An overview on inactivated and live‐attenuated SARS‐CoV‐2 vaccines

After about 2 years since severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), first infections were detected in Wuhan city of China in December 2019, which was followed by a worldwide pandemic with a record of 5.41 million deaths. Due to urgent need for the development of a safe and effective vaccine for coronavirus disease 2019 (COVID‐19), attempts for producing efficient vaccines are inexhaustibly continuing. According to a report by the World Health Organization (WHO) on COVID‐19 vaccine tracker and landscape, there are 149 vaccine candidates all over the world. Inactivated SARS‐CoV‐2 vaccines as a conventional vaccine platform consist of whole virus particles grown in cell culture and inactivated by chemicals. Because of benefits such as antigenic similarity to real virion inducing humoral and cellular immune responses and ease for transport and storage, these vaccines, including the vaccines produced by Bharat Biotech, Sinopharm, and Sinovac, are in use at large scales. In this study, we have a review on inactivated SARS‐CoV‐2 vaccines that are passing their phase 3 and 4 clinical trials, population which was included in the trials, vaccine producers, the efficiency, adverse effects, and components of vaccines, and other vaccine features.     

Orbital inflammatory disease following mRNA SARS‐CoV‐2 vaccine

A 65‐year‐old woman reported orbital symptoms two days after her first dose and presented exacerbation of signs after the second dose of BNT162b2 mRNA vaccine. The temporal relationship between the COVID‐19 vaccination and orbital symptoms suggests a probable link between SARS‐CoV‐2 mRNA vaccine and this orbital inflammatory disease.     

Prolonged SARS‐Cov‐2 shedding with rapid IgG antibody decay in a COVID‐19 patient: A case report

BackgroundThe coronavirus disease 2019 (COVID‐19) epidemic is still spreading rapidly around the world. Recent cases with prolonged severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) RNA detection have been successively reported, and the phenomenon of false‐negative real‐time polymerase chain reaction (RT‐PCR) results of SARS‐CoV‐2 RNA or “repositive” was also described in COVID‐19 patients.MethodsWe report a 69‐year‐old female patient with hypertension, suspected lung tumor, and previous history of total hysterectomy for hysteromyoma who presented with moderate COVID‐19 symptoms and was positive for SARS‐CoV‐2 RNA by RT‐PCR when she traveled from the USA to China.ResultsThe patient required second and third re‐hospitalizations due to “repositive” SARS‐CoV‐2 throat swab test results during post‐charge solitary isolation and observation, and serum SARS‐CoV‐2‐IgG decayed rapidly before disappearing on illness Day 139 when the throat swab was still positive. The virus shedding lasted for at least 146 days (the last positive throat swab test result was on illness Day 146, and the first true‐negative test result was on illness Day 151) since her initial positive test.ConclusionProlonged SARS‐CoV‐2 RNA viral shedding is prone to occur in an immunocompromised host, wherein changes in the host immune status can lead to repeated positive SARS‐CoV‐2 detection. Moreover, the SARS‐CoV‐2‐IgG may decrease rapidly and disappear before virus removal, indicating there may be certain limitations on the protective effect of the SARS‐CoV‐2 antibody, which deserves clinical attention.     

Hypersensitivity in the lungs is responsible for acute respiratory failure in COVID‐19 patients: Case series of patients who received high‐dose/short‐term methylprednisolone

BackgroundCOVID‐19 is a highly contagious respiratory disease caused by the SARS‐CoV‐2 virus. Patients with severe disease have a high fatality rate and face a huge medical burden due to the need for invasive mechanical ventilation. Hypoxic respiratory failure is the major cause of death in these patients. There are currently no specific anti‐SARS‐CoV‐2 drugs, and the effect of corticosteroids is still controversial.MethodsThe clinical data of 102 COVID‐19 patients, including 27 patients with severe disease, were analyzed. The serum levels of total IgE and anti‐SARS‐CoV‐2 specific IgE were compared in healthy controls and COVID‐19 patients, changes in the level of anti‐SARS‐CoV‐2 specific IgE and clinical response to methylprednisolone (MP) treatment were analyzed, and the effect of high‐dose/short‐term MP therapy for patients with critical illness and respiratory failure was determined.ResultsCOVID‐19 patients had elevated serum levels of anti‐SARS‐CoV‐2 specific IgE, and patients with severe disease, especially critical illness, had even higher levels. Application of short‐term/high‐dose MP significantly reduced the level of these IgE antibodies and also blocked the progression of hypoxic respiratory failure. Hypoxic respiratory failure in patients with COVID‐19 is related to pulmonary hypersensitivity.ConclusionsHypersensitivity in the lungs is responsible for acute respiratory failure in COVID‐19 patients. Application of high‐dose/short‐term MP appears to be an effective life‐saving method for COVID‐19 patients who have hypoxic respiratory failure.     

