The most common pathogens in coinfection were Influenza virus , Rhinovirus and Respiratory syncytial virus (A/B). In contrast, bacterial coinfection was infrequent (Bordi et al., 2020; Corman et al., 2020b). Even though most of the available diagnostics have focused on RT-PCR, additional methods include using microarray or microfluidic technologies, CRISPR to isolate gene segments for diagnostics, serological and full genetic sequencing are available. It is important to note that the FDA has so far granted Emergency Use Authorization status only to some PCR-based tests.
Recombinant subunit vaccine strategies use the Sf9-baculovirus insect cell expression system resulting in the production of high-quality antigen that can be used to elicit immune responses. D) Purified antigen vaccine strategies implicate the replication of large numbers of virus in cell cultures and the subsequent purification of viral antigens to be used for vaccination. E) Attenuated vaccines contain whole pathogen that has been submitted to heat or chemical treatment inactivation. F) Attenuated live pathogen vaccine strategies consist in administering a live pathogen that due to cell culture passaging has lost its virulence. They usually elicit robust and long-term memory immune responses without the need to administer an adjuvant.
Rosenberg E.S., Dufort E.M., Udo T., Wilberschied L.A., Kumar J., Tesoriero J. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State. Qin C., Zhou L., Hu Z., Zhang S., Yang S., Tao Y. Dysregulation of immune response in patients with COVID-19 in Wuhan. Nelemans T., Kikkert M. Viral innate immune evasion and the pathogenesis of emerging RNA virus infections.
19. Recovery from COVID-19 infection
Acute respiratory distress syndrome is a major complication of COVID pneumonia in patients with severe disease. Currently, there are a plethora of antibody tests for COVID-19 with variable performance (sensitivity varying from 45 to 100%, specificity from 96 to 100%, reviewed in (FIND, n.d.). Different manufacturers of serological assays declare that their assays have no cross reactivity to other human coronaviruses and other respiratory candle timer indicator viruses. In specific patient groups, particularly the elderly and those with chronic health conditions, symptoms may progress into pneumonia, with tightness-chest pain and fatigue. After a week, it can lead to difficulty breathing, with approximately 20% of patients requiring hospital treatment. COVID-19 infection rarely seems to cause a runny nose, sneezing, or sore throat [these symptoms have been seen in approximately 5% of patients].
So far, despite the avalanche of information, there are isolated descriptions of cases of PLWH and COVID-19. The emergence and outbreak of SARS-CoV-2, the causative agent of COVID-19, has rapidly become a global concern that highlights the need for fast, sensitive, and specific tools to monitor the spread of this infectious agent. In areas of limited resources, the suggestion is to prioritize cases that require hospital care, and in this way guide the epidemiological fence to order isolation and protect the most vulnerable people , as well as test those with the greatest possibility of exposure . Anyone who has resided or been traveling in areas where widespread community transmission has been reported. The document was developed by the Infectious Diseases Division in conjunction with the front-line support departments.
G) In DNA vaccines the DNA codifying a highly immunogenic antigen is administered and captured by professional antigen presenting cells leading to antigen production and presentation by these cells. H) Moderna’s vaccine candidate already in Phase I clinical trials uses an mRNA vaccine approach whereby the genetic information codifying for the S protein of SARS-CoV-2 is delivered in LNPs to enhance absorption by APCs. Once uptaken by APCs the mRNA induces the expression of S antigen that is subsequently mounted on and presented by MHC molecules to elicit adaptive immune response. Liu L., Wei Q., Alvarez X., Wang H., Du Y., Zhu H. Epithelial cells lining salivary gland ducts are early target cells of severe acute respiratory syndrome coronavirus infection in the upper respiratory tracts of rhesus macaques. Liu W., Fontanet A., Zhang P.-H., Zhan L., Xin Z.-T., Baril L. Two-year prospective study of the humoral immune response of patients with severe acute respiratory syndrome.
