COVID‐19 vaccine‐related new‐onset lichen planus

Coronavirus disease 2019 (COVID‐19) vaccines significantly impacted world health and well‐being. However, various adverse events have been observed following severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination. Cutaneous reactions have been prevalent following many vaccines, including COVID‐19 vaccines. Here, we present a case of new‐onset lichen planus in a patient who received the COVID‐19 vaccine at the same time as being infected with SARS‐CoV‐2. A 52‐year‐old woman presented to the clinic with extensive pruritic skin lesions. The eruptions had appeared a week after her second dose of the Sinopharm COVID‐19 vaccine. She mentioned a history of SARS‐CoV‐2 infection approximately 10 days following the first dose of her vaccine, causing a 1‐month delay in getting the second dose. Her past medical history was not significant. On examination, erythematous and squamous papules were demonstrated predominantly on the extremities, including inguinal and axillary folds. Moreover, desquamation of the lips was visible, and buccal lesions were also found. After consultation with a dermatologist, a skin biopsy was indicated for the patient, but she refused to undergo the procedure. Therefore, considering the typical appearance of the eruptions, lichen planus was suspected, for which she was treated with oral antihistamines and topical corticosteroids.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

The role and significance of angiotensin‐converting enzyme 2 peptides in the treatment of coronavirus disease 2019

Since the end of 2019, coronavirus disease 2019 (COVID‐19) caused by the novel coronavirus (2019‐nCoV) posed a serious threat to human health and life. Therefore, the discovery of drugs that can effectively prevent and treat COVID‐19 is urgently warranted. In this article, the role and significance of angiotensin‐converting enzyme 2 in drug development and the treatment of COVID‐19 are discussed. It was found that the binding of ACE2 to SARS‐CoV‐2‐RBD involved two core regions (31st and 353rd lysine) and 20 amino acids of the ACE2 protein. The mutation of these amino acids could lead to a great change of the binding ability of ACE2 and SARS‐CoV‐2‐RBD. This information was important for us to find more efficient ACE2 peptides to block the 2019‐nCoV infection. So during this study, we summarized the role of ACE2 in the regulation of 2019‐nCoV infection and stress, and hypothesized that the development and optimization of ACE2 peptide can effectively block 2019‐nCoV infection and reliably treat the COVID‐19.     

Clinical manifestations,treatment options,and comorbidities in COVID‐19 relapse patients: A systematic review

IntroductionInterest revolving around coronavirus disease 2019 (COVID‐19) reinfection is escalating rapidly. By definition, reinfection denotes severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), PCR redetection, and COVID‐19 recurrence within three months of the initial symptoms. The main aim of the current systematic review was to evaluate the features of COVID‐19 relapse patients.Materials and methodsFor this study, we used a string of terms developed by a skilled librarian and through a systematical search in PubMed, Web of Science, and Embase for eligible studies. Clinical surveys of any type were included from January 2019 to March 2021. Eligible studies consisted of two positive assessments separated by a negative result via RT‐PCR.ResultsFifty‐four studies included 207 cases of COVID‐19 reinfection. Children were less likely to have COVID‐19 relapse. However, the most patients were in the age group of 20–40 years. Asthenia (66.6%), headache (66.6%), and cough (54.7%) were prevalent symptoms in the first SARS‐CoV‐2 infection. Asthenia (62.9%), myalgia (62.9%), and headache (61.1%) were most frequent in the second one. The most common treatment options used in first COVID‐19 infection were lopinavir/ritonavir (80%), oxygen support (69.2%), and oseltamivir (66.6). However, for the treatment of second infection, mostly antibiotics (100%), dexamethasone (100%), and remdesivir (80%) were used. In addition, obesity (32.5%), kidney failure (30.7%), and hypertension (30.1%) were the most common comorbidities. Unfortunately, approximately 4.5% of patients died.ConclusionWe found the potency of COVID‐19 recurrence as an outstanding issue. This feature should be regarded in the COVID‐19 management. Furthermore, the first and second COVID‐19 are similar in clinical features. For clinically practical comparison of the symptoms severity between two epochs of infection, uniform data of both are required. We suggest that future studies undertake a homogenous approach to establish the clinical patterns of the reinfection phenomena.     