SARS‐CoV‐2, HIV,and Mycobacterium tuberculosis triple co‐infection

Tuberculosis (TB)‐related death has increased for the first time in a decade due to the coronavirus disease 2019 (COVID‐19), globally. People living with HIV (PLWHIV) might be at a higher risk of developing COVID‐19‐related complications. Herein, we describe the first case of a patient surviving from SARS‐CoV‐2‐TB‐HIV triple co‐infection in Cameroon. A 36‐year‐old Cameroonian woman presented at the emergency unit of the Jamot Hospital, Yaoundé with symptoms of anorexia, productive cough, weight loss, and fever. The SARS‐CoV‐2 rapid antigen test on nasopharyngeal sample was positive. Chest X‐ray showed bilateral parenchymal and tracheal calcifications most consistent with prior pulmonary histoplasmosis, varicella, or TB. She was tested HIV positive, and the sputum sample tested positive for TB on auramine staining. TB therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol) and COVID‐19 treatment were initiated, and the symptoms improved after 2 weeks of treatment. The SARS‐CoV‐2 rapid antigen and real‐time polymerase chain reaction tests were negative after 2 weeks. She was discharged home on antiretroviral therapy and TB therapy. Coinfection with both TB, HIV, and SARS‐CoV‐2 may be common in Cameroon but not reported. The similar clinical features of COVID‐19 and TB usually lead to misdiagnosis. Early diagnosis and initiation of appropriate treatment improve outcome.     

The utility of SARS‐CoV‐2 nucleocapsid protein in laboratory diagnosis

BackgroundThe Coronavirus Disease 2019 (COVID‐19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which has now become a global pandemic owing to its high transmissibility. The SARS‐CoV‐2 nucleocapsid protein tests are playing an important role in screening and diagnosing patients with COVID‐19, and studies about the utility of SARS‐CoV‐2 nucleocapsid protein tests are increasing now.MethodsIn this review, all the relevant original studies were assessed by searching in electronic databases including Scopus, Pubmed, Embase, and Web of Science. “SARS‐CoV‐2”, “COVID‐19”, “nucleocapsid protein”, and “antigen detection” were used as keywords.ResultsIn this review, we summarized the utility of SARS‐CoV‐2 nucleocapsid protein in laboratory diagnosis. Among the representative researches, this review analyzed, the sensitivity of SARS‐CoV‐2 nucleocapsid protein detection varies from 13% to 87.9%, while the specificity could almost reach 100% in most studies. As a matter of fact, the sensitivity is around 50% and could be higher or lower due to the influential factors.ConclusionIt is well suggested that SARS‐CoV‐2 nucleocapsid protein is a convenient method with a short turnaround time of about half an hour, and the presence of N antigen is positively related to viral transmissibility, indicating that SARS‐CoV‐2 N protein immunoassays contribute to finding out those infected people rapidly and segregating them from the uninfected people.     