10. Diagnosis methods to detect COVID-19
To date of this review, only a few cases of children without underlying comorbidities have died as a result of COVID 19 have been reported. This difference of severity of illness between adults and children has not been clarified, however, several theories have been postulated. These include that children express more ACE2 receptors in their lungs which confer some protection to severe injuries such as those caused by RSV and which would decrease dramatically with age (Gu et al., 2016; Xia et al., 2020). In Spain, less than 1% of cases in a cohort correspond to PLWH, which have had a satisfactory evolution and less than half required an intensive care unit (Blanco et al., 2020). In the US, of the 5,700 hospitalized patients in the New York area, only 47 patients had HIV, while in San Francisco, data was published on 1233 people who had diagnosed with SARS-CoV-2 infection, of which less than 3% had HIV and none of them developed severe COVID-19 (Richardson et al., 2020b). Taking into account that, at the moment the SARS-CoV-2 pandemic exceeds 3 million people, case reports of an HIV and COVID-19 co-infection have not shown any evidence that PLWH are at increased risk of acquiring said infection or suffering serious complications.
- Including SARS-CoV-2 and other respiratory viruses (Park et al., 2020; Shen et al., 2020a).
- Grifoni A., Sidney J., Zhang Y., Scheuermann R.H., Peters B., Sette A. A sequence homology and bioinformatic approach can predict candidate targets for immune responses to SARS-CoV-2.
- Regarding SARS-nCoV infection in pregnant women, there is currently limited evidence about the effect of the virus on the mother or fetus.
Alraddadi B.M., Qushmaq I., Al-Hameed F.M., Mandourah Y., Almekhlafi G.A., Jose J. Noninvasive ventilation in critically ill patients with the Middle East respiratory syndrome. The authors of this study examined the most important literature available in terms of the genetic, virology, clinical and therapeutic evidence on the SARS-CoV-2 virus and the novel Coronavirus diseases 2019 (COVID-19). Al., concluded that, even a relatively short exposure to UV radiation destroys viral infectivity of SARS (strain CoV-P9) Coronavirus. Other studies also correlate vitamin D secretion and influenza immunity, due to the UV role in vitamin D production (Helming et al., 2005; Cannell et al., 2006). The latter, and the reduced immune system due to melatonin oscillations during the dark winter seasons could further explain winter outbreaks of influenza at high latitude regions . A diagnosis of COVID-19 alone is not an indication for the termination of pregnancy, rather it should be made in combination with consideration of morbidity and mortality of both the fetus and mother.
Some representative existing drugs act on targets in similar RNA viruses like Ebola, hepatitis C, influenza, and others as MERS and SARS viruses. The most important studied targets are the 2 viral proteases involved in cleavage viral peptides for replication of the virus, 3CLpro and PLpro. RdRp is other important target as the polymerase in charge of viral RNA synthesis, RNA polymerase, sttopped by Remdesivir and Favipiravir. About endocytosis process into host cells, viral spike protein and its interaction with ACE2 receptor constitute other important target blocked by arbidol, used also in Influenza. ACE2 is a negative regulator, receptor of renin-angiotensin system, involved in pressure control and inflammatory lung disease. By the knowledge of physiopathology of COVID-19 infection, we know that activities of ACE2 receptors are altered, thus some drugs are being studied around these targets, but also in vitro and experimental way.
Numerous studies confirm that climate has an impact on virus (i.e., influenza, coronavirus, etc.) spread through manipulating the conditions of i) its diffusion, ii) the virus survival outside the host, and iii) the immunity of host population (Tamerius et al., 2011). While in some regions, such as temperate climate zones, human influenza peaks have clear seasonal cycles, in others it is not as predictable (Tamerius et al., 2011; Cox, 2014; Lowen and Steel, 2014; Caini et al., 2018; Mendelson, 2020). Other drugs like ivermectin, nitazoxanide, and others have been studied in the context of COVID-19 treatment, but the results are inconsistent.
