, the therapeutic potential and clinical use of these drugs are limited and specifically based on the stage of the illness. The pathogenesis of COVID-19 illness occurs in two distinct phases, an early stage characterized by profound SARS-CoV-2 viral replication followed by a late phase characterized by a hyperinflammatory state induced by the release of cytokines such as tumor necrosis factor-alpha(TNF alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), Interleukin-(IL-1), IL-6, interferon (IFN)-gamma and activation of the coagulation system resulting in a prothrombotic state. Antiviral therapy and antibody-based treatments are likely to be more effective if used during the early phase of the illness, and immunomodulating therapies either alone or in combination with antiviral and antibody-based therapies may be more effective when used in the later stage to combat the cytokine-mediated hyperinflammatory state that causes severe illness.[1] Individuals of all ages are at risk for infection and severe disease. However, individuals aged >=60 years and with underlying medical comorbidities (obesity, cardiovascular disease, chronic kidney disease, diabetes, chronic lung disease, smoking, cancer, solid organ or hematopoietic stem cell transplant recipients) are at increased risk of developing severe COVID-19 infection. The percentage of COVID-19 patients requiring hospitalization was six times higher in those with preexisting medical conditions than those without medical conditions (45.4% vs. 7.6%) based on an analysis by Stokes et al. of confirmed cases reported to the CDC during January 22-May 30, 2020.[2] A promising approach to address the COVID-19 associated mortality and prevent the increased utilization of healthcare resources is by terminating the progression of viral replication, thereby preventing the progression to the hyperinflammatory stage of COVID-19, which causes severe illness in high-risk nonhospitalized patients. Initially, the focus of treatment was directed mainly towards hospitalized patients with COVID-19 illness. However, the clinical focus over the course of the pandemic has expanded toward combatting the illness early on by reducing the viral load in patients with early disease, thus attempting to halt the disease progression. Monoclonal antibodies targeting the spike protein of the SARS-CoV-2 have yielded positive in vitro results.[3][4] They are considered a promising approach in managing nonhospitalized patients with mild to moderate COVID-19 who are at high risk of developing severe illness. This review discusses the mechanism of action of monoclonal antibodies against SARS-CoV-2 and current clinical indications of monoclonal antibody therapy for nonhospitalized patients with mild to moderate COVID-19 illness who are at high risk of developing severe illness. Monoclonal Antibodies in COVID-19 Monoclonal antibodies (mAbs) are immune system proteins developed from a single

Gastrointestinal And Hepatic Manifestations Of Coronavirus (COVID-19)

On March 11, 2020, The World Health Organization (WHO) declared Coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a global pandemic after the first cases of an atypical acute respiratory illness initially reported in China in December 2019 spread to more than 100 countries. Since then, the ongoing pandemic has overwhelmed many healthcare systems worldwide, resulting in significant morbidity and mortality emerging as a major global health crisis since the influenza pandemic of 1918. This viral infection readily spreads from person to person via respiratory droplets, mucosal contact, and through contaminated surfaces. SARS-CoV-2 primarily affects the respiratory system;however, it can affect other major organ systems such as the gastrointestinal tract (GI), liver, cardiovascular, central nervous system, and kidneys. Emerging data have shown that patients with COVID-19 infection presented with higher rates of isolated gastrointestinal symptoms in the absence of respiratory symptoms. Patients with any primary GI-related symptoms or concurrent symptoms were at increased risk of hospitalization[1][2][3]. Emerging evidence is notable for the detection of SARS-CoV-2 RNA in fecal samples of asymptomatic COVID-19 patients who tested negative by the nasopharyngeal swab. Continued fecal shedding in symptomatic COVID-19 patients days after clinical recovery for an extended period has been reported which is concerning for possible fecal-oral transmission of this virus[4].COVID-19 is also frequently associated with the elevation of liver biochemistries in patients with or without clinical symptoms. Patients with COVID-19 illness are increasingly being recognized as being at risk of developing prothrombotic complications such as acute mesenteric ischemia and portal vein thrombosis respectively. In this article, we review the latest available data regarding the impact of COVID-19 on the gastrointestinal tract and the liver function in adult patients.