Recombinant subunits of SARS‐CoV‐2 spike protein as vaccine candidates to elicit neutralizing antibodies

ObjectivesThe spike protein has been reported as one of the most critical targets for vaccine design strategies against the SARS‐CoV‐2 infection. Hence, we have designed, produced, and evaluated the potential use of three truncated recombinant proteins derived from spike protein as vaccine candidates capable of neutralizing SARS‐CoV‐2 virus.MethodsIn silico tools were used to design spike‐based subunit recombinant proteins (RBD (P₁), fusion peptide (P₂), and S1/S2 cleavage site (P₃)). These proteins were checked for their ability to be identified by the anti‐SARS‐CoV‐2 antibodies by exposing them to COVID‐19 serum samples. The proteins were also injected into mice and rabbit, and the antibody titers were measured for 390 days to assess their neutralization efficiency.ResultsThe antibodies that existed in the serum of COVID‐19 patients were identified by designed proteins. The anti‐spike antibody titer was increased in the animals injected with recombinant proteins. The VNT results revealed that the produced antibodies could neutralize the cultured live virus.ConclusionTruncated subunit vaccines could also be considered as robust tools for effective vaccination against COVID‐19. Using a combination of in silico, in vitro, and in vivo experiments, it was shown that the injection of spike‐based truncated recombinant proteins could stimulate long‐lasting and neutralizing antibody responses.     

Nucleocapsid protein of SARS‐CoV‐2 is a potential target for developing new generation of vaccine

BackgroundSARS‐CoV‐2 has spread worldwide causing more than 400 million people with virus infections since early 2020. Currently, the existing vaccines targeting the spike glycoprotein (S protein) of SARS‐CoV‐2 are facing great challenge from the infection of SARS‐CoV‐2 virus and its multiple S protein variants. Thus, we need to develop a new generation of vaccines to prevent infection of the SARS‐CoV‐2 variants. Compared with the S protein, the nucleocapsid protein (N protein) of SARS‐CoV‐2 is more conservative and less mutations, which also plays a vital role in viral infection. Therefore, the N protein may have the great potential for developing new vaccines.MethodsThe N protein of SARS‐CoV‐2 was recombinantly expressed and purified in Escherichia coli. Western Blot and ELISA assays were used to demonstrate the immunoreactivity of the recombinant N protein with the serum of 22 COVID‐19 patients. We investigated further the response of the specific serum antibodies and cytokine production in BALB/c mice immunized with recombinant N protein by Western Blot and ELISA.ResultsThe N protein had good immunoreactivity and the production of IgG antibody against N protein in COVID‐19 patients was tightly correlated with disease severity. Furthermore, the N protein was used to immunize BALB/c mice to have elicited strong immune responses. Not only high levels of IgG antibody, but also cytokine‐IFN‐γ were produced in the N protein‐immunized mice. Importantly, the N protein immunization induced a high level of IgM antibody produced in the mice.ConclusionSARS‐CoV‐2 N protein shows a great big bundle of potentiality for developing a new generation of vaccines in fighting infection of SARS‐CoV‐2 and its variants.     

Anticoagulated de novo atrial flutter complicated by transitory ischemic attack in fatal COVID‐19

SARS‐CoV‐2 may not only manifest as pneumonia (COVID‐19) but also in other organs, including the brain (neuro‐COVID). One of the cerebral complications of SARS‐CoV‐2 is ischemic stroke. Transitory ischemic attack (TIA) in a SARS‐CoV‐2 positive has not been reported. A 78‐year‐old poly‐morbid male (diabetes, hypertension, and coronary heart disease), admitted for COVID‐19, developed atrial flutter on hospital day (hd) 2. Anticoagulation with enoxaparin was started. On hd5, he experienced a TIA despite sufficient anticoagulation. The patient expired on hd28 due to multi‐organ failure from sepsis due to superinfection with staphylococcus aureus. Infection with SARS‐CoV‐2 may be complicated by atrial flutter. Atrial flutter may be complicated by TIA despite sufficient anticoagulation, suggesting that standard anticoagulation may be insufficient to meet SARS‐CoV‐2‐associated hypercoagulability syndrome. Forced anticoagulation and adequate antibiosis in poly‐morbid SARS‐CoV‐2‐infected patients with hypercoagulability and cytokine storm are warranted.     