1. Chronology of the pandemic
As an intracellular obligate microorganism, the coronavirus exploits the host cell machinery for its own replication and spread. Since virus–host interactions form the basis of diseases, knowledge about their interplay is of great importance, particularly when identifying key targets for antivirals. The incubation period of COVID-19 typically ranges from 2 to 14 days (98% of patients), with an average of 5 days, although there have been cases with incubations periods of up to 24 days. The epidemiological dynamics of COVID-19 has changed dramatically over the course of months. At the beginning of the outbreak, the most affected continent was Asia, with China being the most affected country worldwide, however, nowadays, the Americas, driven mainly by the USA and Brazil, have converted the region in the most affected on the planet (Simbana-Rivera et al., 2020). At the beginning of the outbreak it was believed that a viral jump occurred between a wild animal and a human being in one of the most populated wet market in Wuhan, China during the November 2019.
The first PCR test for COVID-19 was developed within 2 weeks of the disease being identified (Li et al., 2020). About the imaging findings, COVID 19 viral pneumonia has similar features on imaging to other viral infections. In general, leukopenia and/or leukocytosis can be found in the interpretation of blood biometry; however, the most widely described finding is lymphopenia . It should be considered that in the context of viral pneumonia biomarkers such as Procalcitonin and PCR are not useful, as often these biomarkers are in the normal range for patients with COVID-19. In cases of severe respiratory distress of undetermined etiology and that do not meet the previously indicated criteria, a screening for COVID-19 would be indicated.
Any patient who has had potential exposure through attending events or has spent time in specific settings where cases of COVID-19 have been reported. In different case reports, the need for supplemental oxygen via the nasal cannula was required in approximately 50% of hospitalized patients. 30% required non-invasive mechanical ventilation, and less than 3% required invasive mechanical ventilation with or without Extracorporeal Membrane Oxygenation (Wu et al., 2020d). Asymptomatic infection was described both in the first cases in Wuhan and in other cohorts. A group of isolated patients were screened for SARS-CoV-2, where 17% were positive for the test, and half of these cases had no symptoms.
Security teams are able to react quickly to digital criminals, respond to Zero-Day incidents faster, and reduce the risk exposure timeline. Roussel M., Pontier D., Cohen J.-M., Lina B., Fouchet D. Quantifying the role of weather on seasonal influenza. Richardson S., Hirsch J.S., Narasimhan M., Crawford J.M., McGinn T., Davidson K.W. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area.
Support provided should be adapted to take into account risk factors such as advanced age, neutrophilia and organic dysfunction for the development of ARDS. The diagnostic support of pulmonary tomography is undoubtedly a valid tool; images in patients with different clinical types of COVID-19 have characteristic manifestations, but it can become an operational problem due to the difficulty in performing imaging on critically ill patients. On the contrary, lung ultrasound at the bed-side could provide an alternative to radiographs and tomography during the diagnosis of COVID-19 (Soldati et al., 2019; Soldati et al., 2020). Apart from the sustained inflammation and cytokine storm, lymphopenia has been implicated as a major risk factor for ARDS and mortality in the context of COVID-19 (Chan et al., 2020a).
6. Molecular diagnosis methods to detect COVID-19
On the same day Moderna’s infectious disease research team finalized the sequence for mRNA-1273, the company’s first vaccine candidate against SARS-CoV-2. On February 24, 2020, the clinical batch was shipped from Moderna to the NIH to be used in their own Phase I financial intelligence book review clinical study. Twelve days later, on March 16, 2020, the NIH announced that the first participant in its Phase I clinical study received the first dose of mRNA-1273. The time between virus sequencing to beginning of Phase I trials was a record total of 63 days.
Supplementary Table 2 Amino acid replacements in SARS-CoV-2 genomes according to the CoV-GLUE project.
8. Clinical features of COVID-19
Shen C., Wang Z., Zhao F., Yang Y., Li J., Yuan J. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. Rothan H.A., Byrareddy S.N. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. Duan K., Liu B., Li C., Zhang H., Yu T., Qu J. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Corman V., Müller M., Costabel U., Timm J., Binger T., Meyer B. Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections. Commissioner O of the First FDA-approved vaccine for the prevention of Ebola virus disease, marking a critical milestone in public health preparedness and response. Chen W.-H., Du L., Chag S.M., Ma C., Tricoche N., Tao X. Yeast-expressed recombinant protein of the receptor-binding domain in SARS-CoV spike protein with deglycosylated forms as a SARS vaccine candidate.