Coronavirus (COVID-19) Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT)

Coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to cause significant morbidity and mortality across the world, with many nations enduring multiple outbreaks of this viral illness. Besides the importance of infection control measures to prevent or decrease the transmission of SARS-CoV-2, the most crucial step to contain this global pandemic is by vaccinating individuals to prevent SARS-CoV-2 infection in communities across the world. Many vaccines have been developed at an unprecedented speed using distinctive technologies to prevent COVID-19. Vaccination triggers the immune system resulting in the production of neutralizing antibodies against SARS-CoV-2. Four vaccines, namely the BNT162b2, mRNA-1273, Ad26.COV2.S and ChAdOx1 nCoV-19 have been approved or granted emergency use authorization(EUA) to prevent COVID-19 in many nations worldwide, including the United States. One exception to this is the ChAdOx1 nCoV-19 vaccine, which has not yet received a EUA or approval from the U.S. Food and Drug Administration (FDA) for use in the U.S. The BNT162b2 and mRNA-1273 vaccines are both mRNA-based, while the Ad26.COV2. S and ChAdOx1 nCoV-19 vaccines incorporate replication-incompetent adenoviral vectors in them. In late February 2021, a new clinical syndrome characterized by thrombosis at atypical sites combined with thrombocytopenia was observed in multiple patients' days after vaccination with the ChAdOx1 nCoV-19 vaccine.[1] In April 2021, similar clinical sequelae were reported in patients after vaccination with the Ad26.COV2. S vaccine.[2] Preceding the approval of these vaccines, the clinical constellation of this new syndrome was not observed in clinical trials of the ChAdOx1 nCoV-19 vaccine, and a single case was observed in the Ad26.COV2. S vaccine trial recipient.[3] Furthermore, the incidence of major adverse effects has remained exceptionally low following the vaccination of more than 400 million people worldwide.[4] This novel clinical syndrome demonstrated striking similarities to heparin-induced thrombocytopenia;however, in the absence of prior heparin exposure was named vaccine-induced immune thrombotic thrombocytopenia (VITT). It is also known as vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) in some European nations and Canada. Conversely, of more than 180 million doses of BNT162b2 or mRNA-1273 vaccines administered so far, this clinical syndrome has not been reported. Per the American Society of Hematology, vaccine-induced immune thrombotic thrombocytopenia (VITT) is defined as a clinical syndrome characterized by all of the below described abnormal laboratory and radiologic abnormalities occurring in individuals 4 to 30 days after vaccination with Ad26.COV2. S or ChAdOx1 nCoV-19 vaccines. Development of thrombosis at uncommon sites includes cerebral venous sinus thrombosis (CSVT)/splanchnic venous thrombosis. Mild to severe thrombocytopenia. However, a normal platelet count does not exclude the possibility of this syndrome in its early stages. Positive antibodies against platelet factor 4(PF4) identified by enzyme-linked immunosorbent assay (ELISA) assay. Although the extraordinary speed of vaccine development against COVID-19 and robust ongoing mass vaccination efforts worldwide, the incidence of this newly described vaccine-induced phenomenon is associated with vaccination with Ad26.COV2.S or ChAdOx1 nCoV-19 vaccines attempt to overturn the significant progress made so far in halting the spread of SARS-CoV-2. This review article aims to describe the etiology, epidemiology, pathophysiology, clinical features, diagnosis, and management of COVID-19 vaccine-induced thrombotic immune thrombocytopenia based on the latest available published literature.