Beware of the ambiguous enemy of multisystem inflammatory syndrome in adult (MIS‐A) following Covid‐19 infection or vaccination

Multisystem Inflammatory Syndrome is a rare and novel clinical presentation described during the evolving COVID‐19 pandemic. The condition is usually presenting as a sepsis‐like syndrome leading to secondary multi‐organ dysfunction post–COVID‐19 infection. Although the syndrome has been mainly described in children, rare adults'' form has been similarly described. We are describing a 37‐year‐old female patient presented with fever and neck pain after 1 month of a mild SARS‐CoV‐2 infection course and 10 days post her second COVID‐19 vaccine. Examination demonstrated fever, hypotension, and hypoxemia, in addition to multiple tender cervical lymph nodes. Initial laboratory workup showed evidence of significant inflammation with raised markers, including C‐reactive protein, ferritin, and interleukin‐6. Extensive evaluation to rule out active infection was done, and all return negative, including repeat SARS‐CoV‐2 test. Furthermore, cardiac evaluation showed moderately reduced systolic ventricular function. Despite all negative test and supportive measures, the patient continued to deteriorate requiring critical care admission for ionotropic support, non‐invasive ventilation in addition to presumptive broad‐spectrum antimicrobial management. There was no significant improvement with supportive care until the presentation of multisystem involvement on in the context of a recent history of COVID 19 and negative infective screen was raised. The diagnosis of multisystem inflammatory syndrome‐adult form (MIS‐A) was embraced, and the patient was commenced on methylprednisolone leading to a dramatic resolution of symptoms both clinically and biochemically with stabilization of vital functions allowing for safe outcomes.     

COVID‐19 vaccine‐induced Radiation Recall Dermatitis: Report of a case

Radiation Recall Dermatitis (RRD) is an inflammatory process in the site of irradiation, induced by physical and medical agents. Few cases of RRD in the skin and lung have been reported after COVID‐19 vaccination. Here, we report radiation recall dermatitis after both doses of inactivated SARS‐CoV‐2 vaccine (Sinopharm, China).     

Recent advances and developments in COVID‐19 in the context of allergic diseases

BackgroundSince the first reports of coronavirus disease 2019 (COVID‐19) in Wuhan, China, in December 2019, there have been 198 million confirmed cases worldwide as of August 2021. The scientific community has joined efforts to gain knowledge of the newly emerged virus named severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the immunopathological mechanisms leading to COVID‐19, and its significance for patients with allergies and asthma.MethodsBased on the current literature, recent advances and developments in COVID‐19 in the context of allergic diseases were reviewed.Results and ConclusionsIn this review, we discuss the prevalence of COVID‐19 in subjects with asthma, attacks of hereditary angioedema, and other allergic diseases during COVID‐19. Underlying mechanisms suggest a protective role of allergy in COVID‐19, involving eosinophilia, SARS‐CoV‐2 receptors expression, interferon responses, and other immunological events, but further studies are needed to fully understand those associations. There has been significant progress in disease evaluation and management of COVID‐19, and allergy care should continue during the COVID‐19 pandemic. The European Academy of Allergy & Clinical Immunology (EAACI) launched a series of statements and position papers providing recommendations on the organization of the allergy clinic, handling of allergen immunotherapy, asthma, drug hypersensitivity, allergic rhinitis, and other allergic diseases. Treatment of allergies using biologics during the COVID‐19 pandemic has also been discussed. Allergic reactions to the COVID‐19 vaccines, including severe anaphylaxis, have been reported. Vaccination is a prophylactic strategy that can lead to a significant reduction in the mortality and morbidity associated with SARS‐CoV‐2 infection, and in this review, we discuss the proposed culprit components causing rare adverse reactions and recommendations to mitigate the risk of anaphylactic events during the administration of the vaccines.     

COVID‐19 infection presenting as paroxysmal nocturnal hemoglobinuria

A diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) was elicited during acute COVID‐19 infection. COVID‐19 spike proteins trigger the alternative pathway of complement. Acute SARS‐CoV‐2 infection possibly expanded an existing PIG‐A mutation.     

