ABSTRACT
Coronaviruses have caused devastation in both human and animal populations, affecting both health and the economy. Amidst the emergence and re-emergence of coronaviruses, humans need to surmount the health and economic threat of coronaviruses through science and evidence-based approaches. One of these approaches is through biotechnology, particularly the heterologous production of biopharmaceutical proteins. This review article briefly describes the genome, general virion morphology, and key structural proteins of different coronaviruses affecting animals and humans. In addition, this review paper also presents the different systems in recombinant protein technology such as bacteria, yeasts, plants, mammalian cells, and insect/insect cells systems used to express key structural proteins in the development of countermeasures such as diagnostics, prophylaxis, and therapeutics in the challenging era of coronaviruses. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
ABSTRACT
Introduction Little is known about the rates of asymptomatic COVID-19 carriers among cancer patients. The rate of asymptomatic carriers is important to understand in this population given the use of myelosuppressive and immunomodulating therapies and the risk of transmission to other patients in shared infusion centers. At UC San Diego, in June 2020, we implemented a COVID-19 asymptomatic screening protocol in which cancer patients receiving anti-cancer therapy in an infusion center must undergo symptom-based screening and then SARS-CoV-2 PCR testing prior to their infusion. Here, we describe the results of this asymptomatic screening protocol. Methods This was a single-center retrospective analysis of patients with active cancer receiving infusional anti-cancer therapy in 5 infusion centers who underwent at least 1 asymptomatic SARS-CoV-2 PCR test between 6/1- 12/1/2020. The primary endpoint was the rate of COVID-19 positivity among asymptomatic patients. Symptomatic patients were excluded. Secondary endpoints included COVID-19-related outcomes and patterns of oncologic management for asymptomatic COVID-19 positive patients. Results A cohort of 2,202 cancer patients received at least 1 asymptomatic SARS-CoV-2 PCR test prior to receipt of infusional anti-cancer therapy. 0.95% (N=21/2202) of patients were found to be PCR-positive on asymptomatic screening. Among positive patients, 9.5% (N=2/21) had hematologic malignancies and 90.5% (N=19/21) had solid tumors. In terms of therapy, 76.2% (N=16) were treated with cytotoxic chemotherapy, 9.5% (N=2) with targeted therapy, 4.7% (N=1) with immunotherapy, and 9.5% (N=2) were on a clinical trial. With a median follow-up of 122 days from positive PCR test (range: 8-186), only 2 of 21 (9.5%) of the cohort ultimately developed COVID-related symptoms. Both patients had a diagnosis of acute leukemia and 1 patient required hospitalization for COVID-related complications. No patients died from COVID-related complications. With regards to oncologic management, 95.2% (N=20/21) of patients had their therapy delayed or deferred with a median delay of 21 days (range: 7- 77 days). Only 1 patient proceeded with cytotoxic chemotherapy on schedule in the setting of adjuvant chemoradiation for oropharyngeal squamous cell carcinoma. Among the overall cohort, an additional 26 patients (1.2%) developed cases of symptomatic COVID-19 infection during the study period. Conclusions A strategy of asymptomatic screening of cancer patients receiving anti-cancer therapy in an infusion center detected an extremely low rate of asymptomatic carriers of COVID-19. This low rate of asymptomatic carriers may be due to a number of factors including multiple symptom-based screenings prior to infusion, behavior modification among patients, and/or differential immune responses to COVID-19 infection. Asymptomatic carriers in this cohort appeared to have favorable outcomes with few developing symptoms or requiring hospitalization, though the number of positive patients in our cohort is low, precluding definitive conclusions in this population.
ABSTRACT
Background Patients with cancer appear to have poor outcomes with COVID-19 infection. Cohort analyses of short-term outcomes of COVID-19 (C19)-infected cancer patients (pts) have reported mortality rates ranging from 10 to 30%. Little is known about the long-term outcomes of cancer pts infected with C19. Here, we present an analysis of long-term outcomes of a cohort of active cancer pts with C19 infection. Methods This was a single center retrospective analysis of active cancer pts who tested positive for SARS-CoV-2 virus between 3/1/20- 9/30/20. Key inclusion criteria included a positive SARS-CoV-2 PCR test and an active cancer diagnosis within 90 days of a positive C19 test. We examined the rates of hospitalization for C19 infection, readmission, and C19-related mortality at 30-, 60-, 90-, and 120-day follow-up. Rates of persistent symptoms and systemic complications of C19 infection were described. Results We identified 81 active cancer pts with PCR-confirmed SARS-CoV-2 infection. Among this cohort, the median age was 55 years (range: 19- 89). 77% (N=62) had solid tumors and 23% (N=19) had a hematologic malignancy. 75% (N=61) were receiving an anti-cancer therapy at the time of C19 diagnosis. Median follow-up time from C19 diagnosis to last follow-up was 4.8 months (range: 0.1-9.0 mos). 32% (N=26) of the cohort required hospitalization for C19-related complications within 30 days of C19 diagnosis. Among those hospitalized, 35% (N=9/26) died from C19-related complications. Of the 17 pts who were discharged, 2 pts required readmission with a median time to readmission of 37 days. For these 2 pts, readmission was due to persistent dyspnea and hypoxia and both were treated for pneumonia with presumed bacterial superinfection. There were no additional hospitalizations for C19-related complications at 60-, 90-, and 120-day follow-up. At 90- day follow-up, 6 pts (7.4%) had been diagnosed with PE/DVT. No long-term cardiac, neurologic, or renal complications were observed. With regards to C19-related mortality, 30-day mortality was 8.6% (N=7) and 90-day mortality was 11.1% (N=9). No further C19-related deaths were observed after 90 days. All pts who died were hospitalized within 30 days of initial C19 diagnosis and remained hospitalized at the time of death. Persistent C19-related symptoms were noted in 8.2% (N=6/73) of the cohort at 60-days and 2.8% (N=2/71) at 90-day follow-up. Dyspnea was the most common symptom. Conclusions Among a cohort of active cancer pts with C19 infection, these data suggest that much of the morbidity and mortality associated with C19 infection appears to occur early, with decreased incidence of late complications beyond 30 days. Cancer pts who do not require hospitalization early in their infection course appear to have a decreased rate of late complications. Readmissions for C19-related complications were low, but this analysis was limited by a low number of pts. Achieving a better understanding of long-term outcomes of C19 pts with cancer will help us to better approach oncologic care as the pandemic continues.
ABSTRACT
BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.