Emerging Variants of SARS-CoV-2 And Novel Therapeutics Against Coronavirus (COVID-19)

Coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a devastating effect on the world's population resulting in more than 2.8 million deaths worldwide and emerging as the most significant global health crisis since the influenza pandemic of 1918. Since being declared a global pandemic by the World Health Organization (WHO) on March 11, 2020, the virus continues to cause devastation, with many countries enduring a second or a third wave of outbreaks of this viral illness. Adaptive mutations in the viral genome can alter the virus's pathogenic potential. Even a single amino acid exchange can drastically affect a virus's ability to evade the immune system and complicate the vaccine development progress against the virus.[1] SARS-CoV-2, like other RNA viruses, is prone to genetic evolution while adapting to their new human hosts with the development of mutations over time, resulting in the emergence of multiple variants that may have different characteristics compared to its ancestral strains. Periodic genomic sequencing of viral samples helps detect any new genetic variants of SARS-CoV-2 circulating in communities, especially in a global pandemic setting. The genetic evolution of SARS-CoV-2 was minimal during the early phase of the pandemic with the emergence of a globally dominant variant called D614G, which was associated with higher transmissibility but without increased disease severity of its ancestral strain.[2] Another variant was identified in humans, attributed to transmission from infected farmed mink in Denmark, which was not associated with increased transmissibility.[3] Since then, multiple variants of SARS-CoV-2 have been described, of which a few are considered variants of concern (VOCs), given their impact on public health. VOCs are associated with enhanced transmissibility or virulence, reduction in neutralization by antibodies obtained through natural infection or vaccination, the ability to evade detection, or a decrease in therapeutics or vaccination effectiveness. The first VOC, the B.1.1.7 lineage (or VOC 202012), was described in the United Kingdom (UK) in late December 2020, followed shortly by the detection of the B.1.351 lineage (or 501Y.V2) in South Africa. In early January 2021, a new VOC, B.1.1.248/B1.1.28/P1 (or 501Y.V3), was reported in Brazil, and more recently, the B.1.427/B.1.429 lineage was identified in California. The B.1.427/B.1.429 lineage is classified as VOC by the US Centers for Disease Control and Prevention (CDC) but is considered a variant of interest by the WHO. All three reported VOCs (B.1.1.7 variant, B.1.351 variant, and P.1 variant) harbor mutations in the receptor-binding domain (RBD) and the N-terminal domain (NTD), of which the N501Y mutation located on the RBD is common to all variants. RBD plays a vital role in facilitating viral entry into the host cell by binding to the host cell angiotensin-converting enzyme-2 (ACE-2) receptors. Along with NBD, it is the dominant neutralization target and facilitates antibody production in response to antisera or vaccines.[4] Two recent preprint studies (not peer-reviewed) reported that a single mutation of N501Y alone increases the affinity between RBD and ACE2 approximately ten times more than the ancestral strain (N501-RBD). Interestingly the binding affinity of B.1.351 variant and P.1 variant with mutations N417/K848/Y501-RBD and ACE2 was much lower than that of N501Y-RBD and ACE2.[5][6] Despite the extraordinary speed of vaccine development against COVID-19 and continued mass vaccination efforts across the world, the emergence of these new variant strains of SARS-CoV-2 threatens to overturn the significant progress made so far in halting the spread of SARS-CoV-2. This review article aims to comprehensively describe these new variants of concern, the latest therapeutics available in managing COVID-19 in adults, and the efficacy of different available vaccines against this virus and its new variants. SARS-CoV-2 Variant

Management of hematological malignancies during the COVID-19 pandemic

Patients with hematological malignancies (HM) appear to be at increased risk of acquiring COVID-19 infection and its complications. General measures to protect patients with HM from COVID-19 include limiting exposure of patients to medical environments with the use of telemedicine and virtual clinics, delaying elective diagnostic services, modifying treatment modalities in a manner that reduces the probability of further immune suppression such as shortening the treatment course or prolonging the interval between treatment courses, and growth factor support to reduce the risk of neutropenia. Reducing the threshold for packed RBC and platelet transfusions to mitigate reduced blood product supplies, and a careful attention to drug interactions in patients who get the COVID-19, are also important management measures. Physicians caring for patients with HM need to carefully evaluate each individual patient to optimize therapies, take measures to maximize safety of patients and staff, without significantly compromising outcomes. This paper discusses management of HM during the COVID-19 pandemic.