Large scale production and characterization of SARS‐CoV‐2 whole antigen for serological test development

BackgroundThe rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has generated a pandemic with alarming rates of fatality worldwide. This situation has had a major impact on clinical laboratories that have attempted to answer the urgent need for diagnostic tools, since the identification of coronavirus disease 2019 (COVID‐19). Development of a reliable serological diagnostic immunoassay, with high levels of sensitivity and specificity to detect SARS‐CoV‐2 antibodies with improved differential diagnosis from other circulating viruses, is mandatory.MethodsAn enzyme‐linked immunosorbent assay (ELISA) using whole inactivated virus cultured in vitro, was developed to detect viral antigens. WB and ELISA investigations were carried out with sera of convalescent patients and negative sera samples. Both analyses were concurrently performed with recombinant MABs to verify the findings.ResultsPreliminary data from 10 sera (5 patients with COVID‐19, and 5 healthy controls) using this immunoassay are very promising, successfully identifying all of the confirmed SARS‐CoV‐2‐positive individuals.ConclusionThis ELISA appears to be a specific and reliable method for detecting COVID‐19 antibodies (IgG, IgM, and IgA), and a useful tool for identifying individuals which have developed immunity to the virus.     

A rapid and highly effective approach for SARS‐CoV‐2 nucleic acid daily testing in more than four thousand single‐tube samples

BackgroundPresently, the global spread of COVID‐19 is still going on, with more than 0.6 million new cases confirmed per day (as of November 20, 2021). However, since China entered a post‐epidemic phase in mid‐March 2020, the daily number of new domestic infections in the Chinese mainland has been maintained at almost zero or single digits, which was attributed to a series of effective measures for COVID‐19 prevention and control adopted by the Chinese government. Among these measures, SARS‐CoV‐2 nucleic acid testing holds key role for the timely confirmation and isolation of the infections to prevent further transmission.MethodsReferring to the national policy requirements, since April 30, 2020, The Affiliated Hospital of Qingdao University has conducted SARS‐CoV‐2 nucleic acid testing in its PCR laboratory for patients and social workers, as well as for environmental monitoring and employee screening. As of mid‐November 2020, the daily amount of single‐tube samples for nucleic acid testing rose above 4,000.ResultsIn this article, a rapid and highly effective approach for SARS‐CoV‐2 nucleic acid daily testing is presented, allowing five technicians to complete nucleic acid testing in 6,500 single‐tube samples in one day with a high level of quality. Using this approach, since the samples entered the PCR laboratory, all testing results were reported in 2.5–3 h with satisfactory quality control and precise reporting criterion as prerequisites.ConclusionThis testing approach provides a referable workflow for other testing institutions and is expected to play an important role in COVID‐19 prevention and control.     

Dynamic observation of SARS‐CoV‐2 IgM,IgG, and neutralizing antibodies in the development of population immunity through COVID‐19 vaccination

BackgroundCurrently, mass vaccine inoculation against coronavirus disease‐2019 (COVID‐19) has been being implemented globally. Rapid and the large‐scale detection of serum neutralizing antibodies (NAbs) laid a foundation for assessing the immune response against SARS‐CoV‐2 infection and vaccine. Additional assessments include the duration of antibodies and the optimal time for a heightened immune response.MethodsThe performance of five surrogate NAbs—three chemiluminescent immunoassay (CLIA) and two enzyme‐linked immunosorbent assays (ELISAs)—and specific IgM and IgG assays were compared using COVID‐19‐vaccinated serum (n = 164). Conventional virus neutralization test (cVNT) was used as a criterion and the diagnostic agreement and correlation of the five assays were evaluated. We studied the antibody responses after the two‐dose vaccine in volunteers up to 6 months.ResultsThe sensitivity and specificity of five surrogate NAb assays ranged from 84% to 100%. Our cVNT results indicated great consistency with the surrogate assays. At 28 days after primary vaccination, the seropositivities of the NAbs, IgG, and IgM were 6%, 4%, and 13%, respectively. After the booster dose, seropositivities reached 14%, 65%, and 97%, respectively. Six months after receipt of the second dose, the NAb positive rate was eventually maintained at 66%. In all COVID‐19 convalescents, patients were detected with 100% NAb sat three months after discharge.ConclusionCOVID‐19 vaccine induced a humoral immune response lasting at least six months. Rapid serological detection was used as a proxy for identifying changes in immunity levels and as a guide to whether an individual may require a booster vaccination.