COVID‐19 in HIV‐positive patients: A systematic review of case reports and case series

IntroductionCoronavirus disease 2019 (COVID‐19) and acquired immune deficiency syndrome (AIDS) are two viral diseases for which there are currently no definitive treatments. Nowadays, because of the health system''s focus on the COVID‐19 epidemic, the control of human immunodeficiency virus (HIV) has received less attention. In this review, we will discuss the characteristics of COVID‐19 in HIV‐positive patients.Material and MethodsUsing the PRISMA guideline, the databases of Scopus, PubMed, and Web of Science were searched systematically from January 1, 2019 to February 24, 2021. The following keywords were used: “Human Immunodeficiency Virus,” “acquired immune deficiency syndrome,” “HIV,” “AIDS,” “COVID‐19,” “severe acute respiratory syndrome coronavirus 2,” “novel coronavirus,” “SARS‐CoV‐2,” “nCoV disease,” “SARS2,” and “2019‐nCoV disease.”ResultsTwenty‐one percent of studies were conducted in the USA (n = 13), 16% in China (n = 10), and 13% in Italy (n = 8), respectively. The majority of the patients were men (74.3%). Tenofovir disoproxil fumarate was used in 47.4% of patients, emtricitabine in 58.4%, and lamivudine in 34.8% to treat HIV. Symptoms of HIV patients with COVID‐19 included coughing (81.3%), fever (62.8%), and dyspnea (60%). Hydroxychloroquine (39.34%) and azithromycin (36.58%) were the common treatment options for COVID‐19. The total death rate in HIV‐positive patients with COVID‐19 was about 9%.ConclusionIn the current systematic review, we demonstrated that HIV‐positive patients co‐infected with COVID‐19 have high comorbidity of hypertension and diabetes mellitus. HIV/COVID‐19 co‐infection might have negatively influenced the HIV treatment and diagnosis, which indicates the need to regularly screen HIV patients in the COVID‐19 pandemic.     

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.     

Heterogeneity assessment of vaccine‐induced effects using point‐of‐care surrogate neutralization test for severe acute respiratory syndrome coronavirus 2

IntroductionCoronavirus disease (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has become a global pandemic even after vaccination. We aimed to identify immunological heterogeneity over time in vaccinated healthcare workers using neutralization antibodies and neutralizing activity tests.MethodsSerum samples were collected from 214 healthcare workers before vaccination (pre) and on days 22, 90, and 180 after receiving the first dose of BNT162b2 vaccine (day 0). Neutralization antibody (NAb, SARS‐CoV‐2 S‐RBD IgM/IgG) titers and two kinds of surrogate virus neutralization tests (sVNTs) were analyzed (UMIN000043851).ResultsThe NAb (SARS‐CoV‐2 S‐RBD IgG) titer peaked on day 90 after vaccination (30,808.0 μg/ml ± 35,211; p < 0.0001) and declined on day 180 (11,678.0 μg/ml ± 33,770.0; p < 0.0001). The neutralizing activity also peaked on day 90 and declined with larger individual differences than those of IgG titer on day 180 (88.9% ± 15.0%, 64.8% ± 23.7%, p < 0.0001). We also found that the results of POCT‐sVNT (immunochromatography) were highly correlated with those of conventional sVNT (ELISA).ConclusionsNeutralizing activity is the gold standard for vaccine efficacy evaluation. Our results using conventional sVNT showed large individual differences in neutralizing activity reduction on day 180 (64.8% ± 23.7%), suggesting an association with the difference in vaccine efficacy. POCT‐sVNT is rapid and user‐friendly; it might be used for triage in homes, isolation facilities, and event venues without restrictions on the medical testing environment.     

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.