Due to the many sequence similarities of SARS-CoV-2 with SARS-CoV and MERS-CoV it would be enticing to speculate that similar mechanisms are also present, however further studies are needed to shed light to this hypothesis. Following the release and uncoating of viral RNA to the cytoplasm, coronavirus replication starts with the translation of ORF1a and ORF1b into polyproteins pp1a and pp1ab via a frameshifting mechanism (Fig. 4) (Weiss and Navas-Martin, 2005). Subsequently, polyproteins pp1a and pp1ab are processed by internal viral proteases, including the main protease Mpro, a potential drug target whose crystal structure was recently determined for SARS-CoV-2 (Lu et al., 2020). Polyprotein cleavage yields 15 mature replicase proteins, which assemble into a replication-transcription complex that engages in negative-strand RNA synthesis. The former serves as template for new full-length genomic RNAs and the latter template the synthesis of the subgenomic mRNAs required to express the structural and accessory protein genes residing in the 3′-proximal quarter of the genome (Knoops et al., 2008). Coronavirus RNA replication occurs on a virus-induced reticulovesicular network of modified endoplasmic reticulum membranes (Neuman et al., 2011).
Patients with cancer are generally more susceptible to infections than healthy people, because they have a state of systemic immunosuppression that is exacerbated during chemotherapy or radiotherapy (Liang et al., 2020). The symptoms children present with are similar to adults, as is the incubation period ranging from 1 to 14 days (mean of 5.2). There is a higher occurrence of gastrointestinal symptoms including diarrhea (15%), nausea, vomiting (10 %) and abdominal pain. These gastrointestinal symptoms are usually more variable in children than adults and are sometimes the only clinical manifestation in associations with fevers. On the other hand, controlled PLWHs by having a longer life expectancy may have more comorbidities, which have been related to a higher risk of having COVID-19 (diabetes, hypertension, etc.) without this being directly related to HIV and some kind of synergy with the SARS-CoV-2.
Some homologue target-drug models have been proposed between SARS-CoV and SARS-CoV-2 because of some viral similarities as the receptor RBD in S protein with 76% of sequence similarity. In a study tradeallcrypto of 452 Chinese patients in Wuhan, severe cases tended to have lower lymphocyte counts. This dearth of lymphocytes was mainly attributed to significantly lower T cell counts in severe cases.
China had much lower percentages of the population that was tested and developed complex disease compared to Spain (13.8% vs. to 23% respectively). During the first week of January, China’s authorities announced that the new atypical pneumonia was not caused by either the SARS or the MERS Coronavirus, but a new variant of the Coronaviriade family, a newly discovered virus called SARS-CoV2 . Subsequent investigations discovered that the etiological agent was a RNA virus related to the same family of Coronavirus that caused the Severe Acute Respiratory Syndrome and to Respiratory Syndrome of Middle East pandemic during 2003 and 2012 respectively (Lu et al., 2020). In order to offer a clear insight of the extensive literature available, we have conducted a comprehensive literature review of the SARS CoV-2 Virus and the Coronavirus Diseases 2019 (COVID-19). The large amount of information received daily relating to COVID-19 is so abundant and dynamic that medical staff, health authorities, academics and the media are not able to keep up with this new pandemic.
RBD is the most variable part of SARS-CoV-2 genome (Andersen et al., 2020; Gralinski and Menachery, 2020). Six RBD amino acids are involved in the binding to ACE2 receptors (Donoghue et al., 2000), and 5 of these 6 residues differ between SARS-CoV and SARS-CoV-2 (Liu et al., 2011) (Fig. 3a and b). For best practices on efficiently downloading information from SEC.gov, including the latest EDGAR filings, visit sec.gov/developer.